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.


[Defluoridation of household water].

[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.


[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.


[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.


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.


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.


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.


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.


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.


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.


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.


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.


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.


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.


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+.


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.


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.


[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.


[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.


[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.


[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.


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.


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.


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.


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.


[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.


[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.


[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.


[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.


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.


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.


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.


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.


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.


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.


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.


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.


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.


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.


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.


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.


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.


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.


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.


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.


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.


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.


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.


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.


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.


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.


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.


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.


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.


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.


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.


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.


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.


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.


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.


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.


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.


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.


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.


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.


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.


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.


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.


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.


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.


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.


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.


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.


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.


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.


Mechanism for phenothiazine oxidation.

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.


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.


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.


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.


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.


Fluorescence properties of glafenine.

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.


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.


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.


Combining therapeutic approaches.

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.


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.


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.


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.


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.


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.


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.


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.


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.


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.


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.


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.


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.


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.


Pleural effusions.

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.


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.


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.


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.


[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.


[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.


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.