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The incretin concept today.
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1. The insulinogenic factor of the gastrointestinal mucosa named "incretin" is only one part of the complex enteroinsular axis. --2. Of the chemically defined gastrointestinal hormones GIP is the strongest incretin candidate. --3. Because of the dual function of GIP as gastrone and insulinotropic substance several safeguards against GIP-mediated insulin hypoglycaemia exist. --4. No pathological condition has yet been found which is causally related to hyper- or hyposecretion of GIP. However, an exaggerated GIP response (usually secondary to the disease) may participate in the pathogenesis of hyperinsulinaemia of patients with obesity and duodenal ulcer. --5. The injection of GIP antibodies only partially abolishes the incretin effect. Therefore, GIP, although important, is not the only incretin.
| 32,119
|
The hospital and optimal chemotherapy in schizophrenia.
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With some schizophrenics, response to antipsychotic drugs is best monitored in the hospital. They include dysphoric responders, those whose illness has been only minimally responsive to antipsychotic drugs, and habitual noncompliers with drug regimen. Dysphoric responses need to be acknowledged and regarded as a danger signal. Patients whose illness is only modestly sensitive to drugs are particularly in danger of psychotoxicity due to excessive dosage. Habitual noncompliers have little investment in staying well, and cannot be expected to bear even mild drug side-effects.
| 32,128
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Phytohemagglutinin stimulation of enhanced immunoglobulin G production in mice inoculated with type III pneumococcal polysaccharide.
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In BALB/c mice previously inoculated intraperitoneally with an immunogenic dose of the T-independent antigen type III pneumococcal polysaccharide, the intravenous administration of the T-cell activating agent phytohemagglutinin P causes a pronounced increase in the number and relative proportion of immunoglobulin G-producing cells. These results, detected by a modified hemolytic plaque assay, were supported by finding increased levels of serum immunoglobulin G anti-type III pneumococcal polysaccharide in the treated mice. A comparable stimulation of immunoglobulin G antibody-producing cells was not induced in phytohemagglutinin P-treated nude mice, indicating that the change in class of the predominant antibody is attributable to the activation by the phytohemagglutinin P of a T-cell population. Under the conditions of these experiments, phytohemagglutinin P also promotes a progressive suppression of the antibody-forming cells during the response to type III pneumococcal polysaccharide.
| 32,142
|
Dissociation between clinical and exercise responsiveness to beta-blockade in angina.
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Twenty outpatients with mild angina were prescribed placebo tablets b.i.d. for 7 weeks followed by acebutolol, a cardioselective beta-blocker, 200 mg b.i.d. for 21 weeks under single-blind conditions. One graded multistage treadmill test was carried out after each treatment period and an angina diary was filled daily for the 6 months of the trial. Attack frequency declined by 71% from 2.59 per week on placebo to 0.76 per week on acebutolol (p less than 0.05). Exercise duration on the treadmill increased by 56%, from 5.95 minutes on placebo to 9.32 minutes on acebutolol (p less than 0.001). A satisfactory clinical response (50% or greater decline in attack frequency per week) occurred in 15 out of 19 patients (79%; a 100% or greater increase in exercise duration on the treadmill was observed in 10 out of 19 cases (53%). Exercise responsiveness was well predicted by exercise duration on placebo (r = 0.91, p less than 0.0005), patients with the least initial tolerance being the most improved. Clinical responsiveness was not well predicted by initial exercise tolerance (r = 0.38, N;S.) or by the improvement in exercise tolerance (r = 0.33, N.S.). It is concluded that acebutolol substantially reduces anginal attack frequency even in patients in whom exercise tolerance is not significantly improved, at the dose of 400 mg/day.
| 32,144
|
[The dental soldering by means of high frequency induction heating (author's transl)].
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The authors examined the methods of high frequency induction soldering, especially Loop-method, other than the gas flame soldering which was known generally. The details which was done are: (1) about the form of induction coil, and the relative places of the coil and restrative appliance, and some supplementary appliances of them. (2) about strength of soldered joints of Co-Cr wire using silver solder and Pd-solder, and observation on the corrosion of soldered-joints by the scanning electron-microscope. (3) about the comparison of the characteristics of Co-Cr wire by means of high-frequency induction heating and gas-flame one. (4) about the examples of soldering of porcelain crown-bridge and clasp wire attached on the dental cast, and possibility of soldering techniques of them on the dental cast. The authors found that the high frequency induction method was preeminent from the other method on the point of (a) the characteristic of heated wire, (b) the strength of soldered joints, (c) the easiness of operating of them, and (d) the possibility of soldering using the high-melting point of Pd-solder, and the soldering of them on the dental cast. Therefore we can enough respect the application on the dental area of this apparatus and this techniques of the high-frequency induction soldering.
| 32,215
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The major fraction of deoxyribonuclease activity from human urinary proteins. Purification and properties.
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The major fraction of deoxyribonuclease activity from human urinary protein was purified 40-fold in about 14% yield. The enzyme shows an isoelectric point at pH 4.2 and has a molecular weight of 33,600+/-3,000. Optimum activity was shown at pH 6.8 in the presence of 12.5 mmol/l Mg2+ plus 1 mmol/l Ca2+. The enzymic reaction is inhibited by high ionic strength (greater than 300 mmol/l Na+). The purified enzyme readily hydrolyzes native DNA to oligodeoxyribonucleotides with an average chain length of 5.3+/-0.2 after exhaustive digestion. Therefore, this endonuclease may be designated as neutral deoxyribonuclease (deoxyribonucleate oligonucleotidohydrolase, EC 3.1.4.5).
| 32,220
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Purification and properties of an NAD(P)+-linked formaldehyde dehydrogenase from Methylococcus capsulatus (Bath).
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Crude soluble extracts of Methylococcus capsulatus strain Bath, grown on methane, were found to contain NAD(P)+-linked formaldehyde dehydrogenase activity. Activity in the extract was lost on dialysis against phosphate buffer, but could be restored by supplementing with inactive, heat-treated extract (70 degrees C for 12 min). The non-dialysable, heat-sensitive component was isolated and purified, and has a molecular weight of about 115000. Sodium dodecyl sulphate gel electrophoresis of the protein suggested there were two equal subunits with molecular weights of 57000. The heat-stable fraction, which was necessary for activity of the heat-sensitive protein, was trypsin-sensitive and presumed to be a low molecular weight protein or peptide. A number of thiol compounds and other common cofactors could not replace the component present in the heat-treated soluble extract. The purified formaldehyde dehydrogenase oxidized three other aldehydes with the following Km values: 0.68 mM (formaldehyde); 0.075 mM (glyoxal); 7.0 mM (glycolaldehyde); and 2.0 mM (DL-glyceraldehyde). NAD+ or NADP+ was required for activity, with Km values of 0.063 and 0.155 mM respectively, and could not be replaced by any of the artificial electron acceptors tested. The enzyme was heat-stable at 45 degrees C for at least 10 min and had temperature and pH optima of 45 degrees C and pH 7.2 respectively. A number of metal-binding agents and substrate analogues were not inhibitory. Thiol reagents gave varying degrees of inhibition, the most potent being p-hydroxymercuribenzoate which at 1 mM gave 100% inhibition. The importance of possessing an NAD(P)+-linked formaldehyde dehydrogenase, with respect to M. capsulatus, is discussed.
| 32,222
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Role of vitamin B12 and enzymes related to methylmalonyl-CoA mutase in a methanol-utilizing bacterium, Protaminobacter ruber.
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A methanol-utilizing bacterium, Protaminobacter ruber, required cobalt ion or vitamin B12 as its growth factor, which could be replaced by succinate among various additions to the cobalt-deficient medium. The presence of adenosylcobalamin (adenosyl-B12)-dependent methylmalonyl-coenzyme A (CoA) mutase was demonstrated in the cell-free extracts of P. ruber. The specific activity of this mutase was not only fairly high in comparison with that reported with other organisms but also detected at a similar level throughout the cultivation period. The cell-free extracts of P. ruber grown on non-C1 compounds as a sole carbon and energy source also had methylmalonyl-CoA mutase activity. Furthermore, the extracts of this microorganism catalyzed the reactions from propionyl-CoA to succinyl-CoA and from alpha-ketoglutarate to alpha-hydroxyglutarate.
| 32,234
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The effect of PGE1 on peristalsis and on perivascular nerve inhibition of peristaltic activity in guinea-pig isolated ileum.
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The effect of PGE1 on peristalsis of guinea-pig isolated ileum was examined using a modified Trendelenburg method to evoke and record peristaltic activity. PGE1 (14 nM, 0.11 microM and 0.56 microM) increased peristaltic activity of both longitudinal and circular muscle, mainly by increasing the amplitude of contraction. Preparations of ileum subjected to a 'minimal' peristaltic stimulus were more sensitive to the effects of PGE1 than were preparations subjected to a 'just-maximal' peristaltic stimulus. The inhibition of peristaltic activity caused by perivascular nerve stimulation was antagonized by 0.56 microM PGE1 but slightly increased by 14 nM PGE1.
| 32,240
|
A comparison of the cardiovascular effects of centrally administered clonidine and adrenaline in the anaesthetized rat.
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Intracerebroventricular (i.c.v.) injections of clonidine and adrenaline-induced hypotension and bradycardia in urethane anaesthetized spontaneous hypertensive rats. The hypotension induced by clonidine (3 microgram i.c.v.) was antagonized by pretreatment with the alpha-antagonists piperoxan, which also antagonized clonidine-induced bradycardia, and yohimbine. The hypotension and bradycardia induced by adrenaline (10 microgram i.c.v.) were unaffected by alpha-antagonist pretreatment, while beta-antagonist pretreatment with (--)-propranolol or metoprolol was effective against adrenaline but not clonidine-induced hypotension and bradycardia. Pretreatments with the histamine H2-receptor antagonists metiamide and cimetidine antagonized clonidine but not adrenaline-induced hypotension. These data indicate that different central mechanisms are involved in mediating the hypotension and bradycardia induced by centrally administered clonidine and adrenaline and do not, therefore, support the hypothesis that the hypotensive effects of clonidine (i.c.v.) are mediated by central adrenaline receptor activation in urethane-anaesthetized spontaneous hypertensive rats.
| 32,359
|
Comparative study of the dopamine-sensitive adenylate cyclase in the striatum and hypothalamus of rat brain.
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Stimulation by dopamine of adenylate cyclase in homogenates of rat brain striatum was enhanced in the presence of ATP (0.6--3 mM) and GTP (10--100 micrometer). The stimulation by dopamine appeared to be the result of its antagonism of inhibition of adenylate cyclase by GTP or higher concentrations of ATP. Stimulation of the enzyme by dopamine was also dependent on MgCl2, and was maximal at MgCl2 concentrations of at least two fold excess over ATP. While ATP did not inhibit adenylate cyclase in homogenates of the ventral hypothalamus, GTP (10--100 micrometer) significantly stimulated it. Dopamine stimulated the adenylate cyclase in the hypothalamus. This action was blocked by chlorpromazine (10 micrometer) and phentolamine (100 micrometer) but not by an analogue of chlorpromazine having no neuroleptic activity or by propranolol (100 micrometer).
| 32,363
|
Effects of beta-adrenergic blocking agents on peripheral vascular resistance.
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The effects of the beta-adrenergic blocking agents propranolol, pindolol, atenolol, bunitrolol, and methypranol on the vascular resistance of isolated perfused hindlimbs of rats were investigated. At concentrations of 0.01 microgram/ml in the perfusate dl-propranolol and pindolol significantly increased vascular resistance by blockade of beta2-receptor mediated vasodilatation, whereas atenolol, bunitrolol and methypranol had no effect on peripheral resistance at this concentration. With increasing concentrations up to 10 microgram/ml all drugs, with the exception of atenolol, caused vasodilatation. We conclude that the specificity of beta-blocking agents can be established in the isolated perfused hindlimb vasculature of rats through its effect on vascular resistance. The lack of inhibition of vascular beta2-receptors at low concentrations of atenolol and also bunitrolol and methypranol show relative selectivity for beta1-receptors. The differential effects of beta-adrenergic agents on vascular resistance may have significance for the clinical use of the drugs.
| 32,434
|
Impaired distal nephron acidification in chronically phosphate depleted rats.
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Renal tubular bicarbonate reabsorption and acidification were evaluated in phosphate depleted rats (PD) and controls. After 33 days of phosphate depletion, urine pH of PD rats (N = 5, 5.36 +/- 0.15) was significantly higher than control (N = 5, 5.64 +/- 0.09, P less than 0.005) following an NH4Cl load. Urinary titratable acid of PD rats (9.6 +/- 1.8) was significantly reduced compared to control (117.2 +/- 19.7 muEq/3 h, P less than 0.001), whereas NH+4 excretion was not different. The plasma HCO-3 thresholds at which bicarbonaturia occurred (approximately 25 mEq/l) were identical in controls and phosphate depleted rats during isotonic bicarbonate infusion. The higher urine pH of phosphate depleted rats following NH4Cl administration was not due to low urinary phosphate as 3-day phosphate depleted rats could normally acidify urine after NH4Cl (pH = 5.86 +/- 0.09, N = 6 vs. control 5.87 +/- 0.08, N = 6, P = N.S.) despite urinary phosphate excretion as low as in 33-day PD rats. These data indicate the presence of impaired distal tubular acidification in chronically phosphate depleted rats.
| 32,521
|
Competitive inhibition of benzodiazepine binding by fractions from porcine brain.
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Fractions of porcine cerebral cortex extract separated by molecular weight on a Sephadex G-75 column were tested for their activities and potencies to inhibit [3H]benzodiazepine binding to rat brain homogenates. The fractions spanned molecular weights from 500 to 100,000. A potent inhibitor (benzodiazepine-competitive factor I, BCF-I) was discovered in the fraction containing substances with molecular weights from 40,000 to 70,000. Equilibrium binding studies indicated that BCF-I was a competitive inhibitor, making it a candidate as a benzodiazepine endogenous factor or profactor. BCF-I was heat stable, but trypsin digestion destroyed its activity. Another inhibitory fraction (BCF-II) was 1/5th as active as BCF-I and contained substances with molecular weights from 1000 to 2000.
| 32,539
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The peripheral platelet count in response to adrenergic alpha-and beta-1-receptor stimulation.
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The aim of the present work was to investigate the effect of adrenergic alpha- and beta-1-receptor stimulation on the peripheral platelet count. The experiments were carried out on 8 healthy male volunteers using radioisotopically labelled platelets. 3 subjects received i.v. infusions of adrenaline (0.09 microgram X kg-1 X min-1) before and after the ingestion of 40 mg propranolol. In response to the first infusion there was an instant increase in the venous platelet-bound radioactivity (PBR) which amounted to 12% over basal value. This effect of adrenaline seemed to be potentiated by propranolol pretreatment. 5 subjects received i.v. infusions of the highly selective beta-1-receptor agonist H 133/22 (prenalterol, Hässle, Sweden). In response to a cumulative dose of 4.75 mg prenalterol a slight but significant (P less than 0.05) decrease in PBR occurred. It is concluded that alpha-receptor stimulation causes a depletion of platelets from the exchangeable splenic platelet pool resulting in a concomitant increase in the peripheral platelet count. Beta-receptor stimulation has an opposite effect on the spleen. The trapping of platelets by the spleen is mediated both via beta-1- and beta-2-receptors, but the effect of beta-2-receptor stimulation seems to predominate.
| 32,612
|
[Abnormal involuntary movements in the elderly and their treatment (author's transl)].
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In the elderly, there are two main types of abnormal involuntary movements: tremors on one hand and dyskinesias on the other. Among tremors, senile and parkinsonian types have to be separated because they have different semeiologic signs and distinct therapeutics. Senile tremor is present during movements and tonically maintained attitude. It affects upper extremities (often asymmetrically) and the head; it is reduced by alcohol. When possible (in the absence of contrindications) its best treatment is by beta-blockers. Parkinsonian tremor is typically present at rest and is reduced by a voluntary movement. L-dopa is active but in the elderly the dosis has to be reduced. Dyskinesias are repetitive but not rythmic involuntary movements which are made at the speed of a normal movement. There are at least two types of dyskinesias: spontaneous and post neuroleptics (i.e. tradive). Spontaneous dyskinesias essentially involve the axial muscles and are chiefly bucco-linguo-facial. They are well controlled by various neuroleptics. If eventual side effects are taken into account, tiapride appears to represent the good choice. Tardive dyskinesias do not disappear when responsible neuroleptics are stopped and are usually permanent. Paradoxically, when necessary, their treatment consists in resuming a neuroleptic prescription.
| 32,624
|
[Changes in cerebrospinal fluid pressure following administration of sodium hydroxybutyrate and viadril-G to patients with brain tumors].
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The effect of sodium oxybutyrate and viadril-G on intracranial pressure was tested in 30 patients with tumours in injecting an anaesthetic. The electromanometric method was applied in measuring the pressure of cerebrospinal fluid and central venous pressure. A considerable reduction of intracranial pressure was noted in inducing anaesthesia by sodium oxybutyrate (by 34.5%) and viadril-G (by 24%), which was attended by an increase in perfusional brain pressure.
| 32,712
|
Lorazepam, a new benzodiazepine derivative, in the treatment of anxiety: a double-blind clinical evaluation.
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Ninety-five adult outpatients suffering from moderate to severe anxiety were randomly assigned to treatment with lorazepam or placebo in a double-blind four-week study. Patients were evaluated at pretreatment and after two and four weeks of treatment using three rating scales. Lorazepam, at an average daily dose of 3.2 mg twice daily, was highly effective in relieving anxiety as documented by clinically and statistically significant differences over placebo in most of the items on all rating scales at all rating periods. No serious adverse effects were reported, and there were no adverse interactions with other medications, including digitalis and aspirin.
| 32,776
|
[Determination of dipotassium clorazepate in the plasma by gas chromatography (author's transl)].
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The authors present a method of estimation of dipotassium clorazepate by gas chromatography with a detector for electron capture. It requires 2 ml of blood. Two separate extractions are necessary, including one immediately after the sampling to determine the nordiazepam present at the time of the blood sample. The second extraction permits one to determine the total nordiazepam obtained by transformation of all the dipotassium clorazepate. This method is simple and rapid and permits one to determine with precision, specificity and good reproducibility (CV -- 3%) the therapeutic concentrations of this drug.
| 32,817
|
Estimation of alcohol intake from laboratory results.
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Subjects with abnormalities in a number of laboratory tests were shown to have higher than usual probabilities of being heavy drinkers. Quantitative estimates have been made of the probabilities of heavy drinking from the results of the following tests: gamma-glutamyl transpeptidase, mean corpuscular volume, uric acid, triglyceride, and aspartate aminotransferase. In men, but not in women, there was a clear increase in this probability with increasing test results for these five tests, which may prove useful in the detection of individuals who are at risk from their drinking habits.
| 32,827
|
"Acute chest syndrome" in adults with sickle cell anemia. Microbiology, treatment, and prevention.
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Fifty-two episodes of fever, chest pain, increased leukocytosis, and pulmonary infiltrate ("acute chest syndrome") were studied in 28 adults with sickle cell anemia. Possible bacterial pathogens were identified in sputum cultures from less than half of the episodes; no pneumococci were found, and Staphylocococcus aureus was the only bacterium associated with a longer illness than that seen when only normal flora were recovered. Much disease diagnosed as "pneumonia" in adults with sickle cell anemia is probably pulmonary infarction. Many of these patients will recover with no more than modest supportive care; if antibiotics are used they should be directed against S aureus (and possibly Hemophilus species). Pneumococcal polysaccharide vaccine has great potential for preventing life-threatening infection in children with sickle cell anemia, but may not change the incidence or severity of the acute chest syndrome in adults.
| 32,855
|
Adenylate cyclase in bloodstream forms of Trypanosoma (Trypanozoon) brucei sp.
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1. The adenylate cyclase in Trypanosoma brucei is located in the plasma membrane. 2. A partial kinetic analysis of the properties of the enzyme revealed a Km for ATP of 1.75 mM and a Km for Mg2+ of 4mM. 3. At low concentrations, Mg2+ activated the enzyme directly in addition to its effect of lowering the concentration of inhibitory free ATP species. 4. At high concentrations, Mg2+ inhibited the enzyme. Furthermore, the enzyme was inhibited at any Mg2+ concentration if the concentration of ATP exceeded that of Mg2+. 5. The opposing effects of Mg2+ at low and high concentrations would be consistent with more than one binding site for Mg2+ on the enzyme. 6. A study of the patterns of product inhibition revealed little or no effect of 3':5'-cyclic AMP, but a profound inhibition by pyrophosphate, which was competitive with respect to ATP (Ki 0.135 mM). This result suggests that the substrate-binding domain on T. brucei adenylate cyclase interacts mainly with the triphosphate portion of the ATP molecule. 7. The enzyme activity was unaffected by the usual mammalian enzyme effectors glucagon, adrenaline, adenosine, GTP and guanyl-5'-yl imidodiphosphate. 8. The enzyme was not activated by fluoride, instead a powerful inhibition was found. The enzyme was also inhibited by relatively high concentrations of Ca2+ (1 mM).
| 32,875
|
The kinetics of the active and de-energized transport of O-methyl glucose in Ustilago maydis.
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The kinetics of the uptake and efflux of 3-O-methyl-glucose in sporidia of Ustilago maydis were measured, both in active cells and in cells whose metabolic activity had been inhibited by azide and iodoacetate. The de-energized transport system proved to be carrier mediated with apparent affinity constants 13 +/- 2 mM outside (Ko) and 18 +/- 2 mM inside (K1). The apparent maximum rate constants for the same system were 0.66 +/- 0.05 mmol/1 cell water per min for uptake (V+) and 0.53 +/- 0.04 mmol/l cell water per min for efflux (V-). For the active system K0 = 0.08 +/- 0.01, K1 greater than 40, V+ = 9.7 +/- 0.5 and V- = 1.1 +/- 0.9 (in equivalent units). These results are discussed in the context of the carrier mechanism as proposed by Regen and Morgan (Regen, D.M. and Morgan, H.E. (1964) Biochim. Biophys. Acta 79, 151--166). The antifungal compound carboxin had no effect on de-energized transport but was shown to decrease both K0 And V+ in the active system. Phloretin and phlorizin were also found to be without effect on de-energized cells but the former enhanced while the latter inhibited active uptake.
| 32,904
|
Yellow lupin (Lupinus luteus) aminoacyl-tRNA synthetases. Isolation and some properties of enzyme-bound valyl adenylate and seryl adenylate.
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As a continuation of our studies on plant (yellow lupin, Lupinus luteus) aminoacyl-tRNA synthetases we describe here formation and some properties of valyl-tRNA synthetase-bound valyl adenylate (EVal(Val-AMP)) and seryl-tRNA synthetase-bound seryl adenylate (ESer(Ser-AMP)). Valyl-tRNA synthetase-bound valyl adenylate was detected and isolated by several approaches in the pH range 6--10. In that range inorganic pyrophosphatase increases the amount of valyl adenylate by factor 1.8 regardless of pH. 50% of valine from the EVal(Val-AMP) complex isolated by Sephadex G-100 gel filtration was transferred to tRNA with a rate constant greater than 4 min-1 (pH 6.2, 10 degrees C). The ratio of valine to AMP in the enzyme-bound valyl adenylate is 1 : 1 and it is not changed by the presence of periodate-oxidized tRNA. In contrast to enzyme-bound valyl adenylate, formation of ESer(Ser-AMP) is very sensitive to pH. Inorganic pyrophosphatase increases the amount of seryl adenylate by a factor 6 at pH 8.0 and 30 at pH 6.9 60% of serine from the ESer(Ser-AMP) complex was transferred to tRNA with a rate constant greater than 4 min-1 (pH 8.0, 0 degrees C). The ratio of serine to AMP in the enzyme-bound seryl adenylate is 1 : 1. The rate of synthesis of the enzyme-bound aminoacyl adenylates was measured by ATP-PPi exchange. Michaelis constants for the substrates of valyl-tRNA and seryl-tRNA synthetases in ATP-PPi exchange were determined. Effects of pH, MgCl2 and KCl on the initial velocity of aminoacyl adenylate formation are described. For comparison, catalytic indices in the aminoacylation reactions catalyzed by both lupin enzymes are given and effects of pH, MgCl2 and KCl on tRNA aminoacylation are presented as well. Under some conditions, e.g. at low pH or high salt concentration, lupin valyl-tRNA and seryl-tRNA synthetase are active exclusively in ATP-PPi exchange reaction.
| 32,907
|
[Metabolic activation of N-methyl-N-nitrosourea in normal and tumor cells].
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N-methyl-N-nitrosourea is metabolised by mouse liver microsomes yielding highly reactive product(s) capable of alkylating cellular macromolecules. Based on cofactor requirement (NADPH, oxygen), inhibition (NaN3) and induction by phenobarbital, 3,4-benz(a)pyrene, and MNU, the reaction is cytochrome P-450-dependent. Analysis of the kinetics and dose dependence of alkylation in vivo and in tissue homogenates confirms the fact that MNU must undergo metabolic activation in vivo.
| 32,924
|
[Chemical modification of lysine epsilon-NH2-groups in horseradish peroxidase. Its effect on enzyme stability. Temperature dependence of thermo-inactivation constants for native and modified peroxidase].
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Thermostability of horseradish peroxidase modified by acetic, propionic, butyric, valeric and succinic anhydrides and trinitrobenzolsulfonic acid (TNBS) is studied within the temperature range of 56-80 degrees C. Acylation of 4 amino groups and arylation of 3 amino groups with TNBS are found to stabilize the enzyme, while modification of 6 groups decreases the enzyme stability. Chemical modification of peroxidase does not change its pH-dependence with respect to enzyme thermostability. Thermodynamic activation parameters of irreversible thermoinactivation are determined for native and modified peroxidase. Native peroxidase has deltaH not equal to = 30+/-1 kcal/mole and deltaS not equal to = 14 e. e.; modified by acid anhydrides peroxidase has deltaH not equal to within 64-87 kcal/mole and deltaS not equal to within 110-178 e. e. depending on the nature of a modifying agent. The effect of the structure of a radical introduced into the enzyme molecule, and of a number of modified epsilon-amino groups on thermoinactivation deltaH not equal to and deltaS not equal to values is discussed.
| 32,926
|
Perinatal development of the tyrosine oxidizing system.
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The enzymes of the tyrosine oxidase (TO) system of rat liver were measured during pre- and postnatal development. At all ages, the rate of tyrosine oxidation was limited by the activity of tyrosine aminotransferase (TAT). TAT of liver was undetectable from 4 days to 1 day before birth and was lower than p-hydroxyphenylpyruvate oxidase (pHPPO) and homogentisate oxidase (HO) postnatally. At birth, TAT, pHPPO, and HO were 2.9, 13, and 40% of adult values, respectively. Relative levels in fetal liver were HO greater than pHPPO greater than TAT. When enzyme activities were adjusted to compensate for dilution by hematopoietic cells, absolute activities increased, but other relationships remained the same. pHPPO rose at 15-17 days after birth and exceeded adult values at 31 days. HO was unchanged after birth. We conclude that each enzyme of TO follows a unique developmental path, with no concerted control of the entire TO system.
| 32,931
|
Hair cell polarization in the gravity receptor systems of the statocysts of the cephalopods Sepia officinalis and Loligo vulgaris.
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The complete patterns of polarization of the sensory epithelia of the various gravity receptor systems of the decapods Sepia and Loligo have been described (Fig. 6). Each individual receptor cell (hair cell) bears up to 150 kinocilia, but is polarized unidirectionally by 3 morphological features: (I) by the orientation of the internal 9X2+2 tubuli structure of each kinocilium, (II) by the location of their basal feet. Each hair cell is additionally polarized (III), in that its kinociliary group is inclined toward the plane of the macula surface, forming an angle of 40-60 degrees with it (Figs. 1-3); the direction of polarization, as given by the ultrastructural features (I and II), is always opposite to this acute angle (Fig. 4). The results are discussed with reference to their physiological consequences.
| 32,954
|
Effects of fluoride on in vitro calcification of tendon matrix.
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Ca2+ and Pi uptake induced in vitro by a collagenous matrix derived from bovine tendon is inhibited by 1 X 10(-6) to 2 X 10(-5) M NaF and stimulated by 2 X 10(-5) to 2 X 10(-3) M NaF. Fluoride uptake occurs only over the latter concentration range. The uptake of Ca2+, Pi, and F-1 progresses toward a limiting extent at which the molar Ca/P and Ca/F values are 1.6 to 1.7 and 4.5 to 5.7, respectively. Although the matrix-bound mineral, previously formed in the absence of NaF, readily undergoes dissolution when exposed to a Ca2+- and P-free medium of pH less than 7.4, the bound mineral phase formed in the presence of NaF does not. We conclude that fluoroapatite is the primary matrix-bound mineral. The uptake of fluoride, Ca2+. amd Pi by both uncalcified and previously calcified matrices is inhibited by methylenediphosphonate and by phosphonoacetate as is calcification in the absence of NaF. Kinetic studies indicate that formation of a CaP complex precedes the uptake of F-1 and suggest that F-1 and OH-1 compete for interaction with that CaP complex during the calcification process. We concluded that fluoroapatite formation induced by the collagenous matrix occurs by a multistep pathway comparable to that proposed previously for hydroxyapatite formation.
| 32,959
|
gamma-Glutamyl transpeptidase and malignant transformation of cultured liver cells.
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The relationship between gamma-glutamyl transpeptidase (GGT)and malignant cell transformation was analyzed in malignant and nonmalignant culture epithelial cell lines derived from rat livers and fibroblastic cell types derived from hamsters and mice. GGT activity was prominent (25 to 90% of cells) in 3 of 5 malignant epithelial liver cell lines. None of the 9 fibroblastic or 4 nonmalignant epithelial cell lines exhibited GGT activity. Our results suggest that by use of GGT activity we can detect in cultured liver cells a significant fraction of the spontaneously or chemically induced malignant cells. Thus, in conjunction with other markers, this marker may help in identifying tumorigenic cells in liver epithelial cultures.
| 32,965
|
Enzymatic conjugation and hydrolysis of [18O]isoborneol glucuronide.
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Introduction of 18O into the acetal linkage of isoborneol glucuronide has been accomplished through the in vitro enzymatic conjugation of 18O-labeled isoborneol by use of immobilized, partially purified, rabbit liver UDP-glucuronyltransferase supplemented with UDP-glucuronic acid. Mass-spectrometric analysis of 18O enrichment in both the aglycon and the intact conjugate made it possible to study both enzymatic conjugation and enzymatic hydrolysis. Analysis by gas chromatography-mass spectrometry indicated that the labeled hydroxyl oxygen of isoborneol is retained during both conjugation and hydrolysis.
| 33,031
|
Repeat laparotomy as a preclinical diagnostic and therapeutic method for treating ovarian carcinoma.
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One hundred forty-two cases of epithelial ovarian carcinoma were treated from 1972 to 1976 in the Department of Obstetrics and Gynaecology, University Central Hospital, Turku, Finland. Repeat laparotomy was performed on 37 of the patients about six months after total extirpative surgery (group I). In addition, a second laparotomy was performed on 14 patients after partial surgery or exploratory laparotomy (group II). All patients were given external radiation therapy combined with cytostatic treatment prior to the repeat laparotomies. A preclinical carcinoma was detected in six of the 37 patients in group I. Two of them are asymptomatic after five years of follow-up. In group II, total surgery after initial partial or exploratory laparotomy succeeded in half of the cases. Serous and endometroid carcinomas appeared to respond best to conservative therapy preceding repeat laparotomy.
| 33,077
|
Consumption coagulopathy associated with intrauterine fetal death: the role of heparin therapy.
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A gravida with intrauterine fetal death who developed progressive chronic consumption coagulopathy was treated with heparin. When serial fibrinogen levels fell below 100 mg% and the prothrombin time was significantly prolonged, intravenously injected heparin corrected hypofibrinogenemia. A safe delivery followed administration of oxytocin. The authors emphasize the infrequent need for heparin therapy in the majority of cases of the intrauterine fetal death syndrome. Therapeutic guidelines for its use in selected cases are reviewed.
| 33,082
|
Risks and benefits of culdoscopic female sterilization.
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This paper reviews the risks and benefits of the culdoscopic approach to female sterilization in an alnalysis of 2153 culdoscopic sterilization procedures performed at 11 centers in nine countries. Inability to occlude the tubes as planned was reported for approximately 6.0% of the cases including 1.4% in which one or both tubes could not be occluded by any technique. Surgical difficulties were reported for about 13.0% of the procedures, and surgical complications, of which the most frequent was torn or bleeding tubes, occurred in 2.0% of the cases. Pregnancy rates were significantly higher for patients whose tubes were occluded by tantalum clips (7.7 per 100 women at 12 months), indicating that this is not the preferred technique of tubal occlusion; the 12-month life table pregnancy rates were 0.1 per 100 women for tubal ring and 0.0 for Pomeroy and fimbriectomy. Comparison of these data with similar pooled data on laparoscopy and minilaparotomy indicates that culdoscopy is associated with greater technical difficulty and morbidity. Thus, abdominal procedures will continue to be preferred for use in most large-scale programs.
| 33,087
|
Effect of leukocyte hydrolases on bacteria. X. The role played by leukocyte factors, cationic polyelectrolytes, and by membrane-damaging agents in the lysis of Staphylococcus aureus: relation to chronic inflammatory processes.
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A heat-stable factor present in extracts of human blood leukocytes is capable of lysing young Staphylococcus aureus at pH 5.0. Lysis is characterized by breakdown of cell-wall components as judged by electron microscopic and biochemical analysis. The leukocyte extracts can be replaced by a variety of agents known to injure cell membranes, e.g., leukocyte cationic protein histone, polymyxin B, colimycin, phospholipase A, and lysolecithin. The mechanisms by which all these agents bring about the degradation of the staphylococcal walls was studied. By using 14C-labeled cell walls devoid of cytoplasmic structures, it was demonstrated that none of the above-mentioned agents had a direct lytic effect on purified cell walls. On the other hand, when any of these agents first interacted with intact staphylococci, a factor (presumably an autolysin) was generated that directly lysed the cell walls. Lysis of cell walls in the presence of intact staphylococci used as a source of autolysin was strongly inhibited by a variety of anionic polyelectrolytes such as heparine and liquoid. The possible role played by bacterial autolysins in the generation of microbial cell-wall components capable of triggering chronic inflammation is discussed.
| 33,120
|
Cerebrovascular effects of YC-93, a new vasodilator, in dogs, monkeys and human patients.
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Cerebrovascular effects of YC-93, a new 1,4-dihydropyridine derivative, was examined in experimental animals and in human patients using a variety of methods. YC-93 in doses ranging from 0.001 to 0.03 mg/kg i.v. increased regional cerebral cortical blood flow and cerebral venous outflow in anesthetized dogs, and internal carotid blood flow in anesthetized monkeys. The increase in cerebral blood flow was accompanied by an increase in oxygen delivery to the brain and an elevation of cerebrospinal fluid pressure. Both intracarotid injection and intraduodenal administration of YC-93 also resulted in cerebral vasodilation in monkeys. In patients with cerebrovascular diseases and other chronic diseases, measurements of cerebral blood flow by 133-xenon clearance method showed that an intracarotid injection of 1 microgram/kg of YC-93 increased cerebral blood flow by 28.8% without changing arterial blood pressure and arterial pCO2, and that an intravenous injection of 0.01 mg/kg of YC-93 increased cerebral blood flow by 17.0% with a minimal decrease in the arterial blood pressure but without changing arterial pCO2. Thus, YC-93 produced a potent cerebral vasodilation not only in experimental animals but also in human patients in the same dose, and seemed to act perhaps directly on the cerebral vascular beds.
| 33,121
|
Mixed function oxidases in sterol metabolism. Separate routes for electron transfer from NADH and NADPH.
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Oxidative deformylation of 4-hydroxy[14C]methylene-5alpha-cholest-7-en-3-one and oxidative demethylation of [30,31-14C]4,4-dimethyl-5alpha-cholest-7-en-3beta-ol by rat liver microsomes have been compared with regard to the manner in which electrons are introduced from both NADH and NADPH. Evidence suggests that NADH and NADPH support oxidation of both substrates via separate routes of electron transfer. Thus, 10 micron cytochrome c will inhibit NADPH-supported oxidation to 40 to 50% of control activity leaving NADH-supported oxidation unaffected. Also, treatment of microsomes with subtilisin diminishes NADPH-supported oxidation to 10 to 30% of control activity for either substrate to 70 to 90% of control activity while NADH-supported oxidative activity is virtually unaffected. Studies on the oxidase activities and NADPH-cytochrome c reductase as well as NADH-ferricyanide reductase have shown marked differences in activity in the presence of inhibitors. Thus, 9 mM 2'-AMP inhibits NADPH-cytochrome c reductase to 10 to 20% of control activity while NADPH-supported oxidative demethyl ation and deformylation are essentially unchanged. Mersalyl at 15 to 25 nmol/mg of microsomal protein inhibits both reductases to 20 to 40% of control activity; oxidative demethylation is unaffected and oxidative deformylation stimulated slightly when NADPH is used. Finally, antibody to NADPH-cytochrome c reductase inhibits oxidase activity for either substrate to 70 to 90% of control activity while reductase activity is inhibited to 10 to 30% of control activity.
| 33,169
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Evidence for a high molecular weight factor(s) in serum which increases alkaline phosphatase specific activity in HeLa.
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HeLa (substrain Ho) grown in serum free medium showed an increase in the specific activity of alkaline phosphatase when fetal calf serum (10%) was added to the medium (9.7 nmoles/sec/mg protein to 86.8). Under the same conditions, eight intracellular enzymes showed no increase in activity. Similar results were obtained using a different serum or medium, and with a second strain of HeLa (substrain ATC). For a given set of growth conditions, the effect of serum was dependent on its concentration and required one or more culture generations to develop. The type of isozyme expressed did not change. Neither zinc nor a total serum lipid extract would substitute for serum. The enzyme expressed by HeLaHo was not induced by prednisolone, while that in HeLaATC was. However, for cells grown in excess prednisolone without serum, the specific activity was 25% of that found for cells grown with prednisolone and serum. Cortexolone, an antagonist of prednisolone, was without effect for HeLaHo grown in A3 medium with or without serum. The serum factor had the following characteristics. It was not lost on dialysis, treatment with DNase and RNase, or removal of lipoproteins. It was reduced after heating by 65% and after treatment with Pronase by 82%. The data are interpreted to indicate the presence of a factor (s) in serum, probably a protein, which is involved in stimulating alkaline phosphatase specific activity.
| 33,190
|
Immunological studies of T-cell receptors. II. Limited polymorphism of idiotypic determinants on T-cell receptors specific for major histocompatibility complex alloantigens.
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These studies explore the extent of genetic polymorphism in the expression of anti-MHC receptors by T cells in different strains of rats. This question was approached with the use of the model of specifically induced GVH resistance in F1 rats which has been shown to reflect a specific T-cell mediated immune response against parental strain T cell anti-MHC receptors specific for host alloantigens. When A/B F1 rats derived from MHC incompatibile matings are immunized with lymphocytes from one parental strain (A they display a specific resistance to anti-B GVH reactivity caused by T cells from that parental strain, but not anti-AGVH reactions from the other. In addition, they resist anti-B GHV reactivity by T cells from third-party donors (C, D, E,...), a finding taken to indicate that the idiotypes of anti-MHC receptors on T cells, recognized by other T cells, show little or no polymorphism. This conclusion suggests that anti-MHC receptors are shared in the species and may be encoded, at least partially, by germ-line genes.
| 33,224
|
[The effect of chenodesoxycholic acid on cholesterol gallstones (author's transl)].
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30 patients with radiolucent gallstones and 2 patients with radioopaque stones recieved chenodesoxycholic acid (CDC). In 12 patients stones were dissolved completely by CDC therapy, in 6 of the patients the size of the stones decreased by 40-70%. Only 1 patient developed severe diarrhea, so therapy had to be stopped. In 5 patients there was a slight and transient increase in SGOT and SGPT, in 2 other patient gammaGT increased; value normalized while treatment was continued. In 23 cases liver biopsies were done before and during treatment: no histological changes could be found in the specimens. 5 of the patients, whose gallstones had been dissolved, received 500 mg CDC/day thereafter, another 5 patients received 500 mg/d every other day. No recurrence of lithiasis was observed in either group. One patient on 500 mg CDC twice a week developed lithiasis after 6 months, another one stopped treatment completely and gallbladder stones reappeared after 8 months. The patients with radioopaque stones did not show any changes during treatment.
| 33,309
|
Neuropharmacology of sedatives and anxiolytics.
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Sedative drugs are intended to cause various degrees of drowsiness. Animal experiments indicate that barbiturates induce these effects primarily by depression of the reticular activating system in the rostral brainstem. This in turn potentiates the thalamic recruiting system, thereby inducing 'barbiturate bursts' in the EEG. Anxiolytic drugs are intended to reduce anxiety or tension at doses which do not cause sedation or sleep. Propanediols may depress deactivating centers in the caudal brainstem, thereby releasing the activating centers in the rostral brainstem and depressing the thalamic recruiting response. These drugs may also act on the amygdala. Benzodiazepines have depressant effects on the amydala or hippocampus. These effects may release the reticular formation from inhibition. Enhanced activity of the activating and deactivating centers, to a different extent in different animals, would produce restlessness in some animals and sedation in others, accompanied by a mixture of fast and slow waves in the EEG. Sedative and anxiolytic agents also have central relaxant effects. The barbiturates act directly on the spinal cord, depressing both monosynaptic and polysynaptic reflexes. Propanediols and benzodiazepines act primarily on the descending facilitatory influence of the brainstem. Reduction of this influence depresses spinal polysynaptic but not monosynaptic reflexes. Biochemical studies suggest that barbiturates may act by antagonizing synaptic excitation induced by glutamate. Benzodiazepines may act by enhancing presynaptic inhibition mediated by GABA. The mechanism of action of propanediols is unknown.
| 33,329
|
[Treatment of bronchitis with cefaclor (Panoral) (author's transl)].
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14 patients from the Allergy Unit of an outpatient clinic suffering from acute exacerbation of chronic bronchitis and 13 outpatients with acute bronchitis were treated with 250 mg cefaclor (Panoral) 3 times daily per os for 5 days. 59% of the organisms isolated from cefaclor-sensitive sputum at the time of prominent clinical symptoms were resistent to tetracycline, 53% of them were resistant to penicillin, and 37% were resistant to ampicillin. 12 out of the 14 patients with acute exacerbation of chronic bronchitis became asymptomatic, and no organisms could be detected in the sputum of 13 out of the same 14 patients two days after cessation of cefaclor treatment. In 12 out of the 13 patients with acute bronchitis, the acute clinical symptoms disappeared and in 11 out of the 13 patients the initial sputum organisms were two days after stopping cefaclor treatment.
| 33,333
|
Studies on the mechanisms of central action of alpha-adrenergic receptor blocking agents.
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The article summarizes the results of experiments, partly published, on the central action of alpha-adrenergic receptor blocking drugs given systemically in rats. Phenoxybenzamine, phentolamine and aceperone increase utilization of noradrenaline (NA in whole brain and antagonise NA--stimulated formation of cyclic AMP in brain cortical slices. They also counteracts locomotor hyperactivity and flexor reflex stimulation induced by NA receptor agonists. The investigated alpha-adrenolytics do not antagonize brain dopamine (DA) or acetycholine (ACh) receptor stimulation, although they weakly reduce the effects of central serotonin (5-HT) system activation. It is concluded, that phenoxybenzamine, phentolamine and aceperone block directly central NA receptors. They do not block DA or ACh receptors in the brain but they are weak antagonists of 5-HT system stimulation. The investigated compounds decelerate utilization of DA and increase those of ACh in the brain, these effects seem to be secondary to NA system hypofunction.
| 33,369
|
Evidence that catecholamine transport into chromaffin vesicles is coupled to vesicle membrane potential.
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The effects of ATP, Mg(2+), and various agents on pH gradient, membrane potential, and catecholamine transport across membranes of intact bovine chromaffin vesicles were investigated. Methylamine and thiocyanate (SCN(-)) distributions across the vesicle membrane were used to estimate the H(+) concentration gradient and membrane potential, respectively. The H(+) concentration ratio (intravesiculanmedium) equals 16 when the medium pH is 6.9 and is unaltered by ATP and Mg(2+). In the absence of ATP and Mg(2+), the steady-state intravesicular S(14)CN(-) concentration is lower than the medium concentration. ATP and Mg(2+) cause an increased influx and a decreased efflux of SCN(-) that results in SCN(-) being concentrated in the vesicles 6- to 8-fold over the medium. The findings are consistent with an ATP,Mg(2+)-induced potential of approximately 50 mV (intravesicular side positive). Carbonyl cyanide p-trifluoromethoxyphenylhydrazone (FCCP), a H(+) translocater, and N-ethylmaleimide (NEM), a sulfhydryl reagent, decrease the SCN(-) ratio and, thus, the membrane potential in the presence of ATP and Mg(2+). They have no effect on the H(+) concentration gradient. The rate of catecholamine uptake into vesicles is increased 4- to 6-fold by ATP and Mg(2+). The ATP,Mg(2+)-stimulated uptake is inhibited by FCCP and NEM over the same concentration ranges that reduce the SCN(-) distribution (membrane potential). FCCP increases and NEM decreases vesicular membrane ATPase activity. Thus, catecholamine uptake is correlated to an inside-positive membrane potential, and not to ATPase activity. If catecholamine uptake is coupled to membrane potential, then a charged species must be involved in the transport mechanism. Reserpine and rotenone inhibit catecholamine influx but have no effect on the H(+) electrochemical gradient; they probably act at a step before coupling to the membrane potential (or the H(+) electrochemical gradient). Atractyloside, an inhibitor of nucleotide transport, has no effects on catecholamine transport or the H(+) electrochemical gradient.
| 33,385
|
The position of regenerating cambia: auxin/sucrose ratio and the gradient induction hypothesis.
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To account for the positions in which vascular cambia regenerate in wound callus, a gradient induction hypothesis was proposed in 1961 in terms of gradients in 'some factor as yet unknown'. It now seems likely that the gradient is based on morphogen diffusion between source and sink on opposite sides of existing cambia, with morphogen diffusing into the adjoining wound callus. It is specifically proposed that there are two morphogens, auxin diffusing centrifugally and sucrose diffusing centripetally. The cambium then regenerates along a path where the ratio of auxin to sucrose concentration is similar to that at the original cambium, and its orientation (as regards xylem and phloem formation) is determined by the direction of the gradient in this ratio. These proposals are supported by published evidence on auxin and sucrose concentration gradients across the cambium, and on their sources, movements, and known effects on vascular differentiation. Simulations of the proposed positional control system predict patterns of cambial regeneration and orientation corresponding to those observed in four different types of wound and graft.
| 33,389
|
Hydrolysis of long-chain fatty acyl-CoA in homogenates of human blood platelets: the existence of a platelet palmitoyl-CoA hydrolase.
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The existence of a very active long-chain fatty acyl-CoA hydrolase in homogenates of human blood platelets is reported. The highest activity was found with palmitoyl-CoA as the substrate. Palmitoyl-CoA hydrolase activity was not found in intact platelets indicating that the enzyme is localized within the platelet membrane. No palmitoyl-CoA hydrolase activity was found in fasting plasma. Mg2+, Mn2+, Ca2+ and Triton X-100 inhibited the palmitoyl-CoA hydrolase activity. Sulphydryl reagents had no effect, whereas high concentrations of D- and L-carnitine inhibited the activity. Carnitine palmitoyltransferase did not interfere with the assay of palmitoyl-CoA hydrolysis as the activity of carnitine-palmitoyl hydrolase was less than 1% of the palmitoyl-CoA hydrolase activity.
| 33,445
|
Metronidazole in the prophylaxis and treatment of anaerobic infection.
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The influence of prophylactic metronidazole on vaginal carriage rates of anaerobes and the development of postoperative anaerobic infection was studied in 104 women who underwent abdominal hysterectomy. Metronidazole prophylaxis in 54 patients led to a decrease in the anaerobe vaginal carriage rate from 65% pre-operatively to 17% and 28% on the 3rd and 7th postoperative days respectively. In the control group (50 patients) no significant decrease in anaerobe yield was noted, corresponding percentages being 72%, 64%, and 74%. Postoperative infection occurred in 36 patients (28 controls; 8 on prophylactic metronidazole). Wound swabs from all 8 patients in the latter group yielded aerobes, and in 1 patient mixed infection (aerobes/anaerobes) occurred. In 7 of these patients (including the patient with mixed infection), the infection resolved spontaneously, while the 8th patient responded to therapy with metronidazole, kanamycin and ampicillin. In the control patients, 21 cases of postoperative wound infection and 4 of vault infection were seen; wound swabs from patients in the former group yielded aerobes in only 6 cases, and mixed growth of aerobes/anaerobes in 10 cases. Postoperative wound/vault infections in control patients cleared spontaneously in 18 cases and responded to imidazole therapy, with or without ampicillin and kanamycin, in 7 cases.
| 33,454
|
[Evaluation of results of therapy with cast removable partial prosthesis. I. Significance of the residual teeth].
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On the basis of results from follow-up examinations in patients with removable cast partial prostheses, the author points to injuries to the remaining teeth which are attributable above all to errors of indication, insufficient preliminary measures, and inadequate metaphylaxis.
| 33,474
|
The effect of beta-adrenoceptor blocking drugs on free fatty acid and glucose utilization of the isolated canine heart with normal and restricted flow in the presence and absence of noradrenaline.
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Effect of adrenergic beta-receptor blockade on the myocardial utilization of the main substrates by the isolated fibrillating dog heart perfused with constant volume of blood from a donor animal was studied at normal and restricted flow, and in the presence of noradrenaline. A direct metabolic action of the beta-blockade by increasing glucose uptake in the normal and reducing it in the ischemic heart, furthermore moderating the ischemic diminution of the lactate uptake could be shown. The intervention reduced elevated serum free fatty acid level and increased myocardial free fatty acid uptake observed in the presence of noradrenaline.
| 33,514
|
The influence of aging on the myosin type of the rabbit soleus and longissimus dorsi muscles.
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The influence of aging on the myosin type, and on the fibre composition of both the slowly contracting ("red") M. soleus and the fast ("white") M. longissimus dorsi was examined in the rabbit. For myosin characterization isolated myofibrils were electrophoresed on SDS-polyacrylamide gels, and the fibre pattern within the respective muscles was analyzed with an immunocytochemical method. Antisera against either fast or slow rabbit myosin were collected from guinea pigs after longterm immunization. After incubation of the paraformaldehyde-fixed muscle thin sections the fibres containing either fast or slow myosin could be distinguished from each other by indirect immunofluorescence. The soleus muscles of 1 day old rabbits were composed of 25% slow and 75% fast fibres. In young-adult (5--8 mo.) rabbits the fibres were mostly slow (over 90%), while in old age (4--7 y.) again up to 50% of the soleus fibres contained fast myosin. In contrast, in the longissimus dorsi muscle constantly around 95% of the fibres contained fast myosin. In accordance with the immunocytochemical finding of an increase of fast fibres in the aging soleus muscle, the presence of fast myosin could also be demonstrated electrophoretically. With this method, soleus myofibrils from young-adult animals were observed to contain virtually slow myosin only. No slow, but only fast myosin was identified in SDS-gels of longissimus dorsi myofibrils at all ages. These results are discussed in relation to the well known metabolic alterations occurring in the mammalian skeletal muscle during aging.
| 33,562
|
[Disablement and needs among the elderly of several population groups in Switzerland (author's transl)].
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A preliminary communication is made about an epidemiolocial survey in Switzerland concerning the habits and problems of several groups of elderly under different life conditions. Special interest is given as well the aspects of health and competence in the activities of daily life as the question of disablement and need for personal aid.
| 33,575
|
[Myocardiopathies during pregnancy. Possible role of beta-mimetics].
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The authors report two cases of severe non-obstructive cardiomyopathy presenting at the end of pregnancy in young women treated for long periods and at high dosage with beta 2-adrenoceptor stimulants, prescribed for threatened abortion or premature labour. The circumstances of the presentation, the clinical prescribed for threatened abortion or premature labour. The circumstances of the presentation, the clinical picture and the course towards complete recovery suggest that this might be a pathological process different from "cardiomyopathy of pregnancy" and be an "adrenergic myocarditis" induced or made worse by these drugs. The authors deduce some simple preventive measures.
| 33,631
|
Purification and properties of beta-N-acetylhexosaminidase from the mollusc Helicella ericetorum Müller.
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1. A beta-N-acetylhexosaminidase was purified 330-fold from the digestive gland of the terrestrial mollusc Helicella ericetorum Müller. 2. Its pH optimum is 4.5 for both beta-N-acetylglucosaminidase and beta-N-acetylgalactosaminidase activities in two buffer solutions; it is fully stable at 37 degrees C for 2h in the pH range 3.8--4.6 and shows one isoelectric point (pH 4.83). 3. The estimated mol.wt. is between 120,000 and 145,000. 4. The enzyme shows an endo-beta-N-acetylhexosaminidase activity on natural substrates such as ovalbumin, ovomucoid, chondroitin 4-sulphate, chitin and hyaluronic acid. 5. Two forms of the enzyme were separated by preparative polyacrylamide-gel electrophoresis. 6. Km and Vmax. for p-nitrophenyl 2-acetamido-2-deoxy-beta-D-glucopyranoside and p-nitrophenyl 2-acetamide-2-deoxy-beta-D-galactopyranoside are 0.43 mM, 30.1 micronmol of p-nitrophenol/min per mg and 0.19 mM, 8.6 micronmol of p-nitrophenol/min per mg respectively. 7. It is inhibited by Hg2+, Fe3+, acetate, some lactones, N-acetylgalactosamine, N-acetylglucosamine and mannose. 8. Mixed-substrates analysis and Ki values for competitive inhibitors indicated that beta-N-acetylglucosaminidase and beta-N-acetylgalactosaminidase activities are catalysed by the enzyme at the same active site.
| 33,660
|
Exchange of free and bound coenzyme of flavin enzymes studied with [14C]FAD.
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The exchange of bound FAD for free FAD was studied with D-amino acid oxidase (D-amino acid:oxygen oxidoreductase (deaminating), EC 1.4.3.3) and beta-D-glucose oxidase (beta-D-glucose:oxygen 1-oxidoreductase, EC 1.1.3.4). For a simple measurement of the reaction rate, equimolar amounts of the enzyme and [14C]FAD were mixed. The exchange occurred very rapidly in the holoenzyme of D-amino acid oxidase at 25 degrees C, pH 8.3 (half life of the exchange: 0.8 min), but slowly in the presence of the substrate or a competitive inhibitor, benzoate. It also occurred slowly in the purple complex of D-amino acid oxidase. In the case of beta-D-glucose oxidase, however, the exchange occurred very slowly at 25 degrees C, pH 5.6, regardless of the presence of the substrate or p-chloromercuribenzoate. On the basis of these findings, the turnover of the coenzymes of flavin enzymes in mammals is discussed.
| 33,712
|
Destruction and resynthesis of mouse beta-glucosidases.
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1. Injection of a single dose of conduritol B epoxide into mice produced almost complete destruction of glucocerebrosidase (D-glucosyl-N-acylsphingosine glucohydrolase, EC 3.2.1.45) in liver, spleen, brain, and kidney within 5 h. Restoration of activity became noticeable within 1 day (2 days in the case of brain) and was about 80% of normal within 16 days. 2. The same injection produced less destruction of aryl beta-glucosidase (EC 3.2.1.21), measured at pH 5.4 with methylumbelliferyl glucoside in the absence of taurocholate. Brain showed the least amount of destruction, about 50%, but measurements of activity at lower pH values revealed complete loss of activity. This suggests that brain contains two different aryl glucosidases with differing sensitivity to the inhibitor. Liver, on the other hand, did not show differential destruction when assayed at different pH values. Resynthesis of the enzyme activities was almost complete by 16 days. 3. Injection of phenylhydrazine produced hemolysis and spleen enlargement, with concomitant increases in specific activities of glucocerebrosidase and aryl glucosidase in liver and spleen (but not in kidney). When this experiment was done in mice previously treated with conduritol B expoxide, the reappearance of cerebrosidase was found to be accelerated. This is interpreted to mean that the increased load of glucolipids from the erythrocytes had induced an enhanced synthesis of the glucohydrolase. A similar explanation may apply to aryl glucosidase and glucopeptides in the cells.
| 33,720
|
[Effect of lecithin on liver microsomal lipid peroxidation].
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The effect of exogeneous (egg) lecithin on peroxidation of microsomal lipids was studied with the view of elucidating the role of various components of lipid substrate in the overall oxidation rate of the lipids. The following processes were studied a) NADPH-dependent microsomal lipid peroxidation in the presence of lecithin; b) ascorbate-dependent microsomal lipid peroxidation in the presence of lecithin; c) oxidation of lipid mixture, isolated from the microsomes, and that of lecithin in the presence of the Fe2+ + ascorbate system; 4) oxidation of lecithin induced by the Fe2+ + ascorbate system. It was found that in the presence of exogeneous lecithin the oxidation of microsomal lipids in inhibited, which is probably due to the peculiarities of lecithin oxidation. It was shown that the specific rate of lecithin oxidation is decreased with an increase in lecithin concentration. Possible mechanisms of lecithin effect on microsomal lipid peroxidation are discussed.
| 33,726
|
Sequential patterns of haemodynamic and metabolic changes in experimental hypovolaemic shock. I. Responses to acute haemorrhage.
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Little is known about cardiorespiratory changes during the development of hypovolaemia. This study attempts to provide such information and compares the period of bleeding with that of established hypovolaemia. Eleven anaesthetized and ventilated greyhounds were bled and analyses of cardiopulmonary function made at fixed intervals both during and after haemorrhage. Six sequential patterns of cardiopulmonary and metabolic change were recognized. It was apparent that bleeding caused the first three phases of change, recovery from the effects of bleeding the next two and steady hypovolaemia the last. The event of bleeding is the main factor that elevates total peripheral resistance and reduces tissue perfusion with consequent lowering of oxygen consumption and alkalosis secondary to impaired carbon dioxide production; when bleeding ceases these changes partially reverse in a manner characteristic of that induced by the reinfusion of shed blood; and hypovolaemia per se has a relatively weak influence. These findings provide an explanation for disparities in previous published reports and have obvious clinical implications.
| 33,740
|
Phenytoin and transmitter release at the neuromuscular junction of the frog.
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The effects of phenytoin (diphenylhydantoin, DPH) on transmitter release were studied at the frog neuromuscular junction. It was found that in Ringer's solutions containing a normal concentration of Ca2+ ions, DPH (1-2 X 10(-4) M) depresses neurally evoked transmitter release, whereas in Ca2+-deficient Ringer's solutions it produces an increase in evoked release. Spontaneous transmitter liberation is augmented by DPH under all the above conditions. An abrupt disappearance of the evoked response occasionally occured with stimulation at 0.5 Hz, but a normal response could be elicited by a second stimulus delivered shortly after the first. At 100-200 Hz, DPH regularly induced a partial block in synaptic transmission. In 8 mM MgCl2, this phenomenon appeared at 50 Hz and developed into a total neuromuscular blockade.
| 33,744
|
Toleration of artificial tears - the effect of pH.
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We studied the effect of altering the pH of an artificial tear preparation on the tolerance of 20 patients with keratoconjunctivitis sicca. Of those who expressed a preference, 11/17 preferred a tear substitute more alkaline than any preparation now available in North America. We recommend an alkaline tear substitute as a valuable alternative in patients with keratoconjunctivitis sicca.
| 33,753
|
Contact dermatitis from ethylenediamine.
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This study of seven patients with an allergic contact dermititis from ethylenediamine has shown that sensitisation to topical antihistamines and disodium ethylenediamine tetra-acetate is not inevitable in a allergic contact dermatitis from ethylenediamine.
| 33,781
|
Pre- and postsynaptic effects of alpha-agonists in the anococcygeus muscle of the pithed rat.
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In the pithed rat electrically induced contractions of the anococcygeus muscle were inhibited by clonidine (0.1--3.0 microgram/kg, i.v.), mecamylamine (1 mg/kg, i.v.) and guanethidine (1 mg/kg, i.v.). Only the inhibition produced by clonidine was antagonised by yohimbine (0.3 mg/kg, i.v.). At higher concentrations (10 microgram/kg, i.v.) clonidine increased the resting tension of the tissue; this effect was antagonised by phentolamine (1 mg/kg, i.v.). The anococcygeus muscle of the pithed rat was used to simultaneously assess pre- and postsynaptic alpha-adrenoceptor agonist activity. Guanfacin was more selective and tiamenidine less selective than clonidine for presynaptic alpha-adrenoceptors. Naphazoline and oxymetazoline were selective postsynaptic alpha-adrenoceptor agonists.
| 33,816
|
Comparative trial of sulphasalazine and oral sodium cromoglycate in the maintenance of remission in ulcerative colitis.
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Patients with ulcerative colitis in remission were randomly allocated to treatment with sulphasalazine (2 g/day) or oral sodium cromoglycate (160 mg/day or 2 g/day), and the relapse rates in these treatment groups were compared during continued treatment for one year. The percentage cumulative relapse rate after 12 months' treatment was 30% in the 33 patients treated with sulphasalazine compared with 71% in the 25 treated with high dose sodium cromoglycate, a highly significant difference (P less than 0.01). Patients allocated low dose sodium cromoglycate were only treated for a maximum of six months, and the relapse rate in these 12 patients was similar to that in patients on the high dose. These results suggest that oral sodium cromoglycate is considerably less effective than sulphasalazine in maintaining remission, and by analogy with results in other trials may be no more effective than placebo tablets.
| 33,875
|
[Drug interactions in the intestinal tract].
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The mechanisms of drug-drug interactions are generally classified and interferences within the gastrointestinal tract are discussed. The latter mainly concern interactions in which absorption of a drug is affected. Unwanted reactions may easily be avoided by choosing carefully combination and time of administration of two or more drugs to be used in a patient.
| 33,886
|
[Testing antacid with intragastric Ph measurements and gastroscopy].
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In connection with the testing of an antacid in form of a suspension, pH-measurement and gastroscopy are carried out in the same 11 patients. Essential criteria of the efficacy of an antacid are its buffering capacity and its retention in the stomach as a mechanical protective for the gastric mucosa. The Talcid suspension tested in this way showed a good period of stay in the stomach, often exceeding the period of acid-binding capacity. Compared with bicarbonate, its buffering period is about twice as long above pH 4.5 and about 2 1/2 times as long at lower pH's.
| 33,887
|
A plasmid in Streptococcus pneumoniae.
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Plasmid deoxyribonucleic acid has been detected in three related laboratory strains of Streptococcus pneumoniae. Strains D39S, R36, and R36NC each contain a minimum of two copies per cell of a 2.0-megadalton plasmid (pDP1). A plasmid twice as large as this smaller one is also present in much lower quantity in these strains, but neither plasmid is present in four strains related to these or in a drug-resistant clinical isolate from Paris. The plasmid yield was not amplified in the presence of chloramphenicol. No phenotype has been correlated with the presence of pDP1, which has existed in strains carried for many years in laboratory collections.
| 33,961
|
A survey of psychotropic medication in mental retardation facilities.
|
A survey of psychotropic drug usage by questionnaires was conducted at 5 regional residential centers for the mentally subnormal in Eastern Ontario, Canada. Of the 2238 residents studied, 42% were given psychotropics, 27% anticonvulsants, and 11% a combination of both. Prolonged medication and polypharmacy were observed in all facilities. The therapeutic responses to psychotropic medication were generally poor, especially among the disturbed epileptics who had received psychotropic and anticonvulsant simultaneously. It is estimated that between one-half to two-thirds of those on psychotropics were given the agents too liberally.
| 33,967
|
Selective extraction of marker enzymes of bovine milk fat globule membrane by nonionic detergents.
|
Large amounts (66-97%) of marker enzymes such as alkaline phosphatase, 5'-nucleotidase, phosphodiesterase I, and gamma-glutamyl transpeptidase of bovine milk fat globule membrane (MFGM) were selectively solubilized by nonionic detergents such as Triton X-100, Tween 20, Nonidet P-40, Liponox NCK, and Emulgen 109-P. On the other hand, the extractability of MFGM protein with these detergents was less than 50%. Judging from the recovery of total activity, it is likely that alkaline phosphatase, phosphodiesterase I, and gamma-glutamyl transpeptidase are activated by nonionic detergents, whereas 5'-nucleotidase is somewhat inhibited by the detergents, except for Tween 20, and acid phosphatase is strongly inhibited by all detergents. In addition, solubilization of the protein with the nonionic detergents was found to be somewhat selective by SDS-polyacrylamide gel electrophoresis. There was no appreciable difference between the five brands of nonionic detergents used as regards the extractability of protein and the enzymatic activity of the extracted marker enzymes of MFGM, except that the solubilizing ability of Tween 20 was relatively low.
| 33,979
|
Starting transients in sea urchin sperm flagella.
|
Live sea urchin spermatozoa were rendered immotile by lowered pH; Triton-extracted spermatozoa were rendered immotile by either lowered pH or by deprivation of ATP. The spermatozoa began to beat after an increase in pH or as ATP was supplied, and the first bends were recorded on ciné film. Triton-extracted spermatozoa deprived of ATP retained a partially formed basal bend which could be either principal or reverse, and which resumed its development and propagation as ATP was supplied. Both live and tritonated flagella straightened at low pH. As the pH was increased, a series of principal bends formed near the base and propagated to the tip. Reverse bends began to develop as the pH continued to increase. The principal and reverse bends thus exhibited different sensitivities to pH, which suggests differences in the mechanisms that produce them. Straight flagella began to move by synchronous sliding all along the flagellum, thus forming principal bends. Flagella that contained a basal bend began to move by primarily metachonous sliding within that bend.
| 33,997
|
Neurotransmitter release statistics: moment estimates for inhomogeneous Bernoulli trials.
|
Evoked release of quanta of neurotransmitter is generally treated as a set of homogeneous, stationary Bernoulli trials, hence governed by the binomial distribution. Relaxing the assumptions of uniformity and stationarity leads to a more realistic physiological model of transmitter release but also introduces systematic biases in the moment estimates of the binomial parameters. We derive probability generating functions for quantal release and expressions for the moment estimates of n and p for a generalized model that incorporates temporal variation and nonuniformity in individual release probabilities and in numbers of release sites.
| 34,005
|
The uptake of choline by Streptococcus pneumoniae.
|
Uptake of choline, a structural component of pneumococcal C- and F-teichoic acids, into bacteria growing in a defined medium was very efficient with an uptake constant ([S]10 5) of 3.2 microns. It was inhibited by iodoacetate, dinitrophenol and oligomycin but not by structural analogues of choline. Ethanolamine, however, was transported in the absence of choline but with a reduced affinity ([S]0.5 71.4 microns). The same constitutive system was probably used by both ethanolamine and choline. It is suggested that this system required ATP and probably involved choline kinase.
| 34,010
|
Muscle pH monitoring.
|
The evaluation of muscle pH is a recent method of monitoring the critically ill. We have found it a useful, safe, and reliable method. We, therefore, urge its routine use during and after major surgery. We think it will also be very useful in clinical patients with perfusion problems.
| 34,013
|
Solubility of doxycycline in aqueous solution.
|
The solubility of doxycyline monohydrate and doxycycline hydrochloride dihydrate was investigated in aqueous solution. The hydrochloride dihydrate salt was isolated and identified from solutions initially containing doxycycline hyclate in water. The pKa' = 3.09 (mu = 0.1 and 25 degrees) for protonation of doxycycline was determined spectrophotometrically. The pH-solubility profiles were determined for doxycycline monohydrate in water and in 1.0 M NaNO3-HNO3 and NaCl-HCl. The pH-solubility profile at 25 degrees for doxycycline in aqueous hydrochloric acid without added salt reached a sharp maximum fo 50 mg/ml at pH 2.16. Added chloride ion strongly suppressed the solubility of the hydrochloride dihydrate salt. The apparent solubility product was not constant but decreased as the concentration of added salt increased. A theoretical model was developed involving dimerization of doxycycline and applied to the experimental data. The dimerization constant, Kd = 24 M-1, and true solubility product, K0sp = 1.8 X 10(-3) M2, were calculated. The effect of concentration on NMR and visible spectra indicated that dimerization resulted from intermolecular hydrogen bonding of the phenolic beta-diketone portion of the molecule.
| 34,018
|
Study of the two pathways for arachidonate oxygenation in blood platelets.
|
During collagen-induced blood platelet aggregation, arachidonic acid is set free from membrane phospholipids and subsequently converted into 12-hydroxyeicosatetraenoic acid by arachidonate lipoxygenase and into thromboxane A2, 12-hydroxyheptadecatrienoic acid (HETE) and malondialdehyde by cyclooxygenase and thromboxane synthase. Lipoxygenase and cyclooxygenase have optimal activity at neutral to basic pH, while the thromboxane synthase is pH-independent between 5 and 9. These enzymes are membrane-bound. The cyclooxygenase is rapidly inactivated upon membrane disruption by nonionic detergents or phospholipid degradation with phospholipase A2. It was found that platelet phospholipase A2 preferentially splits off fatty acid with four double bonds. Eicosatetraynoic acid was used to investigate the physiological function of the arachidonate lipoxygenase during collagen-induced aggregation of rat blood platelets. This fatty acid is a more efficient inhibitor of lipoxygenase than of cyclooxygenase. At an inhibitor concentration of 0.6 microgram/ml, platelet aggreation, 12-hydroxyeicosatetraenoic acid production as well as 15-hydroxytryptamine release are completely inhibited, while there is an apparent stimulation of the cyclooxygenase. These results indicate that arachidonate lipoxygenase is essential for irreversible blood platelet aggregation.
| 34,075
|
Modification of the tyrosine hydroxylase assay. Increased enzyme activity in the presence of ascorbic acid.
|
A modification of the tyrosine hydroxylase assay is described in which ascorbate, rather than 2-mercaptoethanol or dihydropteridine reductase with NADPH, is used as the reductant. Enzyme activity is 3-4 times higher with ascorbate than with the other reducing agents. Low blanks are obtained with the ascorbate system provided that catalase is also included. The tissue distribution and kinetic activation of the enzyme have been studied with the ascorbate assay. The results obtained are consistent with the biological and regulatory properties of the enzyme which have been determined with the other reducing systems.
| 34,115
|
The "neuroleptic" antipsychotic drugs. 2. Neurologic side effects.
|
The specific neurologic side effects of the antipsychotic agents include acute dystonias, parkinsonism, motor restlessness, and late choretoathetosis. Treatment of the acute reactions is usually effected by the use of anticholinergic agents; treatment of the later dyskinesias is unsatisfactory, and these reactions are to be avoided by judicious use of antipsychotic drugs for long-term treatment.
| 34,142
|
Formation and properties of 1000-A-diameter, single-bilayer phospholipid vesicles.
|
Two methods are reported for the formation of large, uniform-sized phospholipid vesicles. The methods involve the treatment of phospholipid, in the form of either small, sonicated vesicles or a dry lipid film, at a molar ratio of deoxycholate to phospholipid of 1:2. Subsequent removal of deoxycholate yields a stable preparation of vesicles. These vesicles are bounded by a single bilayer, have an average diameter of 1000 A, and are readily separated from sonicated vesicles (230 A) by gel filtration on Sepharose 4B. Since the 1000-A vesicles are capable of trapping enzymes and other macromolecules, they may prove valuable for the delivery of liposome-entrapped solutes to cells and for the localization of peptide segments of a spectrum of membrane-bound proteins.
| 34,148
|
Individual variations in the effects of flurazepam, clorazepate, L-dopa and thyrotropin-releasing hormone on REM sleep in man.
|
The comporative effects of flurazepam, clorazepate, L-dopa, and thyrotropin-releasing hormone (TRH) on REM sleep were investigated in normal, healthy adults. A single dose of each drug was given orally to the subjects 30 min before bedtime. A dose of 30 mg flurazepam significantly decreased REM sleep-time when compared to the mean baseline record. No change was noted in REM sleep-time on the clorazepate (15 mg) night, L-dopa (1000 mg) night, or TRH (2 mg) night, when compared to the mean baseline record. Because large individual variations were found in REM sleep time on each drug night, and in percentage increase in REM sleep following partial differential REM deprivation (PDRD), correlation was investigated between them. The percentage decrease in REM sleep during flurazepam was found to have a significant negative correlation with the percentage increase in REM sleep after PDRD in individual subjects. Although there was no significant change in REM sleep on TRH night when compared to the mean baseline record, a similar significant negative correlation was noted. On the L-dopa night, there was a tendency toward a negative correlation between them. No significant correlation was noted on the clorazepate night.
| 34,186
|
Comparison views in extremity injury in children: an efficacy study.
|
Routine comparison views in cases of suspected extremity injury in children have not been adequately substantiated, in the authors' opinion. Three hundred such cases were reviewed, with pediatric radiologists requesting comparison views of the uninjured side in 8%. In no case did the comparison view change the initial diagnosis. When the initial interpretation is made by pediatric radiologists, selective use of comparison views is more cost-efficient and delivers less radiation to patients and personnel, compared to obtaining them routinely in all cases.
| 34,193
|
[Pharmacological treatment of syndromes of aggressivity].
|
In the treatment of violent-aggressive behavior, four major groups of drugs emerged: 1. Major tranquilizers in the treatment of aggressive-violent behavior associated with psychotic syndromes. 2. Anti-epileptic drugs such as diphenylhydantoin and barbiturates in the treatment of aggressive-violent behavior within the epileptic syndrome. 3. Psychostimulants in the treatment of aggressive behavior of adolescents and children within behavior disturbances. 4. Anti-male hormones such as cyproterone acetate in the treatment of violent-aggressive behavior associated with pathological sexual hyperactivity. Whereas each category of drug is predominantly effective in one type of aggressive syndrome, it may also be effective in other conditions as well. Aggression as a result of a personality disorder is most difficult to treat with drugs.
| 34,189
|
Physiological significance of secretin in the pancreatic bicarbonate secretion. I. Responsiveness of the secretin-releasing system in the upper duodenum.
|
In nine normal subjects intraduodenal pH was measured by means of a glass electrode placed in the passage from the first to the second part of the duodenum. The physiological variations in pH were simulated by intraduodenal injection of 2.5, 5, or 10 ml of 0.1 mol x 1(-1) HCl and subsequent neutralization by injection of bicarbonate. A total of 26 injections of acid was followed by a pH spike from a median pH of 7.0 to a median of pH 2.1 Median spike duration was 45 sec. The concentration of secretin in plasma increased from a median of 1.2 pmol x 1(-1) to a peak value of 2.2 pmol x 1(-1) after 4 min. It is concluded that the secretin response to a brief acidification of the first 4--6 cm of the duodenum is sufficient to explain the physiological variations in the concentration of secretin in human plasma.
| 34,207
|
[Cases of abnormal movements].
|
Four patients with abnormal movements were treated with tiapridal. Very good results were obtained in a case of buccofacial dyskinesia associated with an extrapyramidal syndrome and dementia, and in another patient with middle-of-the-dose dyskinesias induced by L-dopa treatment for Parkinson's disease. No effect was observed, however in a case of beginning of the dose dyskinesias, and the extrapyramidal symptoms increased in severity. A dopadecarboxylase-inhibitor was associated with the L-dopa treatment in these three cases. In the fourth case, there was an increase in the spasms of the medial part of the face.
| 34,219
|
5 alpha-Reductase activity in human placenta.
|
The concentration of 5 alpha-pregnane-3,20-dione in peripheral blood of pregnant women is higher than that found in blood obtained from nonpregnant women throughout the luteal phase of the ovulatory cycle. The in vitro synthesis of 5 alpha-reduced pregnanes from [3H]progesterone by placental tissue was investigated using tissue minces and homogenates in the presence of added nicotinamide-adenine dinucleotide phosphate. The metabolites, [3H]5 alpha-pregnane-3,20-dione and [3H]3 beta-hydroxy-5 alpha-pregnan-20-one, were isolated and characterized employing a combination of chromatographic techniques, derivative formation, and crystallization with authentic [14C]5 alpha-pregnane-3,20-dione and [14C]3 beta-hydroxy-5 alpha-pregnan-20-one to constant 3H:14C ratios. In short-term incubations with placenta homogenates, the apparent pH optimum for the synthesis of 5 alpha-pregnane-3,20-dione was 8.8. There was no evidence for the formation of 5 beta-reduced pregnanes from [3H]progesterone by placental tissue. The in vitro metabolism of [3H]progesterone by minces of five term placentas, during 1 hour incubations at pH 7.4, was studied. The rate of formation of 5 alpha-pregnane-3,20-dione varied from 109 to 197 pmoles/gm placental tissue/hr.
| 34,324
|
Adenovirus aggregation and preservation in extracellular environment.
|
The conditions of adenovirus aggregations are analyzed. Adenovirus type 2 was propagated on Hep2 cells; virion aggregation analysis was performed by sedimentation velocity on sucrose gradients. The results show that aggregation depends on: 1) Ionic strength: aggregate formation was verified between 0.005 M and 0.05 M NaCl; 2) pH: at pH 7.1 virus particles are dispersed, 90 per cent of particles are aggregated at pH 4--5; at pH lower than 4 aggregation is not reversible; 3) Particle concentration: the dilution of a stock containing 5 X 10(11) particles/ml decrease rate of aggregate formation until all aggregation is inhibited; 4) Temperature: the degree of aggregation in the 25 to 37 degrees C range is constant but decreases when the temperature falls below 20 degrees, at +4 C there is no aggregation. The aggregation reaction presents a positive deltaH of 17.9 Kcal/mol and a deltaG of --1.32 Kcal/mol.
| 34,378
|
Interaction of dinitrophenyl groups bound to bovine serum albumin with univalent fragments of anti-dinitrophenyl antibody.
|
Two lysine residues of bovine serum albumin reacted with 1-fluoro-2,4-dinitrobenzene with apparent second-order rate constants approx. 500-times greater than those observed in similar reactions with low-molecular-weight lysine derivatives. A series of dinitrophenyl (Dnp)-bovine serum albumins were prepared and their ability to bind univalent fragments of anti-Dnp antibody was measured by fluorescence-quenching titrations. Compared with the Dnp group of the free hapten, 6-N-Dnp-aminohexanoate, the majority of the protein-bound Dnp groups were unavailable to the antibody at pH8.0. When the same Dnp-albumins were titrated at pH3.0 the availability of the Dnp groups increased approx. 3-fold. Dnp-albumins were treated with pepsin at pH3.0 and Dnp-containing fragments isolated by chromatography on DE-52 DEAE-cellulose. Fluorescence-quenching titrations showed that the Dnp groups on the fragments behaved like the free hapten with respect to quenching efficiency, although with an increased dissociation constant. The association between the Dnp-albumins and the antibody was measured also by difference-spectral titrations at high protein concentrations. Antibody binding was increased under these conditions, but the Dnp group of mono-Dnp-albumin remained unavailable to antibody. We propose that the reactive lysine residues are located in clefts between the globular sub-domains of the single polypeptide chain. Dnp groups attached to these lysine residues are fully exposed to the solvent, but binding of the macromolecular probe, anti-Dnp antibody, is sterically hindered by the adjacent surface of the albumin molecule.
| 34,387
|
Near-heme histidine residues of deoxy- and oxymyoglobins.
|
Proton NMR titration curves of the histidine Cepsilon-H resonances of the deoxy and oxy forms of human, horse, and sperm whale myoglobins (Mb) were determined and compared with the results for the met and azide forms. One extra titrating resonance (H-8) was observed for each deoxy-Mb compared with the corresponding met-Mb, and a further extra resonance (H-9) was observed for the oxy-Mb form. These resonances correspond to the two additional resonances previously described for azide-Mb [Hayes, M., Hagenmaier, H., & Cohen, J. S. (1975) J. Biol. Chem. 250, 7461--7472]. This new evidence prompts us to reassign these resonances to the near-heme histidine residues.
| 34,431
|
The analysis of terbutaline in biological fluids by gas chromatography electron impace mass spectrometry.
|
A highly sensitive and specific assay is described for the bronchodilator drug terbutaline in human plasma and urine, based on single ion monitoring gas chromatography mass spectrometry and employing a homologue of the drug as internal standard. Recovery of terbutaline and internal standard into ethyl acetate is effected at pH 9.8, while back-extraction into dilute acid serves to purify the initial extract. Following preparation of O-TMS, N-TFA derivatives, the drug and its homologue are detected by selected ion monitoring of their common base ion at m/e 355. The limit of detection of terbutaline by this procedure is 0.3 ng ml-1 from a 4 ml sample of plasma.
| 34,445
|
Continuous peritoneal dialysis as treatment of acute experimental pancreatitis in the rat. II. Analysis of its beneficial effect.
|
In acute sodium-taurocholate-induced pancreatitis in the rat, peritoneal dialysis reduced serum amylase levels and the amount of fat necrosis, but did not influence the damage to the pancreas itself. Pancreatic ascites obtained in the early course of the disease was found to have a hypotensive effect when given intraperitoneally to healthy rats. This effect vanished in the later course of acute experimental pancreatitis and was reduced by acidification of the ascites or by administration of an antihistaminic drug. Thus the beneficial effect of continuous peritoneal dialysis on survival time and mortality rate seems to be of systemic origin.
| 34,505
|
Rapid screening for urease inhibitors.
|
Two methods are described that are suitable for the rapid screening of compounds as urease inhibitors. The first utilizes an electrode sensitive to NH4+ ions; the second is dependent on pH rise. A feature of both is a direct readout of reaction rate.
| 34,578
|
Observations on the gubernaculum during descent of the testis.
|
The mechanisms that influence the descent of the testis are not clearly understood. The gubernaculum is a structure worthy of scrutiny inasmuch as it is conspicuous during descent, but virtually disappears after descent is complete. Early in gestation, the rat gubernacular bulb consists of loose mesenchymal cells that develop into fibrillar cells. These later thicken into rhabdomyoblasts that, near the end of gestation, differentiate into spiral striated muscle bundles, and eventually migrate outward into the abdominal/scrotal wall. The rhabdomyoblasts of the female gubernaculum do not differentiate further but rather undergo fatty degeneration. It is possible that spiral contractions of the attached gubernaculum produce tension on the testis and induce descent. The gubernaculum as the receptor organ for testicular descent may be responsive to local testicular hormones. Likely candidates are testosterone, dihydrotestosterone, or Mullerian Inhibiting Substance. A thorough knowledge of the sequential differentiation of the gubernaculum during embryonic development sets the stage for the study of its response to hormonal manipulation both in vivo and in vitro.
| 34,579
|
Some properties of RNA polymerases of different influenza viruses.
|
The transcriptases of several influenza viruses were tested for pH and temperature dependence and for thermal stability. Marked differences in pH dependence and thermostability were determined.
| 34,580
|
Non-routine extractions in orthodontic treatment.
|
A four-unit symmetrical premolar extraction case demands meticulous levelling, overjet reduction, space closure, rotating, paralleling and torqueing to justify the gambit of having extracted the teeth at the commencement of treatment. This involves the patient in complex therapy which may, for any of several reasons, be contra-indicated for that particular patient, though a decision based on the plaster casts alone may have upheld such an approach. The purpose of this article is to discourage automatic decisions to extract first premolars in orthodontic extraction cases. The clinician is offered a classification of special cases in which an alternative should be sought, based on careful consideration of the general dental, facial, physical, psychological and economic state of the patient.
| 34,582
|
Characterization of the molecular defect in infantile and adult acid alpha-glucosidase deficiency fibroblasts.
|
Different clinical expressions of acid alpha-glucosidase deficiency have been described. The present study was undertaken to investigate the basic metabolic defect in the infantile and adult forms of the disease. Acid alpha-glucosidase (EC 3.2.1.20) was purified from normal and from adult acid alpha-glucosidase deficiency fibroblasts. The pH optimum; Michaelis constant; electrophoretic mobility in starch; thermal denaturation at pH 4.0 and 7.0; and inhibition by turanose, alpha-methylglucoside and trehalose were the same in purified enzyme from normal and mutant cells. Placental acid alpha-glucosidase was purified to, or near, homogeneity. Monospecific antibodies raised against the enzyme in each of three enzyme peaks obtained from the last purification step were found to cross-react with the enzyme of all three peaks, and with purified, normal fibroblast enzyme. Cross-reacting material (CRM) also was identified in fibroblast lysates from normal subjects and from both forms of acid alpha-glucosidase deficiency. The amount of CRM in the adult form appeared to be significantly less than in normal cells or cells from the infantile form. Enzyme activity was demonstrated in the immune complexes of the normal and adult acid alpha-glucosidase deficiency fibroblasts, but not of the infantile form. Competition for antibody binding sites was observed between normal and both types of mutant enzymes. The findings indicate that this case of infantile acid alpha-glucosidase deficiency is the result of a structural gene mutation which causes the synthesis of a catalytically inactive (CRM-positive) enzyme protein. It appears that in the adult form, the mutation causes a reduction in the amount of the enzyme protein present in the cells.
| 34,626
|
A model for the use of physician's assistants in primary care.
|
The function and long-term viability of physician's assistants in primary care is controversial. The authors hypothesize that to remain a viable entity the physician's assistant (PA) must meet criteria including ability to make independent decisions, to obtain the complete trust of the supervising physician, to deliver care of quality equal to that of physicians, and to produce revenue in excess of the PA's cost and overhead. A model for the use of a PA in primary care is described which has been in operation for four years. This model is tested against these criteria to see if conditions for long-term viability are met. The results show physician's assistants do have a valuable role im primary health care delivery which should not be eliminated by future increases in physician manpower.
| 34,667
|
Alterations in cartilage metabolism by neurostimulant drugs.
|
Suppression of growth without significant alterations in hormonal patterns has been demonstrated for the neurostimulant drug pemoline. Comparison of the in vitro effect of pemoline, methylphenidate, and methamphetamine on somatomedin-stimulated sulfate uptake by cartilage showed all three drugs to be inhibitory. Sulfate uptake by cartilage can be directly related to growth and glycosaminoglycan biosynthesis. Assay of two of the enzymes involved in the glycosaminoglycan biosynthetic pathway showed that methamphetamine and methylphenidate caused a marked depression of xylosyl- and galactosyltransferase enzyme activity. These data suggest an interference with cartilage metabolism as one possible mechanism for the growth retardation observed in children on neurostimulant drug therapy.
| 34,681
|
A comparative study of the microbiological assays currently available for nystatin raw material.
|
The classical agar diffusion and turbidimetric methods of assay for nystatin are compared with the more recently documented assays for this antibiotic which depend upon physicochemical measurement of the response of micro-organisms. Liquid nitrogen stored inocula were used throughout. It is concluded that the newer methods of assay are as reproducible and reliable as the agar diffusion and turbidimetric methods and that they are generally more sensitive. The choice between the assay methods compared can thus be based on speed, cost and sample through-put.
| 34,693
|
Kinetics of dopamine oxidation by dialkylaminoalkylphenothiazine cation radicals.
|
The kinetics of dopamine oxidatinon dialkylaminoalkylphenothiazine cation radicals (with two- or three-carbon side chains) were investigated. The two-carbon side-chain derivatives have reaction rates higher than the three-carbon ones. For chlorpromazine and promazine, extrapolation of pH 1-6 data shows that reaction rates become very fast at physiological pH.
| 34,724
|
[Flunitrazepam with anterograde amnesia and reduction of blood pressure before local anaesthesia without intubation in 3000 ENT operations (author's transl)].
|
After premedication with flunitrazepam=Rohypnol 2 mg orally (2--3 hours preop.) and morphine-atropine (30 min preop.) the patient receives slowly "Ro" i.v. until the phenomenon of volume reduction when speaking is observed. This allows for the smallest possible dosis to achieve sufficient amnesia. After about 20 min the patient becomes responsive again, while his amnesia lasts for about 3 hours more. The cardiovascular functions remain stable with a 25% decrease of systolic blood pressure. Vomiting is reduced. The dry operative field makes microsurgery much easier and improves the final result of the operation. After gaining sufficient experience of the staff, 100% amnesia was achieved in all operations during the last 3 months.
| 34,760
|
Lergotrile in Parkinson disease: further studies.
|
Lergotrile was administered to 53 patients with advanced Parkinson disease (PD), who had increasing disability despite optimal treatment with levodopa/carbidopa (Sinemet). Thirty-nine patients who could tolerate at least 20 mg per day lergotrile (thus considered "adequately treated") had significant descreases in rigidity, tremor, bradykinesia, gait disturbance, and total score without increased involuntary movements. Twenty-one of these 39 patients improved by at least one stage. Among the 39 patients, 23 had "on-off" effects, and in 13 of these the "on-off" effects decreased on lergotrile. The mean daily dose of lergotrile in adequately treated patients was 49 mg, permitting a 10 percent reduction in the dose of levodopa. Lergotrile was discontinued in 33 of the 53 patients because of adverse effects, including hepatotoxicity (11 patients), mental changes (12 patients) and orthostatic hypotension (8 patients). Although lergotrile, when added to levodopa, has a definite antiparkinsonian effect, the incidence of adverse effects, particularly hepatotoxicity, makes it unlikely that this ergot alkaloid will become widely available for the treatment of PD. Analogues of lergotrile have been synthesized, and it is hoped that they will duplicate the antiparkinsonian effect of this drug without its toxicity.
| 34,808
|
Blood eosinophil leucocyte and eosinophil cationic protein. In vivo study of the influence of beta-2-adrenergic drugs and steroid medication.
|
The in vivo effect of beta-2-adrenergic stimulating and blocking drugs and of corticosteroid medication on blood eosinophils and serum eosinophil cationic protein (S-ECP) has been studied. The beta-2-adrenergic drugs, salbutamol and terbutaline, had an eosinopenic effect. They were able to decrease S-ECP concentration, which administration of steroid was not, indicating that only the adrenergic stimulators affect leucocyte secretion. Care must be taken in interpretation of blood eosinophil count and S-ECP concentration, and the actual medical treatment must be known.
| 34,874
|
Azulfidine therapy for ulcerative colitis in infancy.
|
The reported patient represents an example of extensive colonic disease at an uncommon age of involvement. The significant response to salicylazosulfapyridine therapy with this degree of involvement at this age is uncommon. This case suggests the value of an initial trial of medical therapy with salicylazosulfapyridine before the use of steroids or colectomy is contemplated in infants with ulcerative colitis.
| 34,887
|
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