Prognostic factors in polyarteritis.

Prognostic factors in polyarteritis. The clinical course of 40 patients with polyarteritis was reviewed to determine prognostic factors and response to treatment. The first three months were the most critical to survival. Survivorship was 57 per cent at five years. Older age of onset, involvement of skeletal muscle and presence of peripheral neuropathy weighted against a satisfactory outcome. Cutaneous vasculitis was associated with a more benign course. Myocardial disease, central nervous system involvement, or hypertension were not invariably poor prognostic factors. Muscle biopsies, even in the absence of clinical involvement, were a useful diagnostic procedure, and renal angiograms were found to be a valuable alternative to renal biopsy. An unequivocal distinction on clinical and histopathologic criteria could not be made among polyarteritis nodosa, hypersentitivity angiitis, and allergic granulomatosis. Australia antigenemia occurred in six per cent of patients. Although evaluation of therapy was difficult, data from this study did not show a superiority of high vs. low dosage of corticosteroids in suppressing active disease.


Importance of the aromatic ring in adrenergic amines. 2. Synthesis and adrenergic activity of some nonaromatic six- and eight-membered ring analogs of beta-phenylethanolamine. The synthesis of beta-phenylethanolamine analogs in which the phenyl ring is replaced by cyclohexyl, cyclohexen-4-yl, cyclooctyl, cyclooctenyl, cycloocta-1,3-dien-2-yl, cycloocta-1,5-dienyl, and cyclooctatetraenyl was accompanied by conversion of the corresponding aldehydes to the cyanohydrins followed by reduction with lithium aluminum hydride. A preparatively useful synthesis of 1-formylcyclooctatetraene is described utilizing the photocycloaddition of methyl propiolate to benzene followed by reduction to the alcohol and oxidation with MnO2. All compounds, as their hydrochloride salts, exhibited indirect adrenergic activity on the rat vas deferens. On the reserpinized rat vas deferens all compounds potentiated the effects of exogenous norepinephrine. The results are in agreement with the conclusion that the more saturated the ring moiety, the greater the affinity for the amine uptake site of the vas deferens and suggest that there is no important interaction between the drug and this uptake site that involves pi-complex formation.


Conformationally restricted analogs of histamine H1 receptor antagonists: trans and cis-1-benzyl-3-dimethylamino-6-phenylpiperidine. The syntheses of trans- and cis-1-benzyl-3-dimethylamino-6-phenylpiperidine (1 and 2) are described. Compounds 1 and 2 were found to be inhibitors to histamine, acetylcholine, and barium chloride induced contractions of the isolated guinea pig ileum. Compounds 1 and 2 do not exhibit appreciable stereoselectivity in their ability to inhibit smooth muscle contractions. The cis compound 2 is a more effective inhibitor of histamine N-methyltransferase than the trans isomer 1.


Synthesis and adrenoreceptor blocking action of aziridinium ions derived from phenoxybenzamine and dibenamine. Crystalline perchlorate salts of aziridinium ions derived from phenoxybenzamine and dibenamine were prepared. Both aziridinium ions were tested on the rat vas deferens and found to possess alpha-adrenergic potencies which were nearly identical with those of the parent compounds. The hydrolysis rates of phenoxybenzamine and dibenamine aziridinium ions (2a,b) in physiological medium were found to be 6.0 4 x 10(-4) and 8.35 x 10(-4) sec-1, respectively. The rates of cyclization of the parent amines to 2a and 2b in aqueous medium were 1.9 x 10(-2) and 7.2 x 10(-3) sec-1, respectively. The potencies and kinetic profiles indicate that the aziridinium ion is the only active species in alpha-adrenergic blockade. Moreover, differences in potency between phenoxybenzamine and dibenamine appear to be exclusively to a difference in receptor affinity rather than to a difference in intrinsic alkylating ability.


Prebiotic peptide-formation in the solid state. II. Reaction of glycine with adenosine 5'-triphosphate and P1,P2-diadenosine-pyrophosphate. When a solution containing gly-N-pa and imidazole is evaporated to dryness and then maintained at a temperature between 65 degrees C and 100 degrees C, high yields of AppA and obligoglycines are obtained. We believe that ImpA is formed first, and then activates the carboxyl group of glycine or gly-A-pA. If glycine, ATP or AppA, and imidazole are heated together in the solid state, ImpA is formed and ATP , or indirectly from imidazole and gly-N-pA. Next the carboxyl group or glycine is activated by the ImpA formed in situ. The subsequent reactions of activated glycine leads to the formation of oligoglycines and the 2' (3')-glycylester of pA. Under plausible prebiobic conditions, good yields of oligoglycines up to the octamer can be obtained from glycine, ATP and imidazole.


Prebiotic peptide-formation in the solid state. III. Condensation reactions of glycine in solid state mixtures containing inorganic polyphosphates. The reactions of glycine with inorganic polyphosphates in the solid state have been studied. The formation of peptides up to the decamer occurs at moderate temperatures(r.t.-100 degrees C) in the presence of imidazole and magnesium chloride. If adenosine 5' -monophosphate is added to the reaction mixture, 2'(3') -o-glycyl adenosine 5'-monophosphate is also obtained. These reactions could have occurred on the primitive earth.


The prebiotic synthesis of deoxthymidine oligonucleotides. II. Comparison of condensing agents. A reaction which oligomerizes nucleotides under possible prebiotic conditions has been characterized. Nucleoside monophosphate in the presence of cyanamide at acid pH condenses to form dithymideine pyrophosphate and phosphodiester bonded compounds. Imidazole compounds and activated precursors such as nucleoside triphosphate are not necessary for this ologomerization reaction which produces primarily cyclic ologonucleotides.


Formation of nucleoside 5'-polyphosphates from nucleotides and trimetaphosphate. When solutions of nucleoside 5'-phosphates and trimetaphosphate are dried out at room temperature, nucleoside 5'-polyphosphates are formed. The Mg++ ion shows a superior catalytic function in this reaction when compared with other divalent metal ions. Starting with nucleoside 5'-phosphates, Mg++ and trimetaphosphate, the predominant products in the nucleoside 5'-polyphosphate series pnN are p4N, P7N and p10N. Nucleoside 5'-diphosphates yield p5N and p8N, nucleoside 5'-triphosphates give p6N and p9N. The prebiological relevance of these reactions is discussed.


On the possible role of organic melanoidin polymers as matrices for prebiotic activity. One of the major diagenetic pathways of organic matter in recent sediments involves the condensation of cellular constituents, particularly amino acids and sugars, into insoluble melanoidin-type polymers. These polymers consist mainly of humic and fulvic acids and make up the major part of the organic carbon reservoir in recent sediments. We suggest that a similar set of reactions between abiotically formed amino acids and sugars, and more generally between aldehydes and amines, occurred on a large scale in the prebiotic hydrosphere. The rapid formation of this insoluble polymeric material would have removed the bulk of the dissolved organic carbon from the primitive oceans and would thus have prevented the formation of an "organic soup". Melanoidin polymers have several properties which make them attractive hypothetical precursors of contemporary oxidation-reduction coenzymes: 1. they contain heterocyclic nitrogen compounds similar to the nitrogenous bases; 2. they contain a high concentration of stable free radicals; and 3. they tend to concentrate those heavy metals which play prominent roles in contemporary enzymic redox processes. The prebiotic formation of similar polymers could, therefore, have provided the starting point for a basic class of biochemical reactions. We suggest that the prebiotic scenario involved chemical and protoenzymic reactions at the sediment-ocean interface in relatively shallow waters and under conditions not much different from those of the recent environment.


Hemoglobin function in the vertebrates: an evolutionary model. Comparative data on quaternary structure, cooperativity, Bohr effect and regulation by organic phosphates are reviewed for vertebrate hemoglobins. A phylogeny of hemoglobin function in the vertebrates is deduced. It is proposed that from the monomeric hemoglobin of the common ancestor of vertebrates, a deoxy dimer, as seen in the lamprey, could have originated with a single amino acid substitution. The deoxy dimer has a Bohr effect, cooperativity and a reduced oxygen affinity compared to the monomer. One, or two, additional amino acid substitutions could have resulted in the origin of a tetrameric deoxy hemoglobin which dissociated to dimers on oxygenation. Gene duplication, giving incipient alpha and beta genes, probably preceded the origin of a tetrameric oxyhemoglobin. The origin of an organic phosphate binding site on the tetrameric hemoglobin of an early fish required only one, or two, amino acid substitutions. ATP was the first organic phosphate regulator of hemoglobin function. The binding of ATP by hemoglobin may have caused the original elevation in the concentration of ATP in the red blood cells by relieving end product inhibition of ATP synthesis. The switch from regulation of hemoglobin function by ATP to regulation by DPG may have been a consequence of the curtailment of oxidative phosphorylation in the red blood cell. The basic mechanisms by which ATP and DPG concentrations can respond to strss on the oxygen transport system were present before the origin of an organic phosphate binding site on hemoglobin. A switch from ATP regulation to IP5 regulation occurred in the common ancestor of birds.


Aminoacyl transfer from an adenylate anhydride to polyribonucleotides. Imidazole catalysis of phenylalanyl transfer from phenylalanine adenylate anhydride to the hydroxyl groups of homopolyribonucleotides was investigated as a chemical model of the biochemical aminoacylation of tRNA. Imidazole catalyzed transfer of phenylalanine to poly(U) increases from pH 6.5 to 7.7 and decreases above pH 7.7. At pH 7.7 approximately 10% of the phenylalanyl residues are transferred to poly(U). At pH 7.1, transfer to poly(U) was five times as great as to poly(A) and transfer to a poly(A) poly(U) double helix was negligible. At pH 7.1 approximately 45 mole percent linkages to poly(U) were monomeric phenylalanine; the remainder of the linkages were peptides of phenylalanine. The number of linkages and their lability to base and neutral hydroxylamine indicates that phenylalanine and its peptides are attached as esters to the 2' hydroxyl groups throughout poly(U) and the 2' (3') hydroxyl groups at the terminus of poly(U). These results do model the contemporary process of aminoacyl transfer to tRNA and continue to suggest that a histidine residue is in the active site of aminoacyl-tRNA-synthetases.


Hybrid-versus-parental strain reaction. I. Comparative mortality in allogenetic and parental strain male and female mice. Lethally irradiated male and female hybrids, parental strains, and the third party strain A mice were inoculated with reciprocal hybrid marrow from donors of the same sex. A graft-versus-host reaction was produced against H-Y antigens of reciprocal hybrids. Although the late mortality in inbred strain males was generally greater than that of females, without further tests this difference was not automatically attributable to an X or a Y chromosome disparity. Hybrids did not recognize the qualitative difference in antigenicity of their reciprocals, but they were able to recognize the quantitatively greater antigenicity of their parental strains, and a hybrid-versus-parental strain reaction occurred. The graft-versus-host reaction in the third party strain A mice was significantly more severe than that produced by hybrid marrow in their reciprocal hybrid recipients, but significantly less severe than that produced in the parental strains. The relationship between antigenicity and responsiveness was such that the severity of the graft-versus-host reactions masked the maternal influences observed with other reciprocal hybrids.


Graft versus leukemia. VI. Adoptive immunotherapy in combination with chemoradiotherapy for spontaneous leukemia-lymphoma in AKR mice. A three-step treatment plan incorporating adoptive immunotherapy and chemoradiotherapy was used to treat AKR (H-2k) mice bearing spontaneous leukemia-lymphoma (SLL). 1) Leukemic mice were treated with chemoradiotherapy for immunosuppression and leukemia cytoreduction. 2) To introduce a graft-versus-leukemia reaction against residual malignant cells, the immunosuppressed AKR mice were given immunocompetent cells from H-2 mismatched DBA/2 (H-2d) donors. 3) To "rescue" the AKR hosts from incipient graft-versus-host disease, the mismatched DBA/2 cells were killed with combination chemotherapy, and cells from allogeneic H-2 matched RF (H-2k) donors were administered to restore hematopoiesis. Leukemic AKR mice thus treated had significant prolongation of their median survival time and a higher 60-day survival rate post treatment than did untreated controls, chemoradiotherapy controls, or control mice that received chemoradiotherapy plus cells from syngeneic donors. Therefore, adoptive immunotherapy may be useful as an adjunct to conventional therapy for treatment of SLL in AKR mice.


A study of tobacco carcinogenesis. XIII. Tumor-promoting subfractions of the weakly acidic fraction. The weakly acidic fraction (WAF) of cigarette smoke particulate matter was fractioned by silica get chromatography. We assayed the various primary subfractions for potential tumor-promoting activity by measuring the incorporation of tritiated thymidine into mouse epidermal DNA as induced by these subfractions. Based on these results and on chemical composition, the primary subfractions, were then combined into four major subfractions and tested on initiated mouse skin for tumor-promoting activity by long-term application. Two of these subfractions (40% of WAF) were inactive, whereas the other two (18 and 35% of WAF) showed tumor-promoting activity. The two active portions were then further chromatographed and tested by the short-term bioassay. Some major components of the resulting active fractions included alkyl-2-cyclopenten-2-ol-1-ones, catechols, hydroquinone, fatty acids, and 3-hydroxypyridines. Among these components, catechol, hydroquinone, 3-hydroxypyridine, 6-methyl-3-hydroxypyridine, linolenic acid, and linoleic acid were inactive as tumor promoters in the experimental animal. The activity of the alkyl-2-cyclopenten-2-ol-1-ones is unknown. Other components remain to be identified.


Metabolic characteristics of cells infected with a herpesvirus of turkeys. Chicken embryo fibroblasts infected with the nononcogenic herpesvirus of turkeys (HVT) displayed an increased rate of glucose uptake, a pronounced alteration of the pH of the medium, and an increased production of lactic acid when compared to mock-infected cultures. Objective estimates of cytopathology (quantifiable neutral red uptake and cell protein determination) showed that cell deterioration was a slow process in HVT-infected cells when compared to infection by herpes simplex virus. Experiments with irradiated host cells demonstrated that HVT required functional cell DNA for replication. The inactivation of the necessary host cell function displayed multihit kinetics. In agreement  with data on other herpesviruses, HVT damaged by UV light could be photoreactivated in chick cells. The results indicate that HVT shares biologic properties in common with other herpes and transforming viruses.


Control of mercury pollution.

Control of mercury pollution. When a 203Ng(NO3)2 solution was kept at 25 degrees C in glass or polypropylene containers, 50 and 80% of original radioactivity was adsorbed to the containers' walls after 1 and 4 days, respectively. However, no loss in radioactivity was observed if the solution was supplemented with HgCl as carrier (100 mug Hg2+/ml) and stored in either container for 13 days. When 203Hg2+ was dissolved in glucose basal salt broth with added carrier, levels of 203Hg2+ in solution (kept in glass) decreased to 80 and 70% of original after 1 and 5 days and decreased even more if stored in polypropylene (60 and 40% of original activity after 1 and 4 days, respectively). In the absence of carrier, decreases of 203Hg2+ activities in media stored in either container were more pronounced due to chemisorption (but) not diffusion. The following factors affecting the removal of mercurials from aqueous solution stored in glass were examined: type and concentration of adsorbent (fiber glass and rubber powder); pH; pretreatment of the rubber; and the form of mercury used. Rubber was equally effective in the adsorption of organic and inorganic mercury. The pH of the aqueous 203Hg2+ solution was not a critical factor in the rate of adsorption of mercury by the rubber. In addition, the effect of soaking the rubber in water for 18 hr did not show any statistical difference when compared with nontreated rubber. It can be concluded that rubber is a very effective adsorbent of mercury and, thus, can be used as a simple method for control of mercury pollution.


Enzymic deacetylation of carcinogenic arylacetamides by tissue microsomes of the dog and other species. The relative ability of arylacetamide deacetylase enzyme systems of dog liver to carry out the deacetylation of the carcinogens, 4-acetylaminobiphenyl, 2-acetylaminofluorene, and 2-acetylaminaphthalene, was examined. The arylacetamides were incubated with unfortified dog liver microsomes, and enzyme activity (nmol arylamine/mg protein/hr) was estimated by colorimetric quantitation of the resulting arylamines. The dog liver enzyme system displayed characteristics similar to those described for the rodent liver enzyme system in that enzyme activity was greatest in liver tissue, was localized in the microsomal subcellular fraction, required no cofactors, and was inhibited by heat, sodium fluoride, and thiol reagents. In five replicate assays, the relative rates of deacetylation were about 10, 6, and 1 with 4-acetylaminobiphenyl (84.8 +/- 12.4), 2-acetylaminofluorene (52.5 +/- 5.1), and 2-acetylaminonaphthalene (8.8 +/- 3.3), respectively. As a canine urinary bladder carcinogen, 4-acetylaminobiphenyl is considered more potent than 2-acetylaminofluroene, while 2-acetylaminonaphthalene is devoid of detectable carcinogenic activity, despite the fact that 2-aminoaphthalene is a well-established canine urinary bladder carcinogen. Removal of the acetyl group may be a requirement for urinary bladder carcinogenesis; accordingly, the present studies demonstrate the appearance of a direct relationship between dog liver deacetylase enzyme specificity and urinary bladder susceptibility to these carcinogenic arylacetamides.


Renal chromium accumulation and its relationship to chromium-induced nephrotoxicity. This report is an attempt to study the renal handling of chromium under in vitro conditions and to relate this to the actions of the ion in the production of nephrotoxicity. Renal slice techniques were employed in these studies and were used to examine the effects of chromium on various renal transport processes. In addition, the accumulation of chromium by the renal tissue has also been studied. Marked accumulation by renal cortical slices of the rat was observed when 51Cr-labeled chromate or dichromate was added to the bathing solution. Some metabolic inhibitors interfered with this uptake process; in addition, some substrates metabolized by renal tissue reduced the accumulation of 51Cr. The use of [51Cr] dichromate and [51Cr]-chromate, as well as alterations in the bathing solution pH, indicated that in the rat chromium can interfere with renal transport processes, but that the oxidation state of this metal is not important. On the other hand, in the rabbit a greater interference with 51Cr uptake was noted at lower bathing solution pHs. This is interpreted to mean that chromate is the effective inhibitor in this species.


Sodium bicarbonate administration during cardiac arrest. Effect on arterial pH PCO2, and osmolality. Arterial pH, Pco2, and osmolality were determined serially during cardiac resuscitation in patients and in dogs, with and without administration of sodium bicarbonate. These studies demonstrate that (1) in the absence of preexisting acidosis, severe acidosis can be prevented by adequate ventilation alone; (2) sodium bicarbonate administration results in a significant rise in arterial Pco2, which parallels the rise in pH despite adequate ventilation; (3) during prolonged cardiac and resuscitation, there is a rise in arterial osmolality that is accentuated by sodium bicarbonate. These studies suggest that sodium bicarbonate should not be used during resuscitation (1) in the absence of effective hyperventilation or where carbon dioxide removal is inadequate despite adequate ventilation, (2) in repeated doses, without confirmation of substantial acidosis, or (3) when cardiac arrest has been of brief duration and preexisting acidosis is unlikely. These studies also point to the need for a reappraisal of other buffers that do not elevate the arterial Pco2.


Sarcotubular anomalous rectification of frog sartorius muscle. The membrane site responsible for anomalous rectification was determined in frog sartorius muscle fibers. The total current-voltage relation of glycerol-treated fibers which represents mainly the properties of the sarcolemma was linear for membrane potentials between about -90 and -50 mV. Thus moderate depolarization-induced anomalous rectification in intact fibers represents a property of the sarcotubular system. The absence of slow hyperpolarization in glycerol-treated fibers was caused by the abolition of early conductance increase, and the sarcotubular system is responsible for the inward rectifier. Picrotoxin selectively inhibited both moderate depolarization-induced anomalous rectification and hyperpolarization-induced early conductance increase. This suggests that the same component in the sarcotubular system is responsible for these conductance changes. The inhibition with picrotoxin of moderate depolarization-induced anomalous rectification suggests the possibility that it is caused by an electrogenic effect rather than a decrease in K conductance. A sarcolemmal hyperpolarization-activated slow conductance increase was revealed.


Properties of sarcolemmal delayed rectification in glycerol-treated fibers of frog sartorius muscle. Total current-voltage relations were analyzed on nine glycerol-treated surface fibers of frog sartorius muscles in tetrodotoxin-containing isotonic normal Ringer solution. The results indicate that delayed rectification occurs in the sarcolemma on large depolarization and that delayed rectification is only partially inactivated during 1 sec of depolarization and not converted into anomalous rectification. The time to peak, the time course of inactivation and the potassium activation potential determined in glycerol-treated fibers were comparable to those analyzed previously in intact fibers. The value of the conductance increase during delayed rectification in glycerol-treated fibers appeared to be smaller than that in intact fibers.


Sarcolemmal slow conductance increase of frog sartorius fibers during hyperpolarization. The properties of the hyperpolarization-activated sarcolemmal slow conductance increase in frog sartorius muscle fibers have been investigated using ethylenediaminetetraacetic acid disodium salt (EDTA) and propionate Ringer solution. More than 1 sec was required for maximum activation of the sarcolemmal slwo conductance increase. It is suggested that, although the sarcolemmal slow conductance increase was affected by deterioration, the conductance increase is not a direct product of deterioration but it represents a property of the sarcolemma which is encountered in physiological range. The sarcolemmal conductance increase was rather insensitive to the change in pH of Ringer solution. It is inferred that the absence of bellying in newly penetrated intact fibers at neutral and alkaline pHs is caused mainly by the shunting effect of large parallel conductance. Apparent augmentation with EDTA of the sarcolemmal conductance increase infers that Ca ions affect the conductance increase. The conductance increase occurred also in the EDTA-containing Cl-deficient solution. The sarcolemmal slow conductance increase has been compared with the change in Cl conductance reported by Hutter and Warner, and Warner.


Effects of antidepressant drugs on amygdaloid after-discharge in rats. Effects of antidepressant drugs on the amygdaloid after-discharge induced by stimulating the amygdala in rats implanted with chronic electrodes, were investigated in correlation with anti-muricidal effects as well as neurotoxicity. Tricyclic antidepressants such as amitriptyline, imipramine and nortriptyline markedly depressed both after-discharge and muricide at doses smaller than neurotoxic doses. The effect of PF-257 was also the same as tricyclic antidepressants. On the other hand, methamphetamine and pipradrol blocked the muricide at doses smaller than neurotoxic doses without depressing the amygdaloid after-discharge. Major tranquilizers, chlorpromazine and clozapine depressed both after-discharge and muricide only at doses larger than those which impaired rotarod performance. Haloperidol, on the contrary, depressed the after-discharge without selectively blocking the muricide. Minor tranquilizers, diazepam and chlordiazepoxide did not block the muricide at doses smaller than neurotoxic doses, although they showed a marked depression of the after-discharge.


Effects of several beta-blockers on blood pressure in the rat. Effects of practolol, alprenolol and pindolol on blood pressure in the rat were studied. Also effects of these three beta-blocking agents on blood pressure and heart rate in spinal rats during adrenaline infusion were studied and compared with those of propranolol. The beta-blocking agents produced a sustained pressor action in the rat, and in the spinal rat infused with adrenaline. The magnitude of the pressor action induced by the beta-blockers was in the following order: pindolol larger than or equal to propranolol larger than or equal to alprenolol greater than practolol. Minimum doses of these beta-blockers required to cause a pressor action in the spinal rat infused with adrenaline were in the following order; practolol greater than alprenolol larger than or equal to propranolol larger than or equal to pindolol. The magnitude of the pressor action produced by the same dose of these beta-blockers and minimum doses of these beta-blockers required to cause a pressor action in the spinal rat infused with adrenaline seemed to be roughly proportional to their beta-receptor blocking activities. It was concluded that the minimum doses of these beta-blockers required to cause a pressor action and the magnitude of the pressor action induced by the beta-blockers in the spinal rat infused with adrenaline could be used to compare their beta-blocking activities and that practolol, a cardioselective beta-blocker, seems to block not only cardiac beta-receptor but to some extent also peripheral vascular beta-receptors.


The clinical use of dopamine in the treatment of shock. Dopamine is a direct-acting catecholamine with a short half-life that has many advantages in treating visceral hypoperfusion states such as shock and refractory heart failure. Unlike other inotropic drugs, dopamine directly dilates the mesenteric, renal, and cerebral vessels and redirects blood flow to essential viscera. This dopaminergic effect is prominent with doses of 100-700 mug/min in adults and is attenuated by phenothiazines and haloperidol. At doses of 700-1400 mug/min, dopamine also has a significant beta-adrenergic, inotropic effect, increasing myocardial contractility. The inotropic effect is equivalent to that of isoproterenol, epinephrine, and norepinephrine, but tachycardia, tachyarrhythmias, and angina may be less frequent with dopamine. In doses greater than 1400 mug/min, dopamine is a vasoconstrictor with pressor effects usually equivalent to that of norepinephrine. Dopamine dilates pupils, does not dilate bronchi, and does not shunt blood from viscera to skeletal muscles as does isoproterenol. Because dopamine increases myocardial contractility, selectively redistributes perfusion to essential viscera and allows a pharmacologic titration of effect, it is a logical first-choice catecholamine for treatment of shock and refractory heart failure.


[Certain problems of treatment of ischemic heart disease]. On the basis of extended personal experience and of the literature data, the authors give recommendations for differentiated rational drug therapy of different stages of ischaemic heart disease. The results of a study of comparative efficacy of 15 coronary-active drugs used in 709 patients with ischaemic heart disease are presented along with their clinical pharmacology, side effects, indications and counterindications. The conclusions were arrived at on the basis of an objective clinical and laboratory study of the effect of the drugs. The methods of evaluation of the drug's efficacy and of the selection of patients for the administration of adequate therapy are described, which permits to use these recommendations for practical purposes. Some problems of the pathogenesis of ischaemic heart disease are discussed in terms of the selection of pathogenetic therapy.


[Stimulators of beta-adrenergic structures in treatment of ischemic heart disease]. The beneficial effect of stimulators of beta-adrenergic structures (Myophedrin on the haemodynamics and the inotropic function of the myocardium was demonstrated experimentally (in 12 rabbits) and clinically (in 53 patients with ischaemic heart disease). A positive effect of the treatment was noted in 45.5% of those patients in whom ischaemic heart disease manifested itself in angina decubitus and angina of effort.


[Nonachlasine--a new drug for treatment of ischemic heart disease]. Data on the pharmacology of a new antianginal drug--Nonachlasine--are presented. Nonachlasine was found to increase the blood flow intensively and for long periods of time, increasing the oxygen reserve of the myocardium, thus increasing the cardiac output and the contractile function of the heart. The prevailing action of Nonachlasine on the blood supply and the function of the myocardium seems to be the result of several mechanisms: decreasing resistance of the coronaries due to the activation of the beta2-adrenergic structures; influence upon the extravascular factors of the regulation of the coronary circulation (changes in the metabolism and cardiac activity due to the excitation of the beta-adrenergic structures). The mechanism of the positive effect of Nonachlasine upon the blood supply and function of the heart is connected with its action on the adrenergic processes. The drug accumulates noradrenaline in the myocardium and increases the activity of phosphorilase-a. This coincides in time with the increased blood supply and contractile capacity of the heart. The beta-adrenoblocking agents prevent these effects. It was postulated that the effect of Nonachlasine in the blood supply and the activity of the heart is connected with its ability to utilize the energy reserve of the myocardium by way of switching over to the anaerobic way.


[Cordaron and nonachlasine in treatment of chronic coronary insufficiency]. In a double blind study of the clinical effect of Cordaron conducted in 55 patients with chronic ischaemic heart disease a positive effect was obtained in 80.4% of the cases, an effect of placebo-in 24.3%. Cordaron was especially effective in patients with localized stenoses of the coronary arteries. Nonachlasine (an activator of the cardiac beta-adrenergic receptors) proved effective in 10 of 13 patients with chronic ischaemic heart disease.


[Effect of certain drugs, used in treatment of chronic coronary insufficiency, on adenosine metabolism]. It has been demonstrated that the study of the activity of 5'-nucleotidase and adenosine-desaminase permits to interpret the metabolism of adenosine. Curanthil, Sustac and Intensain influence the adenosine metabolism favouring an elevation of its content. The therapeutic effect of Obsidan is not conditioned by the "adenosine" metabolism.


Renal response to short-term hypocapnia in man. This study examines the renal response to moderate hyperventilation in healthy man. Eight men hyperventilated for 26 hr (PaCO2 approximately 30 to 32 mm Hg) in normoxia (barometric pressure, PB approximately 740 mm Hg) and hypobaric hypoxia (PB approximately530 mm Hg). Anaerobic samples of arterial blood and urine were studied at two-hour intervals. Plasma [HCO3-] fell with time during sustained hypocapnia and after 26 hr was reduced 2.5 mEq/liter, with plasma pH compensated approximately 60%. Statistically significant changes in renal H+ handling were observed within the initial 2 hr of hyperventilation and were evident over the first 12 hr. Over 26 hr, mean total HCO3-excretion in hypocapnia was 10.2 mEq above control and mean total acid excretion (UVTA + UVNH4+) was 17.5 mEq below control. An increased urinary excretion of cations, especially sodium, accompanied the decrease in acid excretion. Plasma lactic acid accumulation was negligible. We conclude that renal mechanisms contribute significantly and relatively quickly to plasma pH compensation during the early phase of adaptation to hypocapnia in man.


[The influence of isoglaucon on the hydrodynamics and haemodynamics of the eye (author's transl)]. By animal experiments and clinically we could prove that isoglaucon instillation caused the decrease in IOP due to both increase in outflow and reduction of humor secretion; the IOP decrease and changes in hydrodynamics being manifested more markedly in the fellow-eye. As reoophthalmography demonstrated "Isoglaucon" produced lumen narrowing in the anterior portion of the uveal tract. "Isoglaucon" was prescribed to 20 patients having open-angle-glaucoma, Two hours after instillation the 23 decreased in 26 eyes (of 28) by 9.3 +/- 1.0 mm Hg. When prescribed regularly "Isoglaucon" raised the outflow facility coefficient from 0.10 +/- 0.01 to 0.20 +/-0.02. The secretion decreased from 2.0 +/- 0.2 to 0.9 +/- 0.15. Thus, IOP decrease after "Isoglaucon" is accounted for by both improved outflow and reduction of aqueous humor secretion. The "isoglucon" instillation produced a rather moderate decrease in the total arterial pressure, though no expected parallelism in arterial and intraocular pressure was marked.


[The immediate effect of beta-isoket on the internal ocular pressure in patients with chronic simple glaucoma (author's transl)]. In 27 patients with non-compensated or medically compensated chronic simple glaucoma, the I.O.P. was measured after the administration of two tablets of beta-isoket (which contain 5 mg isosorbiddinitrate and 40 mg bupranolol). In none of the 54 eyes was the I.O.P. higher after administration of the drug. On the contrary, the I.O.P. was siginificantly or highly significantly reduced for more than 2 hours, probably because of the beta-receptor-blocking component of the preparation.


[Determination of IgM in serum after corneatransplantation (author's transl)]. By measuring the serum IgM-level every fourth day after keratoplasty the primary immune response can be observed. The extent of the graft's reaction corresponds with the fluctuation of IgM.


[Model of an ecological system closed as regards gas metabolism and with a periodically working autotrophic component. I. Conditions for stability of the atmospheric system]. The paper describes a semi-closed ecological system consisting of a man and a photosynthetic autotrophic component. The conditions required to maintain the stability of the atmosphere in the system are described as applied to two alternating modes of the function of the autotrophic component. These conditions express equal quantities of oxygen and carbon dioxide consumed and produced by the components of the system during any time period the length of which is the duration of the cycle of the system. On this basis equations have been derived which help to identify the photosynthetic cultures that can be used as an autotrophic component in a closed man-sustaining life support system.


[Microbiological aspects of the performance of life support systems during prolonged operation]. The environmental control system using superoxides, sillicagels or synthetic ceolites is capable of purifying the atmosphere from microorganisms. The air conditioning system is another means for air purification from microorganisms. The possibility of microbial build-up and multiplication in the atmospheric condensate makes it necessary to assume that an air conditioning system may contribute to the transfer of conditionally pathogenic microorganisms in a space cabin. The reliability of a life support system may degrade due to an accumulation of microorganisms in its components. Further extensive studies are needed to clarify this problem.


[Toxic properties of regenerated water containing methyl alcohol]. The experiments carried out on white male rats have shown no significant changes in the animals that may have resulted from their 30-day consumption of reclaimed water which contained up to 34 mg/l methanol and was produced by sorption purification of the atmospheric condensate during a prolonged manned experiment.


[Development of measures for preventing contamination of the atmosphere in hermetically sealed enclosures]. The kinetics of the outgassing of volatile substances from polymers of different function and composition was studied with respect to their natural ageing. The outgassing rate was exponentially related to the time of the sample storage. Six to nine months after the polymer fabrication the outgassing rate decreased to a minimum. Possible nobilization of synthetic materials with the aid of diffusion stabilization and thermostatization was investigated. Practical recommendations on how to prevent contamination of the enclosed atmosphere with outgassed products of synthetic materials were developed.


[Mathematical model of an experimental ecological system with spatially separated components]. The paper describes a model of an experimental ecological system consisting of autotrophic and heterotrophic components and a nutrient medium. The system has a zero stationary state and needs a correction. The life time of the system and the level of the necessary correction have been determined for the experimental ecological system: lettuce - slugs - nutrient solution. Optimal conditions for the conjugation of trophic components of the system have been established.


[Control of mineral nutrition of higher plants in biological life support systems]. Control of mineral nutrition of higher plants is one of the problems involved in the development of life support systems. The experiments on carrots cultivated aeroponically have demonstrated that mineral nutrition of plants can be controlled by means of a correction solution applied in accordance with the protocols derived from experimental studies of increase in the plant dry biomass.


[Comparative evaluation of results of intertrochanteric femur osteotomy and conservative hip joint releaving treatment in Perthes-Legg-Calvé disease]. In this paper the comparative evaluation of the results of the surgical and conservative treatment applied in patients with Perthes-Legg-Calvé disease is given. The results obtained with intertrochanteric femur osteotomy performed in 39 patients and those obtained in 66 patients with conservative treatment are reported. The results are evaluated from the point of view of the patients' age, the localization of the process and the stages of the disease. The surgical treatment brought about in 1/3 of the cases excellent-in 1/3 good - and in 1/3 unsatisfactory results. Int the group of patients who received conservative treatment 1/3 of the cases showed excellent - 1/5 of the cases good - and 3/5 of the cases unsatisfactory results. The advantage of the surgicat treatment is that the patients are not confined to bed for long time and they must nol use walking splint releasing the hip-joint.


[Model of an ecosystem closed as regards gas metabolism and with a periodically working autotrophic component. II. Stability of the periodic cycles]. The literature data concerning the effect of the atmosphere composition on the photosynthetic productivity of an intensive microalgal culture were used to build a mathematical model of a semiclosed ecological system working in the light-dark alternating cycles. The type of the relationship between time cycles and composition of the stationary atmosphere of the ecological system has been established. The conditions of the existence and stability of the stationary atmosphere have been determined.


[Respiratory insufficiency in severely burned patients]. The increasing number of respiratory insufficiency, as well as of pulmonary complications after burns and their role in the post-traumatic mortality are pointed out by the author. The pathophysiological processes responsible for the development of post-traumatic pulmonary complications are shortly resumed. In respect of the clinical picture, three groups are distinguished by the author. One case is reported in detail. In the development of post-traumatic respiratory insufficiency important role is attributed by the author to the syndromes of micro-embolism. This supposition is supported by the laboratory examination of 10 patients. Finally the problems of prevention and therapy are discussed and the importance of the iatrogenic damages is emphasized.


[Past and present management burns].

[Past and present management burns]. The management of burns consists essentially of the surgical removal of the necrotic skin layers and the substitution of the skin defects. Secondary skin transplantation does not prevent completely the cicatrization and all complications of the burn. The management of burns is partially classed among the problems of the conservative therapy. Early excision excludes the danger of demarcation and infection, and immediate transplantation may prevent the destruction of the subcutaneous skin layers. This advantages are assured in the cases concomitant with partial necrosis by xenotransplantation.


[Skin substitution in neck and facial burns]. The surgeon assuming the task of reconstruction of burned face must be skilled in plastic surgery. Primary surgical treatment and reconstruction are inseparable, therefore it is desirable that the treatment is performed since the day of the injury to the completion of the reconstruction by the same surgeon. In the surgical management of the facial burns relative conservatism is advisable. The excision is to be performed after the recovery of the second-degree burned areas. The above-mentioned principles are documented by the author on the basis of a few cases.


[Experience with the treatment of open fractures]. The number of the injuries and of the open fractures is steadily increasing. These latter are regularly due to traffic accidents. Characteristics of the open fractures are the extended lesion of the soft parts and the piece-like fractures. The treatmend depends on the patient's general state, the extension of the lesion of the soft parts, the contamination and the infection of the wound, as well as on the localization and the type of the fracture. In the case of proper indication the osteosynthesis yields satisfactory results, but it is not always to be performed and its use to exposed to dangers. The conservative treatment assures good results, if the lesion of the soft parts is minimal, the reduction of the dislocation is easily accoplished and the bone ends are to be held together. On the other hand, the method is unsuitable, if extended lesion of the soft parts occurs, as well as in the treatment of multifragmental fractures. In this group of the open fractures we must try to find other, new methods.


[Presence of foreign body in hand and foot, diagnosed too late]. On the basis of 7 years' material, the distribution of 73 foreign bodies - of non-metallic intensity - in the hand and the foot is discussed. The foreign bodies did not appear as new, fresh lesions, but they have been diagnosed after longer or shorter symptom-free state. In the case of fistulous process immediate removal has been performed, and in the case of closed cases - on the basis of the clinical picture - immediate removal - or removal after fixation for a few days was effective. In the author's opinion, fixation is - so long as acute symptoms are present - in all cases indispensable, - fixation is immediately followed by physicotherapy, in order to assure good functional results.


[Therapeutic principles and results in the management of open fractures of the tibial]. In open fractures of the leg, in which because of any reason no primary stable osteosynthesis can be performed, threading with Kirschner wire is preferred by the authors. This method assures adaptation stability, with minimal osteosynthesis. Primary closure of the wound in the soft parts is striven by the authors, - if necessary, even by plastic surgery. If primary healing of the wound is obtained and also the other conditions are favourable, the treatment after 7-10 days is the same as after covered fractures: stable osteosynthesis is performed. On the other hand, if suppuration of the wound occurs, the opposing fixed fracutre bone ends assure favourable conditions for the successful surgical treatment of the fracture. A further advantage of the method is that it may be performed without special instruments and without greater surgical experience. The results obtained with this surgical treatment of open leg fractures in the 4 years' material of the Traumatological Department of the First Surgical Clinique of the University Medical School, Pécs, are discussed by the authors.


[Infectious complications of primary osteosynthesis in aged patients]. In respect of iatrogenic infections the elderly patients are to be considered as endangered. Modern traumatology increases this danger in consequence of the foreign materials placed in the wounds. The role of the antibiotic and chemotherapeutic prophylaxis is of utmost importance. Regrettably, the resistance of the pyogenics, especially of the strains in the hospitals is increasing, - in consequence, besides the maximal sterility the further improvement of the surgical technique and of the after-treatment are the most important tasks. In the case of infection aimed antibiotic and chemotherapeutic, resp., treatment may be successful.


[Soft tissue complications and their reconstruction following osteosynthesis of open tibial fractures]. The nowadays accepted principles of the treament of open leg fractures are discussed. The open character of the lesion multiplies the possibilities of complications. In the present paper the complications of the bone recovery are not dealt with, only the complications observed in the soft parts and the possibilities of their treatment are analysed by the authors. According to the severity of the soft parts complications free transplantation of semi-thick skin, pedicle flap plasty, double-end graft plasty, crossed flap grafting, as well as the primary and secondary variations of these methods are used by the authors. The satisfactory results obtained with these methods even in spite of the complications are pointed out by the authors.


[Experience with the treatment of open leg fractures]. Open leg fractures observed in 81 patients are analysed by the authors. In case of conservative treatment alone and in the group, which has been treated with primary osteosynthesis satisfactory results have been observed by the authors. False joint and osteomyelitis happened only in the group, in which the patients obtained firstly conservative treatment and in the case of the failure of this treatment osteosynthesis has been carried out. In the authors' opinion the most frequent complications are due - besides the damage of the soft parts - to the repeated and sometimes erroneous interventions.


[Primary humero-radial arthrodesis].

[Primary humero-radial arthrodesis]. The surgical treatment of a severe injury in the cubital region of a bus-driver, aged 47, is reported. Because of the extended contamination and the splintered fracture radical wound excision - involving also the chondral surfaces - has been performed and hereupon humero-radial arthrodesis was carried out. The skin defect has been successfully treated secondarily by insert of a flap. After uneventful recovery the patient could resume his work 6 months after the injury again.


[Xenograft in the treatment of burns].

[Xenograft in the treatment of burns]. The injury due to burns embraces three, nearly concentric zones. The necrobiosis of the central and marginal zones is reversible and the pig-skin - assuring biological ligature - plays important role in turning for better of the process. The preparation and use of Xenograft - applied in the author's department - is discussed.


Mosquito-borne arboviruses in arctic america. Mosquito-borne arboviruses are prevalent throughout subarctic regions of Canada and Alaska, principally in the boreal forest extending between latitudes 53 and 66 degrees N, but they have been identified in tundra regions as far north as 70 degrees N. All mosquito-borne agents have been bunyaviruses, comprising principally the snowshoe hare subtype of California encephalitis (CE) virus, but also Northway virus. Mosquito vectors comprise several Aedes species and Culiseta inornata, all of which have supported replication of CE virus following incubation at 13 degrees C or lower temperatures. Isolation of virus from wild-caught larvae points towards transovarial transfer. Principal vertebrate reservoirs of infection are mammals, especially snowshoe hares (Lepus americanus) and ground squirrels (Citellus undulatus). Where the boreal forest merges into prairie grassland around 53 degrees N, Culex tarsalis mosquitoes become prevalent, and an alphavirus, western equine encephalomyelitis, is detected more frequently than CE virus.


The significance of mosquito longevity and blood-feeding behaviour in the dynamics of arbovirus infections. Mosquito longevity and blood-feeding behaviour are very important but neglected factors in the dynamics of arbovirus infections as changes in them affect transmission rates exponentially. Some mosquito species feed on a narrow range of vertebrates, some on a wide range, both influenced by host-availability and other environmental and behavioural factors. Only those which feed on maintenance hosts contribute to maintenance of the infection. Some species change their feeding pattern with season. The frequency of blood-feeding depends inter alia on environmental temperature. Longevity is perhaps most important: the majority of mosquitoes infected probably do not survive long enough to become infective; it is influenced by relative humidity, temperature and predation. Longevity, feeding frequency and the extrinsic incubation period are all temperature dependent and are therefore important rate determinants in seasonal epizootics or epidemics. Equally, their relative stability in the tropics contributes to the equilibrium of an enzootic or endemic.


Properties of Semliki Forest virus nucleocapsid. The nucleocapsid of the Semliki Forest virus is composed of 34% RNA and 66% protein, or one RNA and about 240 capsid protein molecules. The particle is spherical, with a diameter of 38--39 nm. If the nucleocapsid is exposed to slightly acid pH (6.4--5.6) it undergoes a structural change and is contracted to a 32 nm state. A similar contraction can be effected by RNase treatment, in this case, however, in connection with a loss of RNA. Treatment of the nucleocapsid with 0.2 mM SDS results in dissociation of capsid protein from RNA, an effect which suggests strong RNA-protein interaction. At 0.05 mM SDS the protein remains associated with the RNA, but the S-value is reduced from 150 S to 100 S. Electron micrographs of the 100 S ribonucleoprotein showed irregular and strand-like structures.


[Demonstration of T-cell activation using synthetic polynucleotides]. The present data show that SPN have a striking influence on thymus dependent T cells. The enhancing effect of gvh reactions on antibody formation against thymus dependent antigens give a good explanation for the antitumor effects of this substance.


[Stress incontinence in the woman (author's transl)]. The morphology and function of the urethrovesical junction are described to give some understanding of the pathogenesis and therapy of female stress incontinence. Conservative procedures can only be helpful in stage-1 stress incontinence, whereas in stage 2 surgical treatment provides excellent results.


Regulatory function of pyruvate dehydrogenase and the mitochondrion in lipogenesis. The activity of pyruvate dehydrogenase from freshly isolated mitochondria was shown to be dependent upon the nutritional and metabolic state of the animal prior to sacrifice, such that mitochondria from the livers of 48 hr starved, diabetic, or high fat fed rats had lower enzyme activity than normal, chow fed rats. The activity of pyruvate dehydrogenase and the rate of lipogenesis were shown to correlate to a certain extent when a reconstituted, cell free system consisting of 105,000 x g supernatant of rat liver and isolated mitochondria was used. This system was employed so that the role of the mitochondrion and pyruvate dehydrogenase in lipogenesis could be investigated. Dichloroacetate increased the activity of pyruvate dehydrogenase and increased the rate of lipogenesis, suggesting that the activity of pyruvate dehydrogenase is an important factor in determining the rate of lipogenesis in the reconstituted system. It was observed, however, that dichloroacetate was more effective in stimulating the activity of pyruvate dehydrogenase than the rate of lipogenesis when mitochondria from starved animals were used to reconstitute lipogenesis. Furthermore, the cytoplasmic adenosine triphosphate/adenosine diphosphate ratios and phosphorylation potentials (ATP/ADP x Pi) maintained in the reconstituted system by mitochondria isolated from starved animals were found to be significantly lower than those maintained by mitochondria isolated from chow fed animals. It is proposed that the lower "energy pressure" maintained in the reconstituted system by mitochondria isolated from starved animals severely limits lipogenesis at the ATP requiring steps of the process.


Studies in vitro of lipogenesis in rat testicular tissue. Testicular tissue was shown to contain the full complement of enzymes required for de novo synthesis of fatty acids. The enzymes capable of snythesizing palmitic acid from citrate, acetate, or acetyl CoA were found to be present in the soluble (cytoplasmic) fraction. These included fatty acid synthetase, acetyl CoA carboxylase, citrate-cleavage enzyme, malic enzyme, glucose-6-phosphate dehydrogenase, and 6-phosphogluconate dehydrogenase. Optimal conditions for assaying activities of fatty acid synthetase and acetyl CoA carboxylase in the soluble fraction from rat testes were established, and the activities of these two enzymes were determined to be 0.54 +/- 0.1 and 0.030 +/- 0.002 (nmoles of substrate incorporated into fatty acid per min per mg of soluble fraction protein), respectively. The activities of citrate-cleavage enzyme, malic enzyme, and the glucose-6-phosphate dehydrogenase/6-phosphogluconate dehydrogenase pair were also measured. The activities were 6.0 +/- 0.7, 34.9 +/- 4.2, and 29.9 +/- 9.3 nmoles/min/mg, respectively.


Fatty acid synthesis from 2-14C-acetate in rat testis mitochondrial and cytosol fractions in vitro. An in vitro system for acetate incorporation into fatty acids by the mitochondrial and the cytosol fractions of rat testis is described. The rate of incorporation of acetate into fatty acids was twice as fast with the mitochondrial as with the cytosol fraction; both systems were stimulated in the presence of adenosine triphosphate, reduced nicotinamide adenine dinucleotide phosphate, coenzyme A, and MgC1(2). The optimum pH was between 7.0-7.5 for the mitochondrial fraction and between 6.5-8.0 for the cytosol fraction. Radio gas chromatography showed that palmitic acid was the most highly labeled acid, followed by stearic acid, in the mitochondrial fraction in accord with the pathway of de novo fatty acid synthesis. Some of the labeled acetate was also incorporated into the 16:1 and 18:1 fatty acids of this fraction. Distribution of radioactivity among the mitochondrial lipid classes was highest in the phospholipids and monoglycerides, followed by diglycerides and cholesterol; little radioactivity was present in the triglyceride fraction. These observations are in accord with studies of the incorporation of labeled metabolites into testicular lipids following intratesticular injection and indicate the validity of the in vitro system for studies of specific reactions occurring in vivo.


Fat metabolism in higher plants: metabolism of medium chain fatty acids. Cell free preparations of avocado mesocarp and spinach leaf tissue rapidly convert lauryl CoA to DL-3-hydroxyl lauric acid as well as 2-, and 3-dodecanoic acids. The conversion does not occur under anaerobic conditions unless a suitable redox carrier such as ferredoxin is present. H2 18O is incorporated into the 3-hydroxyl function, but O2(18) is not. The characteristics of this system are presented and a possible function of this system is proposed.


Stearoyl-CoA desaturase activity in mammary adenocarcinomas carried by C3H mice. Transplantable mammary adenocarcinomas and livers of C3H mice fed a stock diet or a linoleate rich diet (15% corn oil) contain similar amounts of oleate (ca 3 mg/gm tissue). On feeding either a high carbohydrate, fat free or a high carbohydrate, saturated fat-containing (15% hydrogenated coconut or cottonseed oil) diet for 6 weeks, oleate levels increased 2-fold in tumor and 5-fold in liver. The specific activity of stearoyl-CoA desaturase in liver microsomes was similar to that in the corresponding fractions of mammary glands of lactating mice. In liver, this activity was enhanced 2- to 3-fold by feeding a high carbohydrate, fat free or a high carbohydrate, saturated fat diet. The desaturase activity in mammary tumor microsomes, while only 10% of that in hepatic microsomes, remained unaltered regardless of the type of diet fed. These observations suggest that (a) a major portion of the oleate in the mammary tumor is not produced within the tissue, (b) dietary adaptation is not a general characteristic of stearoyl-CoA desaturase in neoplastic tissues, and (c) enhanced desaturase activity in liver is directly related to the absence of linoleate or oleate, or to a large decrease in oleate in the diet.


Iowa wrestling study: changes in the urinary profiles of wrestlers prior to and after competition. During the 1973 and 1974 state high school wrestling championships, urine samples were obtained from wrestlers prior to the weigh-in, immediately before they wrestled, and immediately after the subjects had completed their match. Specific gravity, osmolarity, pH, sodium and potassium determinations, as well as qualitative tests for protein and ketones, indicated that the wrestlers were in a dehydrated state at the time of weigh-in. After the five hour interim between the weigh-in and the first match, all but the pH measure remained essentially unchanged. This absence of significant changes in the urinary profile suggests that the wrestlers were unable to rehydrate during the five hour time period between the weigh-in and the first match and that they were competing in a dehydrated state. Urine samples collected after competition were significantly lower in specific gravity, osmolarity and potassium concentration than samples obtained before the match. The urinary potassium levels were of interest because at the three conditions (weigh-in, before the first match, after competition) they were 73-182% higher than values reported for high school students who were nonwrestlers.


Vasculitis with hepatitis B antigenemia: long-term observation in nine patients. The development of generalized necrotizing vasculitis in association with hepatitis B antigenemia is the first example in man of a chronic rheumatic disease presumably caused by a viral infection. This report reviews the experience in nine biopsy-proven cases of hepatitis B-associated necrotizing vasculitis followed for up to six years. The natural history of the disease is emphasized and the manifestations of patients with vasculitis who carry hepatitis B antigen are compared with those of vasculitis patients who are antigen negative.


Polyarthritis, polyarteritis and hepatitis B. An association between viral hepatitis and two rheumatic disease syndromes has been observed. Twenty-nine patients manifested a transient polyarthritis, sometimes associated with a rash (Group I). Ten patients were seen with a multisystem disease (Group II). Histologic evidence of arteritis or glomerulonephritis was present in seven of ten patients with multisystem disease. Liver tissue from 18 patients showed morphologic evidence of hepatitis with viral features in 9 of 10 patients in Group I and in 6 of 8 patients in Group II. Hepatitis B surface antigen (HBsAg) and/or antibody to HBsAg were detected in sera of all 39 patients. Abnormal liver functions were present in 36. Twelve Group I patients and 2 Group II patients became jaundiced. Rheumatoid factor was present in sera of seven patients in each group. The third component of complement (C3) was depressed in 13 patients in Group I and 7 patients in Group II. The fourth component of complement (C4) was decreased in 8 of 21 Group I and 3 of 7 Group II patients. Synovial fluid C3 was decreased in 2 of 11 Group I and 1 of 4 Group II patient's fluids. Articular inflammation in patients with transient polyarthritis responded in three to seven days to aspirin, acetominophen and/or bedrest alone and rashes disappeared spontaneously. Patients with multisystem disease generally had a prolonged illness and responded somewhat unpredictably to prednisone or a combination of prednisone and cyclophosphamide.


Some evidence for aldosterone action on 2,3-diphosphoglycerate level in human red cells. In healthy male subjects aldosterone excretion and plasma renin activity were reduced by a 4-6 hr head-out immersion in thermoindifferent water baths (35.5 +/- 0.1 degrees C). The red cell 2,3-diphosphoglycerate (DPG) concentration before and throughout immersion period was positively correlated both with aldosterone excretion in 2 hr pooled urine (r = +0.69; 2 p less than 0.001) and with renin activity (r = + 0.54; 2p less than 0.001) despite a concomitant increase of cubital venous pH and inorganic phosphate concentration. These findings furnish evidence for a regulatory role of aldosterone in DPG metabolism, possibily by a direct influence on red cell glycolysis.


[Alcohol dehydrogenase activity of nonsulfur purple bacteria]. Rhodopseudomonas palustris, Rh. viridis, Rh. acidophila, and Rhodomicrobium vanniellii grow on media containing ethanol, n-propanol, and n-butanol. The highest amount of lower alcohols is utilized by the strains of Rh. palustris. Only Rh. acidophila accumulates methanol. Alcohol dehydrogenase of Rh. palustris, Rh. viridis, and Rhodospirillum rubrum requires for its activity NAD, that of Rhodomicrobium vanniellii--NADP, and the enzyme of Rh. acidophila is active in the presence of phenazine metasulphate (PMS) and ammonium ions. Aldehyde dehydrogenase from two strains of Rh. palustris also requires NAD; the Nakamura strain is active in the presence of PMS. Aldehyde dehydrogenase of Rh. acidophila is active in the presence of PMS and ammonium ions. Different bacterial species vary in the substrate specificity of their alcohol dehydrogenases.


[Development of Mycobacterium lacticolum and its synthesis of exopolysaccharide under conditions of varying acidity of the medium]. Mycobacterium lacticolum 121 grows and synthesizes exopolysaccharide at the initial values of pH of the medium from 5.0 to 11.5. The accumulation of biomass is maximal (10 to 12 gram/litre) at pH 6.0 to 11.5; the rate of growth is highest at pH 8.0 to 11.5. The largest amount of exopolysaccharide (2.0 to 2.4 gram/litre) is produced in the medium at pH 8.0 to 11.0; the rate of its production is highest at pH 9.0 to 11.0. The growth of Mycobacterium lacticolum 121 and the biosynthesis of polysaccharide are optimal at pH 8.0 to 8.2. Changes in acidity of the medium have no effect on the qualitative composition, structure, and molecular weight of the polysaccharide.


[Effect of H+ and OH- ions on the physiological and biochemical properties of a Pseudomonas methanolica culture]. The growth of Pseudomonas methanolica was inhibited by unfavourable values of pH in the conditions of chemostat; the rate of the substrate assimilation was higher, and anabolic and catabolic reactions were decoupled. Hydrogen ions inhibited the activity of enzymes of the Krebs cycle, hydroxyl ions inhibited the activity of methanol dehydrogenase. Changes in pH are presumed to involve the energy apparatus of the cell membrane.


[Panarteritis nodosa-Special aspects of glucocorticoid and immune suppressive therapy (author's transl)]. Report dealing with the clinical and pathoanatomical course as well as the autopsy findings in a 54 year old female suffering from panarteritis nodosa. Onset of the illness with polyneuritis and arthralgia. One year later diagnosis of panarteritis nodosa verified by muscle biopsy. Deterioration of the disease leading to the development of peripheral gangrene could not be prevented in spite of intensive therapy with steroids, immune suppressive agents, digitalis and antihypertensive drugs. Death 4 years later by myocardial infarction. Autopsy revealed generalized healed panarteritis nodosa with scarring and obliteration of vessels. A short description of the symptoms of the disease is given and the efficacy of the therapy with steroids and immune suppressive drugs is discussed from the clinical as well as the pathoanatomical point of view. Immunopathologic mechanisms are considered to be the responsible factors for pathogenesis.


[Factors causing lysis of an Actinomyces rimosus culture, the producer of the antibiotic, oxytetracycline]. The lysis of Actinomyces rimosus producing oxytetracycline during its mass growth can be caused by two factors which were separated by differential centrifugation. The first factor is phage particles of a temperate phage produced by the culture; they are incapable of growth but may induce the lysis. The phage particles treated with low pH and a temperature of 70 degrees C lose the lytic activity. The second factor is a lytic enzyme produced under the control of the temperate phage during its induction; it seems to consist of at least two enzymes, a lytic enzyme and a proteolytic enzyme.


[Pulmonary vascular pressures and blood gases in young patients with thoracic scoliosis (author's transl)]. Pulmonary artery and pulmonary wedge pressures were measured at rest and during exercise in 25 young patients with moderate to severe scoliosis. Simultaneous determinations of arterial blood gases and pH were performed. The results of the vascular pressure measurements were compared with those obtained in 15 healthy young subjects. In all patients the pulmonary artery and pulmonary wedge pressure were normal at rest. During mild ergometer exercise, however, an abnormal rise in pulmonary artery pressure occurred in 9 patients. Moreover, an increased diastolic pressure gradient across the pulmonary vascular bed was found in some scoliotic patients indicating an elevated pulmonary vascular resistance. It is supposed that this haemodynamic abnormality is primarily due to a restriction of the pulmonary vascular bed. Relationships between pulmonary artery pressure and arterial oxygen tension and blood pH, respectively, could be found. The possible significance of these results is discussed.


Role of hyperkalemia in the metabolic acidosis of isolated hypoaldosteronism. We studied the relative importance of hyperkalemia and mineralocorticoid deficiency in the metabolic acidosis of a patient with proved isolated hyporeninemic hypoaldosteronism and moderate kidney failure. The hyperkalemia and acidosis were severe in relation to the slight azotemia. Despite the systemic acidosis and urinary pH of 4.9, urinary ammonium excretion was distinctly blunted. Correction of the hyperkalemia by potassium-sodium exchange resin alone resolved the acidosis and restored the previously diminished urinary ammonium excretion to normal. Administration of mineralocorticoids only partially corrected the hyperkalemia and the acidosis. Hyperkalemia by itself, rather than hypoaldosteronism per se, caused the acidosis in this patient. Hyperkalemia apparently suppresses urinary ammonium excretion and thus interferes with urinary acidification.


Isolation of Penicillium corylophium Dierckx from acid mine water and its optimal growth on hydrocarbons at acid pH. Penicillium corylophilium Dieckx was isolated from sludge collected at the interface of an aqueous, copper-bearing leachate and an organic, kerosene based, ion exchange solvent. The organism assimilated kerosene and various straight chain and cyclic hydrocarbons including dodecane, hexadecane, octadecane, toluene, benzene, and cyclohexane. Assimilation of kerosene and hexadecane was optimal at pH 2 and was stimulated by yeast extract.


The effect of microbial mycolytic agents on Trichophyton rubrum. Chitinolytic microorganisms isolated from forest soil and from healthy gypsy moth larvae (Porthetria dispar (L.) were screened for their ability to lyse Trichophyton rubrum mycelia. A few of these isolates were mycolytic on both autoclaved and on actively growing, intact, T. rubrum mycelia. Supernatants from these isolates, utilizing live T. rubrum as the sole carbon source, showed the same mycolytic ability. Assays of the supernatants for enzymatic activity revealed exocellular, stable enzymes that releases reducing substances including N-acetylglucosamine from the mycelia.


Models for metal ion function in carbonic anhydrase. A model catalyst is described which has properties in common with carbonic anhydrase. The model demonstrates the availability of a mechanism, previously only hypothetical, for the action of the enzyme. It also shows, however, that this mechanism alone is not adequate to produce the high activity of the enzyme.


[Regulation of lipid synthesis in animal organs]. Studies were made of the mechanisms regulating the quantity and catalytic efficiency of hepatic acetyl coenzyme A carboxylase, which plays a critical role in the control of fatty acid biosynthesis. The microsomal enzyme system responsible for the formation of phosphatidic acid, the initial step in glycerolipid biosynthesis, was resolved into two component enzymes. The acyl-donor specificities of these and other acyltransferases account for the asymmetric fatty acid distribution in naturally occurring glycerolipids.


Comparison of properties between virulent and attenuated strains of transmissible gastroenteritis virus. Strains of transmissible gastroenteritis (TGE) virus possessing different pathogenicity were examined for stability to digestive enzymes and acid, and growth at various temperatures. In growth experiments, virus titer obtained at 37 degrees C were about equal between attenuated and virulent strains, but titers attained by the attenuated strain were higher at 30 degrees C. The attenuated virus multiplied at 28 degrees C, but the virulent virus did not at this temperature. The virulent virus was significantly stable to trypsin and pepsin, but the attenuated virus was inactivated rapidly by these proteolytic enzymes. No significant differences were observed in stability to acid between the attenuated and virulent strains. At different pH, both lost their infectivity more rapidly at 37 degrees C than at 22 degrees C.


Growth of Ibaraki virus in suspension culture of HmLu-1 cells. The established hamster lung cell line, HmLu-1 cells could grow in a suspended state. The initial cell count, 40 X 10(4)/ml, increased to 200 X 10(4)/ml on the 4th day of culture. The suspension culture of HmLu-1 cells was proved satisfactory for propagation of Ibaraki virus. The viral titer reached a maximum of 10(6.75) TCID50/0.1 ml. The input multiplicity ranging from 0.003 to 3.0 exerted no influence on the final yield of the virus. The optimal pH value of initial culture ranged from 6.8 to 7.6. In comparison of virus yield per cell among the suspension culture and two methods of monolayer culture in stationary and rolling condition, there was no noticeable difference in it among the three methods. The cell population per unit volume was the largest and, therefore, virus titer in the culture fluid the highest in the suspension culture of the three methods.


Studies on the mechanism of the action of morphine on the peristalsis of guinea pig ileum in situ. The influence of some drugs on the effect of morphine on the threshold pressure required to elicit peristalsis in the guinea pig ileum in situ was studied, in order to test the hypothesis that this effect of morphine is mediated by catecholamine release. Tachyphylaxis to this effect of morphine was confirmed. Pretreatemnt with two 8 mg/kg doses of reserpine, 24 and 48 hrs before the experiment, significantly reduced the effect of morphine on the pressure threshold. The i.v. administration of 10 mg/kg dl-Dopa re-established the effect of morphine in reserpinized animals to the level of the untreated controls. Pretreatment with guanethidine (15 mg/kg) decreased and even prevented this effect of morphine. Phentolamine pretreatment (10 mg/kg) also significantly inhibited the effect of morphine. Neither DCI nor propranolol influenced this morphine effect. Pretreatment with reserpine, guanethidine or phentolamine reduced the basic pressure threshold needed to elicit peristalsis. The possibility that the decrease of local circulation induced by hypotenison would reduce the local concentration of morphine was rejected because the same doses of guanethidine or phentolamine did not modify the effect of hexamethonium given i.v. in this preparation. All these results support the idea that the effect of morphine on intestinal peristalsis is mediated by a catecholamine acting on alpha-receptors, e.g. norepinephrine.


Effects of alpha-ketomonocarboxylic acids upon insulin secretion and metabolism of isolated pancreatic islets. In perifused isolated pancreatic islets alpha-ketoisocaproic acid (KIC) or alpha-ketocaproic acid (KC) induced a high insulin secretion rate and a steep increase of the fluorescence of reduced pyridine pyridine nucleotides [NAD(P)H] which fell again to almost prestimulatory levels 6 min after medium change. Insulin release in response to alpha-ketooctanoic (KO) acid started slowly and was accompanied by a decrease of the NAD(P)H-fluorescence trace. Beta-phenylpyruvate which is known to initiate insulin release also caused a fluorescence decrease. Alpha-keto-isovaleric (KIV) acid or pyruvate had no significant effects upon insulin secretion or NAD(P)H-fluorescence. In contrast to l-leucine, l-norleucine or l-valine did not enhance insulin release or fluorescence of NAD(P)H. KIV, alpha-keto-beta-methylvaleric acid (KMV), KIC and KC raised the production their corresponding amino acids by islet cells. From these results it is concluded that alpha-ketomonocarboxylic acids as such trigger insulin release by acting upon receptor sites which differ from those occupied by amino acids.


The preparation and properties of nerve growth factor protein at alkaline pH. The nerve growth factor (NGF) subunit of 7S NGF was isolated by chromatography at high pH on QAE-Sephadex. It has the same specific NGF activity as betaNGF isolated at acid pH, showing that this activity is an intrinsic property of the subunit and is independent of the pathway of dissociation. Continued exposure of the NGF subunit to high pH resulted in an increase in the amount of the minor species beta2NGF and the formation of a new species, beta3NGF, of even lower isoelectric point. These two species and the original major species of the preparation, beta1, were isolated by isoelectric focusing. All three species had the same specific NGF activity, but differed in their ability to reform 7S NGF. The beta2 species was one-fifth as competent as beta1, while beta3 was unable to regenerate 7S NGF. Addition of alpha- and gamma-subunits to beta1NGF decreased the amount of NGF protein required to produce one Biological Unit of activity in the bioassay, but had no effect when added to beta3NGF. The interactions between the subunits in 7S NGF therefore determine, in part, the specific activity of the NGF subunit.


Concanavalin A-binding glycopeptides from rat brain glycoproteins. The affinity of concanavalin A for neutral and acidic glycopeptides derived from rat brain glycoproteins was investigated by studying the inhibition of a concanavalin A-glycogen precipitation system. The neutral, mannose-rich glycopeptides obtained by column electrophoresis of the dialyzable glycopeptides that had been solubilized by proteolytic treatment of defatted brain tissue were powerful inhibitors, with an inhibitory activity 20 to 26 times that of the standard inhibitor, methyl-alpha-D-mannoside. The acidic sialoglycopeptides had activities one to nine times that of the mannoside. Therefore, both acid and neutral glycopeptides were capable of interacting with concanavalin A. The especially strong affinity of the neutral mannose-rich glycopeptides, however, enabled their retention on concanavalin A-Sepharose and subsequent elution with methyl-alpha-D-mannoside. This provided the means of separation of the acidic sialoglycopeptides from the neutral, mannose-rich glycopeptides by affinity chromatography. Glycopeptides that contain N-acetylgalactosamine are not retained by concanavalin A-Sepharose.


The use of hybrid molecules in a study of the equilibrium between nerve growth factor monomers and dimers. The major protein in beta nerve growth factor preparations, beta1NGF, is a dimer in which both peptide chains have COOH-terminal arginine residues. Digestion of beta1NGF with carboxypeptidase B produced a dimer, beta3NGF, in which both chains lack these terminal arginine residues. Exposure of mixtures of beta1 and beta3NGF dimers to 8 M urea to produce monomers, followed by removal of urea to allow recombination, resulted in the formation of the hybrid beta2NGF, comprising one arginine-containing and one arginine-less chain, as well as the parent dimers. The amount of the three dimers formed was close to that expected from random association of monomers. Hybrid beta2NGF was also formed from mixtures of beta1 and beta3NGF where incubated at pH 2.6 to 4.5. The formation of beta2NGF has a half-time of 6 h at pH 4.0 and 4 degrees C. Its rate of formation decreased above pH 4.5, becoming minimal between pH 9.5 and pH 10.5, and increased with increasing temperature. The amount of beta2NGF formed was determined by the lowest pH to which the parent mixture was exposed, irrespective of its prior history. These data suggest that the hybrid is formed by the same mechanism in the absence and presence of the urea step. An approximate value for Kd, the equilibrium dissociation constant of the dimer equilibrium monomer equilibrium was derived. Its value was 3 - 10(-10) M at pH 4.0 and 4 degrees C. The alpha-subunit of 7S NGF decreased the rate of formation of beta2NGF not only at pHs where an alphabeta complex is stable, but also at an acid pH where no complex formation is observed by sedimentation analysis, suggesting that the present methodology offers a more sensitive probe of subunit interactions. In contrast, the gamma subunit and a number of indifferent proteins had little or no effect on the appearance of beta2NGF at the pHs studied.


Changes in hypothalamic neurotransmitter uptake following pinealectomy, superior cervical ganglionectomy or melatonin administration to rats. Rats subjected to pinealectomy or to pinealectomy plus bilateral superior cervical ganglionectomy exhibited depressed serotonin uptake by hypothalamic synaptosomes; norepinephrine, dopamine or glutamate uptake was not affected by any of the surgical procedures. Treatment with melatonin resulted in inhibition of hypothalamic serotonin accumulation but it did not modify the uptake of norepinephrine, dopamine or glutamate. These data suggest a relationship between the pineal gland and the serotoninergic nerve endings of the hypothalamus.


Timolol maleate (Blocadren) in the treatment of essential hypertension. The antihypertensive activity of timolol (Blocadren, FROSST-MSD), a new beta blocking agent, was assessed in a single blind crossover placebo-controlled study in 14 patients with essential hypertension. Ten patients completed the trial. The average standing pressure during the placebos periods was 168/109mmHg and during the periods on treatment with timolol the average standing pressure was 139/92mmHg. All 10 patients showed some hypotensive response. The average daily dosage was 21 mg with a range of 15-30 mg. Four patients achieved optimal levels of blood pressure by the end of one week's therapy with the maximum time required being four weeks. Timolol appears to be an effective antihypertensive agent. Side effects were insignificant.


Effects of ritodrine hydrochloride on uterine activity and the cardiovascular system in toxemic patients. The effects of ritodrine hydrochloride were evaluated in 25 toxemic patients in active labor utilizing continuous electronic monitoring of fetal and maternal cardiovascular systems and uterine activity. Fetal scalp blood and free flowing maternal antecubital venous blood was obtained for pH, Po2, Pco2, base deficit and blood glucose determinations prior to and immediately following the study period. The initial ritodrine dose was 50 mug/min for 15 minutes. The dose was increased by 50 mug/min each 15 minutes until there was a clinically apparent reduction in uterine activity. Once this was accomplished, the infusion was maintained for 30 minutes. There was a consistent increase in the maternal heart rate (MHR) and a significant rise in fetal heart rate (FHR) late in the infusion and in the postinfusion period. There was a widening of the maternal pulse pressure mainly due to a reduction in diastolic pressure with little change in the mean blood pressure. Maternal and fetal pH decreased and base deficit increased during the study although the PO2 and PCO2 remained unchanged. Maternal and fetal blood glucose rose significantly following ritodrine infusion.


Treatment of ovarian hyperstimulation syndrome by antihistamine. Ovarian hyperstimulation was produced by human menopausal gonadotropin and chorionic gonadotropin in rabbits. A more rapid regression of the hyperstimualted ovaries was observed in an antihistamine-treated group than in a control group. The difference in regression was found to be statistically significant. The possibility of treating the ovarian hyperstimulation syndrome by antihistamine is cited.


High pH ammonia toxicity, and the search for life on the Jovian planets. Jovian plants have enviroments apparently suitable for the evolution of life, but nevertheless, present severe challenges to organisms. One such challenge arises from the presence of ammonia. Ammonia is an efficient biocide, its effect being dependent on pH as well as on concentration. The effects of pH and ammonia concentration were studied separately, where possible, on a variety of organisms, including some isolated from natural enviornments of high pH and/or ammonia concentration. Escherichia coli and Bacillus subtilis are both extremely sensitive to ammonia. An aerobic organism (growth up to pH 11.4) from an alkaline spring is more resistant, but exhibits a toxic response to ammonia at a pH much lower than its maximum for growth. The greatest ammonia resistance has been found in an unidentified organism growing at near neutral pH. Even in this case, however, survival at ammonia concentrations reasonably expected on the Jovian planets is measured in hours. This is, nevertheless, two to three orders of magnitude longer than for E. coli. Our data support the tentative conclusion that contamination of the Jovian planets with terrestrial organisms that can grow is unlikely. However, the range of toxic response noted, coupled with the observation that terrestrial life has not been exposed to high ammonia concentrations for millions of years, suggests that adaptation to greater ammonia tolerance may be possible.


Gamma-glutamyltranspeptidase in the rat liver after portacaval shunt. Gamma-Glutamyltranspeptidase (GGTP) activity was studied in livers of rats submitted to an end-to-side portacaval shunt (PCS) and in developing animals. To correlate the evolution of the enzymatic activity measured in vitro, histochemical techniques were used to localize enzyme activity in liver tissue. The GGTP activity in the adult rats was low and amounted to 2.0 +/- 0.1 mumol/min/g. During fetal development the enzyme activity rose beginning on the 15th gestational day from 630 +/- 97 to 1,058 +/- 20 on the first postnatal day. Then the values declined and reached nearly adult values from the 10th postnatal day. After PCS the GGTP activity exhibited a three- to sixfold increase (130 +/- 69 to 371 +/- 131) as compared with unoperated adult controls (53 +/- 13). the highest levels corresponded to those observed between the 3rd and 5th postnatal day in the developing rats. The histochemistry of GTTP in the fetal and newborn liver showed a regular distribution of the enzyme as a fine deposit in the hepatocytes throughout the whole tissue. Ten days after birth the activity was low, at the same level as in the adult rat. In the period after PCS hepatocytes began to show signs of enzymatic activity at the periphery of the hepatic lobules, which subsequently spread through the whole lobules. The increase of GGTP activity after PCS equaled the activity found in fetal animals. That correlated well in both groups with the reappearance of histologically demonstrable enzyme activity in hepatocytes.


Cardiovascular effects of electrical stimulation of the forebrain in the fetal lamb. Modified stereotaxic techniques were applied to fetal lambs during the latter third of gestation. Electrical stimulation in the region of the hypothalamus in 10 acute experiments was associated with three patterns of arterial blood pressure and heart rate changes: a pressor-tachycardia response; a pure tachycardia response (abolished by propranolol); and a pure bradycardia response (abolished by atropine). The pressor-tachycardia response was examined in detail in 13 chronic preparations (115-135 days of gestation at operation). The systolic arterial blood pressure increase was never greater than 35 mm Hg and was probably blunted by the large noninnervated placental circulation. This pressure increase was abolished by phentolamine and was thus mediated by stimulation of alpha-adrenergic receptors. The initial tachycardia was prevented by propranolol and was due to beta-adrenergic stimulation. The tachycardia was followed in a few seconds by a bradycardia, abolished by atropine and possibly a vagal baroreflex. The pressor-tachycardia response was accentuated in two lambs who were delivered spontaneously and were studied after birth. These studies indicate that a suprabulbar neural framework exists in the fetal lamb for influencing the cardiovascular system from as early as 90 days of gestation.


Elevated levels of immunoglobulin E in the acute febrile mucocutaneous lymph node syndrome. Mucocutaneous lymph node syndrome (MCLS) is a newly recognized disease characterized by fever persisting for more than 5 days, an erythematous skin eruption, conjunctival congestion, dry red fissured lips, reddened tongue, palms, and soles, nonpurulent lymphadenopathy, and sometines diarrhea, arthralgia, and aseptic meningitis. Additional features may include carditis, pericarditis, aneurysmal dilation and thrombosis of coronary arteries, and sudden death. There is a striking similarity of fatal cases to infantile polyarteritis nodosa, a disease recently reported to be associated with elevated levels of serium IgE. Indeed, it is likely that MCLS represents a disease which can progress to polyarteritis nodosa in infants and young children. The paired acute and convalescent serum IgE levels of 20 subjects with acute nonfatal MCLS were studied along with 20 near-age unaffected controls from the same communities in Japan. The results indicate that most if not all subjects with MCLS in the study had an elevation of total serum IgE during the acute phase of the disease (geometric mean 157 IU/ml compared with the control value of 38 IU/ml, P = 0.005). The level appeared to reach a peak 1-2 weeks after onset and declined over the ensuing 1-2 months.


Diminished pulmonary lecithin synthesis in acidosis: experimental findings as related to the respiratory distress syndrome. Lung slices from term fetal rats were incubated in vitro at various pH values and the rates of the two de novo pathways for lecithin biosynthesis were determined by measuring the conversion of either 14C-choline (pathway 1) or 14C-methionine (pathway 2) to the phospholipid. It was observed that the choline pathway, but not phosphatidylethanolamine methylation, is pH-sensitive with maximum rates occurring at pH levels between 7.3 and 7.5; significantly less activity was found at pH levels between 7.0 and 7.2 and at pH levels between 7.6 and 8.0. Adjustment of the pH from 7.0 to 7.4 in vitro simulating the clinical correction of acidosis by alkali infusion was found to increase the conversion of choline to lecithin to a rate approximating that observed at pH 7.4. Since lecithins are the principal phospholipid components of pulmonary surfactant, and since pathway 1 is predominantly responsible for lung lecithin synthesis, the demonstration of impaired production with reduced pH offers a biochemical explanation for the pathophysiological effects of acidosis in the respiratory distress syndrome. A comparison of pH effects on choline pathway rate with the pH profiles of pathway enzymes suggests that these effects are mediated by the catalysts of lecithin synthesis.


pH and bicarbonate excretion in the rat parotid gland as a function of salivary rate. The bicarbonate concentration in rat parotid saliva increases with increasing flow rates and approximates plasma values at highest salivation. At lowest flow rates the bicarbonate concentration in the secretory fluid markedly exceeds the plasma levels. Intravenous administration of acetazolamide has no influence on the bicarbonate excretion of the parotid gland. Following retrograde application of acetazolamide into the gland duct the concentrations of both bicarbonate and sodium are elevated. The potassium concentrations in final saliva exceed 70 mEq/l at flow rates below 5 mul/min g gland weight. With increasing flow rates a precipitous decrease in potassium concentration below 10 mEq/l occurs. With further increase in flow rate the potassium concentration remains unchanged. The sodium concentrations increased with augmented salivation rate. At lowest flow rates the sodium concentrations showed an increase of modest degree. Our findings can best be explained by the existence of two independent ductular mechanism: a) bicarbonate reabsorption probably in the striated ducts of the parotid gland; b) secretion of potassium with concomitand secretion of bicarbonate in the main excretory duct.


H+ transport and membrane-bound HCO - 3 ATPase in salivary duct epithelium. An ATPase stimulated by HCO -  ions and other oxybases and inhibited by SCN- has been found in main excretory duct of rat submaxillary gland, a tissue, capable of actively secreting HCO - 3 ions. No such ATPase was found in the rabbit duct, which normally does not secrete HCO - 3. The HCO - 3 ATPase was localized in the plasma membrane fraction of the homogenate, as evidenced by the marker 5'-nucleotidase. The activities of the HCO - 3 ATPase increased in metabolic alkalosis and decreased in metabolic acidosis in parallel to secretion of HCO - 3 and K+ ions by the duct epithelium. These findings provide further evidence that the membrane-bound HCO - 3 ATPase is involved in active H+/HCO - 3 transport.


Effects of cyanide and doxapram during hypothermia. The ventilatory responses, blood gases and acid-base status to intravenous injections of KCN and doxapram hydrochloride were studied in anesthetized dogs during normothermia and at two levels of hypothermia. In the normothermic animal, KCN evoked significant elevations of minute and alveolar ventilations. For the mildly hypothermic (32-33 degrees C) dog, minute and alveolar ventilations were proportionally greater than for normothermia. Bolus infusions of KCN to deeply hypothermic dogs (28-29 degrees C) elicited larger and nearly similar increases of minute and alveolar ventilations as compared, respectively, with normothermia and mild hypothermia. Compared to their controls, injections of doxapram during normothermia, mild and deep hypothermia augmented VE 43.3%, 63.6% and 31.5%, respectively. With doxapram there was a feeble increase in alveolar ventilation. These results demonstrate that the peripheral (arterial) chemoreceptors preserve the capacity to respond to stimuli given acutely while lowering core temperature and in some circumstances this capacity is even enhanced as compared to normothermia.


Effects of cyanide and doxapram during panting. The ventilatory responses, blood gases and acid-base status to intravenous injections of KCN and doxapram hydrochloride were studied in anesthetized dogs during normothermia and thermally induced panting. In the normothermic animal, KCN evoked elevation of VE (154.7%), VT (70.1%), f (48.3%, PaO2 (12.1%) and pH (0.098 units), while PaCO2 diminished by 9.7 mm Hg. During panting, KCN infusions resulted in increases of VE (24.5%), VT (46.6%), PaO2 (3.9%) and pH (0.034 units), while f decreased (10.1%). Bolus injections of doxapram during normothermia increased VE (32.6%), VT (18.8%) and f (17.1%). During panting VE, VT and f increased by 18.0%, 18.2% and 1.5%, respectively. These results demonstrate that the peripheral (arterial) chemoreceptors preserve the capacity to react to acute chemical stimuli in animals in which the thermal stimuli override the normal chemical control of respiration in order to control body temperature, and that this reaction contributes to the integrated respiratory drive.


The effect of alpha-adrenolytics on the levels of 5-hydroxytryptamine and 5-hydroxyindoleacetic acid in rat's brain. Alpha-Adrenolytics (ABA)-phenoxybenzamine, phentolamine and aceperone-increase 5-hydroxyindoleacetic (5-HIAA) acid content in rat's brain. At the same time, these compounds either increase or do not affect 5-hydroxytryptamine (5-HT) level. Moreover, they potentiate L-dopa and reserpine-induced increase in 5-HIAA level and antagonized clonidine-induced decrease in 5-HIAA content. The experiments with probenecid indicate that the observed increase in 5-HIAA does not result from the deficient elimination of the metabolite from brain. The increase in 5-HT turnover in brain, due to ABA, is suggested.


Combating diabetic ketoacidosis and other hyperglycemic-ketoacidotic syndromes. Diabetic ketoacidosis is an acute medical emergency that requires immediate diagnosis and treatment. Diagnosis may be established rapidly by measurement of urinary glucose and ketones, arterial blood pH and blood gases, and serum ketones. Rapid infusion of large volumes of fluids and electrolytes, together with continuous infusion of low doses of insulin, provides effective restoration of fluid and electrolyte balance and correction of metabolic derangements. Hyperosmolar nonketotic coma is characterized by marked hyperglycemia in the absence of ketoacidosis and occurs usually in patients with mild adult-onset diabetes. Symptoms develop more slowly than in diabetic ketoacidosis. Treatment is the same for both conditions. In alcoholic ketoacidosis, hyperketonemia is present without hyperglycemia. The syndrome differs from diabetic ketoacidosis in that blood glucose levels are lower and glycosuria is absent. Treatment consists of intravenous administration of dextrose in water and, if necessary, of sodium bicarbonate. Insulin administration usually is not necessary.


[Current conception of the Bohr effect]. The molecular mechanism of the Bohr effect is explained according to the molecular model proposed by Perutz et al. The Bohr effect is due to changes in the pK of specific carboxyl and amino groups of the four globin chains following the transition between the deoxy and oxy conformations of the molecule. Carbon dioxide binds to the N terminal valine of the 4 monomers to form carbamino compounds. This carbaminoformation depends upon pH, PCO2 and predominates on deoxygenated haemoglobin. It is lowered when O2 binds to the heme groups (O2 linked carbamino compounds). Through the carbamino compounds Carbon dioxide lowers both the affinity of haemoglobin for O2 and the Bohr effect. Diphosphoglycerate also binds to the haemoglogin molecule. This organophosphate lowers the affinity for O2 but increases the Bohr effect. In whole blood, the Bohr effect is therefore dependent upon pH, O2 saturation, PCO2 and DPG concentration into the red blood cells.


The central action of drugs influencing beta-adrenergic receptor. part V. The interaction of drugs affecting beta-adrenergic receptor in motility test. Propranolol, alprenolol and sotalol given intraventricularly (ivc) to rats reduce depressing effects of isoprenaline (IPS) and antagonize stimulating effects of noradrenaline (NA). Phentolamine given by the same route of administration does not affect IPS action.