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T-lymphocyte heterogeneity in the rat: separation of functional subpopulations using a monoclonal antibody.
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W3/25 antibody is the monoclonal product of a hybrid cell resulting from the fusion of a mouse myeloma cell line with spleen cells from a mouse immunized with rat thymocytes. Pure clones have been derived, and segregants free of parental myeloma chains have been isolated. Previous studies have shown that this antibody recognizes a subpopulation of T cells among rat thoracic duct lymphocytes. In the work reported here, three T-cell functions were assayed after separating rat thoracic duct lymphocytes on the fluorescence-activated cell sorter on the basis of labeling with W3/25 antibody. Two of the functional activities appeared to be completely segregated by this procedure. Thus, helper cell activity for an anti-hapten plaque-forming cell response was confined to the labeled population, whereas the allogeneic suppressive effect produced in a parental vector F1 adoptive transfer was mediated by cells in the unlabeled fraction. The third function, graft-versus-host activity, was almost entirely contained within the labeled subpopulation. It is concluded that the antigenic determinant recognized by the monoclonal antibody W3/25 is a differentiation marker for T-cell functional subpopulations.
| 29,936
|
In vivo desensitization to beta receptor mediated bronchodilator drugs in the rat: decreased beta receptor affinity.
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When tracheas were isolated from rats pretreated with isoproterenol (ISO) or terbutaline, they were found to be considerably less sensitive to the relaxant action of ISO than tracheas which were isolated from saline-pretreated rats. The dissociation constant (Kb) for the propranolol-beta receptor complex was determined to be up to 400-fold larger in the tracheas isolated from beta agonist-pretreated rats (1.1 +/- 0.1 X 10(-6) M) than in tracheas isolated from saline-pretreated rats (3.0 +/- 0.3 X 10(-9) M). The longer the duration of pretreatment and the higher the dose of ISO or terbutaline used, the more attenuated was the response of tracheal smooth muscle to ISO, and the greater was the Kb for propranolol-beta receptor complex. These findings provide strong evidence which shows that desensitization, which occurs as a result of in vivo pretreatment with beta agonist drugs, results from pronounced reduction in this affinity of the beta receptors for beta agonist drugs. We observed that the in vivo treatment of rats with aminophylline (Amino), a phosphodiesterase inhibitor, did not affect the responsiveness of their isolated tracheas to either ISO or Amino. In addition, the responsiveness to Amino was determined in tracheal preparations taken from rats desensitized to ISO in vivo. The response to ISO was attenuated and the Kb for the propranolol-beta receptor complex was elevated (1.1 +/- 0.1 X 10(-6) M); however, Amino was half as effective in these tissues as in the saline control tissues. It is postulated, therefore, that the intracellular enzymes controlling the levels of cyclic adenosine monophosphate may be affected by the ISO-induced desensitization process, but are not affected by pretreatment with Amino.
| 29,962
|
Renal bicarbonate reabsorption in the new-born dog.
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1. Renal bicarbonate reabsorption was measured in thirty new-born dogs 2-27 days of age. Plasma bicarbonate was varied in the puppies by exchanging their blood with blood containing high levels of bicarbonate and low levels of chloride.2. The exchange transfusion resulted in increases of plasma pH, P(CO2) and bicarbonate in the puppies without changing plasma sodium and potassium or glomerular filtration rate (g.f.r.) and body weight.3. There was no tubular reabsorption maximum (T(m)) for bicarbonate and reabsorption values as high as 50 muequiv/ml. g.f.r. could be attained. No animals excreted bicarbonate at plasma levels below 25 mM and some animals had plasma bicarbonate threshold values in excess of 40 mM.4. Bicarbonate reabsorption increased as arterial P(CO2) rose (r = 0.62) but this was due to the rise of filtered bicarbonate since (a) there was no correlation between arterial P(CO2) and bicarbonate reabsorption when factored by filtered bicarbonate and (b) lowering arterial P(CO2) by mechanical hyperventilation did not reduce bicarbonate reabsorption corrected for filtered load.5. Inhibition of renal carbonic anhydrase by acetazolamide (50 mg/kg) resulted in an inhibition of bicarbonate reabsorption of only 4.5 muequiv/ml. g.f.r. (less than 20% of the total). Even with renal carbonic anhydrase inhibited, there was no bicarbonate T(m) and bicarbonate reabsorption values as high as 40 muequiv/ml. g.f.r. could be attained.6. There was good correlation (r = 0.82) between inhibition of sodium and bicarbonate reabsorption during renal carbonic anhydrase inhibition. However, with carbonic anhydrase inhibited, there was no correlation between arterial P(CO2) and bicarbonate reabsorption.7. These results demonstrate that tubular bicarbonate reabsorption mechanisms in the new-born dog are as efficient as those reported for the adult as long as body fluid and plasma sodium and potassium levels are carefully maintained.8. The results are also consistent with a bicarbonate reabsorptive mechanism explained either by direct ionic bicarbonate reabsorption or by hydrogen ion secretion with diffusion of carbonic acid.
| 29,966
|
Glutamine and glutamic acid uptake by rat renal brushborder membrane vesicles.
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Glutamine uptake by rat renal brushborder vesicles occurred via two distinct saturable processes with Km values of 0.145 and 8.5 mM which were stimulated by both ionic and sodium gradients with a pH optimum of 6.8--7.1. Glutamic acid uptake also occurred by a two-component system with Km values of 0.016 and 3.60 mM. Both components were stimulated specifically by a sodium gradient. The low Km system for glutamic acid had a pH optimum of 7.2--7.4. Glutamine entry at 0.06 mM was inhibited by a variety of amino acids at 3 mM, including dibasic amino acids, glycine, valine, and phenylalanine. Glutamic acid entry at 0.06 mM was inhibited 20--30% by 3 mM phenylalanine, valine, alpha-aminoisobutyric acid, and glutamine. No metabolic alteration of glutamic acid was observed on incubation with membrane vesicles, but glutamine was significantly hydrolyzed to glutamic acid upon prolonged incubation. Hydrolysis of glutamine was negligible at 15 sec incubation which was employed for measurement of initial rate of entry. These studies provide support for the existence of an uptake system in the brushborder of the renal proximal tubule cell capable of handling the reabsorption of glutamine normally present in glomerular filtrate.
| 29,969
|
Postperfusion lung syndrome. Comparison of Travenol bubble and membrane oxygenators.
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To examine the role of the oxygenator in the postperfusion lung syndrome, we studied 16 patients undergoing aorta-coronary bypass with a bubble oxygenator and 14 similar patients with a membrane oxygenator both before and for 2 days after the operation. To maintain the same pulmonary artery occluded pressure and hemoglobin level at the end of the surgical procedure, significantly more blood was required in the bubble than in the membrane group. Postoperative pulmonary dysfunction in the bubble group was characterized by increased pulmonary vascular resistance (PVR) and lung water. The increase in lung water was present after bubble oxygenation on three successive measurements, whereas there was no increase in lung water above control value at any measurement time in the membrane group. The bubble group had a significantly greater increase in PVR at the immediate postoperative study time than did the membrane group. PVR returned to control value for the duration of study. These differences in lung water and PVR measurements may be related to greater blood component trauma with a Travenol bubble oxygenator than with a membrane lung.
| 29,994
|
Kainic acid and synaptic transmission in the stellate ganglion of the squid.
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Kainate, a conformational analogue of glutamate, blocks synaptic transmission across the giant synapse of the squid. In the presence of blocking doses of kainate, impulses continue to propagate into the nerve terminal, but action potentials are slightly reduced in size and the subsequent hyperpolarization is greatly diminished. Kainate depolarizes the postsynaptic axon. Since the depolarizing action of kainate is confined to the postsynaptic membrane, it appears that kainate can combine with the receptors which are normally activated by the transmitter. This results in a diminished effect of the transmitter released by a presynaptic nerve impulse.
| 30,092
|
Brain catecholamines metabolism in offspring of amphetamine treated rats.
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Previous observations have pointed out that treatment with amphetamine during pregnancy produces behavioral modifications in adulthood. In order to elucidate some possible brain biochemical mechanisms that could explain the behavioral changes observed we have determined the endogenous content of brain dopamine and noradrenaline, the in vivo rate of conversion of tyrosine-C14 in such amines and the activity of tyrosine-hydroxylase, the rate limiting enzyme in catecholamines biosynthesis. We did not observe modifications in the endogenous content of dopamine and noradrenaline but did observe an increase in the conversion rate of tyrosine-C14 in such amines and also in the tyrosine-hydroxylase activity. These results indicate that treatment with amphetamines during fetal age produces catecholamine metabolism modifications that persist throughout adulthood, although the influence of behavioral modifications of the mothers cannot be ruled out. The relationship with behavioral changes is discussed.
| 30,095
|
Effect of alcohol and benzodiazepines on performance as related to personality characteristics. Personality characteristics among healthy "placebo reactors" and nonreactors.
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For 2 weeks 40 volunteers received either 5 mg diazepam, t.i.d., or 10 mg chlordiazepoxide, t.i.d., and placebo. A choice reaction test, two coordination tests, and an attention test were administered to the subjects on the 14th day of each treatment. Thirty minutes before the tests, the subjects ingested either alcohol., 5g/kg or a placebo drink, incombination with the last capsule. After the test the subjects rated the quality of their treatment as placebo, tranquilizer, or stimulant. The psychological tests taken before the treatments were Eysenck's EPIC-NESI, Taylor's Manifest Anxiety Scale (MAS), and Cattell's 16 PF inventory. A multiple regression analysis was computed. Personality factor scores found to be associated with a strong effect of the benzodiazepines were 16 PF's A, C, L, N, and Q, and EPIC's E. The effect of alcohol was associated with a high score of 16 PFs B factor. Personality factors associated with "placebo reactors" and nonreactors were investigated, as well. Those subjects on placebo indicating their treatment to be active were classified as "placebo reactors". A discriminant analysis revealed that 16PF's O and I factors discriminated effectively "placebo reactors" from nonreactors, and EPIC's SE and 16 PF's L factor nonreactors from "reactors".
| 30,099
|
Activation of guanylate cyclase by arachidonic acid in mammary gland homogenates from mice.
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Arachidonic acid stimulated guanylate cyclase activity about two fold in homogenates of mammary glands obtained from midpregnant mice; effects of arachidonic acid were observed during incubation periods between 5 and 20 minutes. Stimulatory effects of arachidonic acid on guanylate cyclase activity were observed when 10 to 100 microgram arachidonic acid was added to the reaction mixtures (150 microliter). When 250 microgram or more arachidonic acid was added to the reaction mixtures, the activity of guanylate cyclase was inhibited. Other fatty acids including linoleic acid, linolenic acid and oleic acid also stimulated guanylate cyclase activity but neither arachidic acid nor stearic acid had an effect. The arachidonic acid stimulation of guanylate cyclase activity was abolished by incubation with indomethacin and aspirin, thus suggesting the arachidonic acid effect may be carried out via the prostaglandins. A variety of prostaglandins, however, at several concentrations did not stimulate guanylate cyclase activity when added to the reaction mixtures. The failure of the prostaglandins to have an effect may be due to several reasons which are discussed.
| 30,119
|
Separator isoelectric focusing for identification of alpha-1-antitrypsin (Pi M) subtypes.
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A modified analytical isoelectric focusing procedure on polyacrylamide gel slabs, offering increased resolving capacity, has been developed for identification of six subtypes of the most common alpha-1-antitrypsin (A-1-AT) phenotype, Pi M. Combination of commercial Ampholine and other ampoteric substances, so called separators, produces pH plateaus, determined by the properties of the the additatives. Equilibrium is reached after extended focusing time, whereby stabilization of A-1-AT through alkylation is advantagous. The significance of this high resolution method for applications of the Pi system in genetic studies, and the general relevance of the modifications for other analytical purposes are discussed. A new nomenclature recommendation is presented.
| 30,163
|
Effects of beta-adrenergic stimulating and blocking agents on the dynamics of the human bladder outlet.
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The alpha-adrenergic innervation of the functional urethra is a well-known fact, while beta-adrenergic influence is rather unknown until now. We studied the influence of beta-stimulating and beta-blocking agents on the human urethra by the urethral pressure profile (UPP). A decrease of the UPP under orciprenaline sulfate and an increase under propranolol could be mentioned.
| 30,200
|
[The coincidence of visceral lupus erythematosus and epilepsy].
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It is reported on course and problems of the diagnosis of a lupus erythematodes visceralis with epilepsy. In the demonstrated case the initial stage was characterized by the nearly simultaneous appearance of relapsing arthritides and epilepsy. The diagnosis was made in the stage of an acute exacerbation with cardiac symptomatology which began after the medicamentous treatment with diphenylhydantoin. Up to this moment an oligosymptomatic lupus erythematodes visceralis had not yet been diagnosed. Anamnestic data and the laboratory-clinical findings of the further course of the disease proved the actual lupus erythematodes visceralis. It is referred to the necessity of an aimed anamnesis and a determination of the antinuclear factors before every application ofhydantoin derivations when an epilepsy and joint symptomatology are present.
| 30,220
|
The effect of stannous fluoride on human plaque acidogenicity in situ (Stephan curve).
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A system employing an Ingold glass electrode was shown to give reliable measurements of pH drops in dental plaque in situ (Stephan curve readings). The system was used to demonstrate that mouthrinses of 0.2 per cent aqueous solutions of stannous fluoride reduced the pH drops markedly for at least seven hours. A reduction of the stannous fluoride concentration increased the pH drops and decreased the duration of the inhibiting effect. A commercial toothpaste containing stannous fluoride and stannous pyrophosphate had an effect similar to the 0.2 per cent mouthrinse. It was shown that tin accumulated in dental plaque after application of solutions containing stannous fluoride. About 40 per cent of the amount of tin present in the plaque immediately after the mouthrinse was still retained seven hours later. It is suggested that the reduction in acid formation may be caused by stannous ions adsorbing to the bacterial cell wall thus disturbing membrane transport mechanisms, or through inhibition of enzyme systems essential in the fermentation of sugars. The observed effect may be a part of the mechanism involved in the caries preventive function of stannous fluoride.
| 30,252
|
Binding of bile acids by dietary fiber.
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Binding of bile salts to food residue was studied in vitro and in vivo. In the in vitro experiments, residues of a number of foods were incubated with each of several bile salts at different concentrations and pHs. All food residues tested adsorbed more dihydroxy than trihydroxy bile salts. Bile salt binding increased as bile salt concentration increased and was greater at a low pH. The extent of bile salt adsorption to some food residues could be clinically important. In patients with short ileal resections, we compared the rates of fecal excretion of labelled cholic and chenodeoxycholic acids and of a nonabsorable marker during ingestion of an ordianry diet (approximately 5 g of fiber) and a residue-free liquid diet. Coefficients of bile salt adsorption were calculated. Both bile acids were absorbed more efficiently during the liquid diet. Chenodeoxycholic acid was preferentially bound to the particulate matter of stools of patients eating the fiber-containing diet. It seems possible that dietary fiber could affect the enterohepatic circulation of bile salts in certain patients with ileal resection.
| 30,273
|
Inhibition of canine gastric acid secretion by an H-1 receptor antagonist to histamine.
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Histamine H-2 receptors are thought to mediate gastric acid secretory responses, whereas H-1 receptors supposedly regulate mucosal vascular responses to histamine. In an in vivo chambered canine stomach flap preparation, the H-1 receptor antagonist, tripelennamine, injected intraarterially (22.1 mumol/kg) into the stomach flap reduced histamine-stimulated (1.25 micron/kg/min intravenously) acid secretion by approximately two thirds with a secondary reduction in gastric mucosal blood flow. This antisecretory action does not appear to be due to nonspecific mucosal damage. The H-2 receptor antagonist, metiamide, injected intraarterially (2.5 mumol/kg) also inhibited gastric acid secretion by about two thirds as did intravenously injected metiamide (4.5 mumol/kg), whereas intravenously administered tripelennamine (40.8 mumol/kg) was ineffective as an acid secretory inhibitor. Intraarterial tripelennamine reduced the secretory actions of the H-2 agonist, 4-methylhistamine (2.2 micron/kg/min intravenously), while intravenous metiamide depressed the gastric mucosal dilator responses to the H-1 agonist, 2-methylhistamine (5 micron/kg/min intravenously). Both histamine-receptor antagonists also reversed the systemic circulatory depressor effects of histamine and its analogs. These results suggest the need for reevaluation of inferences based upon the assumed specificity of H-2 and H-1 agonists and antagonists.
| 30,277
|
[Medical check-ups and selection of subjects: some results from a gerontological field-study (author's transl)].
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In a gerontological field-study in Cologne, West-Germany, 1114 subjects of a random sample of elderlies were successively offered three modalities for a medical check-up, which covered a physical examination and a psychiatric interview: 1. in the out-patient department of a psychiatric hospital (Rheinische Landesklinik Köln) (38% of the subjects); 2. in the subjects' home by a psychiatrist of the hospital (13%); 3. by having the general practitioner fill out a questionnaire (21%). There remained a fourth group of subjects who refused any medical check-up (28%). Data on social and economic problems had been obtained for all subjects in a preceding interview. These data were used to find out to what extent selection mechanisms were effective. Results indicate that to a certain extent the modality of the medical check-up chosen by the subject is related to some of the variables analyzed.
| 30,295
|
[Study on the effectiveness of the "Berlin Letters for Seniors (author's transl)].
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The effectiveness of the "Berlin Letters for Seniors" (LFS) will be tested by a longitudinal study. Two Measurement Points (MP) are scheduled: 1976 and 1978. The total sample (N = 3000) comprehends two subsamples of receivers and non-receivers. Data were/will be collected by a questionnaire. A preliminary analysis of the MP I data shows that the two subsamples are comparable as to demographic variables and relevant attitudes; so they may serve as experimental versus control group. An examination of what the readers' concept of the LFS was like, proved that though reservation was recognizable approval prevails.
| 30,297
|
[Anesthetic evidence of pheochromocytoma].
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The authors report the clinical case of a patients who underwent four anaesthetic inductions during a period of 3 months. Two were associated with severe acute hypertension making the intended operation impossible at that time. Thorough investigations led to a diagnosis of phaeochromocytoma. Reviewing the protocol of the four anaesthetic inductions, the authors discuss the mechanism of provocation of paroxysmal hypertension which was seen on two occasions.
| 30,356
|
Calcium ion regulation in barnacle muscle fibers and its relation to force development.
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It is possible to use the photoproteins aequorin and obelin within the slowly responding striated muscle films to provide both qualitative and quantitive information as to the nature of the calcium-dependent reactions for force development. It seems that these reactions are not in equilibrium with the Ca2+ during a transient response. In addition, these experiments suggest that kinetically at least two calciums are required per functional unit for force development and that this active site is competed for by Mg2+, H+, and K+ ions.
| 30,379
|
Influence of aminophylline or beta-adrenoceptor blockade on glucagon release by a vasoactive adenosine analogue.
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The glucagon-releasing activity of adenosine-5'-ethyl-carboxamide (744-96) was studied in conscious dogs pretreated either with aminophylline or with bupranolol, a beta-adrenoceptor blocking drug. The adenosine antagonist, aminophylline, inhibited both the glucagon-releasing and the blood pressure lowering effects of 744-96 (10 microgram/kg i.v.). The actions of the adenosine analogue on glucagon release and haemodynamics were not affected by bupranolol pretreatment. These results indicate that the adenosine analogue mediates glucagon release by interaction with so-called adenosine receptors. A beta-adrenoceptor mediated release secondary to 744-96-induced hypotension and baroreceptor-activation can be excluded.
| 30,423
|
The effect of methylphenidate on serum growth hormone: influence of antipsychotic drugs and diagnosis.
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Intravenously administered methylphenidate, 0.5 mg/kg, causes a consistent rise in human serum growth hormone level, with peak values usually occurring 30 minutes after infusion. This rise is attenuated in patients receiving various antipsychotic medications administered on a long-term basis and is decreased in schizophrenic and drug-dependent patients. Methylphenidate causes increases in talkativeness, blood pressure, and pulse that generally parallel increases in serum growth hormone level. However, in contrast to the methylphenidate-induced rise in serum growth hormone level, methylphenidate-induced changes in cardiovascular variables and talkativeness are not altered by antipsychotic medications or diagnostic classification.
| 30,430
|
Metal chelate affinity chromatography of hamster interferon.
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Syrian hamster interferon, produced by benzo(a)pyrene-transformed embryo cells does not display an affinity for Zn++ chelate-agarose. However, the interferon binds to Cu++ chelate-agarose and can be displaced from the column by a falling pH-gradient. The chromatography of crude hamster interferon preparation on a tandem of columsn: Zn++ chelate-agarose in equilibrium Cu++ chelate-agarose results in a 25-fold purification of interferon.
| 30,433
|
The effect of bovine serum albumin on partial reactions of palmitoyl-CoA chain elongation by rat liver microsomes.
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In the absence of albumin, v/s curves for both condensation and overall chain elongation demonstrated that the specific activity for overall chain elongation was 3.7 times that of condensation. When the molar ratio of palmitoyl-CoA to albumin was greater than 2 : 1, the specific activity of chain elongation exceeded that of condensation. At these low albumin concentrations, in the absence of NADPH, the beta-ketostearoyl-coA was converted back to palmitate. This cleavage reaction is inhibited by albumin in a concentration-dependent manner. When the palmitoyl-CoA to albumin molar ratio was less than 2 : 1, the specific activity for condensation exceeded that for overall chain elongation and some beta-ketostearate was shown to accumulate under chain elongation conditions. The specific activity for dehydration of beta-hydroxystearoyl-CoA was maximal when the acyl-CoA to albumin molar ratio was between 10 : 1 and 4 : 1 but the rate of this reaction was not markedly influenced by variations in albumin concentration. The specific activity for the NADPH-dependent reduction of 2-trans-octa-decenoyl-CoA was 18 nmol . min(-1) . mg(-1) in the absence of albumin and increased to a maximum of 112 when the substrate to albumin molar ratio was 2 : 1. At higher albumin concentrations the reductase reaction was inhibited. Conversely, the specific activity for the reverse dehydrase was maximal at low albumin concentrations and the rate of this reaction declined as the albumin concentration increased. Our results demonstrate that albumin not only alleviates a substrate induced inhibition but also regulates the metabolic fate of 2-trans-octadecenoyl-CoA and in this regard may possibly substitute for acyl-CoA binding proteins.
| 30,485
|
Release of 3H-purines from [3H]-adenine labelled rabbit kidney following sympathetic nerve stimulation, and its inhibition by alpha-adrenoceptor blockage.
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1 Rabbit kidneys were isolated and perfused with Tyrode solution. Release of 3H-purines was studied after labeling of the adenine-nucleotide stores with [3H]adenine (more than 60% uptake during a single passage). 2 One hour after labelling the spontaneous 3H-outflow amounted to 0.1 to 0.2% of the total tissue content per minute. The release rate was enhanced following nerve stimulation (3 to 10 Hz), or brief infusion of noradrenaline (0.1 to 2.4 microgram i.a.). Release of radioactivity was also enhanced by angiotensin II, by interruption of perfusion flow for 0.5 to 2 min and by hypoxia (5 to 25% O2). 3 The release of tracer induced by nerve stimulation or noradrenaline was markedly reduced or abolished by phenoxybenzamine, which also inhibited the vasoconstrictor response. The release following angiotensin II, ischaemia and hypoxia could not be antagonized by this alpha-adrenoceptor antagonist. 4 the radioactivity in the kidney was predominantly in nucleotide form, while that released was composed mainly of nucleosides, of which adenosine predominated. 5 The results indicate that in the rabbit kidney vasocontriction, arterial clamping or reduced perfusion oxygen tension, cause release of adenosine and related compounds. In view of the reported actions of adenosine on noradrenaline effects and release in the kidney a possible physiological role is discussed.
| 30,505
|
Differences between presynaptic and postsynaptic alpha-adrenoceptors in the isolated nictitating membrane of the cat: effects of metanephrine and tolazoline.
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The alpha-adrenoceptor blocking agent, tolazoline, and the O-methylated metabolite of adrenaline, metanephrine, produced a concentration-dependent increase of tension in the smooth muscle of the cat isolated nictitating membrane. These effects were considered to be due to the activation of postsynaptic alpha-adrenoceptors. 2 The responses to nerve stimulation of this muscle were neither potentiated nor blocked by tolazoline (0.1 to 10 micrometer) or metanephrine (1 to 10 micrometer). 3 3H-transmitter overflow evoked by electrical stimulation was not modified by tolazoline or metanephrine in concentrations in which these drugs stimulated the postsynaptic alpha-adrenoceptors. 4 Since tolazoline and metanephrine failed to activate the presynaptic alpha-adrenoceptors of the cat nictitating membrane under experimental conditions in which they stimulated the postsynaptic alpha-adrenoceptors, these results further support the view that the presynaptic (alpha2) adrenoceptors differ from the postsynaptic (alpha1) adrenoceptors.
| 30,506
|
A presynaptic component of the action of iontophoretically applied flurazepam on feline cortical neurones.
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The effect of iontophoretically applied flurazepam on the spike activity of pericruciate cortical neurones of the cat was studied. Flurazepam increased cortical inhibition produced either by local electrical stimulation (which is known to release gamma-aminobutyric acid (GABA) or by iontophoretically applied GABA. Following intravenous treatment with thiosemicarbazide (a GABA-synthesis inhibitor), flurazepam still augmented the action of GABA but was much less effective on electrically evoked cortical inhibition. These findings suggest that part of the action of flurazepam on inhibitory cortical transmission might be at the presynaptic level.
| 30,528
|
Chemical characteristics of a high molecular weight renin from the renal cortex of the dog.
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We found an acid extract of normal dog kidneys to contain two distinct molecular weight forms of renin-like activity. Gel filtration chromatography showed peaks of activity as estimated molecular weights of 65,000 and 41,000. The high molecular weight fraction (HMW) comprised only 1% of the total activity of the extract. Both HMW and low molecular weight (LMW) fractions were inhibited by anti-human renin antibody and had similar broad pH-dependent activity optima between pH 6.0 and 7.5 in homologous substrate. The Michaelis constant (Km) of HMW was 3.6 times the Km of LMW. Both renins bound reversibly to concanavalin A-Sepharose with comparable affinities. HMW and LMW eluted from DEAE-Sephadex at similar salt concentrations without conversion of HMW to LMW. Transient acidification effected partial conversion of HMW to LMW without changing the total activity. Preincubation of HMW with trypsin increased the activity 40% and effected complete conversion of HMW to LMW. The apparent molecular weight difference between HMW and LMW is probably due to a covalently bound fragment(s) and not to a noncovalently bound moiety such as has been described in the rabbit and the hog. Both HMW and LMW are glycoproteins whose terminal sugar constituents possibly are similar. HMW dog renin is a new molecular form of renin that is convertible to a more active lower molecular weight renin with tryptic proteolysis.
| 30,545
|
A new automated method for the determination of true creatinine in serum by means of the centrifichem centrifugal analyzer, based on Slot's principle; with special reference to low substrate concentrations.
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A new automated method is proposed for the accurate determination of the true creatinine concentration in 20 microliter serum, based on the measurement of the initial rate of the decomposition reaction of the creatinine picrate complex caused by decreasing the pH. The results of this method, performed with a Centrifichem centrifugal analyzer system (type 300 F), are compared with the results obtained by two other methods: a manual method based upon the adsorption on Fuller's earth, and the Auto Analyzer method. In these comparative studies special attention is paid to the analysis of sera containing low (normal) substrate concentrations. Calculation of the orthogonal regression between the results obtained by the adsorption method (x) and the proposed method (y) gave: y=0.97x +/- 5 mumol/l (x=91.3 mumol/l, y-93.5 mumol/l), while for the correlation coefficient (r) 0.9721 was found. All sera (n=113) had creatinine concentrations between 40 and 180 mumol/l.
| 30,551
|
The effect of bile on the crystallisation of calcium carbonate, a constituent of gallstones.
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When calcium and bicarbonate ions were mixed at room temperature (approximately 20 degrees C) to give concentrations of 4 mmol/1 and 21 mmol/1 respectively and the pH of the solution was kept at 8.3, vaterite, a form of calcium carbonate, was precipitated almost immediately as spheres of diameter 45 micron. The crystallisation of this material could be slowed down by adding to the crystallising medium small amounts of pyrophosphate or citrate which often inhibit crystal growth. High concentrations of sodium chloride (90 mmol/1) did not, however, affect the reaction. Very small amounts of gallbladder bile from patients with only cholesterol on the surface of their gallstones inhibited the crystallisation of calcium carbonate, and the size of the spheres was only 0.37 times those produced in water. The activity of the bile could be attributed to material with a molecular weight greater than 10 000. On the other hand, bile from patients having some calcium carbonate on the gallstone surface had less activity than comparable amounts of bile from patients with only cholesterol in this area. The active material may, therefore, play a part in preventing the deposition of calcium carbonate in gallstones.
| 30,554
|
Comparative physiological disposition of ellipticine in several animal species after intravenous administration.
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The physiological dispositon of ellipticine (NSC 71795) has been studied in the mouse, rat, dog and monkey after administration of [1-14C]ellipticine at 6 mg/kg iv (3 mg/kg to monkey). Ellipticine was very rapidly distributed from the blood of all species and was deposited in tissues. The rate of elimination of ellipticine from blood was species-dependent, half-times ranging from 22 min in mouse to 210 min in rat, and probably reflected the rate of metabolism of the drug. The rate of elimination of metabolites from blood was also species-dependent, half-times ranging from 140 min in mouse to 380 min in rat, and probably reflected the rate of biliary secretion of the metabolites. Ellipticine was widely but not uniformly distributed throughout the tissues including brain, and some of the highest concentrations of drug and metabolites were in liver, which is probably the primary site of metabolism. The concentrations of ellipticine and metabolites in tissues were species-dependent, correlating with species differences in rates of metabolism and excretion. All species excreted 80% of the dose via the fecal route and 10% via the urinary route, primarily as metabolites during the first 24 hr after dosing. Metabolites entered the gastrointestinal tract by biliary secretion and ellipticine entered by an ion-trapping mechanism. Evidence is presented that the major pathway for ellipticine metabolism in rat was to 9-hydroxyellipticine, which did not accumulate in liver but was conjugated to its glucuronide and sulfate, which were secreted in bile. Other pathways involved hydroxylation and glucuronide conjugation. The pharmacokinetics of ellipticine are correlated with its toxic side effects, such as acute hypotention and neurological symptoms. They are also correlated with its potential as an antitumor agent, such as its ability to achieve values for the area under the curve of concentration vs. time (CXt) in tumors, which would be adequate for therapy. Based upon these correlations, the drug should be administered in the clinic by iv infusion, or, provided its bioavailability is found to be satisfactory, by the oral route.
| 30,602
|
[Biochemistry of depression. Literature analysis].
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The author goes briefly over the metabolism of the main cerebral monoamines, the functioning of synapses, as well as the methods used in studying the biochemistry of depression. Beyond all existing contradictory results, a review of the main works in this field enables us to point out some leading ideas:--Depression would be due to and/or accompanied by a monoaminergic deficiency: some authors emphasize the serotonin one, others the noradrenaline one.--The regulation of mood most probably finds its origin in the monoaminergic balance, rather than in the gross rates of any particular monoamine.--Disturbances are to be found on all metabolic levels: monoaminergic, hydroelectrolytic, hormonal, glucidic, lipidic, lipidic... Close intrication exists between those different metabolisms.--The interaction between the different aminergic systems and the metabolic ways, as well as the dispersion of the acknowledged results, impose more and more the necessity of a biochemical typology of depression, which would lead to a predictive approach to the evolution and treatment of depressive illness.
| 30,616
|
Stimulation of immune reactivity by methoxy-substituted glycerol ethers incorporated into the feed.
|
In mice, the plaque-forming cell response to sheep red blood cells was stimulated by a mixture of methoxy-substituted glycerol ethers isolated from Greenland shark liver oil and by synthetic 1-0-(2-methoxyhexadecyl)-glycerol, given in the diet. In preliminary experiments, this synthetic compound also increased the ability of parental spleen cells to induce graft-vs.-host reactions in F1 hybrid mice. Glycerol ethers occur in the bone marrow fat of mammals and in the membrane phospholipids. It is postulated that the methoxy-substituted glycerol ethers supplied in the diet may stimulate the bone marrow and/or may be incorporated into membrane lipids, thereby changing the structure and function of the membranes.
| 30,635
|
Reconstitution of rabbit muscle aldolase after dissociation and denaturation at alkaline pH.
|
Tetrameric rabbit muscle aldolase is dissociated to the inactive monomer at strongly alkaline pH (pH greater than or equal to 12). As shown by sedimentation velocity, fluorescence emission, and specific activity, the final profiles of dissociation, denaturation, and deactivation run parallel. Increasing incubation time proves the enzyme to be metastable in the pH range of deactivation. At 10 less than pH less than 12 "hysteresis" of the deactivation-reactivation reaction is observed. Short incubation at pH greater than or equal to 12 leads to high yields of reactivation (greater than or equal to 60%), while irreversibly denatured enzyme protein is the final product after long incubation. The kinetics of reconstitution under essentially irreversible conditions (pH 7.6) can be described by a sequential uni-bimolecular mechanism, assuming partial activity of the isolated subunits. The kinetic constants correspond to those observed for the reactivation after denaturation at acid pH or in 6M guanidine. HCl. Obviously the pH-dependent deactivation and reactivation of aldolase at alkaline pH obeys the general transconformation/association model which has been previously reported to hold for the reconstitution of numerous oligomeric enzymes after denaturation in various denaturants.
| 30,685
|
Nucleotides and coenzymes in nuclei isolated from rat liver.
|
In rat-liver nuclei, isolated by the non-aqueous technique, the concentrations and labelling rates of the purine moiety of acid-soluble nucleotides were determined and compared with corresponding data for non-fractionated tissue and nuclei-free cytoplasm. Livers were used from untreated rats, from rats with a highly stimulated synthesis of NAD and from rats following a heavy metabolic load with adenosine. Under all circumstances, the nuclear and cytoplasmic concentrations of nucleotides (e.g. ATP and its dephosphorylated forms, pyridine nucleotides) and of free glucose were practically identical. Specific radioactivities after a pulse with formate also indicated a nucleo-cytoplasmic equilibrium for purine-containing nucleotides. It is concluded that precursor pools for nuclear biosyntheses as well as energy supply for other nuclear activities may be determined by an analysis of the non-fractionated tissue.
| 30,690
|
Effect of pH on the growth and glucose metabolism of Neisseria gonorrhoeae.
|
This study examined the effect of pH on the metabolism of glucose by Neisseria gonorrhoeae. Radiorespirometric studies revealed that cells growing at pH 7.2 or 8.0 metabolized glucose primarily (ca. 80%) via the Entner-Doudoroff pathway. The remainder of the glucose was metabolized via the pentose phosphate pathway (ca. 20%). The tricarboxylic acid cycle was not active during glucose catabolism at either pH 7.2 or 8.0, and acetate accumulated in the medium. Cells growing at pH 6.0 had markedly increased pentose phosphate pathway activity (ca. 50%) and a functioning tricarboxylic acid cycle. The alteration in pathways was not due to differences in growth rate, but to the pH of the medium. Chemical fractionation of labeled cells and total hexose analyses revealed that growth pH markedly affected the composition of the gonococcus.
| 30,699
|
Pharmacological treatment of obesity.
|
Obesity results when the ingestion of energy exceeds its utilization, leading to an excessive expansion of the adipose tissue mass. Current pharmacological therapy for the obese patient focuses primarily on reducing energy intake. Anorectic agents reduce food consumption by modifying central systems in the brain which are involved in appetite regulation. These agents are reviewed in terms of mechanism of action, and clinical safety and efficacy in suppressing appetite and promoting weight loss. Newer anorectic agents which are being evaluated currently in clinical and animal studies are described. Clinical assessments of therapeutic regimens utilizing the thyroid hormones and human chorionic gonadotropin are evaluated. Finally, an overview of novel pharmacological approaches to the treatment of obesity is presented.
| 30,732
|
Coordination chemistry of microbial iron transport compounds: rhodotorulic acid and iron uptake in Rhodotorula pilimanae.
|
The mechanism by which iron uptake is facilitated by the siderophore rhodotorulic acid (RA) in the yeast Rhodotorula pilimanae was investigated with radioactively labeled Fe and RA and kinetically inert, chromic-substituted RA complexes. The weight of the evidence supports a model in which RA mediates iron transport to the cell but does not actually transport iron into the cell. It is proposed that RA exchanges the ferric ion at the cell surface with a membrane-bound chelating agent that completes the active transport of iron into the cell. Uptake of 55Fe in ferric rhodotorulate was much more rapid than uptake of RA itself. Two exchange-inert chromic complexes of RA showed no uptake.
| 30,750
|
Clinical assessment of the safety and efficacy of lorazepam, a new benzodiazepine derivative, in the treatment of anxiety.
|
In a four-week double-blind study of 68 adult outpatients, lorazepam a new benzodiazepine, administered at an average total daily dosage level of 3.1 mg on a b.i.d. regimen, was clearly superior to placebo in the treatment of neurotic anxiety and its related symptoms. The lorazepam-treated group showed significantly greater improvement than the placebo-treated group (both clinically and statistically), as evidenced by the greater changes on the physician-rated Global Scale as well as by the greater changes in almost all categories on the physician-rated Hamilton Anxiety Scale and the patient-rated Lipman-Rickels 35-Item Self-Rating Scale. There were no clinically significant changes in vital signs or laboratory values and only one side effect, urinary retention (resolved without discontinuing the drug), was reported.
| 30,763
|
Lorazepam in anxiety associated with chronic enteritis and ulcerative colitis.
|
Using a common protocol, 9 gastroenterologists assessed the comparative antianxiety efficacy of lorazepam and placebo under double-blind conditions in 48 patients with moderate to severe anxiety associated with chronic enteritis and ulcerative colitis. The initial dose of lorazepam was 3 mg per day given b.i.d., 2 mg h.s. and 1 mg a.m.; the duration of treatment was 4 weeks. The physician-rated Global and Hamilton and patient-rated 35-Item Scales were used. Efficacy was analyzed from the results of the pooled patient data. By all 3 rating scales and at virtually all times of assessment, lorazepam was associated with statistically significantly greater improvement in symptoms related to anxiety associated with chronic enteritis and ulcerative colitis than was placebo. Side effects in general were infrequent. (J Clin Psychiatry 39:[No. 10--2] 53--57, 1978).
| 30,769
|
The sensitivity of hemoglobin oxygen affinity to diphosphoglycerate and the characteristic pH of methemoglobin.
|
The sensitivity of the oxygen affinity of a hemoglobin to 2,3-diphosphoglyceric acid concentration has been defined as the change in log1/2O2 (deltalogp1/2O2) which results from saturating the hemoglobin with 2,3-diphosphoglyceric acid. The sensitivity varies from one hemoglobin species to another and is linearly rated to the difference in the logarithm of the binding constants of 2,3-diphosphoglyceric acid to deoxy- and oxyhemoglobin, the characteristic pH (pHch), and inversely proportional to the magnitude of the alkaline Bohr effect measured in a saturating amount of 2,3-diphosphoglyceric acid. Its magnitude is higher in large animals than in small animals and varies linearly with the charged amino acid composition of the hemoglobin. The charged amino acid residues must have been selected for in mammals with high metabolic needs and against in animals with low metabolic needs. Variability in the effect of 2,3-diphosphoglyceric acid on the oxygen transport in the different animal hemoglobins must therefore be the result of a positive Darwinian Selection of the charged amino acid residues in their hemoglobins. Furthermore, all the charged groups and not those at the binding site alone, affect the 2,3-diphosphoglyceric acid binding constant of a hemoglobin.
| 30,780
|
Cobalamin binding and cobalamin-dependent enzyme activity in normal and mutant human fibroblasts.
|
We have studied the intracellular binding of radioactive cobalamin by normal cultured human fibroblasts grown in medium containing [(57)Co]-cobalamin. We have also assessed the significance of defects in this binding activity exhibited by two classes of human mutants (cbl C and cbl D) each characterized by pleiotropic deficiencies in the accumulation and retention of cobalamin, in the synthesis of cobalamin coenzymes, and accordingly, in the holoenzyme activities of both cobalamin-dependent enzymes, 5-methyltetrahydrofolate:homocysteine methyltransferase and methylmalonyl-CoA mutase. Based on the coincidence of [(57)Co]cobalamin binding and cobalamin-dependent enzyme activities after Sephadex G-150 chromatography and polyacrylamide gel electrophoresis, we conclude that, as in rat liver, the intracellular binding of labeled cobalamin by normal fibroblasts reflects the attachment of the vitamin to the cobalamin-dependent methyltransferase and mutase. Whereas cbl C cells are completely deficient in the binding of [(57)Co]cobalamin to either enzyme, fibroblasts which bear the phenotypically similar but genetically distinct cbl D mutation retain some binding activity, and accordingly, have higher holomethyltransferase and holomutase activities than do cbl C cells. The defect in [(57)Co]-cobalamin binding exhibited by both cbl C and cbl D fibroblasts is almost certainly not a result of mutations which affect the methyltransferase or mutase apoenzymes, since the electrophoretic mobilities and the affinities of these enzymes for their respective cobalamin coenzymes are indistinguishable from those in control cell extracts. These results suggest that both the cbl C and cbl D mutations affect some enzymatic step(s) which converts newly taken up cobalamin to a form capable of being bound by the two cobalamin-dependent enzymes.
| 30,783
|
On testing the activity of proteases from human polymorphonuclear neutrophils on blood smears.
|
A cytochemical method is presented for the demonstration of proteases in human polymorphonuclear (PMN) neutrophils on fixed blood smears. This new technique is based on solubilization of proteases from PMN neutrophils by incubation with 0.25 M NaCl in borate buffer at pH 8.5 which leads to degradation of erythrocytes and plasma in a disclike zone (halo) around centrally situated PMN neutrophils, an effect that is visualized by staining smears using a modified colloidal iron reaction. Halo formation is inhibited by trypsin inhibitors of soya-bean as well as of chicken egg white mucoid and by phenylmethyl-sulfonylfluoride.
| 30,800
|
Microbiology of recurrent and chronic otitis media with effusion.
|
A study was conducted of 274 children who had recurrent acute or chronic otitis media with effusion. Forty-five percent of the ears with effusion were found to contain bacteria, and 11% contained bacteria that were "probable pathogens" (S. pneumoniae, H. influenzae, and S. pyogenes). Bacteria were also found in 40% of the ears without effusions. The type of organism found did not vary with the age of the patient studied or the season of the year. The significance of these bacteria in the etiology of recurrent acute or chronic otitis media with effusion remains to be demonstrated.
| 30,809
|
Hemolytic properties of synthetic glycosides.
|
Cholesteryl alpha-L-rhamnopyranoside, tigogenyl alpha-L-rhamnopyranoside, tigogenyl beta-D-fucopyranoside, smilagenyl beta-D-fucopyranoside, cholesteryl beta-maltoside, tigogenyl beta-maltoside, and smilagenyl beta-maltoside were synthesized and characterized. The rhamnosides and fucosides, as well as some other steroid monoglycosides, proved to be extremely insoluble in water. The concentration giving 50% hemolysis, H50, was of the same order of magnitude for all synthetic glycosides. Ghost cells collected from blood hemolyzed by smilagenyl maltoside and tigogenyl maltoside had appreciable amounts of absorbed aglycones. All results are in accordance with previous investigations on the mechanism of saponin and sapogenin hemolysis.
| 30,839
|
Antagonism by naloxone of narcotic-induced respiratory depression and analgesia.
|
Receptor mechanisms for narcotic-induced respiratory depression and analgesia were compared by apparent pA2 values of morphine-naloxone, levorphanol-naloxone and pentazocine-naloxone. The similarity of apparent pA2 values of the three compunds for respiratory depression suggests that morphine, levorphanol and pentazocine may interact with similar receptors to produce this effect. Significant differences between apparent pA2 values of pentazocine-naloxone and morphine-naloxone or levor-phanol-naloxone for analgesia suggest, as previously shown, that narcotic and narcotic-antagonist analgesics appear to interact with receptors in different manners. Significant differences between apparent pA2 values for respiratory depression and analgesia suggest that these two effects of the narcotic drugs are mediated by different receptor interactions.
| 30,841
|
[Exoprotease properties of Bacillus subtilis var. amyloliquefaciens capable of coagulating blood plasma].
|
The properties of the homogeneous exoprotease preparation from Bacillus subtilis varamyloliquefaciens 759 possessing the coagulase activity were studied. The enzyme is an alkaline protease, has the isopoint at pH 7.8, and not only clots blood plasmo but also hydrolyses such protein substrates as casein, hemoglobin, fibrinogen and fibrin. The enzyme is relatively stable at pH 6.0--9.0. Bivalent metal ions have virtually no effect on the enzyme activity though some of them stabilize it. The inhibitors PCMB and EDTA do not affect the activity of the enzyme whereas diisopropylfluorophosphate completely inactivates it. Fibrinogen is clotted by the enzyme only in the presence of blood plasma factors.
| 30,884
|
[Dehydrogenase isoenzymatic spectrum of alanine, aspartic and glutamic acids in Candida albicans yeasts].
|
The isoenzyme spectrum of dehydrogenases of alanine, aspartic and glutamic acids requiring NAD and NADP as cofactors was studied in Candida albicans. The spectrum of aspartate dehydrogenase was found to depend on a cofactor being used. The isoenzyme systems are related to proteins which posess various physico-chemical and antigenic properties.
| 30,885
|
[Isolation and properties of preparations the branching enzyme of muscles, amylose isomerase].
|
The paper describes a modified method of isolating the branching enzyme of amylose isomerase from muscles and a study of the enzyme activity at different stages of purification. By enzyme fractionation on biogel R-150 and Sepharose 6B the fractions containing different RNA amounts have been isolated. The activity of fractions has been shown to depend on their content of RNA. The paper presents a procedure used to isolate a highly purified fraction of amylose isomerase and its properties (pH and temperature optima, enzyme optimal concentration and Michaelis constant).
| 30,978
|
Physiologic monitoring goals for the critically ill patient.
|
Definition of the appropriate therapeutic goals for physiologic monitoring of patients postoperatively was approached by analyzing more than 50,000 values of the 20 most commonly monitored variables in a series of 113 critically ill patients throughout their immediate postoperative course. In general, normal values were poor criteria for monitoring, since normal values were restored in an average of 75 per cent of the survivors and 76 per cent of the nonsurvivors for the five most frequently measured variables; that is, arterial pressure, heart rate, central venous pressure, wedge pressure and cardiac output. Moreover, an average of 56 per cent of the 20 most commonly monitored variables of nonsurvivors was restored to the normal range. Furthermore, 34 per cent of all the nonsurvivors' values were within the normal range; this was only 2.4 per cent less than the percentage of normal values for the survivors. The empirically determined median value of the survivors taken in the late stage during periods remote from therapy was found to be a better criterion for therapeutic goals for most variables, including blood flow, oxygen transport and most intravascular pressures. However, normal values were satisfactory for arterial pressure, peripheral resistance, pH, mixed venous oxygen tension and arterial carbon dioxide tension, largely because of the biphasic patterns of these variables.
| 31,006
|
3beta-Hydroxysteroid dehydrogenase activity in human fetal membranes.
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A 3beta-hydroxysteroid dehydrogenase (3betaHSD) was demonstrated in term human fetal membranes (chorion and amnion) with both dehydroepiandrosterone (3beta-hydroxy-5-androsten-17-one) and pregnenolone (3beta-hydroxy-5-pregnen-20-one as substrates, and the subcellular distribution substrate and nucleotide specificity of the enzyme was studied. In both membranes the microsomal fraction (particles which sedimented at 105,000 g after 90 min) had the highest specific activity. The chorion was more active than the amnion but the enzyme in both tissues had similar substrate and nucleotide specificity. NAD was the preferred cofactor, and pregnenolone was a better substrate than dehydroepiandrosterone in the presence of NAD. However, with NADP as cofactor both steroids were equally good substrates. When the 3beta-hydroxysteroid dehydrogenase activity of chorion microsomes was compared with that of placental microsomes, the specific activities were found to be of the same order of magnitude, and the substrate, nucleotide specificity and steroid binding properties were almost identical.
| 31,018
|
[Experience obtained in the treatment of recurrent aphthous stomatitis (author's transl)].
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Three different methods employed within the framework of complex therapy were used to treat 195 patients with recurrent aphthous stomatitis: 1. Alterative therapy using prodigiosan, a bacterial polysaccaride. 2. Desensitizing treatment using histaglobulin, an antihistaminic agent. 3. Symptomatic local treatment. The methods of treatment are described in detail. General therapy allowed the frequency of relapses and the duration of disease to be reduced and shortened, respectively. The use of a complex form of therapy is recommended.
| 31,043
|
Comparison between agarose gel electrophoresis and isoelectric focusing of CSF for demonstration of oligoclonal immunoglobulin bands in neurological disorders.
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Isoelectric focusing and agarose gel electrophoresis of CSF and serum revealed similar frequencies of oligoclonal bands in multiple sclerosis (100% with both methods), infectious CNS disorders (38 and 23%) and other neurological diseases (8 and 10%). In selected cases with unsure CSF oligoclonal bands on agarose gel electrophoresis, isoelectric focusing displayed definite oligoclonal bands. In contrast to agarose gel electrophoresis, isoelectric focusing revealed evidence for oligoclonal bands in serum as well as in CSF in 41% of the multiple sclerosis patients, indicating diffusion from CSF to serum. In 4 cases with gammaglobulin bands appearing in both CSF and serum on agarose gel electrophoresis, isoelectric focusing revealed normal CSF and serum protein patterns at pH above 6.4 where most IgG is migrating.
| 31,050
|
Effect of metrizamide on whole blood oxygen affinity.
|
The effects on whole blood oxygen affinity following addition to human blood of either ionic (diatrizoate) or non-ionic (metrizamide) contrast medium were investigated in vitro. No medium changed whole blood oxygen affinity. Solutions of metrizamide produced less changes in plasma pH than solutions of diatrizoate. This difference is explained by lower buffer capacity and lower osmolality of metrizamide solutions. Low osmolality gives less redistribution of anions between plasma and red cells and therefore less decrease in plasma pH.
| 31,064
|
The effects of fractions (chalones) obtained from lymphoid organs on the immune response in vivo.
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Aqueous extracts of calf and pig lymphoid organs were prepared and fractionated by means of gel filtration, ion exchange chromatography, and isoelectric focusing. These fractions, which had been previously assessed on mitogen-stimulated mouse spleen lymphocytes and other cells in vitro, were tested for their in vivo activity on humoral (haemolytic PFC in mice) and on cell-mediated immunity (skin allograft survival in mice, lymph node weight assay in rats, and systemic GvH-reaction in mice). None of these several fractions elicited either biologically significant or reproducible inhibitory effects. In particular, two fractions, a high and a small molecular weight fraction which were strongly inhibitory in vitro, remained without any chalone-like activity in these in vivo assays. Our results therefore failed to support the existence of a lymphocyte chalone.
| 31,079
|
[Process of fumigatin and spinulosin formation by Aspergillus fumigatus Fres and polarographic assay of these toxins (author's transl)].
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A strain of Aspergillus fumigatus (Fresenius) isolated from a milk food for calves was grown on a culture medium containing added saccharose. The purpose was to study the synthesis of two recently discovered mycotoxins, fumigatin and spinulosin. The work was performed under many different conditions of temperature, pH and inoculum. These mycotoxins were measured by analytical differential pulse polarography. Correlations were observed between the growth rate of A. fumigatus and variation in pH of the medium and the formation of fumigatin, which is only possible when pH falls to less than 4.0. Fumigatin appears promptly at the beginning of the growth phase of the fungus but quickly disappears. The production of metabolite depends on limited conditions of culture. Spinulosin, very similar to fumigatin, is substituted for fumigatin in slightly different conditions. During growth, the fungus degrades both metabolites. The nature of the substitution and the reason of these modifications have not been investigated. Fumigatin and spinulosin formation is observed in both toxigenic and non-toxigenic strains.
| 31,124
|
Inosine nucleosidase from Azotobacter vinelandii. Purification and properties.
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An enzyme catalyzing the hydrolysis of purine nucleosides was found to occur in the extract of Azotobacter vinelandii, strain O, and was highly purified by ammonium sulfate fractionation, DEAE-cellulose chromatography, hydroxylapatite chromatography and gel filtration on Sephadex G-150. A strict substrate specificity of the purified enzyme was shown with respect to the base components. The enzyme specifically attacked the nucleosides without amino groups in the purine moiety: inosine gave the maximum rate of hydrolysis and xanthosine was hydrolyzed to a lesser extent. The pH optimum of inosine hydrolysis was observed from pH 7 to 9, while xanthosine was hydrolyzed maximally at pH 7. The Km values of the enzyme for inosine were 0.65 and 0.85 mM at pH 7.1 and 9.0, respectively, and the value for xanthosine was 1.2 mM at pH 7.1. Several nucleotides inhibited the enzyme: the phosphate portions of the nucleotides were suggested to be responsible for the inhibition by nucleotides. Although the inhibition of the enzyme by nucleotides was apparently non-competitive type with respect to inosine, allosteric (cooperative) binding of the substrate was suggested in the presence of the inhibitor. The physiological significance of the enzyme was discussed in connection with the degradation and salvage pathways of purine nucleotides.
| 31,149
|
Effect of intravenous infusion of betasympathomimetic agents on plasma renin activity during pregnancy.
|
The plasma renin activity (PRA) was measured in 26 pregnant patients before and during ritodrine infusion (10 patients), during isoxsuprine infusion (12 patients), and during glucose infusion (4 control patients). All patients were in the third trimester of pregnancy, not in labour and not hypertensive. A low dose of ritodrine, a beta2 adrenergic agent, caused a rise of PRA but no simultaneous rise in heart rate; this suggests that beta2 activity is involved in renin release. Normal doses of ritodrine and isoxsuprine increased the maternal heart rate to 110 to 120 beats/minute and also doubled the PRA level. Two hours after the end of the ritodrine infusion the PRA level was still above that before the infusion. The results suggest high reserves of renin during pregnancy.
| 31,167
|
[Effect of neuromediators on acid-base status].
|
A relationship between the state of adrenergic, cholinergic, and serotoninergic systems, on the one hand, and the acid-alkaline balance of the organism, on the other hand, was revealed in sharp and chronic experiments on dogs. A surplus of each of the mediators was accompanied by respiratory alkalosis, and its deficiency--by combined respiratory and metabolic acidosis.
| 31,211
|
Collateral sprouting in central mesolimbic dopamine neurons: biochemical and immunocytochemical evidence of changes in the activity and distrubution of tyrosine hydroxylase in terminal fields and in cell bodies of A10 neurons.
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The olfactory tubercle of adult rats was examined for the development of collateral sprouts from intrinsic dopaminergic axons following unilateral olfactory bulbectomy. In the ipsilateral tubercle tyrosine hydroxylase (TH) activity began to increase by 10-14 days following the lesion, gradually reaching a maximum of 125% of control (P less than 0.005) by 21 days where it remained permanently elevated. The rise of TH activity in the tubercle reflected changes of the dopaminergic innervation, since dopamine-beta-hydroxylase (DBH) activity was unchanged, and lesions of the dorsal noradrenergic bundle reduced DBH but not TH activity in the tubercle. By immunocytochemical staining the elevation of TH reflected an increased number and altered distribution of TH-containing processes within the olfactory tubercle. By 30 days the uptake of [3H]dopamine into synaptosomes of the olfactory tubercle was also increased to 140% of control (P less than 0.05). In the dopaminergic cell bodies of the ipsilateral A10 group (which innervate the tubercle) TH activity was transiently elevated to 121% (P less than 0.05) by 4 days, returning to control levels by 10 days. Histologically no change in activity was detected. The results indicate that mesolimbic dopaminergic neurons of A10 which innervate the olfactory tubercle will sprout in response to removal of a major non-dopaminergic input, that the new innervation is sustained, and that during collateral sprouting there is a transient elevation of TH activity in the uninjured cell bodies which precedes the period of axonal growth. The activity in the uninjured cell bodies which precedes the period of axonal growth. The findings suggest that (a) the increase of TH activity in the A10 cell bodies during collateral sprouting may be a reflection of an increase in the amount of enzyme protein required for transport into the enlarging terminal fields, (b) that as in development sprouts are in place before they reach biochemical maturity, (c) the biochemical mechanisms underlying collateral sprouting of uninjured neurons are not necessarily the same as those associated with regenerative sprouting in response to axonal injury, and (d) the development and the acquisition of biochemical maturation of collateral sprouts in the CNS involves complex two-way signaling between terminal field and cell bodies. The development of collateral sprouts of dopaminergic neurons may be the cellular substrate of the development of behavioral hyperactivity and aggression produced by bilateral olfactory bulbectomy in rat.
| 31,232
|
Pheochromocytoma in the modern context.
|
The hypertensive patient faces an uncertain future. Therefore a search for those cases in which the condition is potentially curable is eminently worth while and has become increasingly productive because of the specific diagnostic aids now available and because of the present safety of surgical intervention. Detection and localization of a pheochromocytoma allows a planned surgical approach. Correction of hypovolemia preoperatively ensures a safe course postoperatively. The use of blocking agents pre- and peroperatively prevents the hazardous hypertensive crises and arrhythmias that were a part of early surgical experience. Monitoring of central venous and arterial pressures as well as the electrocardiographic tracing during the operation permits prophylactic therapy when necessary. On the basis of a series of 31 patients the authors compare many aspects of the current management with earlier experience of pheochromocytoma in the same institution. The incidence of extra-adrenal lesions (3.8%), multicentric tumours (3.8%) and malignant change (11.5%) was lower in this group of patients than that usually reported. Abdominal exploration remains the approach of choice in most cases. Treatment of the solitary pheochromocytoma has become straightforward. However, management of the familial syndromes and the malignant from of the disease still requires careful scrutiny.
| 31,234
|
A technique for the measurement of breakage and repair of DNA alkylated in vivo.
|
The alkaline elution technique has been adapted for use in the assessment of DNA damage induced in the livers and lungs of mice after administration of an alkylating agent, methylemthanesulfonat (MMS). At 4 h after administration of MMS, damage ot DNA was readily demonstrable; the damage was repaired in liver by 24 h. The lung, particularly of the A/J mouse, exhibited an increased alkaline elution rate when compared to C57BL/6J, and repair was not entirely complete (as judged from the rate of alkaline elution of DNA) by 24 h. The rate of elution was dependent upon temperature. It is believed that this adaptation should have great utility in examining DNA repair in vivo.
| 31,244
|
Sphingolipid composition and catabolism in human fetal tissues.
|
Human fetal tissues derived from prostaglandin-induced abortuses (9--18 wk fertilization age) have been utilized to evaluate sphingolipid composition and catabolism. Sphingolipid composition (lipid-hexose, sulfatide, and lipid-bound NANA) was assessed in fetal brain. Sphingolipid catabolism was evaluated in fetal lung and brain through the measurement of relevant acid hydrolases (arylsulfatase A, beta-galactosidase, and hexosaminidase). During the fetal period studied, the parameters of sphingolipid composition revealed variability but no consistent pattern of change. Each acid hydrolase was readily detected. Enzyme specific activities revealed no variation during the 9 fetal wk studied. Cellulose acetate electrophoresis yielded the anticipated isoenzyme patterns for each acid hydrolase with little variation during the period of study. The compositional values support current concepts of cerebral development during this period of fetal life. Together with the catabolic analyses, these studies provide normative data relative to the assessment of metabolic abnormalities during this period of fetal development.
| 31,273
|
Cobalt hemoglobin: pH dependence of Adair constants and the Bohr effects.
|
Precise oxygen equilibrium curves have been obtained for cobalt hemoglobin at pH values from 5.5 to 8.2. The Hill plots are symmetric having asymptotes with slopes of unity. At pH 7.0, cobalt hemoglobin has p0.5 = 116 toor (15.45 kPa), pm = 117 torr (15.58 kPa) and a Hill coefficient of n = 1.72. The values of n decrease slightly with either decrease or increase of pH; the protein is almost non-cooperative at pH greater than 8.2. The Adair constants have been calculated with a non-linear least-squares program. From deltalnpm/deltapH a maximum of 2.5 Bohr protons was calculated at physiological pH values. The majority of alkaline Bohr protons are released after binding of the first and the third oxygen with maxima at pH 7.6 and 7.3, respectively. The acid Bohr effect was also observed with the majority of the protons taken up following the first and third oxygen bound. Smaller alkaline Bohr effects were obtained by differential titration and at higher pH than that calculated from oxygen equilibria. The discrepancy can be largely attributed to the binding of salt components to cobalt hemoglobin.
| 31,286
|
Assessment of a dental anxiety scale.
|
A number of different sets of data concerning the Corah Dental Anxiety Scale were evaluated. The data indicate that the scale is a reliable, valid, and useful measure of dental anxiety. It can be successfully used in the dental office or in research projects.
| 31,377
|
Pyridoxal phosphatase: cytochemical localization in GERL and other organelles of rat neurons.
|
A phosphatase, hydrolyzing pyridoxal-5-phosphate (P5P), a physiologically active component of the vitamin B6 complex and an essential co-enzyme in the synthesis of neurotransmitters, has been localized cytochemically in the perikarya of neurons in the peripheral, autonomic and central nervous systems of the rat. Neurons in dorsal root ganglia, sympathetic ganglia and ventral horn of spinal cord were studied by light and electron microscopy, while Purkinje cells, neurons in the dentate nucleus of the cerebellum, thalamus, and hypothalamus were studied by light microscopy only. Optimal conditions for demonstrating this activity in aldehyde-fixed tissue were determined with dorsal root ganglia. At the optimal pH of 5.0, neurons in these ganglia and in all other neurons studied show pyridoxal-5-phosphatase (P5Pase) activity in GERL. Small neurons in dorsal root ganglia also display enzyme activity in the endoplasmic reticulum (ER); activities in GERL and ER are also appreciably high at neutral pH. Small and large neurons in these ganglia, and neurons of sympathetic ganglia, show variable P5Pase activity in the Golgi apparatus. These localizations differ from the usual sites of both acid phosphatase and alkaline phosphatase activities. The P5Pase activity, demonstrated cytochemically, is a new acid hydrolase activity in GERL.
| 31,396
|
Some characteristics of Ureaplasma urealyticum. Urease activity in a simple buffer: effect of metal ions and sulphydryl inhibitors.
|
Urealytic activity of the cytoplasmic fraction of Ureaplasma urealyticum prepared by digitonin lysis was assayed in a simple buffer system (HEPES plus EDTA) by measuring the release of 14CO2 from [14C]urea. The Km of this preparation agreed with our previous observations of the same activity measured in a more complex reaction mixture. The substrate concentration at which maximum velocity occurred was approximately 20 mM. The activity was sensitive to heavy metals and inhibitors which react with sulphydryl groups such as N-ethylmaleimide and p-chloromercuribenzoate. It was not inhibited by Ca2+ or Mg2+ or by the reaction products, ammonia and carbon dioxide.
| 31,413
|
Frightening dreams and dosage schedule of tricyclic and neuroleptic drugs.
|
One previous study reported that psychiatric inpatients on bedtime-only doses of tricyclic or neuroleptic drugs reported more frequent frightening dreams than did those on divided daily doses. As a further test of this hypothesis, and in order to see whether differences in frequency of frightening dreams were a function of differences in total dream recall, we administered a questionnaire to outpatients in a Veterans Administration Hospital Mental Hygiene Clinic, asking about frequency of dream recall, frequency of frightening dream recall, and doses and times of any medications taken. Questionnaire reports of medications were checked with the medical record of the patient; for 48 patients on tricyclic or neuroleptic drugs the reports agreed, and the data of these patients were analyzed. Our findings corroborated the previous report of more frequent frightening dreams in patients on bedtime-only dosage schedules (p less than .01). In addition, we found no significant difference between the two groups with respect to frequency of dream recall; thus a difference in the affect of dreams, rather than a difference in quantity of dream recall, constituted the difference between the two groups. When a patient on bedtime doses of tricyclic or neuroleptic drugs has undesirable frightening dreams, the clinician should consider a change to divided daily doses.
| 31,416
|
Synthesis of spiro[isobenzofuran-1(3H),4'-piperidines] as potential central nervous system agents. 4. Central nervous system depressants.
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The synthesis of 1'-[3-(4-fluorobenzyoyl)propyl]-3-phenylspiro[isobenzofuran-1(3H),4'-piperidine] (2a) and eight halo and methoxy analogues is described. The compounds were generally more potent per os than chlorpromazine in the Sidman avoidance paradigm in rats and less potent than haloperido. 1'-[3-(4-Fluorobenzoyl)propyl]-3-(4-fluorophenyl)spiro[isobenzofuran-1(3H),4'-piperidine] (2e) approached the per os potency of haloperidol in this test and was shown to be active in inhibiting monkey avoidance also. Compound 2e was much less active than haloperidol in antagonizing apomorphine-induced emesis in dogs, apomorphine-induced stereotypy in rats, and amphetamine-induced circling in lesioned rats. This lack of nonselective, dopamine-receptor blocking effects makes 2e attrative as a potential neuroleptic.
| 31,478
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Neuroleptics related to butaclamol. An investigation of the effects of chlorine substituents on the aromatic rings.
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The synthesis of analogues of the antipsychotic drug butaclamol bearing chloro substituents on the benzene rings is described. On the basis of a perceived topographical similarity of a putative chlorophenylethylamine pharmacophore present in these analogues and in VUFB-10032 and doclothepin, agents related to octoclothepin which do not induce catalepsy, they have been tested for "noncataleptic" neuroleptic activity. None of the butaclamol analogues exhibit this type of activity. Depending on the position of the chlorine, the analogues either retained butaclamol-like activity or were inactive.
| 31,480
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(exo, exo)-2-Aryltropane-3-carboxylic esters, hypoglycemic agents with accompanying analgesic activity.
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(exo, exo)-2-Aryltropane-3-carboxylic esters of types 6, 7, and 10 lower circulating blood glucose levels by 60--80%. This activity is accompanied by an analgesic activity roughly equal to that of codeine. Both of these activities reside in the 1R enantiomer and extensive structure-activity studies failed to separate them. The specific opioid antagonist nalorphine blocks the analgesic activity but does not diminish the hypoglycemic action. Conformational integrity afforded by the ethylene bridge is neccessary for the observed activities.
| 31,482
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Cardioselectivity as a function of molecular structure in beta-adrenoceptor blocking agents of the 1-(para-substituted aryloxy)-3-(isopropylamino)propan-2-ol type.
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The relationship between molecular structure and cardioselectivity is described in the 1-(para-substituted aryl-oxy)-3-(isoprophylamino)propan-2-ol type of beta-adrenoceptor blocking agents. Cardioselectivity in the aforementioned series requires that the aromatic substitution in the position para to the amino alcohol side chain will have a minimal linear length of 5.0 A. Highest cardioselectivity is obtained when this para substituent is a rigid group coplanar with the aromatic ring. This may result from steric hindrance for binding at the beta2-adrenoceptor subtype which does not occur in the beta1 subtype. Evidence in favor of this suggestion was obtained by the finding that the trans isomer of 1-[4-(1-propenyl)-2-methoxyphenoxy]-3-(isopropylamino)propan-2-ol is cardioselective (beta1/beta2 = 25), whereas the cis isomer is beta2 selective (beta1/beta2 = 0.1).
| 31,488
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Fatty acid biosynthesis in yeast.
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Fatty acid synthetase and acetyl CoA carboxylase mutants have been used to study several aspects of fatty acid biosynthesis in yeast: the contribution of the various enzymes of fatty acid biosynthesis and modification to the overall cellular fatty acid composition, the mechanism of fatty acyl chain elongation in yeast, the molecular structure and the reaction mechanism of the fatty acid synthetase complex and the genetic control of the biosynthesis of this multi-enzyme system. Genetic and biochemical evidence suggest an alpha6beta6 molecular structure of this complex, where alpha and beta are multifunctional proteins comprising, respectively, 3 and 5 of the various fatty acid synthetase component functions. The two subunits alpha and beta are synthesized on two different, unliked genes, fas 2 and fas 1. The biosynthesis of both is coordinated. The various component enzyme activities reside in distinct domains on the multifunctional chains. While most domains appear to be functionally independent, the three acyl transferases exhibit extensive mutual interactions. It is suggested that the biosynthesis of a multifunctional protein is favoured on the grounds of kinetics and regulation as compared with the formation of a complex of the corresponding individual enzymes.
| 31,559
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Continuous fetal tissue pH measurement in labor.
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Fifty-one women in labor had continuous monitoring of fetal scalp tissue pH, fetal heart rate by ECG, and uterine contractions. A miniature pH electrode secured by a double spiral fetal ECG electrode was used for measurement of fetal pH every 15 seconds. The results were correlated with fetal scalp blood pH values obtained simultaneously. Fetal scalp sampling is intermittent, requires repeated scalp incisions, is subject to errors due to air mixing and coagulation of the blood sample, and is uncomfortable for the parturient. Placement of the tissue pH electrode allows continuous data recording with the minimum discomfort to the patient and the least number of fetal scalp incisions. Clinical use of the tissue pH electrode might be a practical alternative to fetal scalp samples, if the data obtained accurately reflect fetal status.
| 31,584
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Studies on proliferation kinetics in liver and spleen during early graft-vs-host reaction in mice.
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Autoradiographic and liquid scintillation counting studies were made during the early graft-versus-host-reaction in mice. At the height of GVHR on the 10th day after transplantation, hepatosplenomegaly correlated with the radioactive disintegrations (DPM). This coincided with a high proliferation rate of the blasts that appeared in the spleen, and of the portal infiltrations and Kupffer cells in the liver. Convenient control groups were used to show that these changes are a specific reaction in GVHR.
| 31,609
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[The role respiratory acidosis in the development of acute pancreatitis (author's transl)].
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The effects of respiratory acidosis on the pancreas were studied in 25 Wistar rats. Ligation of the duct combined wiht respiratory acidosis resulted in the development of acute pancreatitis. In explantation of the results it is suggested that exhaustion of the buffering capacity causes a dramatic fall in pH of the pancreatic juice. The clinical relevance of findings is discussed.
| 31,613
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Drug response and psychiatric nosology.
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The possibility that pharmacological response might help to refine psychiatric nosology has been the subject of recurrent speculation, but few clear-cut results have been obtained. Only bipolar depressives and several other minor patient subgroups manifest consistent drug responses in association with characteristic psychobiological features. The presence of multiple intervening variables, such as individual differences in drug metabolism, drug-taking behaviour and biological sensitivity to drugs, may mitigate against the reliable identification of clinically distinguishable drug-responding subgroups. Futhermore, the majority of available psychoactive drugs have either multiple or broad spectrum effects inconsistent with hypotheses utilizing the mechanism or site of drug action to argue for a diagnosis-specific biological disorder at such sites. Nonetheless, the successful use of drug-response models in other areas of medicine suggests a rationale for continued exploration in this area, and a number of recent advances make this approach potentially more productive. Pharmacological developments have rendered it possible to assess the biological availability of drugs in potential responders, thus eliminating some of the confounding intervening variables. Further consideration should also be given to the use of drugs with more specific neurochemical effects, even when they themselves are not necessarily therapeutic. The comparison of drug responder and non-responder group has also been made more meaningful by the availability of more reliable methods of assessing clinical phenomena, more sophisticated diagnostic models and the introduction of other biological measures. Combining several of these approaches may allow the use of one to validate the other.
| 31,647
|
Effects of LSD and BOL on the catecholamine synthesis and turnover in various brain regions.
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In the rat, lysergic acid diethylamide (LSD) 0.5 mg/kg and 2-bromo lysergic acid diethylamide (BOL) 0.5 mg/kg increased the rate of the striatal in vivo tyrosine hydroxylation as measured by the DOPA accumulation after decarboxylase inhibition. Neither LSD nor BOL significantly changed the DOPA accumulation in the olfactory tubercle, a dopamine-rich part of the limbic system. LSD but not BOL increased the DOPA accumulation in the cerebral cortex and in the brain stem. LSD and BOL appeared not to alter the rate of alpha-MT-induced disappearance of DA or of NA in the whole brain, nor did they change the rate of the alpha-MT-induced disappearance of DA in the striatum. It is suggested that in the striatum LSD and BOL block autoreceptorss (presynaptic receptors) regulating the tyrosine hydroxylation. These receptors may be DA receptor, but may also be 5-HT- or LSD-sensitive receptors. The regional differences observed between LSD and BOL suggest that LSD in the cerebral cortex and in the brain stem increases the DOPA accumulation by mechanism other than that functioning in the striatum. One possible explanation is that LSD and BOL may differ in their effects on 5-hydroxytryptaminergic systems in the cerebral cortex and in the brain stem.
| 31,650
|
The use of percutaneous nephrostomy and urinary alkalinization in the dissolution of obstructing uric acid stones.
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Two patients are described who presented with complete urinary obstruction secondary to nonopaque uric acid stones. They were treated with percutaneous nephrostomy for urinary diversion and urinary alkalinization by local irrigation and oral sodium bicarbonate therapy with complete dissolution of the stone after 16 and 21 days of therapy. Percutaneous nephrostomy with urinary alkalinization is a reasonable, relatively safe alternative to surgical stone removal for patients with obstructing uric acid stones.
| 31,657
|
ECT in the treatment of recurrent psychotic depression.
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Two cases of recurrent psychotic depression are reported in which ECT (electroconvulsive therapy) was administered with good results for previous episodes of depression, but treatment of the current episode with combined drug therapy (antidepressant and antipsychotic drugs) in one case and antidepressant chemotherapy in the other resulted in failure to improve. The patients were transferred to another facility, and improved when ECT was administered. Pertinent literature on ECT and drug treatment of depression is reviewed, and the conditions for which ECT is probably the treatment of choice are enumerated.
| 31,690
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Orchiopexy in prepubertal boys. Five-year survey.
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A series of 141 prepubertal boys with undescended testes operated on in a provincial teaching hospital has been analyzed five years after operation. The main features noted at presentation were the mature age of the patients and the small number of boys referred by pediatricians. The incidence of unsatisfactory results was 36% in unilateral and 35% in bilateral operations. The majority of the patients (81%) were referred for surgery after the age of five years, commonly regarded as the most suitable time for surgical correction. Three patients required a primary orchiectomy for a small atrophic testis, while 2 patients had an orchiectomy done on a previously operated testis. The complication rate for the series was 4.5%. Testicular biopsy was not done at the time of operation, and no patients were referred for semen analysis. Eight patients underwent a second orchiopexy after the first operation failed. In 6 patients an atrophic testis developed after the second procedure. The need for more than one postoperative examination is stressed in view of the fact that an initially favorable result may not persist since the testes may be found, at a later date, to have retracted into an unsatisfactory position. The reasons for the poor results are discussed and compared briefly with previous reports.
| 31,726
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Influence of morphine anaesthesia on the endocrine-metabolic response to open-heart surgery.
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Twelve patients scheduled for aortic valve replacement during extracorporal circulation were randomly allocated to either morphine anaesthesia or fluroxene anaesthesia. Morphine in a total dose of 4 mg/kg was administered before skin incision. At the start of extracorporal circulation all patients received 25 g glucose intravascularly. The endocrine-metabolic response to surgery, as expressed by changes in plasma ACTH, cortisol, insulin, growth hormone, cyclic adenosine-3',-5'-monophosphate (cyclic AMP), glucose, free fatty acids, blood b-hydroxybutyrate and cumulative nitrogen balance was measured before and during anaesthesia and surgery, and on the first five post-operative days. It was found that morphine anaesthesia blocked the increase in ACTH, cortisol, growth hormone, cyclic AMP, and glucose during surgery. However, after initiation of extracorporal circulation only ACTH, cortisol, and, to a lesser degree, the glucose and insulin response to glucose were lowered by morphine anaesthesia. From the first to the fifth days after operation no differences between the two groups could be demonstrated in any parameter. Cumulative nitrogen balance was similar in the two groups. It is concluded that morphine in large doses administered before skin incision inhibits the initial endocrine-metabolic response to open-heart surgery, but that the effect is short-lasting and without effect on overall postoperative protein catabolism.
| 31,757
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Thermal and vortical stability of purified human fibroblast interferon.
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The loss of biological activity upon heating or agitation of human interferons is markedly altered by changing their aqueous environment. Low pH significantly stabilizes liquid fibroblast interferon at 68 degrees C and 37 degrees C whereas chaotropic salts stabilize at 68 degrees C but not at 37 degrees C; this anomalous result may be due to reactivation of biological activity at the higher temperature. The concentration of extraneous proteins influences the apparent thermal stability at any temperature and pH; thus, interferon was not stable even at low pH at protein concentrations less than 5 microgram/ml. Solutions of partially purified fibroblast interferon can be inactivated by mechanical stress; the addition of proteins or nonionic detergents prevents such inactivation. Freeze-dried preparations show the greatest thermal stability. The use of high-temperature, accelerated storage tests makes it possible to predict the shelf-life of freeze-dried interferon.
| 31,770
|
Cefoxitin sodium compatibility with intravenous infusions and additives.
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The compatibility and stability of cefoxitin sodium in solution with a series of frequently used intravenous infusion fluids and injectable additives were studied. Cefoxitin sodium's stability in various solutions was measured by ultraviolet spectrophotometry, iodometry, thin-layer chromatography, high-pressure liquid chromatography, ion-exchange chromatography and microbiological assay. Cefoxitin sodium was shown to maintain 90% of its initial concentration in aqueous solution for 40 hours at room temperature (25 C) and about 30 days at 5 C. The stability of cefoxitin sodium in common i.v. infusion fluids was independent of the concentrations (1 mg/ml to 400 mg/ml) and containers used, and was retained after 30 weeks storage at -20 C. Similar stability patterns were demonstrated for cefoxitin sodium in protein hydrolysate solutions and multivitamin formulations. Cefoxitin sodium was chemically and visually compatible with amikacin sulfate, gentamicin sulfate, kanamycin sulfate and tobramycin sulfate when admixed with normal saline or 5% dextrose in water injections. Cefoxitin sodium (397 mg/ml) in 0.5% lidocaine hydrochloride was stable after 26 weeks of storage at -20 C. Sodium cefoxitin is compatible with a wide variety of commonly used infusion solutions. Its stability is independent of concentration or pH within the ranges studied, and of types of common containers.
| 31,790
|
Pancreatic response to intestinal perfusion with lactic acid or acidified albumin.
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To test the hypothesis that the permeability of weak acids across the intestinal mucosa affects their ability to stimulate pancreatic bicarbonate output, we compared pancreatic bicarbonate secretion in response to intestinal perfusion with an acid presumed to be permeable to cell membranes, lactic acid (90 daltons), and an acid presumed to be impermeable, acidified bovine serum albumin (about 70,000 daltons). These two substances have similar titration curves from pH 2.00 to pH 4.50. In four conscious dogs with pancreatic fistulas, solutions of these weak acids were perfused at 50 ml/15 min into the intestine at concentrations adjusted to deliver 1, 2, or 4 mmol/15 min of acid titratable to pH 4.50 (threshold pH for bicarbonate stimulation) from an initial pH of 2.00 or 3.50. At both pH 2.00 and 3.50 and at all titratable acid loads, bicarbonate secretory responses to lactic acid and acidified albumin were not significantly different. Equal titratable acid loads of HCl produced much larger secretory responses. The data do not support the hypothesis that permeability of weak acids is a factor, but confirm the observation that weak acids are less potent than strong acids in stimulating pancreatic bicarbonate secretion.
| 31,795
|
[Influence of age on biochemical parameters of the rat liver following partial hepatectomy (author's transl)].
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In the present paper measurements of DNA and protein content and lysosomal enzyme (beta-glucuronidase, beta-acetylglucosaminidase, cathepsin D) acitivities were performed in the rat liver following partial hepatectomy. The rats were divided into three age groups: 6 weeks, 10 months and 18 months. The regenerating liver of the 6 week and 10 month old animals disclosed significant higher concentrations of DNA than the controls. The 18 month old rats revealed no differences of the DNA content. In all age groups the protein content of the regenerating liver was significant diminished. There were age dependent differences of the activities of the three lysosomal enzymes. In comparison to the controls the beta-glucuronidase activity of the regenerating liver was significantly decreased in the 6 week and 18 month old animals, but significantly increased in the 10 month old rats. Refering to the protein content there were no differences of the activities of beta-acetylglucosaminidase and cathepsin D between the regenerating and control livers. Refering to the liver fresh weight the beta-acetylglucosaminidase activity of the regenerating liver was significant diminished in the 10 and 18 month old rats.
| 31,815
|
The effect of beta adrenergic blockade on pulmonary hypertension, right ventricular hypertrophy and polycythaemia, induced in rats by intermittent high altitude hypoxia.
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Adult male rats were used to study the effect of a beta blocking agent on pulmonary hypertension and right ventricular hypertrophy induced by intermittent high altitude (IHA) hypoxia (8 hr daily, 5 days a week, stepwise up to the simulated altitude of 7000 m). Trimepranol was injected subcutaneously in a single dose of 10 mg/kg/b.w. one hour before each IHA exposure. Administration of the beta blocking drug caused significant changes of haematocrit values even in animals kept under normoxic conditions. The initial deep decrease was followed by a slow return to control values; prolongation of treatment led to a further significant decrease of the haematocrit curve. The polycythaemic response of IHA-exposed and Trimepranol-treated animals was, therefore, significantly less pronounced as compared with the hypoxic non-treated group. Administration of Trimepranol to IHA-exposed rats significantly decreased the values of right ventricular systolic and mean pressure, right ventricular hypertrophy as well as the degree of muscularization of pulmonary arteries. It may be assumed that the protective effect of Trimepranol is due to a) changes in pulmonary vascularization, b) reduction of polycythaemia, and c) lower cardiac output, induced by the negative inotropic and chronotropic effect of this drug.
| 31,862
|
Sequence of reactions which follows enzymatic oxidation of allylglycine.
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The pathway following flavoprotein-catalyzed oxidation of allylglycine (2-amino-4-pentenoate) has been studied and found to be dependent on the incubation conditions. In N-2-hydroxyethyl-N'-2-ethanesulfonic acid (Hepes) buffer, the oxidation product 2-iminium-4-pentenoate predominantly reacts to form 2-amino-2,4-pentadienoate, a strong noncovalent inhibitor of D-amino-acid oxidase. However, in pyrophosphate buffer, the more rapid reaction is hydrolysis to form 2-keto-4-pentenoate, which has been found to be a substrate for L-lactic dehydrogenase. 2-Keto-4-pentenoate is in rapid equilibrium with 2-hydroxy-2,4-pentadienoate, which is also a strong noncovalent inhibitor of D-amino-acid oxidase. In both systems, these metastable intermediates react in subsequent slower steps to yield trans-2-keto-3-pentenoate, which accumulates in the incubation. Syntheses of trans-2-amino- and trans-2-keto-3-pentenoate are described. Comparisons between the reactivities of acetylenic and olefinic species have been made based on the differences between this pathway and that following oxidation of propargylglycine [Marcotte, P., and Walsh, C. (1978), Biochemistry 17 (preceding paper in this issue)].
| 31,909
|
Proton stoichiometry of the cytochrome c peroxidase mechanism as a function of pH.
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The proton stoichiometry for the oxidation of cytochrome c peroxidase (ferrocytochrome c: hydrogen-peroxide oxidoreductase, EC 1.11.1.5) to cytochrome c peroxidase Compound I by H2O2, for the reduction of cytochrome c peroxidase Compound I to cytochrome c peroxidase Compound II by ferrocyanide, and for the reduction of cytochrome c peroxidase Compound II to the native enzyme by ferrocyanide has been determined as a function of pH between pH 4 and 8. The basic stoichiometry for the reaction is that no protons are required for the oxidation of the native enzyme to Compound I, while one proton is required for the reduction of Compound I to Compound II, and one proton is required for the reduction of Compound II to the native enzyme. Superimposed upon the basic stoichiometry is a contribution due to the perturbation of two ionizable groups in the enzyme by the redox reactions. The pKa values for the two groups are 4.9 +/- 0.3 and 5.7 +/- 0.2 in the native enzyme, 4.1 +/- 0.4 and 7.8 +/- 0.2 in Compound I, and 4.3 +/- 0.4 and 6.7 +/- 0.2 in Compound II.
| 31,913
|
13C NMR investigations on Npi-[13C1]carboxymethyl-histidine-119 ribonuclease.
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The ribonuclease A derivative Npi-[13C1]carboxymethyl-histine-119 ribonuclease prepared by using [13C1]bromoacetate as alkylating reagent has been investigated with high resolution 13C NMR spectroscopy. In the 13C NMR spectra two carbon resonances of relatively high intensity appear which can be assigned to carboxyl groups attached to His-119 and Met-30, their intensity ratio being 10 : 1. The pH dependence of the carbon resonance of the carboxy-methyl group bound to the Npi of His-119 differs in the absence and presence of Cyd-2'-P, thus indicating that the catalytically inactive derivative does bind nucleotides. A mechanism of the alkylation reaction at pH 5.6 is proposed in which the epsilon-amino group of Lys-41 acts as the binding site for the carboxyl group of bromoacetate pushing the bromomethylene group towards the Npi of His-119 or the Ntau of His-12.
| 31,923
|
Studies on the succinate dehydrogenating system. I. Kinetics of the succinate dehydrogenase interaction with a semiquindiimine radical of N,N,N',N'-tetramethyl-p-phenylenediamine.
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1. The activities of the soluble reconstitutively active succinate dehydrogenase (EC 1.3.99.1) measured with three artificial electron acceptors, e.g. ferricyanide, phenazine methosulfate and free radical of N,N,N',N'-tetramethyl-p-phenylenediamine (WB), have been compared. The values estimated by extrapolation to infinite acceptor concentration using double reciprocal plots 1/v versus 1/[acceptor] are nearly the same for ferricyanide and phenazine methosulfate and about twice as high for the WB. 2. The double reciprocal plots 1/v versus 1/[succinate] in the presence of malonate at various concentrations of WB give a series of straight lines intercepting in the third quadrant. The data support the mechanism of the overall reaction, in which the reduced enzyme is oxidized by WB before dissociation of the enzyme-product complex. 3. The dependence of the rate of the overall reaction on WB concentration shows that only one kinetically significant redox site of the soluble succinate dehydrogenase is involved in the reduction of WB. 4. Studies of the change of V and Km values during aerobic inactivation of the soluble enzyme suggest that only 'the low Km ferricyanide reactive site' (Vinogradov, A.D., Gavrikova, E.V. and Goloveshkina, V.G. (1975) Biochem. Biophys, Res. Commun. 65, 1264--1269) is involved in reoxidation of the reduced enzyme by WB. 5. The pH dependence of V for the succinate-WB reductase reaction shows that the group of the enzyme with the pKa value of 6.7 at 22 degrees C is responsible for the reduction of dehydrogenase in the enzyme-substrate complex. 6. When WB interacts with the succinate-ubiquinone region of the respiratory chain, the double reciprocal plot 1/v versus 1/[WB] gives a straight line. The thenoyltrifluoroacetone inhibition of succinate-ubiquinone reductase or extraction of ubiquinone alter the 1/v versus 1/[WB] plots for the curves with a positive initial slope intercepting the ordinate at the same V as in the native particles. The data support the mechanism of succinate-ubiquinone reduction, in which no positive modulation of succinate dehydrogenase by ubiquinone exist in the membrane.
| 31,933
|
Characterization of two quenchers of chlorophyll fluorescence with different midpoint oxidation-reduction potentials in chloroplasts.
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The properties of two redox quenchers of chlorophyll fluorescence in chloroplasts at room temperature have been investigated. (1) Redox titration of the fluorescence yield reveals two n = 1 components with Em7.8 at--45 and --247 mV, accounting for approx. 70 and 30% of the total yield, respectively. (2) Neutral red, a redox mediator often used at redox potentials below --300 mV, preferentially quenches the fluorescence controlled by the --247 mV component. Titrations using neutral red artifactually create an n = 2 quenching component with Em7.8 = --375 mV. (3) Analysis of fluorescence induction curves recorded at different redox potentials indicates that both the --45 and --247 mV components can be photochemically reduced. The reduction of the --247 mV component corresponds to a fast phase of the induction curve whilst the slower reduction of the 45 mV component accounts for the tail phase. (4) The excitation spectra for the fluorescence controlled by the two quenchers show small differences in the ratio of chlorophyll a and b. (5) Whereas the --247 mV component readily shows a 60 mV per pH unit dependency on solution pH, the ability of the --45 mV component to respond to pH change is restricted. (6) Triton Photosystem II particles contain both quenchers but the --247 mV component accounts for approx. 70% of the fluorescence and the high component has an Em7.8 of +48 mV. The relative merits of sequential and parallel models in explaining the presence of the two quenchers are considered.
| 31,935
|
Early increase in phenylethanolamine-N-methyltransferase activity in a new strain of spontaneously hypertensive rats.
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By repeated inbreeding, 2 strains of spontaneously hypertensive and normotensive rats have been simultaneously selected. The activities of tyrosine hydroxylase and phenylethanolamine-N-methyltransferase were determined in various central catecholaminergic nuclei (C1, C2, A6 and A9) and in two peripheral tissues (adrenal glands and superior cervical ganglion). These assays were performed on rats belonging to the normotensive or the hypertensive strain at 3 ages which characterize the development of hypertension (5, 9 and 21 weeks). Except for a decrease in the C1 region of 9-week-old rats, no significant change in tyrosine hydroxylase activity occurred in central or peripheral structures of the spontaneously hypertensive rats when compared to the normotensive rats. In contrast, the activity of the phenylethanolamine-N-methyltransferase (PNMT), was increased in the C2 adrenergic group of the medulla oblongata in young spontaneously hypertensive rats: +43% (P less than 0.001) at 5 weeks of age and +32% (P less than 0.001) in 9-week-old rats. However, there was no significant difference between the 21-week-old rats. No modification of the PNMT activity was found in the C1 adrenergic group of the medulla oblongata. PNMT activity was increased significantly in the adrenal glands of 5-week-old hypertensive rats (+22%, P less than 0.001). By 9 weeks, the difference in PNMT activity in the adrenals was no longer significant. Thus, in young rats of the hypertensive strain, there was an increase in the capacity to synthetize adrenaline in the C2 area of the medulla oblongata and in the adrenal glands. While the enzymatic change present in the adrenals seems to be specific to this new strain of hypertensive rats, the elevation of PNMT activity in a specific region of the medulla oblongata (C2 group) is a characteristic common to at least two independently derived strains of genetically hypertensive rats.
| 31,964
|
DNA-dependent RNA and polyadenylic acid polymerase from phototrophically grown Rhodospirillum rubrum.
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DNA-dependent RNA and polyadenylic acid polymerases have been purified from phototrophic Rhodospirillum rubrum. Their properties have been found to be very similar to those of the previously reported heterotrophic R. rubrum enzymes. However, several important differences do exist between the enzymes from the phototrophic and the heterotrophic cells, such as the lack of response to added polyadenylic acid for poly A synthesis and the presence of the sigma subunit in the phototrophic enzymes. Furthermore, additional purification steps were necessary for preparation of phototrophic enzyme fractions with high DNA-dependence.
| 31,974
|
Enhanced hypothalamic noradrenaline biosynthesis in Goldblatt I renovascular hypertension.
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1. Hypertension was induced in rats by renal artery clip with the contralateral kidney removed (Goldblatt I) or left intact (Goldblatt II). 2. Plasma noradrenaline was increased 62% in the Goldblatt I animals after 3 weeks. 3. Hypothalamic tyrosine hydroxylase and dopamine beta-hydroxylase activities, and the concentration of noradrenaline were increased in the Goldblatt I animals after 3 weeks. 4. Enhanced hypothalamic noradrenaline synthesis may be a pathogenic factor in Goldblatt I renovascular hypertension.
| 32,000
|
Acute influence of different beta-blocking agents upon left heart hemodynamics at rest and during exercise in patients with coronary artery disease.
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The study investigated the acute hemodynamic changes induced in patients with angiographically confirmed coronary artery disease by 3 beta-blockers: metoprolol, cardioselective without intrinsic sympathomimetic activity (ISA), group I, 11 patients; bunitrolol, noncardioselective with ISA, group II, 11 patients; oxprenolol, noncardioselective with ISA, group III, 11 patients. Hemodynamic variables were obtained at rest and during exercise, before and 45 min after 10 mg i.v. of the drug. Changes in LVEDP and cardiac indexes were such as LV function was improved in 1 patient of group I, 7 patients of group II and 5 patients of group III; impaired in 4 patients of group I and in 1 patient of group III; unchanged in the others. Contractility indexes were less influenced by bunitrolol and oxprenolol. During exercise there was a significant difference between groups for LVEDP which was lower in group II (P less than 0.01). The data seem to indicate that the choice of the beta-blocker may be of importance when it is desirable that an already compromised cardiac function be not further impaired by pharmacological intervention.
| 32,041
|
Comparison of disposition and effect of timolol and propranolol on exercise tachycardia.
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The kinetic disposition and beta-adrenergic blocking action in relation to plasma level of a single oral dose of either timolol or propranolol has been compared in healthy male volunteers. The disposition profiles clearly disclosed different properties of the two drugs, although their half-lives were similar. The available fraction of timolol in the systemic circulation was estimated to be approximately 60% of the dose, and 17.4% was exereted unchanged in urine. The logarithm of plasma concentration showed a significant correlation with the beta-blocking activity assessed by an exercise test. The mean potency ratios of timolol to propranolol as an antagonist of chronotropic effects on exercise tachycardia were 11 to 17 and 3.6 to 5.5 in dose- and concentration-effect relationships, respectively. The absolute reduction of exercise heart rate gave the best coefficient of all measures of beta-blockade. When drug action was measured as beta-blockade assessed by a given response to exercise tachycardia, the effect declined linearly with time, even though plasma levels fell exponentially. This results suggest that the pharmacokinetic t1/2 is much shorter than the pharmacological t1/2.
| 32,043
|
A relatively specific and quantitative assay for histamine H2-receptor blocking activity by determination of inhibition of histamine-induced gastric acid secretion in the rat.
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A relatively specific method for the quantitative assay of histamine H2-receptor antagonists has been developed. The method is based on the antagonism of the histamine-induced, and the spontaneous, gastric acid secretion in the stomach-perfused, urethane-anesthetized acute rat. For the induced gastric acid secretion, the animal received two consecutive equal injections of histamine (2 mg/kg, intrajugularly), the second 1.7 h after the termination of the first histamine-induced acid hypersecretion. Atropine (5 mg/kg), chlorisondamine (2 mg/kg), imipramine (10 mg/kg) and tripelennamine (5 mg/kg), administered i.p., failed to inhibit the histamine-induced, or the spontaneous, gastric acid secretion. Metiamide inhibited the histamine-induced acid secretion (ED50 1.85 mg/kg, i.p.) and the spontaneous acid secretion (10 mg/kg, i.p.). These results suggest that in the rat model employed in this study, histamine and H2-receptors play a very important role in the regulation of the gastric acid secretion. Other mechanisms involving cholinergic tone, biogenic amine uptake and histamine H1-receptors do not seem to intervene.
| 32,047
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Blockade by WB 4101 of alpha-adrenoceptors in the rat vas deferens and guinea-pig taenia caeci.
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The effectiveness of WB 4101, a recently described alpha-adrenoceptor antagonist, in blocking an excitatory and two inhibitory responses to alpha-receptor activation was studied. One of the inhibitory responses was the reduction by the selective alpha-agonist amidephrine of carbachol contractures of isolated guinea-pig taenia caeci. WB 4101 antagonised this inhibition with a Schild plot slope of 0.99 and a pA2 of 8.9. The same pA2 value was obtained for blockade of the contractile effect of amidephrine and noradrenaline on the rat vas deferens. WB 4101 was, however, several hundred times less active in antagonising the inhibitory effect of clonidine on the twitch response of the vas deferens to field stimulation. Incidental observations were that the twitch was increased by low concentrations of amidephrine, and by relatively high concentrations of WB 4101. Because of its potency and postsynaptic selectivity, WB 4101 should be useful for adrenoceptor classification.
| 32,052
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A difference in effects of physiological Ca2+ concentrations on activity of guanylate cyclase preparations obtained from the taenia caecum of guinea pig and from the longitudinal muscle of rat duodenum.
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A cholinergic stimulant, butyltrimethylammonium bromide and serotonin increased the tissue levels of cyclic GMP in the taenia caecum of guinea pig but not those in the longitudinal muscle of rat duodenum. On the other hand, physiological Ca2+ concentrations enhanced the activity of a guanylate cyclase preparation obtained from the taenia caecum of guinea pig, while guanylate cyclase in the longitudinal muscle of rat duodenum was not influenced by Ca2+. The difference in the effects of the smooth muscle stimulants on the tissue levels of cyclic GMP in two different smooth muscles in attributed to differences in the properties of guanylate cyclase of smooth muscles.
| 32,054
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Antagonism of central histamine H1 receptors by antipsychotic drugs.
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The activity of 8 widely antipsychotic drugs as antagonists of central histamine H1 receptors was determined from the inhibition of the binding of 3H-mepyramine to a membrane fraction from guinea-pig brain. The phenothiazines examined, clorpromazine, fluphenazine, thioridazine and trifluoperazine, were all potent H1 antagonists. Both alpha- and beta-flupenthixol were potent inhibitors, but butaclamol, although less potent, showed stereospecificity. Haloperidol and spiperone were markedly weaker antihistamines than the phenothiazines.
| 32,056
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