The positive inotropic effect of phenylephrine in the presence of propranolol. Increase in time to peak force and in relaxation time without increase in c-AMP. The effects of phenylephrine on the shape of the contraction curve and on the cyclic adenosine 3',5'-monophosphate (c-AMP) content were studied in electrically driven (frequency 0.2 Hz) cat papillary muscles. All experiments were done in the presence of 1 micron propranolol in order to minimize interference from beta-adrenoceptors. 1. Phenylephrine increased the force of contraction in a concentration-dependent manner. Maximal effects (about 200% of control) occurred at 30 micron phenylephrine. 2. The positive inotropic effect (PIE) of phenylephrine was antagonized by phentolamine. Phentolamine, 5 micron, produced a parallel shift of the concentration-response curve for the PIE of phenylephrine by about two log units to the right. 3. The PIE of 30 micron phenylephrine occurred without any detectable increase in the c-AMP levels of the preparations. 4. The PIE of 30 micron phenylephrine developed about three times more slowly than the PIE of an equieffective concentration of isoprenaline. 5. The PIE of phenylephrine was accompanied by significant, concentration-dependent increases in both time to peak force and relaxation time. 6. It is concluded that the PIE of phenylephrine in the presence of propranolol is mediated mainly by a stimulation of alpha-adrenoceptors. It is unlikely to be related to an increase in c-AMP. With respect to time course and influence on the shape of the contraction curve it is qualitatively different from the effects of beta-adrenoceptor stimulation. These data are taken to support the hypothesis that the mechanical effects of alpha- and beta-adrenoceptor stimulating agents on the heart are produced by different mechanisms.


Isolation and properties of gamma-glutamyltranspeptidase from Morris hepatoma 5123D. gamma-Glutamyltranspeptidase was purified 600-fold from Morris hepatoma 5123D by six-step procedure. Its apparent molecular weight estimated by centrifugation in sucrose gradient with Triton X-100 amounts to 108 000. Some dipeptides particularly glycylglycine and several amino acids considerably increase the enzyme activity but L-serine with borate decreases it. Usually transfer activity of the enzyme towards gamma-L-glutamyl substrates was much higher than hydrolytic. The best substrate for the hepatoma enzyme is reduced glutathione.


Comparative study of miscellaneous properties of cysteine sulfinate transaminase and glutamate oxaloacetate transaminase in chick retina homogenate. The activity, properties, and developmental pattern of cysteine sulfinate transaminase (CSA-T) were studied in chick retina and compared with the activity, properties, and developmental pattern of glutamate oxaloacetate transaminase (GOT). Their optimum pH is identical whereas the effect of pyridoxal phosphate seems to be different. Developmental patterns are also different. The Km and Vm of CSA-T and GOT were determined in chick retina homogenate. These results suggest that two different enzymes are responsible for the transamination of cysteine sulfinate (CSA) and aspartate.


Acid proteinase of hypothalamus. Purification, some properties, and action on somatostatin and substance P. In a continuing study of the physiological role of protein breakdown in the hypothalamus, acid proteinase from bovine hypothalamus was purified about 1000-fold. The molecular weight of the enzyme was approximately 50,000. Masimal activity against hemoglobin was obtained at pH 3.2-3.5; serum albumin was split much more slowly. Hypothalamus acid proteinase was partially inhibited by beta-phenyl pyruvate, or benzethonium Cl, and was completely inhibited by low concentrations of pepstatin. This proteinase splits somatostatin, substance P, and analogs of substance P. The probable sites of enzyme action on these peptides were determined by the end group dansyl technique. The enzyme, most likely cathepsin D, may play an important role in the formation and breakdown of peptide hormones in the hypothalamus.


The pharmacologic inhibition of premature labor. Oxytocin, elevated estrogen-progesterone ratio, fetal corticosteroids, prostaglandins, catecholamines, and changes in uterine blood flow have all been implicated as triggers of labor. In approximately one-third of cases of threatened premature labor contractions stop spontaneously. Thus placebo-controlled randomized trials of any new drug for inhibition of premature labor are necessary, as the spontaneous cessation of contractions always favors the claimed therapeutic efficacy. Alcohol inhibits the release of endogenous oxytocin and has an additional direct effect on the myometrium. In one study alcohol was more effective than placebo in the postponement of delivery. Isoxsuprine, ritodrine, and terbutaline have also been shown to be better than placebo in the inhibition of premature labor, and the beta adrenergic agents appear to be more effective than alcohol. Prostaglandin inhibitors such as indomethacin are currently under investigation. Success is correlated with early administration of the therapy, which requires treating some patients whose contractions might have stopped spontaneoulsy. As different factors may be involved in triggering premature labor, if one therapeutic approach fails another should be initiated promptly.


Studies on vaginal malodor. I. Study in humans. Forty-two percent of collagen sponges tested as an intravaginal barrier contraceptive method developed malodor when retained for 5 days. Only 4% developed odor when the sponge was removed within 24 hours after intercourse, rinsed, and reinserted. While sexually active volunteers found odor in 37% of the sponges, odor formed only in 4% of the sponges worn by sexually inactive users. No difference in the rate of odor formation was found when neutral pH (7.0) and acid pH (3.4) collagen sponges were tested, although we believe that a pH 3.4 is too acid and promotes odor formation. The optimal pH of the sponge should be 4.5 to 5.5. Malodor was efficiently extracted from sponges by washing in acid milieu of tap water and vinegar or 0.1 M acetate buffer, pH 4.0. Alkali extraction procedures were ineffective, and lukewarm water was slightly less effective than acid extraction of odor. At the time of malodor development, the high content of polyamines (putrescine, spermine, spermidine) in the ejaculate decreased to undetectable values. We conclude that the ejaculate is the major source of malodor formation in intravaginally worn collagen sponges. Removal, rinsing optimally in vinegar solution, and reinsertion within 24 hours after intercourse reduces the chance of malodor formation.


The uses of endodontic implant stabilizers in posttraumatic and periodontal disease. Use of the endodontic implant stabilizer presents a sound physiologic procedure for stabilizing mobile teeth. It can increase root length, alter rootcrown ratios, immobilize fractured roots and periodontally compromised teeth, or supply combinations of these benefits. Case selection, operative technique, and case reports with follow-up are presented in order to demonstrate uses and versatility.


Bromsulphthalein retention test and gamma-glutamyl transpeptidase activity in the investigation of liver disease. The usefulness of serum gamma-glutamyl transpeptidase activity (gammaGT) was studied in 39 patients on whom a bromsulphthalein retention test (BSP) was performed. In most patients, the potentially hazardous BSP test did not give any further evidence of hepatic disease over conventional hepatic function tests and the gammaGT.


[Increased resistance of streptococcus pneumoniae to antibiotics and prevalence of their capsular serotypes (author's transl)]. From January 1970 to December 1976, 867 strains of Streptococcus pneumoniae isolated from clinical specimens were routinely typed and tested for sensitivity to 12 antibiotics. The prevalent serotypes were 19, 23, 6, 3, 7 and 14. Twenty seven p. cent of the strains were found resistant to tetracycline, and 4,2% were resistant to tetracycline and chloramphenicol. Two strains were resistant to erythromycin. The minimal inhibitory concentrations of penicillin G, cephalotin, chloramphenicol, tetracycline, minocycline and erythromycin were determined by the agar dilution method on 80 strains. The incidence of tetracycline resistant strains increased from 10% to 40%. These strains were less susceptible to minocycline when tested in vitro and they were clinically resistant. Chloramphenicol resistant strains are isolated since 1972 and represented in 1976 more than 6% of the isolates. They belong to 14 different serotypes. We have previously reported that resistance to chloramphenicol is due to a chloramphenicol-acetyl-transferase which is probably plasmid mediated. The epidemiological and clinical implications of these results are discussed.


Increases of guanosine 3',5'-monophosphate-related enzymes in kidneys of developing rats. Guanylate cyclase, cGMP phosphodiesterase and protein kinase activities were determined in kidneys of developing and adult rats. Guanylate cyclase activities of crude kidney homogenates, 100,000 x g supernatant and pellet of 7- and 21-day-old and adult rats were determined (Table I). In the kidneys of 7-day-old rats activity was 162% of adult controls in the homogenates (P less than .001), 144% in the soluble (P less than .005) and 308% in the particulate fraction (P less than .001). In 3-week-old rats activity was still significantly higher at 144% in the homogenate (P less than 0.02) and at 225% in the particulate (P less than .001). Phosphodiesterase activity for cGMP was 7488 +/- 831 pmol cGMP/mg protein . min in 1-week-old and 7674 +/- 1120 in 3-week-old rats vs. 4042 +/- 122 in the adults (P less than .025) (Table II). Chromatography on Sephadex G-200 showed two peaks of cGMP-stimulatable protein kinase in both the adult and newborn kidney and in addition a minor peak of cGMP-stimulatable kinase in the newborn kidny only (Fig. 2).


Fatal graft-versus-host disease after a small leukocyte transfusion in a patient with lymphoma and varicella. A child with a poorly differentiated lymphoma developed varicella while being treated with maintenance chemotherapeutic agents. He received a transfusion of nonirradiated leukocytes from 1 unit of whole blood donated by a healthy volunteer who had recently recovered from varicella. The clinical course of varicella was aborted, but a classic graft-versus-host reaction developed and ultimately proved fatal. The host may have presented a large population of antigen-bearing cells to an infusion of presensitized immunocompetent donor cells, leading to an overwhelming aggressor lymphocyte reaction. We speculate that a modified approach using irradiated donor cells could be of benefit in the treatment of varicella infections in the immunosuppressed host.


Action and interaction of perivascular H+, K+ and Ca++ on pial arteries. In cats the perivascular space of small pial arteries was perfused with mock CSF by means of micropipettes. Variations of K+, H+ and Ca++ activities in the perfusate cause changes of the diameters of the affected vessels. Increases of H+ and moderate increases of K+ lead to dilatations, Ca++ -increases elicit constrictions. The ions interact in such a way that perivascular Ca++ inhibits the K+ or H+ induced dilator response of the pial arteries. Alkalosis intensifies the constrictor action of Ca++. Perivascular microperfusion with Ca++ -free mock CSF causes dilatation which can be augmented by additional acidosis (pH 6.5). However, an increase of K+ to 10.8-10(-3) mol.1(-1) (4 times normal) does not change the diameters of the vessels already dilated, thus indicating differences in the action of K+ and H+ upon the membranes of the pial vascular smooth muscle cells. Small vessels (less than 80 micron diameter) respond with a significantly stronger dilatation when Ca++ is complexed with EGTA as compared with vessels of more than 80 micron diameter.


Effect of benzolamide on luminal pH in proximal convoluted tubules of the rat kidney. Luminal pH in early and late proximal tubules was recorded continuously with antimony microelectrodes before and during carbonic anhydrase inhibition. Following i.v. application of benzolamide (25 mumol/kg BW), luminal pH decreased almost immediately in early proximal tubules (deltapH--0.42 +/- 0.06SEM), but increased in late proximal tubules (deltapH +0.27 +/- 0.06). Urinary pH increased (deltapH + 1.6 +/- 0.16) after a delay of some 30 s. Similar results, i.e. decrease of pH in early and increase of pH in late proximal tubules, were obtained, when benzolamide containing solutions were microinfused into early proximal tubules or superfused on the nephron surface. In contrast, luminal pH decreased in late proximal tubules, when benzolamide was microinfused into the same nephron segment. The decrease of luminal pH indicates inhibition of luminally active carbonic anhydrase, leading to delayed buffering  of secreted hydrogen ions. The increase of luminal pH in late proximal tubules may be attributed to several factors including increased delivery of bicarbonate, impaired bicarbonate exit at the antiluminal membrane and decreased hydrogen ion formation in the tubular cell due to inhibition of cellular carbonic anhydrase.


Photodissociable dimer reduction products of 2-thiopyrimidine derivatives. Both 4,6-dimethyl-2-thipyrimidine and its 1-methyl derivative undergo polarographic reduction in aqueous medium, via a 1e/1H+ reduction to a free radical which rapidly dimerizes to products isolates and identified as 4,4'-bis-(4,6-dimethyl-3,4-dihydropyrimidin-2-thione) and the corresponding 1-methyl dimer. The dimers may be oxidized electrolytically to regenerate the parent monomers. Both dimers also undergo photodissociation to quantitatively regenerate the parent monomers, in high quantum yield, 0.23 and 0.35 M/Einstein. The correlation between electrochemical and photochemical reductions of 2-thiopyrimidines are discussed, as well as the significance of the dimer photodissociation reactions in relation to nucleic acid photochemistry.


Skin closure with polyglycolic acid (Dexon). Cosmetically satisfactory scars were achieved in 94.5% of skin crease orchidopexy wounds sutured with subcuticular polyglycolic acid. Of twenty-seven similar wounds closed with interrupted black silk sutures 18.5% developed hypertrophy at the medial end.


Rat liver microsomal and lysosomal beta-glucuronidases differ in both carbohydrate and amino acid compositions. To investigate the chemical relationships between rat liver lysosomal and microsomal beta-D-glucuronidases (EC 3.2.1.31), which are essentially identical catalytically and in reactivity with antibody and similar in molecular weight, the two enzymes were isolated by procedures in which modifications of the proteins were avoided. The purified enzymes were found to differ in both sugar and amino acid compositions. The microsomal enzyme contained much more mannose and, in contrast to the lysosomal enzyme, contained sialic acid but no glucose. Moreover, although the amino acid compositions generally agreed closely, the microsomal enzyme contained much more serine and somewhat less arginine than the lysosomal form. These findings of specific differences in composition should have a bearing on the consideration of intracellular glycoprotein synthesis, translocation, and compartmentalization.


Demonstration of high-affinity folate binding activity associated with the brush border membranes of rat kidney. Folate binding activity of high affinity was identified in the particulate fractions of rat kidney homogenates. This binding activity cofractionated with alkaline phosphatase and maltase, two brush border membranes markers. With an enriched preparation of brush border membranes, freed of endogenous folate by acid treatment, the binding of [3H]olate was found to be saturable (Kb = 4.2 X 10(-11)M) and rapid. Binding was optimal at pH 6.4-7.7. At neutral pH, competition for binding with [3H]folic acid required 1.45 equivalents of pteroylheptaglutamate, 6.25 equivalents of N5-methyltetrathydrofolate, 29 equivalents of methotrexate, and 125 equivalents of N5-formyltetrahydrofolate. At alkaline pH, N5-methyltetrahydrofolate was as effective a competitor as folic acid. In view of reports that renal tubular reabsorption of folate includes an initial tight binding step, the binding activity associated with the brush border membranes may participate in this process.


Allosteric regulation of monocyclic interconvertible enzyme cascade systems: use of Escherichia coli glutamine synthetase as an experimental model. The interconversion of Escherichia coli glutamine synthetase [L-glutamate:ammonia ligase (ADP-forming), EC 6.3.1.2] between its adenylylated and unadenylylated forms has been used to verify the prediction derived from a theoretical analysis of the steady-state functions of a model for a monocyclic interconvertible enzyme cascade system [Stadtman, E. R. & Chock, P. B. (1977) Proc. Natl. Acad. Sci. USA 74, 2761-2770]. Because glutamine and alpha-ketoglutarate are multifunctional effectors and because three active enzyme complexes are involved in both adenylylation and deadenylylation of glutamine synthetase, at least 28 constants are required to describe the glutamine synthetase monocyclic cascade. Of these, 22 constants were determined experimentally and 6 were estimated via computer curve fitting. Despite the complexity, when both adenylylation and deadenylylation reactions are functioning, the number of adenylyl groups bound per mole of enzyme, n, assumes a steady-state level as is predicted by the model. This n value is determined by the mole fraction of P(IIA)-given by ([P(IIA)]/([P(IIA)] + [P(IID)])-and the ratio of glutamine to alpha-ketoglutarate (P(IID) and P(IID) are the unmodified and the uridylylated forms of the P(II) regulatory protein). In the presence of 0.5 mM glutamine and 2 mM alpha-ketoglutarate, the value of n increases as a nearly hyperbolic function in response to increasing mole fractions of P(IIA). When the constant level of alpha-ketoglutarate is gradually increased to 40 muM, the hyperbolic function converts slowly to a parabolic function. When the P(IIA) mole fraction was maintained at 0.6 and alpha-ketoglutarate levels were varied from 1 mM to 4 muM, an 800-fold increase in signal amplification was observed with respect to glutamine activation. In addition, because glutamine activates the adenylylation and inhibits the deadenylylation reaction, a sensitivity index of 2.1 (corresponding to a Hill number of 1.5) was obtained for the variation of n values in response to increasing glutamine concentration.


Interaction of methotrexate, folates, and pyridine nucleotides with dihydrofolate reductase: calorimetric and spectroscopic binding studies. The thermodynamic parameters, deltaG, deltaH, and deltaS characterizing the tight binding of methotrexate, folates, and pyridine nucleotides to chicken liver dihydrofolate reductase (5,6,7,8-tetrahydrofolate: NADP+ oxidoreductase, EC 1.5.1.3) have been determined from calorimetric and fluorescence measurements. At 25 degrees the binding of NADPH and NADP+ is characterized by small negative enthalpies and large positive entropies whereas the binding of the folates and methotrexate is accompanied by large negative enthalpies and small negative entropies. In addition, the enthalpy of methotrexate-enzyme interaction demonstrates a proton transfer associated with binding; this is not the case with folate and dihydrofolate, thus confirming the conclusions drawn from the observed difference spectra characteristic of the interaction of methotrexate and substrates with the enzyme. The implications of these results are discussed in terms of the nature of the binding process, conformational changes in the enzyme, and the nature of the active site region.


Fluorescence probe measurement of the intralysosomal pH in living cells and the perturbation of pH by various agents. A quantitative method is described for the measurement of intralysosomal pH in living cells. Fluorescein isothiocyanate-labeled dextran (FD) is endocytized and accumulates in lysosomes where it remains without apparent degradation. The fluorescence spectrum of this compound changes with pH in the range 4-7 and is not seriously affected by FD concentration, ionic strength, or protein concentration. Living cells on coverslips are mounted in a spectrofluorometer cell and can be perfused with various media. The normal pH inside macrophage lysosomes seems to be 4.7-4.8, although it can drop transiently as low as 4.5. Exposure of the cells to various weak bases and to acidic potassium ionophores causes the pH to increase. The changes in pH are much more rapid than is the intralysosomal accumulation of the weak bases. Inhibitors of glycolysis (2-deoxyglucose) and of oxidative phosphorylation (cyanide or azide) added together, but not separately, cause the intralysosomal pH to increase. These results provide evidence for the existence of an active proton accumulation mechanism in the lysosomal membrane and support the theory of lysosomal accumulation of weak bases by proton trapping.


Physicochemical characterization of six monoclonal cryoimmunoglobulins: possible basis for cold-dependent insolubility. The physical and chemical properties of five human and one canine monoclonal cryoimmunoglobulin have been compared. By many criteria, the proteins cannot be distinguished from the noncryoglobulin reference proteins analyzed in parallel; however, certain hydrodynamic and spectroscopic properties of the proteins indicate that cryoimmunoglobulins differ in tertiary structure relative to their cold-soluble counterparts. These differences seem to favor low-temperature-induced association between cryoglobulin molecules as an immediate consequence of increased intermolecular ionic or van der Waals forces. No evidence was found for the formation of cold-dependent antigen-antibody complexes or the ubiquitous presence of low-temperature-dependent conformation changes as a component of cryoprecipitation. Rather, the anomalous solution behavior of monoclonal cryoimmunoglobulins can be considered a direct result of the individual solubility properties of these proteins.


Nerve growth factor-induced fiber outgrowth from isolated rat adrenal chromaffin cells: impairment by glucocorticoids. Addition of nerve growth factor to cultures of dissociated rat adrenal medullary cells caused fiber outgrowth from chromaffin cells. These fibers exhibited all the characteristics of neurites, particularly the formation of typical growth cones exhibiting intense catecholamine-specific fluorescence. Because this nerve growth factor-mediated neurite outgrowth could be abolished by physiological concentrations of glucocorticoids, it is concluded that the high glucocorticoid concentrations normally present in the adrenal medulla prevent the fiber outgrowth from medullary chromaffin cells in vivo. In dissociated sympathetic neurons the same concentrations of glucocorticoids markedly reduce but do not completely abolish neuronal fiber outgrowth.


Presynaptic modulation of voltage-dependent Ca2+ current: mechanism for behavioral sensitization in Aplysia californica. Behavioral sensitization of the gill-withdrawal reflex of Aplysia is the result of a prolonged increase in transmitter release from the presynaptic terminals of sensory neurons. Earlier work suggested that this presynaptic facilitation might be mediated by a serotonin-sensitive adenylate cyclase in the sensory neuron terminals. Here we present evidence that presynaptic facilitation results from a cyclic AMP-dependent increase in the calcium current that underlies action potentials in the sensory neurons. The action potentials of sensory neuron cell bodies have, in addition to a sodium current, a calcium current that is enhanced by blocking the opposing potassium current with tetraethylammonium. Under these conditions, the action potentials show a slowly repolarizing plateau that follows the Nernst potential for a calcium electrode and serves as a sensitive assay for changes in calcium current. Stimulation of the pathway that mediates sensitization, incubation with serotonin or phosphodiesterase inhibitors, or intracellular injection of cyclic AMP produces an increase in the calcium plateau in the presence of tetraethylammonium. In addition, both before and after sensitizing stimulation, the duration of the plateau potential parallels transmitter release as measured by the amplitude of monosynaptic excitatory postsynaptic potentials evoked in the motor neurons by intracellular stimulation of single sensory neurons. These results are consistent with the idea that presynaptic facilitation is caused by a cyclic AMP-mediated increase in a voltage-sensitive calcium current in sensory neuron presynaptic terminals. This synaptic action is novel in that it can produce little or no change in the resting potential, is of long duration, and exerts its influence directly on a conductance triggered by the action potential, rather than on non-voltage-sensitive conductances, as is typical of conventional synaptic actions.


Hydrolysis of cephalosporins in strongly acid medium. The hydrolysis of cephalexin, cephalothin and cephaloridine in strongly acid medium (10--25% sulfuric acid) at high temperature (approximately 100 degrees C) was studied. The hydrolysis proceeds with a high rate (10--15 min are necessary for complete hydrolysis) and results in definite products with low mol.-wt. The hydrolysis under such hard conditions affects the side chain in 3-position, in some cases the C--N bond in the amido group in 7-position, and leads to a total cleavage of the beta-lactam ring, giving thiazine compounds. The reaction products were identified using IR and UV spectral data, thin-layer and gas chromatography, and some characteristic reactions of functional groups. The results of the investigation were used for development of photometric procedures for determination of cephalosporins.


A study in mice of benzodiazephine-anticholinergic interaction: protection against restraint-immersion and forced exertion-induced gastric mucosal erosion. The effectiveness of benzodiazepines and anticholinergics administered alone or in combination in preventing restraint-immersion and forced exertion-induced gastric mucosal erosion was investigated in mice. The benzodiazepines used were diazepam and chlordiazepoxide HCI and the anticholinergics were propantheline bromide and clidinium bromide. The administratio of a benzodiazepine with an anticholinergic resulted in additive or supra-additive protective effects in both systems. In the restraint-immersion system, diazepam combined with propantheline bromide at a ratio of 1 to 13.7 yielded a 4.53-fold supra-additive effect. At ratios of 4.6 or 1.5 parts of propantheline bromide to 1 part of diazepam an additive effect was observed. One part of diazepam, when combined with 1.4 to 12.0 parts of clidinium bromide resulted in supra-additive effects of about 1.5-fold. The co-administration of chlordiazepoxide HCI and clidinium bromide in ratios of 2 to 1 or 2.5 to 1 resulted in supra-additive effects of 2.4- and 1.85-fold, respectively. At higher and lower ratios additive effects were demonstrated. In the forced exertion system, diazepam combined with either anticholinergic resulted in supra-additive effects of 2- to 3-fold which occurred at ratios of diazepam to the anticholinergic varying over an 8-fold range. The co-administration of 2 parts of chlordiazepoxide HCI and 1 part of clidinium bromide resulted in a 2.84-fold supra-additive effect in the forced exertion system. These results are discussed in relation to the use of benzodiazepine anticholinergic combinations in the treatment of human gastric and duodenal ulcer disease.


Tardive dyskinesia and psychotropic drug history. The adult population of a large mental hospital was screened for tardive dyskinesia (TD). Approximately 11% of the hospital population showed signs of TD; females and the elderly were over-represented in the TD group. A representative sample of those with TD was selected and a control (non-TD) patient was chosen to match each of the TD subjects in age, sex, length of hospitalization, diagnosis, and race. The charts of these subjects were searched for any indices of brain damage and the complete psychotropic medication history was recorded. There was no difference between the TD and controls in the amount of psychotropics ingested, in the duration of administration, in the kinds of drugs, or in the organicity history. Women as a group, however, tended to have more polypharmacy than men. The role of neuroleptics in TD is discussed as well as other possible etiological factors.


The effects of a new benzodiazepine derivative, ID-540, on the averaged photopalpebral reflex in man. The effects of 7-chloro-5-(2-fluorophenyl)-1-methyl-1 H, 1.4-benzodiazepin-2(3H)-one (ID-540), a recently introduced benzodiazepine derivative, on the averaged photopalpebral reflex (PPR), subjective symptoms, and serum levels of ID-540 and its principal metabolite, N-desmethyl-ID-540, following an oral dose of 0.5 mg or placebo were investigated in six male Japanese students in a double-blind, crossover design. The peak latencies of PPR showed a statistically significant prolongation, with maximum level at 3 h after administration, which recovered to the initial level within 4 h. The amplitude of PPR failed to show a definite response to the drug. The serum concentration of ID-540 reached a peak level 2-3 h after administration, and then decreased at 4 h. N-Desmethyl-ID-540 exhibited a slow- gradual rise in serum. The latencies of PPR were positively correlated with the serum level of ID-540 but not with the N-desmethyl-ID-540. It is concluded that the PPR test may be a useful method for predicting the clinical effects of psychotropic drugs.


Neuroleptic interference with the cocaine cue: internal stimulus control of behavior and psychosis. The ability of cocaine to exert internal stimulus control of behavior was investigated by training rats to discriminate 10 mg/kg cocaine from saline in a discrete-trial, two-lever, food-reward procedure. Acquisition of response control by cocaine (1) succeeded in all animals tested, (2) proceeded rapidly, and (3) was associated with a high Commission Error: Omission Error ratio. These findings support the hypothesis that cocaine, a prototype of drugs inducing a psychotic condition in humans, can act as a powerful internal stimulus in rats. The cocaine cue was also responsive to the action of the dopamine-receptor-blocking agents spiperone (ED50: 0.06 mg/kg), haloperidol (0.24 mg/kg), and pimozide (1.90 mg/kg). d, l-Amphetamine (1.25 mg/kg) induced stimulus generalization with cocaine, and this generalization was blocked by dosages of the same neuroleptics comparable to those of cocaine antagonism. The results are discussed in terms of internal stimulus control of behavior and its relevance to the psychophysiology of schizophrenia.


[The periarteritis nodosa--diagnosted by angiography. A case with multiple aneurysms (author's transl)]. Periarteritis nodosa is a severe systemic disease which is characterized by an inflammation of the vessel walls and a high incidence of renal involvement. Angiography should be performed immediately when clinical suspicion is aroused. Angiography is superior to the results of skin and muscles biopsy and gives information about the extension of the disease.


[Radiolytic decontamination of Di-n-butyl phthalate from water (author's transl)]. Recently, a considerable amount of phthalic acid esters (PAE), the most widely utilized plasticizer, has been released into and polluted the environment. Since their toxicity and teratogenicity, although fairly low, to experimental animals have recently been shown, the removal of them from the environment, especially from the drinking water, is desirable. As an attempt for the removal, the radiolytic degradation of 7-14C-di-n-butyl phthalate (14C-DBP) in water was investigated at several pHs. Approximately 50% of 14C-DBP (1 ppm aqueous solution) was decomposed by 60Co gamma-irradiation to a dose of 3 X 10(4) rad at pH 7 and the main product was mono-n-butyl phthalate (MBP). At pHs 3 and 11 14C-DBP was more easily radiolyzed and converted to ether-soluble compounds other than MBP or phthalic acid (PA). By irradiation to 10(6) rad 14C-DBP as well as 14C-MBP and 14C-PA, at pH value tested, was almost completely decomposed to volatile or water-soluble substances of possibly low molecular weight. These findings suggest that the gamma-irradiation is effective to make the PAE-polluted water clean.


Rat brain gamma-glutamyl transpeptidase: effects of alcohol. Adult rats were exposed to increasing air ethanol concentrations over a 12-day period without the use of pyrazole. Gamma-glutamyl transpeptidase levels were determined from various regions of rat brain. The enzyme levels in the pons-medulla, mid-brain and the striatum increased significantly during the 12-day exposure to ethanol. Other areas of the brain displayed a slight increase in enzyme activity, but not a significant level.


Tyrosine hydroxylase activity in brain regions after intraventricular 6-hydroxydopamine in the neonatal rat. Intraventricular 6-OHDA treatment to newborn rats produced a marked reduction in tyrosine hydroxylase activity in most brain regions at maturity which correlated moderately well with the catecholamine levels. However, those regions in which NE levels were increased did not show a corresponding increase in total tyrosine hydroxylase activity. There was a much better correlation between NE levels and the particulate form of tyrosine hydroxylase which has been suggested to be the more functionally active form of the enzyme.


Effect of benzodiazepines on age of vaginal perforation and first estrus in mice. Female mice which received chlordiazepoxide, diazepam, oxazepam, prazepam, flurazepam, or nitrazepam prenatally and postnatally had delays in the age of vaginal perforation and first estrus concomitant with reduced postnatal growth. Females exposed prenatally showed no growth deficits, but in four treatments had delayed vaginal opening. However, the age of first estrus was generally less than the control.


Histamine receptors of airway smooth muscle of ferret and rat. Ferret trachea and bronchus contract to carbachol greater than 5-HT greater than bradykinin (BK) greater than PGF2alpha greater than histamine greater than 2-methylhistamine (2-MeH: a specific H1-receptor agonist). Rat trachea is insensitive to the spasmogenic actions of histamine, 2-MeH, PGF2alpha, BK and 5-HT. Ferret trachea and bronchus and rat trachea (which were partially contracted to carbachol) relax to isoproterenol greater than PGE1 greater than E2 greater than 4-methyl-histamine (4-MeH: a specific H2-histamine receptor agonist). High doses of histamine also relax rat trachea. The contractions of ferret airways to 2-MeH coupled with the antagonism of histamine-induced contractions by mepyramine showed the presence of H1-histamine receptors in the trachea and bronchus of ferret. After H1-blockade, the relaxant responses to histamine on ferret bronchus and trachea, and rat trachea were not affecte by "specific" doses of burimamide, metiamide, and cimetidine (H2-receptor antagonists), indomethacin (PG-synthetase inhibitor) and propranolol (a beta-adrenoceptor blocker). These results appear to suggest the existence of an atypical histamine receptor subtype (i.e. not of the classical H1 or H2 type) in the airways of rat and ferret.


The heart production in energy-depleted human erythrocytes induced by glucose, inosine and adenine. The heat production (HP) of glucose deprived human red blood cells was measured, using glucose, adenine and inosine as substrates. Inosine induced a significantly higher HP than glucose and adenine induced no significant HP. At low pH the HP of glucose decreased more than that of inosine, corresponding to an equally lowered lactate production. The results indicate that it should be possible to use the system developed to study the functional state both of the complete glycolytic system and the lower part of it in intact red blood cells during various clinical conditions.


beta-lactamases in bacteroides.

beta-lactamases in bacteroides. Bacteroides fragilis is responsible for most anaerobic infections in man. Most isolates of B. fragilis show resistance to beta-lactam antibiotics. This resistance might be due to beta-lactamase production or permeability barrier in the cell wall. B. fragilis produce beta-lactamase with mainly cephalosporinase activity. Other Bacteroides species such as B. clostridiformis, B. melaninogenicus and B. oralis also produce beta-lactamase but with different biochemical characteristics.


[The mucocutaneous and lymph node syndrome of Kawasaki. 1 case complicated by multiple aneurysms]. We report in a five month old baby a case of the cutaneomucosal and lymph node syndrome described by Kawasaki, remarkable for the onset of multiple aneurysms involving the coronary and the limb arteries. This syndrome has rarely been observed except in Japan where it seems frequent. Possibly is benign forms, without heart complications, producing a picture of febrile erythema of viral type, have not received sufficient attention. The relationship between Kawasaki's disease and periarteritis nodosa in infants is then discussed. The clinical and pathological existence of the fatal forms seems undoubted, but the generally benign course of Kawasaki's disease contrasts with the severe course of polyarteritis nodosa in infants. It is possible that the usually benign forms of Kawasaki's disease represent only the initial stage of periarteritis nodosa in infants, from which they may recover, and we have only identified until now the severe forms which are rapidly fatal. The etiology of Kawasaki's syndrome, like periateritis nodosa remains unknown.


Granulomatous hepatitis associated with salicylazosulfapyridine therapy. Granulomatous hepatitis has been associated with many conditions, including chronic ulcerative colitis and sulfonamide therapy. We report a patient with ulcerative colitis in whom hepatic granulomatosis was associated with salicylazosulfapyridine (Azulfidine). Sulfonamides should be considered a possible cause of hepatotoxicity when used therapeutically in inflammatory bowel disease.


Histopathology of hepatic acute graft-versus-host disease in the dog. A double blind study confirms the specificity of small bile duct lesions. To test the association of small bile duct destructive lesions in the liver with acute graft-versus-host disease,  a blind (coded) histological study was done comparing liver tissue from three groups of dogs given 1,200 R of total-body irradiation: one not given marrow infusions after irradiation, another given autologous hemopoietic grafts, and a third given marrow grafts from DLA-nonidentical unrelated donors. The dogs with unrelated grafts all developed graft-versus-host disease, and their liver histology was distinguished from that of the dogs in the other two groups by three findings: (1) extensive small bile ductule necrosis and atypia; (2) infiltrates of mononuclear cells around and in ductules; and (3) individual hepatocyte necrosis scattered throughout the lobules. Thus, bile duct lesions appear to be a good marker for assessing the presence and severity of hepatic graft-versus-host disease in dogs.


[Activity of NADP-dependent glycerol-3-phosphate dehydrogenase in skeletal muscles of animals]. The NADP-dependent glycerol-3-phosphate dehydrogenase activity was studied in sketetal muscles of the rat, rabbit and frog. The dehydrogenase activity in the skeletal muscles of the rat and rabbit was higher than that of the frog. The enzyme activity was found to depend upon the buffer, being higher in tris-HCl buffer than in triethanolamine buffer.


Megalourethra.

Megalourethra. Two cases of megalourethra are presented, the ninth and tenth cases to be documented in the literature. Both patients exhibited mesodermal abnormalities which justify categorization among the minor forms of prune belly syndrome. One patient, the youngest to have undergone surgical correction, presented with azotemia, dilated posterior urethra, megacystis, and megaureters. The second patient with incomplete or scaphoid form of megalourethra also exhibited undescended testis, corrected by orchiopexy at the time of urethoplasty. In all instances the goal of treatment is preservation of renal function with subsequent functional and anatomic reconstruction of the urinary tract.


Crossed renal ectopia with familial occurrence. A familial occurrence of crossed renal ectopia is presented. No genetic factor has been determined in this congenital anomaly so this familial occurrence is believed to be incidental.


True prostatic tissue in 46,XX female with adrenogenital syndrome. A case is presented of a seventeen-year-old phenotypic male with empty scrotum, hormonal studies consistent with adrenogenital syndrome, a 46,XX karyotype, and a normal prostate on rectal examination. Histochemical evidence of the true nature of the prostatic tissue is presented, and the developmental aspects of the case are discussed.


[An inverse reaction of the ST-T complex in the elctrocardiogram due to beta receptor inhibition]. In this article shall be referred to a special form of reaction of the ST-T-complexes in the propranolol test. Instead of a normalisation of this section of the ECG an inverse reaction develops. It consists in the fact that after application of propranolol the negativities of the T-waves increase and the lowerings of the ST-distances deepen. They appear most frequently after an acute heart attack, such as after a spontaneous angina pectoris, and they can be reproduced only during some days. It is supposed that the cooperation of acute ischaemic myocardial processes with negative sequelae of the blockade of beta-receptors are responsible for this inverse reaction.


[Empirical examination of training programs for the treatment of speech anxiety]. This study is the result of an attempt to get effective methods in order to reduce the students' speaking anxiety in seminars. In a prepost-design, two training programs are compared: systematic desensitization and assertive training. Success is controlled with the help of a subjective anxiety scale, the "Freiburger Persönlichkeitsinventar" (FPI), and by scanning how often and how long somebody is speaking in a seminar. The main results are: both of the training programs reduce speaking anxiety signficantly (perhaps with a little more success of SD), SD also reduces "Gehemmtheit" (FPI-Scale 8). There is a lot of difficulties with regard to the observation of the behavior variables but it seems to be that Ass increases speaking frequency in relation to the groups' mean, while this effect could not be supposed according to SD. At the end of the article, the results are discussed and some questions are raised with regard to the further research of training programs.


[Pancreatic exocrine secretion to the introduction into the blood of amino acid mixtures of varying composition]. Tests conducted on dogs with a fistula of the pancreatic duct evidenced that various amino acids mixtures containing all the essential amino acids and differing mainly in the replaceable nitrogen dissimilarly act on the external secretion of the pancreas after their introduction into the blood. The most intensive secretion produces a mixture in which the replaceable nitrogen is represented by glycine alone. The mixture, one of its constituent is one of the dicarboxylic acids (glutamic) very poorly stimulates this function. At the same time, the action of all the studied amino acids mixtures is less pronounced than is the effect of the caseine hydrolysate. The commercial agent aminofusin L-600, containing all the essential amino acids with addition of polyols (xylitol and sorbitol) with no dicarboxylic amino acids in its composition, produces an intensive pancreatic secretion close to that caused by the caseine hydrolysate.


Phenobarbital increases spontaneous transmitter release at the frog neuromuscular junction. Phenobarbital (1-2 × 10(-4)M) markedly increases the frequency of miniature end-plate potentials at the neuromuscular synapse of the frog. This effect was seen in calcium free media containing EGTA. The drug probably acts presynaptically at an intracellular locus to increase the presynaptic free calcium concentration.


Influence of sodium tripolyphosphate and citric acid on the shelf life of thornback ray (Raja clavata L.). Sodium tripolyphosphate dips (5 min in 12% solution) extended shelf life of thornback ray wings by about 2 days, improved the appearance and eliminated weight losses. With citric acid dips (5 min in 0.5% solution) a 3 day extension of storage life was obtained but the treatment had a slight bleaching effect and caused weight losses of about 5%. Both compounds were effective in retarding the breakdown of urea with formation of ammonia in thorback ray.


[Post mortem determination of bromureides (author's transl)]. Concentrations of carbromal, carbromide and bromisoval are determined in blood, urine, brain, kidney and muscle taken at autopsy from 41 fatal cases after overdosage of bromureides. In addition values of total bromine in blood are presented. Contents of total bromine can only lead to the deduction that a chronical abuse of bromureides is existent or not. Concentrations of bromureides and carbromide show a wide range according to the different time between taking the drug and death particularly in cases of pure carbromal intoxications which sometimes cause death after several days. In such cases quantitative determination of carbromide, a pharmacologically active metabolite of carbromal, is the only way to prove an acute carbromal intoxication. Especially in cases of additional foreign substances death may occur in early the phase of poisoning. Bromureides decompose post mortem by putrefaction a high degree so that the condition of the cadaver is important. Brain tissue is the most usable material for examination but other organs, particularly muscle and kidney, can be analysed with success. For differential diagnosis fatal cases are presented which were not caused by drug intake.


Utilization of industrial and agricultural by-products for fungal amylase production. Attempts were made for using industrial and agricultural by-products and wastes as carbon and nitrogen sources in fermentation medium for alpha-amylase production by Aspergillus niger NRRL-337. The original carbon source of the basal medium was replaced by one of the following materials: rice bran, wheat bran, corn bran, corn starch, cane molasses, and glucose syrup. Rice bran proved to be the best carbon source that secured the highest amylase activity. The nitrogen source of the basal medium was then replaced by different cheap materials, viz: dried yeast, corn steep liquor, gluten-30, gluten-50, and corn steep precipitate. Corn steep precipitate proved to be superior in amylase production. In consideration of these results an economical medium that secured high activity, containing the following ingredients, was suggested: 2.5% corn steep precipitate, 7.2% rice bran, 0.1% MgSO4, 0.1% KH2PO4, and 0.1% CaCO3. From this medium fungal amylase was precipitated and purified. The pure enzyme gave the highest activity at 40 degrees C and pH 4.3.


[Experiences with continuous fetal measurements during pregnancy]. Experiences by continuous ultrasonic measurements during pregnancy. The authors have published earlier a diagram for use to evaluate the fetal development. The aptitude in practice has been proved.--To evaluate normal fetal growth the percentiles curves of Lubchenco are less suitable than of the GDR. But also the last show the normal weight 100 to 150 g to small during the 30th to 36th gestation week in comparison to the calculated fetal weight of normal pregnancies. The intrauterine retardation and hypertrophy can well be diagnosed if the beginning of the measures occurs at the end of the first trimenon of the pregnancy. But it is necessary to know the possibilities of apparent "abnormalities" in normal pregnancy, as ceccation of the fetal growth for 3 or 4 weeks, the late flattening of the biparietal diameter in breech presentation etc.--Our effort to simulatae the fetal growth in intrauterine retardation by using beta-stimulating sympathicomimetics, was without of success.


[Benorylate and indomethacin in cervical syndromes: a comparative double-blind study]. In a double-blind study the effectiveness of benorylate and indomethacin was compared in patients suffering from cervical spine syndromes. From a total of 60 patients, 30 individuals (group A) received 100 mg of indomethacin/day and 30 (group B) were treated with 6 g of benorylate per day. Clinical improvement as judged by several given criteria occurred in 80% of the patients in group A and in 76.7% of the patients in group B. If strict objective criteria (ie. increased mobility) were used, 53.3% improved in both groups, while subjective criteria revealed improvement in 76.7% in both groups. Neurological signs improved in 36.7% in group A and in 30% in group B. In two patients treatment with indomethacin was discontinued because of severe side effects. In the benorylate treated group 3 patients had to be taken off treatment for the same reason. Side effects were mainly gastro-intestinal. The study indicates that with regard to clinical effectiveness benorylate is comparable to indomethacin in patients suffering from cervical spine syndromes; the substance is cheap and relatively tolerable.


[Significance of a general umbilical-cord pH for the evaluation of acidosis morbidity]. The value of a general pH analysis of the artery umbilicalis as a parameter of the postnatal diagnostic of the newborns is shown. The classification of the values in different grades of acidity and the relation to the Apgar score show, that the light and middle-heavy acidoses are not determined sufficiently by the Apgar score. The CTG-monitoring and the stimulation of the Oxytocin had no influence on the frequency of the different grades of the acidity. The meaning of the general blood-gas analysis in the artery umbilicalis for the morbidity of acidity and the check of the obstetrical activity of the clinic is shown.


[In vitro effect of psychopharmacologic drugs on the embryonic brain tissue of the fetuses of schizophrenic mothers]. The author studied the influence on the adaptation of the nervous tissue explantations from 25 fetuses of schizophrenic mothers and a similar amount of fetuses from normal women (embryonal development--7-12 weeks) during the initial period of explantation in vitro (5-6 days) with 10 psychopharmacological preparations (aminasine, majeptile, stelasine, triphtasine, tesercin, theralen, haloperidol, eglonyl, mellipramin, seduxen). Their final concentration in a nourishing medium was approximately the same as in the blood of schizophrenic patients, treated by phenothiasine preparations. The adaptation of the fetus pervous tissue from schizophrenic mothers differed from the corresponding reaction of fetus brain explantation from normal women. There was a tendency to a higher stability of experimental cultures. However, there were differences depending upon the character of introduced drugs.


Regulation of anaerobic glycolysis in Ehrlich ascites tumour cells. 1) In intact Ehrlich ascites tumour cells the anaerobic glycolytic flux rate and pattern of intermediates have been investigated at different pH values of the extracellular medium. 2) As predicted from the dependence of the lactic acid dehydrogenase equilibrium on pH a strong negative correlation between log ([lactate]/[pyruvate]) and pH has been found. 3) The steady state fluxes of glycolysis at pH 8.0 and 7.4 are rather equal, despite significant differences in the intracellular concentrations of glycolytic intermediates. At pH 8.0 the concentrations of ATP, glucose 6-phosphate, and fructose 6-phosphate are lower, and the concentrations of ADP, AMP, fructose 1,6-bisphosphate, triose phosphates, phosphoglycerates, and phosphoenolpyruvate are higher than at pH 7.4. 4) From the analysis of the pH dependent changes of metabolites it follows that different mechanisms are responsible for maintaining equal actual activities of hexokinase, phosphofructokinase and pyruvate kinase at pH 7.4 and 8.0. 5) From an application of the linear theory of enzymatic chains and a calculation of the control strength of the regulatory important enzymes results that hexokinase is evidently rate-limiting for glycolysis, and phosphofructokinase is also significantly influencing the glycolytic flux. Pyruvate kinase and glyceraldehyde phosphate dehydrogenase, on the other hand, do not significantly affect the rate of the overall glycolytic flux in ascites.


The haemodynamic effects of sodium nitroprusside-induced hypotension during beta-adrenergic blockade and anaesthesia. A case report. We present the central haemodynamic data obtained during halothane/nitrous oxide anaesthesia in a patient under antihypertensive treatment with propranolol who underwent surgery for intracranial aneurysms in sodium nitroprusside-induced hypotension. Cardiac output remained unchanged when hypotension was induced. Pulmonary capillary wedge pressure decreased. There was a slight increase in heart rate, as well as a minor decrease in stroke volume. Systemic vascular resistance decreased, but pulmonary vascular resistance remained unchanged. The response observed is discussed.


Accuracy and reproducibility of arterial blood-gas and pH measurements. In 30 patients blood samples were taken from both radial arteries and analysed for PCO2, PO2 and pH. The influence of sampling technique on the accuracy of blood-gas analysis was determined. The 95% confidence limits for PCO2 measurements were +/-0.32 kPa (2.4 mmHg), and for PO2 measurements were +/-1.16 kPa (8.8 mmHg) in the range below 20 kPa, and +/-2.94 kPa (22.0 mmHg) above 20 kPa. For pH, the 95% confidence limits were +/-0.014. Only the PO2 measurements were significantly influenced by the sampling procedure.


Porphyrin biosynthesis. Immobilized enzymes and ligands. VII. Studies on bovine liver porphobilinogenase. Bovine liver porphobilinogenase (PBGase) has been covalently attached to Sepharose, and some of their properties have been studied. The optimal conditions for binding have been determined. The water-insoluble PBGase retained a high percentage of the activity of the soluble enzyme; the coupling yield was also high. Sepharose-PBGase could be stored at 4 C for periods up to 5 weeks with 40% loss of activity; however, both by storage and repeated use, isomerase was inactivated and the percentage of uroporphyrinogen I formed was increased. Attachment of PBGase to Sepharose has led to enhanced thermal stability. pH optima of the insolubilized enzyme was shifted 0.6 units towards the alkaline side as compared to that of the native enzyme.


Dependence of starch synthase activity from maize leaves on light, pH and redox state. The starch synthase activity of bundle sheath cells of maize leaves is very low in darkened plants and increases on illumination. In order to find an explanation of these facts we subjected leaf strips, isolated bundle sheath cells and enzymic preparations to pH-changes and to oxidizing or reducing substances. We found that the increase of the activity produced by light could also be caused in the leaf strips by adding malate to the suspending fluid in the dark. On the contrary, with isolated bundle sheath cells no increase with light or with the addition of malate could be observed. There was a decrease of activity due to acidification or to the addition of dichlorophenol-indophenol (DCPIP). The same effect could be observed with enzymic preparations as with the isolated bundle sheath cells, whereas the decrease of activity was higher by acidification of samples coming from darkened plants than for those enzymes prepared from illuminated plants. Also other substances inhibited the synthase activity: benzoquinone, DOPA, caffeic acid, TMPD or Fe (CN6) 3- and PCMB, while only DTE could increase it. After preincubation with PCMB the enzyme activity could be restored with DTE, not so for the preincubation with DCPIP. With an enzymic preparation that contained intact organelles the increase of activity could also be produced by NADH. Thus we follow that the decrease of synthase activity in the darkened plants is due to acidification and to the presence of oxidizing substances, too.


Correction of severe metabolic acidosis: a physiological approach. 1 - Five patients with severe metabolic acidosis secondary to methanol poisoning were studied before and after receiving 6.7 to 10 mEq NaHCO3/kg body weight. 2 - Two thirds of the infused HCO3- left the extracellular space and, since its apparent volume of distribution was much larger than under normal conditions, it largely overestimated HCO3- needs. On the contrary, the volume of distribution of the buffer base excess was found to be more stable and little affected by the acid-base status. 3 - Based on these observations, a simple method for estimating HCO3- needs in severe metabolic acidosis is proposed, requiring only the initial excess buffer base space which is calculated from body weight and blood buffer base excess values obtained before and after a first dose of bicarbonate.


Effects of ethylephrine on the rat atrial pacemaker. Ethylephrine, assayed in isolated rat atria, as a dose-chronotropic response curve showed a typical bell-dome shape of the sympathomimetic amines. Yet, on the same basis, it was less powerful than epinephrine, norepinephrine or isoproterenol. Pretreatment with reserpine provoked supersensitivity and increase in the maximum. As well, previous administration of pargyline to the animals resulted in augmented accelerating effects, either in normal or reserpinized preparations. Cocaine or phentolamine shifted the dose-response curve to the left. On the contrary, propranolol, produced a marked action, decelerating the effects of ethylephrine and also decreased the maxima with higher doses. It is concluded that ethylephrine: a) is a direct-acting sympathomimetic amine; b) it brings beta-receptor stimulation; c) a certain degree of alpha-receptor decelerating effect is also involved; d) it is a good substrate of monoaminoxidase.


[Effects of emetine and ipecacuana on dopamine central mechanisms. A pilot study]. The lack of any rotational behaviour in unilaterally dopamine lesioned animals after ipecacuana or emetine is a strong indication that these substances lack dopamine receptor stimulating properties when administered systematically. Our results thus support those of Lal et al. (1972). Our results do not allow any conclusions concerning the working mechanism of emetine. However, the lack of central dopamine receptor stimulating properties should probably not be explained by an inability to enter through the blood brain barrier but rather a lack of effect on dopamine receptors. This reasoning  would also exclude the dopamine receptors in the chemo-trigger zone as responsible for the emetic effect. In terms of the clinical usage of ipecacuana it seems highly improbable that this usage may cause adverse psychotic like side effects due to stimulation of central dopamine receptors.


Salazopyrin in rheumatoid arthritis.

Salazopyrin in rheumatoid arthritis. After a 12-week preliminary period of observation 32 patients with consistently active rheumatoid arthritis (RA) were treated for up to 22 weeks with salazopyrin. Seven patients could not tolerate the drug. The remaining 25 patients had a marked improvement in subjective clinical state and significant falls in serum C-reactive protein and the erythrocyte sedimentation rate 6 weeks after treatment began. The improvement was maintained after 22 weeks. The results strongly suggest that further trials with this drug in RA are needed.


[Seroepidemiological investigations in domestic ruminants from Egypt, Somalia and Jordan for the demonstration of complement fixing antibodies against Rickettsia and Chlamydia (author's transl)]. 1450 random serum samples of domestic ruminants from Egypt, Somalia and Jordan were investigated for complement fixing antibodies against Rickettsia and Chlamydia. Between 1.5 and 3.4% of the samples from the animals investigated had antibodies against the RMSF-group of Rickettsia, with exception of the sera from Somalian cattle and sheep from Jordan. Antibodies against Rickettsia of the Typhus-group were found in 4 cattle and 1 goat from Jordan and 2 sheep from Egypt; by agglutination test with type-specific antigen they were identified as antibodies against R. typhi. Using 2 different antigens, antibodies against Coxiella burnetii were found in every population tested. The prevalence was 2.0 to 12.2%, with the exception of cattle in Somalia, where only 1 positive serum (0.2%) was found. 27% of the serum samples from Jordan and 22% from Egypt but none of the 802 samples from Somalia had antibodies against Chlamydia. The results are discussed under an epidemiological point of view.


Concanavalin a receptors on the cell membrane of Trypanosoma cruzi. Epimastigotes and trypomastigotes of T. cruzi obtained from acellular culture as well as bloodstream trypomastigotes agglutinate with concanavalin A (Con A). Con A-binding sites were also localized on the cell membrane by using the Con A-horseradish peroxidase-diaminobenzidine method. Passage of epimastigotes and trypomastigotes from acellular culture through DEAE-cellulose column did not affect Con A-binding sites as detected by agglutination and electron miscroscopy.


Electron microscopic studies on the development of kinetes of Theileria parva Theiler, 1904 in the gut of the vector ticks Rhipicephalus appendiculatus Neumann, 1901. The development of motile stages, called kinetes, from a stationary stage (regarded as zygote) has been followed in Theileria parva by means of electron miscroscopy. This process started after moult of the tick nymphs which had sucked on highly infected calves, i.e. about 20 days after repletion (a.r.) of the ticks. The transformation took place by formation of a growing protrusion (= anlage) into an inner, enlarging vacuole. During this process the limiting membrane of the enlarging vacuole serves as the outer membrane of the developing motile stage, whereas the two inner ones as well as the subpellicular microtubules are newly formed. This transformation proceeds rapidly, so that on the 25th day a.r. most of the kinetes have already left the gut cells and started penetration into the salivary gland cells. On the way to the salivary glands nuclear divisions occurred within the kinetes. The steps of the transformation described were compared to those in T. annulata and to ookinete formation in haemosporidia.


Studies on Dipetalonema viteae (Filarioidea) I. Microfilaraemia in hamsters in relation to worm burden and humoral immune response. The course of a primary infection with Dipetalonema viteae was studied in one randomly bred and in one inbred strain of hamster. Worm recovery and the duration and intensity of the microfilaraemia were analyzed and related to the humoral immune response of the host by using the indirect immunofluorescent antibody test on frozen sections of female worms, on eggs and on intact microfilariae. The inbred strain showed a greater susceptibility to the parasite. This was evidenced by high worm recovery and prolonged microfilaraemia. The duration of microfilaraemia did not depend on the number of recovered female worms. Most of the randomly bred hamsters suppressed microfilaraemia by week 30 post infection whereas some hamsters of the inbred strain were still microfilaraemic. Splenectomy prior to infection did not affect the duration of microfilaraemia. Antibodies to the cuticle of microfilariae always appeared in the sera after immunity to circulating microfilariae had been built up.


Studies on Dipetalonema vitae (Filarioidea). II. Antibody dependent adhesion of peritoneal exudate cells to microfilariae in vitro. Peritoneal exudate cells from normal uninfected hamsters adhered in vitro to microfilariae in the presence of 19S antibody fractions from hamsters which had suppressed or were going to suppress their microfilaremia. The adhering cells were predominantly mononuclear, although eosinophils were occasionally found. Experiments with sensitized microfilariae and peritoneal exudate cells indicated that the macrophage probably recognizes the microfilariae/antibody complex. Macrophage cytophilic antibodies did not seem to be involved. This adhesion reaction may initiate the trapping of microfilariae in vivo, thus contributing to the observed acquired immunity to circulating microfilariae in the hamster.


[A contribution to the biology of Dicrocoelium hospes Looss, 1907 (Trematoda, Dicrocoeliidae)]. In this study, carried out in the Ivory Coast, Dicrocoelium hospes Looss, 1907 was shown for the first time to be a parasite of cattle and it was also detected in sheep by the presence of ova in the faeces. Up to 50% of the sheep in some flocks were found to shed eggs. The adults, sporocysts, "slime balls" and cercariae of D. hospes are described and compared to the respective stages of D. dendriticum. This comparison shows that essential morphological structures are very similar, especially the sensory papillae, which as so called chaetotaxis can serve to distinguish closely related species. The cercariae develop in terrestrial snails of the genus Limicolaria of which several species may play a role (L. flammea, L. felina, L. kambeul). The main habitat of D. hospes seems to be limited to savannah environment; only once could D. hospes be found in the borderzone between savannah and the rain forest. Infected Limicolaria-snails shed the cercariae in amorphous "slime balls" of liquid-jelly-like consistency and yellowish colour. Under the influence of sunlight these liquify; the cercariae, however, can survive for up to 26 h. According to our present knowledge the sunlight seems to be a factor which triggers the shedding of slime balls. This begins shortly after sunrise at a temperature of 22 degrees C and a relative humidity of 100%. Infected snails can shed cercariae on seven consecutive days. This kind of slime ball production might provide a clue to the 2nd intermediate host; efforts to identify this host have, however, so far been fruitless, despite the fact that almost 4000 arthropods, mainly ants, have been investigated.


Leukokinetic studies in Mediterranean kala azar. Two patients with acute Kala Azar were studied with DF32P (diisopropylfluorophosphate) and three patients with 51Cr (chromate) in an attempt to delineate the mechanism producing neutropenia in this disease. The granulocyte life span was found to be reduced in all the patients with exception of one who was studied during Glucantim treatment. The surface radioactivity counts showed that the reduced granulocyte life span was due to pooling and probable destruction of granulocytes in the spleen and to a lesser degree in the liver. Bone marrow neutrophil reserve, evaluated by the response to the intravenous hydrocortisone hemisuccinate, was found to be markedly reduced in all patients. An enlarged marginal granulocyte pool indicated also that the neutropenia may be due to altered intravascular granulocyte distribution.


Non-invasive assessment of left internal mammary-coronary bypass patency using the external Doppler probe. Non-directional blood velocity of left internal mammary bypass grafts was non-invasively studied with the Doppler ultrasonic probe. Thirteen of 14 subjects had angiographic evidence of bypass graft patency and their Doppler signals demonstrated high amplitude phasic blood velocities. A single patient with proximal left internal mammary arterial graft occlusion manifested marked attenuation of Doppler blood velocity signals. It is concluded that this technic offers a potential for ambulatory and in-office screening of internal mammary artery bypass graft function.


Carbohydrate metabolism in renal failure. Hyperglycemia and impaired glucose tolerance are well known phenomena occurring in patients with renal failure. In contrast to true diabetic subjects, an elevated ratio of insulin to glucose during the glucose tolerance test is consistently observed indicating a peripheral insulin insensitivity. Among the possible reasons, a disturbance at the cellular level seems to be most likely. There is some evidence of reduced peripheral glucose utilization on the one hand and increased hepatic glucose output--probably by stimulation of gluconeogenesis--on the other. Agents that have been suggested to be involved in these alterations of carbohydrate metabolism in uremia are hormones, electrolytes, pH, and "toxic" metabolic intermediates or end-products. Of these, an increase in insulin antagonistic hormones; among them growth hormone, catecholamines, and glucagon, seems to be of most significance. Although for the individual hormones no equivocal correlation with glucose intolerance has been proved, the interaction of all of them may result in a preponderance of insulin antagonism thus leading to an apparent insulin resistance.


The role of the kidney in the removal of ketone bodies under different acid-base status of the rat. Arterial blood concentrations of ketone bodies, pyruvate, lactate, citrate, and oxoglutarate were measured in normal and in nephrectomized rats. The rate of removal from the circulation of an infused acetoacetate load has been studied in both groups of animals. Blood oxoglutarate and ketone bodies remained unchanged in nephrectomized rats. Blood citrate level rose rapidly. In rats with normal blood pH the contribution of the kidneys to the removal of ketone bodies is 28%, whereas in metabolic alkalosis, it is less than 2%. In nephrectomized rats with normal blood pH and in rats with metabolic alkalosis the ratio between beta-hydroxybutyrate and acetoacetate is very high in comparison with rats having metabolic acidosis. These data suggest that in metabolic alkalosis the kidneys are not able to utilize ketone bodies.


Digestive-absorptive function of the intestinal brush border in uremia. Amino acid absorption was studied in chronic uremic rats. Intestinal transport of L-leucine appears to be inhibited with mild uremic intoxication, whereas severe uremia enhances absorption. Brush border activity of intestinal maltase and disaccharidases is higher in rats with chronic renal insufficiency. The same holds for gamma-glutamyl-transpeptidase activity.


Ulcerative colitis in association with Takayasu's disease. A case of total ulcerative colitis associated with large-vessel disease consistent with a diagnosis of Takayasu's disease is described in a 21-year-old Pakistani female. The possible relationship between the two disorders is discussed.


Persistent pulmonary hypertension in the neonate: development of an animal model. Chronic intrauterine hypoxia was induced in third-trimester lamb fetuses by daily embolization of the maternal side of the placenta with nonradioactive microspheres. After delivery at term, the chronically hypoxic fetuses had significantly increased pulmonary artery pressures when compared to nonhypoxic control measurements. This preparation appears to be a satisfactory model for experimental study of persistent pulmonary hypertension in the neonate.


Evaluation of continuous monitoring of tissue pH in cats. An improved continuous tissue pH monitoring system, designed for human subcutaneous fetal scalp tissue, was evaluated in 10 cats for total of 60 hours. Respiratory acidosis was induced with and without hypoxia to model the pathology of human clinical fetal distress. Arterial and venous pH were sampled every 15 minutes and the values were compared to those from the pH monitor system. The values paralleled arterial and venous blood pH, with correlation coefficients up to 0.98 under various pathologic acidotic conditions.


Effects of endotoxin on the pregnant baboon and fetus. Effects of E. coli endotoxin upon uterine activity and maternal and fetal condition were studied in four pregnant baboons and their fetuses. Uterine activity increased significantly following administration of endotoxin to the mother. Endotoxin also produced maternal circulatory collapse, severe acidosis, and profound fetal asphyxia resulting in death. Death also occurred in three of the four mothers within 24 hours without amelioration of their conditions.


Electron microscopy of nephropathia epidemica. Renal tubular basement membrane. Tubular basement membranes in kidney biopsies from 18 patients with nephropathia epidemica were studied by electron microscopy. Both in the cortex and in the medulla there was splitting of the basement membrane. Thickened basement membrane around occasional tubules contained membrane vesicles, usually empty but also with a core and a diameter of approximately 180 nm. Membranous convoluted structures and light finely fibrillar areas in the basement membranes were seen. Splitting of the basement membrane was most prominent in the medulla, and the membrane was filled with round to oval particles 55 to 470 nm in diameter. Of the possible mechanisms of damage at the basement membrane level in this disease, the findings suggest liberation of antigen from the tubular cells and reaction of circulating antibodies with the antigen in the basement membrane.


Demethylation in erythrocytes: a reaction involving hemoglobin. A reaction is described in erythrocytes of rat and of man whereby O-methylated metabolites of the catecholamines are demethylated to the corresponding catechols. The reaction was studied by incubating aliquots of erythrocyte lysates with radiolabeled O-methylated compounds and isolating the catechol product by alumina adsorption chromatography. The demethylating activity was located in the cytosol of the erythrocytes. Evidence was strong that oxyhemoglobin was responsible for the reaction: the demethylase activity was inseparable from oxyhemoglobin in several chromatographic separations. In addition, although commercially available hemoglobins were inactive in the reactions, after their conversion to oxyhemoglobin and purification, they did effect demethylation. Methemoglobin did not demethylate guaiacols and in fact inhibited demethylation by oxyhemoglobin. The reaction was inhibited by the addition of reduced pyridine nucleotides and of the methyl acceptor tetrahydrofolic acid.


H + transport in urinary epithelia.

H + transport in urinary epithelia. This review of urinary acidification is primarily based on studies in isolated epithelia such as the turtle bladder. Despite the lack of unambiguous proof, the wealth of indirect evidence suggests that the cause of bicarbonate absorption is H+ secretion into the lumen. The mechanisms that regulate H+ transport are discussed. The electrochemical gradient for protons across the membrane is found to be the most fundamental regulator not only of passive movement but also of active transport. CO2 and aldosterone stimulate H+ transport, the latter by a mechanism apparently separate from the effect of this hormone on sodium transport. Although carbonic anhydrase activity is important for optimal function of the H+ pump, the results with carbonic anhydrase inhibitors need to be interpreted with caution. The evidence for Na:H exchange is reviewed and found to be not very persuasive, The metabolic pathways that fuel H+ transport are found to be all the major energy-yielding reactions in the cell, but particular prominence is given to the new discovery of the role of the pentose shunt in energizing transport. Finally, I discuss the important role H+ transport in energy transduction in subcellular organelles.


Hemodynamic functions and blood viscosity in surface hypothermia. Hemodynamic functions and blood viscosity changes in hypothermia (core approximately 25 degrees C) were studied in 14 pentobarbital-anesthetized dogs subjected to surface cooling. The viscosity of blood (eta B) increased progressively to 173% of that at 37 degrees C when body temperature was lowered to 25 degrees C. The increase in blood viscosity was caused by: a) the direct effect of low temperature on plasma viscosity, b) hemoconcentration as a result of plasma loss, and c) the low-flow (low-shear) state induced by hypothermia. A larger portion of the increased viscosity was caused by the low-flow state in hypothermia. The systemic flow resistance (SFR) increased to 271% of control, and this was attributable about equally to the increases in blood viscosity and systemic vascular hindrance (SFR/eta B). Similarly, the viscosity of blood contributed significantly to raising the pulmonary flow resistance. The relative constancy of mixed venous O2 saturation suggests that the cardiac output at low body temperature is generally adequate to meet the metabolic needs.


Field survey of enteric viruses in solid waste landfill leachates. Because municipal solid waste may contain fecal material from a variety of sources, there is concern that the leachate discharged from some solid waste landfills may contain enteric pathogens, including enteric viruses. In this study, 22 leachate samples from 21 different landfills in the United States and Canada were examined for enteric viruses. The sites represented a broad range of conditions for solid waste landfills and the leachate samples ranged from 10.3 to 18 liters in volume. Enteric viruses were found in only one of the 22 leachate samples examined. Two viruses, identified as poliovirus types 1 and 3, were found in an 11.8 liter sample obtained from a site where solid waste landfill practice was deficient. The low levels of enteric viruses detected in field samples of raw leachate and the opportunities for further reductions in the virus concentration of leachates by such processes as thermal inactivation, removal by soil and dilution in ground and surface waters, suggest that leachates from properly operated solid waste landfills do not constitute an environmental or public health hazard due to enteric viruses.


The effect of pH on platelet and coagulation factor activities. After observing that lavage of the stomach with alkaline solutions has a beneficial effect on the control of gastric hemorrhage, we examined the platelet and coagulation factor activities under conditions of lower and elevated pH. The results showed that change of the pH from acidosis to 7.0 and even to slight alkalosis induces platelet aggregation, platelet calcium and serotonin release, as well as platelet factor II availability. The prothrombin and partial thromboplastin times approached normal levels, whereas the fibrinogen level did not change significantly. The results obtained may serve as an explanation for the control of the intragastric bleeding in patients treated by maintenance of their gastric pH at 7.0.


Glutathione depletion following inhalation anesthesia. Glutathione depletion following inhalation of halogenated anesthetics was investigated as a possible mechanism of toxic reactions associated with anesthesia. Concentrations of reduced glutathione were measured in the blood, liver, lung and kidney of the mouse after anesthesia with enflurane, fluroxene, halothane, isoflurane, methoxyflurane, or trichloroethylene. The anesthetic had no effect on glutathione concentrations in tissues except when fluroxene was used. After two hours of fluroxene anesthesia, glutathione in liver, lung, kidney, and blood was depleted by 93, 85, 85, and 61 per cent, respectively. The depletion was dose-dependent and was more extensive in animals anesthetized after phenobarbital pretreatment. Glutathione was also depleted in livers and lungs of rats anesthetized with fluroxene (60 and 38 per cent, respectively). In blood of rhesus monkeys anesthetized with fluroxene, glutathione was depleted by only 13 per cent. Extents of glutathione depletion are related to fluroxene toxicities in the three species studied.


Systemic arterial blood pH servocontrol of mechanical ventilation. Servocontrol of mechanical ventilation using systemic arterial blood pH, measured by a dual-function pH/PCO2 intra-arterial sensor, as the controlled variable uas carried out in 30 dogs anesthetized with pentobarbital, 30 mg/kg. The control loop consisted of the animal, an intra-arterial dual-function pH/PCO2 sensor and sensor amplifier, a controller, and a Siemans-Elema 900 servoventilator. The system responded appropriately to changes in set-point pH from 7.30 to 7.50, as well as to infusions of lactic acid, which, with the control loop open, decreased systemic arterial blood pH 0.1 TO 0.2 PH units. Long-term (16 hr) ventilation of one dog with the systemic arterial blood pH servocontrol ventilator was shown to be feasible.


Inhibition of cutaneous and mucosal allergy with phenyltoloxamine. A dose-and-time related-effect of oral phenyltoloxamine citrate, a Class I, H1 antihistamine compound, has been demonstrated against allergen-induced wheal-and-erythema skin reactions among 10 adults with a diagnosis of allergic rhinitis and seasonal pollinosis. Clinical improvement in the existing symptoms of rhinorrhea, nasal obstruction, pruritus and sneezing, showed a significant correlation with the inhibition of reagin-mediated skin reactivity caused by phenytoloxamine. No adverse side effects were observed. It can be concluded that oral phenyltoloxamine citrate possesses antihistaminic properties and a range of safety which make it a useful agent for the symptomatic management of upper respiratory allergy.


Serum medazepam, diazepam, and N-desmethyldiazepam levels after single and multiple oral doses of medazepam. 20 mg of medazepam were taken by mouth by 9 healthy volunteers in an acute absorption study. About a 10-fold variation was found during the first 6 hours after the drug in individual serum medazepam, diazepam, and N-desmethyldiazepam levels. In a subacute study 10 mg of medazepam t.i.d. was given to 10 institutionalized mentally subnormal adults with emotional disorders. After 14 days' treatment serum N-desmethyldiazepam levels were generally above 800 ng/ml, 7 to 8 times higher than the serum medazepam or diazepam levels measured 12 hours after the last dose. No correlation was observed between the serum concentration and efficacy of medazepam.


Effects of a new beta1-selective beta-blocker H 87/07 in angina pectoris. The efficacy and toleration of a new beta1-selective beta-blocker, H 87/07, was compared with placebo in 33 patients with angina pectoris. The efficacy was evaluated using subjective assessments of attack rate and nitroglycerin consumption as well as objective assessments of exercise tolerance on a bicycle ergometer. H 87/07 significantly reduced the attack rate and the nitroglycerin consumption compared with placebo. The mean reduction amounted to 13 and 36% respectively. No significant differences were found between H 87/07 and placebo with regard to exercise tolerance. Due to high intrinsic stimulating activity (I.S.A.) H 87/07 altered the heart rate and blood pressure only slightly at rest but during exercise significant reductions were seen. Except for one patient who had cardiac decompensation on H 87/07 no side-effects of clinical importance were seen. No significant changes were seen with regard to the laboratory tests performed.


Chloramphenicol acetyltransferase of Bacteroides fragilis. Chloramphenicol-resistant strains of Bacteroides fragilis (minimum inhibitory concentration, 12.5 mug/ml) were isolated from a stool specimen which contained multiply resistant Escherichia coli. The enzyme responsible for resistance, chloramphenicol acetyltransferase, was produced constitutively by these strains; the specific activity was 10-fold lower than that of the E. coli enzymes. Similar activity was not detected in susceptible B. fragilis strains, nor could it be induced by growth in the presence of chloramphenicol or by mutagenesis. The enzyme had a pH optimum of 7.8 and a molecular weight of approximately 89,000. The K(m) for chloramphenicol was 5.2 muM, and the enzyme was sensitive to inhibition by 5,5'-dithiobis-2-nitrobenzoic acid. The enzyme produced by an E. coli strain isolated from the same specimen had a similar K(m) and sensitivity to 5,5'-dithiobis-2-nitrobenzoic acid.


Biological effects of 5-carboxy-2'-deoxyuridine: hydrolysis product of 5-trifluoromethyl-2'-deoxyuridine. 5-Carboxy-2'-deoxyuridine (5-COOH-2'-dUrd) is a product of the base-catalyzed hydrolysis of 5-trifluoromethyl-2'-deoxyuridine. Hydrolysis of 5-trifluoromethyl-2'-deoxyuridine to 5-COOH-2'-dUrd in phosphate-buffered saline was kinetically first order and was pH dependent. At 37 degrees C and pH 7.0, 7.5, and 8.0, hydrolysis occurred with rate constants of 4.19 x 10(-5), 9.30 x 10(-5), and 1.61 x 10(-4) s(-1), respectively, with corresponding half-lives of 45.7, 20.6, and 11.9 h. 5-COOH-2'-dUrd inhibited growth of HEp-2 cells by 21, 67, and 91% at 1.0, 10, and 100 muM, with no antiviral activity against herpes simplex virus type 1 or herpes simplex virus type 2 at 1.0 or 10 muM. Partial reversal of cytotoxicity in HEp-2 cells was achieved with orotidine, uridine, deoxythymidine, or deoxycytidine, whereas complete reversal of cytotoxic effects was achieved with simultaneous addition of deoxythymidine, deoxycytidine, and uridine. 5-COOH-2'-dUrd at 50 muM inhibited incorporation of [(14)C]orotate into RNA and DNA by 65 and 27%, respectively. 5-COOH-2'-dUrd had no effect on the incorporation of [(3)H]uridine into DNA or RNA. Because of the structural similarities to deoxythymidine, 5-COOH-2'-dUrd was tested as an inhibitor of deoxythymidine kinase. 5-COOH-2'-dUrd was neither a substrate nor an inhibitor of herpes simplex virus type 1 induced deoxythymidine kinase or HEp-2 cell deoxythymidine kinase. Based on these observations, the metabolic block induced by 5-COOH-2'-dUrd has been localized to the de novo pyrimidine biosynthetic pathway between orotate phosphoribosyl transferase and orotidine 5'-phosphate decarboxylase.


Streptococcin A-FF22: nisin-like antibiotic substance produced by a group A streptococcus. Streptococcin A-FF22 (SA) was shown to occur as both a cell-associated (SA-CA) and an extracellular (SA-EX) component of cultures of the producer bacterium, group A streptococcus strain FF22. SA-CA was solubilized by chemical, enzymatic, and mechanical procedures, similar to those used to release M protein. The independence of SA and M protein in strain FF22 was established by chromatographic separation of the two proteins on the basis of molecular weight and isoelectric point differences between the two substances. Media supporting optimal growth of strain FF22 did not necessarily favor SA production. SA was not produced either at elevated temperatures (39 degrees C) or if the culture was maintained at pH 7 or higher. The release of SA from producer cells was enhanced at lower culture pH values. Much of the SA-CA activity seemed associated with the cell walls of the producer strain, and the nature of the binding appeared to be largely nonspecific in nature and attributable to electrostatic interaction.


Mechanism of the antimicrobial action of pyrithione: effects on membrane transport, ATP levels, and protein synthesis. Pyrithione is a general inhibitor of membrane transport processes in fungi. A brief preincubation of Penicillium mycelia with pyrithione resulted in a marked decrease in the activities of a variety of independently regulated transport systems, including those for inorganic sulfate, inorganic phosphate, methylamine (actually, the NH(4) (+) permease), choline-O-sulfate, glucose, l-methionine (a specific system), and several hydrophobic l-alpha-amino acids (the general amino acid permease). The degree of inhibition at any fixed pyrithione concentration and exposure time increased as the pH of the incubation medium was decreased. This result strongly suggests that the active species is the un-ionized molecule and that pyrithione acts by collapsing a transmembrane DeltapH driving force. The degree of transport inhibition caused by a given concentration of pyrithione increased with increasing time of exposure to the inhibitor. However, exposure time and pyrithione concentration were not reciprocally related. At "low" pyrithione concentrations, transport inhibition plateaued at some finite value. This observation suggests that the fungi can detoxify low levels of the inhibitor. The concentration of pyrithione required for a given degree of growth inhibition increased as the experimental mycelial density increased. This phenomenon was consistent with the suggestion that the fungi are capable of inactivating pyrithione.


Piperacillin: in vitro evaluation.

Piperacillin: in vitro evaluation. The in vitro activity of a new semisynthetic penicillin, piperacillin, was determined against 577 clinical isolates of gram-positive cocci and gram-negative bacilli. A concentration of 12.5 mug/ml inhibited 92% of isolates of Pseudomonas aeruginosa, 82% of Serratia marcescens, 73% of Escherichia coli, 61% of Klebsiella spp., and 42% of Enterobacter spp. Most Proteus spp. were extremely susceptible; over 85% were inhibited by 0.10 mug/ml. Piperacillin failed to inhibit the growth of gram-negative bacilli when large inocula were used. The type of media and pH had variable effects on the activity of piperacillin, depending upon the organism. Piperacillin was generally less active than PC-904 against gram-negative bacilli, but was consistently more active than carbenicillin and ticarcillin.


Danger of bucolome in infants with hyperbilirubinaemia. Experimental evidence. Effects of bucolome on congenitally jaundiced Gunn rats were examined. Plasma total bilirubin level fell immediately after a single injection of bucolome and the lowered level persisted for more than 6 hours. Plasma unbound-bilirubin level and cerebellar bilirubin content increased simultaneously with the drop in total plasma bilirubin level. Kernicterus was observed in the brains of the treated rats 6 hours after the treatment. LD50 of the drug in jaundiced rats was about 37 mg/kg, about one-tenth of the value in nonjaundiced rats. It is suggested that bucolome displaces bilirubin from albumin, transferring bilirubin from blood into tissues including the brain, and resulting in kernicterus. The use of bucolome in infants with hyperbilirubinaemia is inadvisable.


[gamma-Glutamyl transpeptidase in human eccrine sweat (author's transl)]. The concentration of gamma-glutamyl transpeptidase was determined in eccrine, thermal sweat of 56 healthy men (ages 20--60 years) and 48 healthy women (ages 17--55 years). Samples of sweat were collected from the chest and back. The concentrations of gamma-glutamyl transpeptidase showed great individual variations. The sex specific comparison of the concentrations of gamma-glutamyl transpeptidase revealed that the women excreted in the sweat from the chest and the back nearly the double amount of this enzyme. The gamma-glutamyl transpeptidase concentrations determined in the sweat from the chest of the examined men and women were three times higher as compared with those excreted simultaneous from the back of the same persons. In the group of the women was this differences statistically significant.


Surgery for short esophagus with stricture: an experimental and clinical manometric study. The surgical management of short esophagus with stricture has been simplified in recent years by the introduction of an esophageal lengthening procedure (Collis gastroplasty) combined with antireflux maneuvers, such as the Belsey and Nissen operations. This report compares the experimental and clinical manometric findings after these procedures. After myectomy of the lower esophageal sphincter (LES) in the cat, three experimental groups were developed including Collis gastroplasty, Collis-Belsey and Collis-Nissen. formation of a gastric tube did not provide protection against reflux while the Collis-Nissen procedure was more effective than the Collis-Belsey in raising pressures at the high pressure zone (HPZ) (26.0 +/- 3.5 cm H2O vs 15.0 +/- 2.7) and in preventing reflux (pH 6.3 +/- 0.5 vs 2.9 +/- 0.04). Of 20 patients with short esophagus and stricture, 11 underwent a Collis-Belsey procedure and nine a Collis-Nissen procedure. The latter procedure resulted in an HPZ of greater amplitude and length than the Collis-Belsey (18.7 +/- 2.3 mm Hg vs 11.6 +/- 1.7 and 3.9 +/- 0.4 cm vs 2.4 +/- 0.2). It also proved to be a more effective antireflux procedure, for no patient so treated had a positive pH reflux test after operation whereas after the Collis-Belsey procedure all but one patient had a positive pH reflux test. Short-term clinical results also support the superiority of the Collis-Nissen operation.


The neuropharmacological actions of amoxapine. Amoxapine possesses a broad spectrum of psychotropic actions, including antidepressant and neuroleptic effects in animals. Antidepressant activity is characterized by its ability to inhibit tetrabenazine-induced depression, antagonize reserpine-induced hypothermia and enhance yohimbine lethality. Neuroleptic activity is demonstrated by the ability of amoxapine to decrease locomotor activity, induce ptosis and catalepsy, inhibit apomorphine gnawing and amphetamine stereotyped behavior and by characteristic changes in monkey discriminated avoidance behavior. The fact that punished responding in squirrel monkeys was present was present after repeated administration may indicate an anti-anxiety action of this drug. Evidence is offered that the conversion of the tertiary terminal nitrogen to a secondary amine may alter the pharmacologica properties of dibenzoxazepines in a similar way to the for the phenothiazines.


Deoxycytidine: a morphine antagonist.

Deoxycytidine: a morphine antagonist. Deoxycytidine antagonizes the analgesic action of morphine in the rat, morphine-induced respiratory depression in the rabbit and mitigates withdrawal in the dependent mouse. Administration of deoxycytidine does not precipitate the abstinence syndrome in dependent mice, a property shared by certain other endogenous morphine antagonsits. Cytidine and thymidine closely related in structure to deoxycytidine, are interchangeable with saline as controls, indicating a high degree of specificity in the receptor involved in the "action-effects" sequence. The requirement for deoxycytidine in countering the effects of morphine parallels the requirement for certain other DNA pyrimidines in the antagonism of barbiturate and alcohol. The rapidity of antogonist action suggests that such a DNA species would presumably be localized in the synaptosome, at outer membrane or the synaptic junction.


The effect of chronic administration of digitoxin on the activity of the myocardial (Na + K)-ATPase in guinea-pigs. When guinea-pigs were treated for 24 days with digitoxin 0.3 mg/kg s.c., the activity of the (Na + K)-ATPase of the heart muscle increased by about 30% compared to controls, whereas the enzymes prepared from kidney and brain showed no significant alteration in their activity. In animal species treated with digitoxin for 1 to 5 days, no increase of enzyme activity was observed. Only after 10 to 15 days of treatment, a significant increase of the (Na + K)-ATPase activity was noted which increased no further with treatment up to 24 days. There was no significant difference in the kinetic properties of the (Na + K)-ATPase prepared from digitoxin-treated animals compared to those from control animals; the KM-values for ATP remained unchanged, and there was the same dependence of the activity on the K+-concentration and the same sensitivity towards digitoxin. As there appears to be no significant change in the specific properties of the enzyme, the increase in activity may possibly be caused by an increase in the amount of enzyme as a result of an adaptive enzyme regulation.


[Research of the soluble microbial substances in organic fluids for the rapid diagnosis of some infections and particularly of bacterial meningitis (author's transl)]. A number of immunological and non-immunological techniques have been recently used to detect soluble microbial substances in body fluids of patients with acute meningitis, bacteremia, and lobar pneumonia. By the immunological methods capsular highly polymerized polisaccharide group- or type-specific antigens of the most common C. N. S. pathogens (N. meningitidis A, B, and C; Str. pneumoniae, H. influenzae type b, E. coli K1, mucoid Pseudomonas, Cryptococcus neoformans) can be detected and quantitated in spinal fluids, sera, urine and other fluids specimens from meningitic patients. Capsular type-specific antigens from pneumococcus, and likely from H. influenzae as well, can be detected in sputum from patients with lower respiratory infection. Among the various techniques, the radioimmunoassay appears as the most sensitive one, but high diagnostic sensitivity can be also achieved by using the latex agglutination, haemoagglutination inhibition and coagglutination tests. Counterimmunoelectrophoresis, however, is still the far most used technique for determining soluble microbial antigens, albeit its sensitivity is significantly less than the one of the above mentioned methods. High specificity and some advantages in serotyping the causal organisms are probably the main reasons of such preferential employment. Among the non-immunological techniques the evaluation of lactate and lactic dehydrogenase has been used by some Author for differentiating between bacterial and non bacterial meningitis, and the limulus test for detecting Gram-negative bacterial endotoxins with a high degree of sensitivity and specificity. Finally, the liquid gas chromatography has been evaluated in detection of some organic products (microbial?), such as acids, amines, neutral compounds, in spinal fluid, allowing the differential diagnosis between bacterial, tuberculous, viral, and cryptococcal meningitis. In the present review sensitivity, specificity, and other properties of each test alone and in comparison with the conventional microbiological methods (Gram and culture) are evaluated and the biological and pathogenic role and significance of the soluble microbial antigens and endotoxin are discussed.