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Urinary excretion of arylsulfatases in malnourished/vitamin A deficient children.
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Serum vitamin A (retinol) levels were generally low in all malnourished children (6-15 microgram/100 ml) compared with control children (50 microgram/100 ml). A significant increase in vitamin A after appropriate therapy was observed in all malnourished groups. Dietary supplements of proteins and calories even without extra vitamin A supplements increased serum vitamin A levels in cases of kwashiorkor indicating active mobilization of liver vitamin A. Total urinary arylsulfatase A activity excreted in 24-h or within 8-h in the morning (6 a.m. to 2 p.m.) was significantly reduced in cases of malnutrition with or without mild vitamin A deficiency symptoms. The excretion of arylsulfatase B was not altered. In cases of severe vitamin A deficiency coupled with malnutrition increased excretion of both arylsulfatases A and B was evident. These results on urinary arylsulfatases excretory pattern have been obtained either in samples collected for 24-h or specifically for 8-h (morning) and it is suggested that this test on urinary arylsulfatases may prove useful for detection of acute vitamin A deficiency with malnutrition in field studies. A ratio of arylsulfatases A/B of 2.0 or less seems to indicate mild malnutrition, the normal ratio being 3.4. Furthermore a low ratio coupled with increased excretion of both arylsulfatases A and B may be considered specific for acute vitamin A deficiency.
| 38,922
|
Drugs for inhibition of premature labor.
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Effective inhibition of premature labor depends on prompt initiation of treatment. The author discusses factors initiating parturition, and the benefits and risks for mother and child of administration of alcohol, beta adrenergic agents, magnesium sulfate, and other agents that may counteract them.
| 38,929
|
Catabolic effects of adrenaline and angiotensin II in the perfused liver of normal and genetically obese (ob/ob) mice.
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1. Rapid effects of hormones on the metabolism of glycogen and fatty acids were studied in the perfused liver of normal and genetically obese (ob/ob) mice. 2. In livers from normal and obese mice adrenaline and angiotensin II stimulated glycogenolysis. 3. These hormones inhibited the synthesis de novo of long-chain fatty acids in livers from normal mice, but not in livers from obese mice. 4. The proportion of acetyl-CoA carboxylase in the active form was decreased by adrenaline but not by angiotensin II in livers from obese mice. 5. The potency of hormone effects on liver suggests that they could occur in the intact animal. 6. The results add to the evidence that hepatic fatty acid synthesis in genetically obese (ob/ob) mice is irreversibly resistant to inhibition by a range of hormones. Such resistance could be of primary significance in the pathogenesis of the obesity.
| 38,934
|
The treatment of glaucoma: role of beta-blocking agents.
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The sudden development of a red painful eye with blurred vision may be an acute attack of angle closure glaucoma which requires emergency attention. Once the attack is controlled with medication, surgical intervention with a peripheral iridectomy is indicated to relieve relative pupillary block. Eyes subject to angle closure glaucoma are anatomically different with 'crowded' anterior segments. In contrast, open angle glaucoma (the more common form) may progress to near blindness without symptoms. Routine screening of intraocular pressure is, therefore, necessary to make the diagnosis before extensive irreparable damage has occurred. Surgery for open angle glaucoma carries risks of cataract and infection, and is unpredictable. Open angle glaucoma patients are usually treated chronically with specific medications. Beta-Adrenoceptor blocking agents appear to provide a significant new addition to the currently available antiglaucoma medications.
| 38,956
|
Effects of 4 beta-adrenoceptor blocking drugs on blood pressure and exercise heart rate in hypertension.
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The effects of 4 beta-adrenoceptor blocking drugs on blood pressure and on exercise tachycardia were compared in a within-patient study of patients with uncomplicated essential hypertension. Twelve patients were treated with propranolol, practolol and atenolol and 7 of the same patients also received oxprenolol. Each patient received each drug separately, withdrawing each drug before starting the next, and each patient was titrated to the lowest attainable blood pressure and heart rate with each compound. All 4 drugs caused reductions in both systolic and diastolic blood pressure and in the heart rate induced by exercise. The maximum reduction by each drug in both systolic and diastolic blood pressure was the same. There were small but significant differences in the effects on heart rate between those drugs which had intrinsic sympathomimetic activity and those which did not have this property.
| 38,965
|
[Comparative characteristics of the effect of noninhalational narcotics on the reflex mechanisms of blood circulation regulation].
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It has been shown in experiments on cats with intact brain, as well as on decerebrated and spinal animals that chloralose, sombrevine and viadril exert no pronounced effect on initial electric activity in the renal nerve or baroreceptor inhibition of the neurogenous vascular tone, but inhibit vasomotor responses at stimulation of highly liminal afferent fibers of the cerebrospinal nerves. In animals with intact brain, sodium hydroxybutyrate inhibiting baroreceptor reflexes enhanced vasomotor reactions caused by activation of cutaneous and visceral nerves.
| 38,996
|
[Toxicity of lithium salts in combined use with neuroleptics].
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Experiments on white mice showed that in combined administration of LD16, LD50 or LD84 of aminazin, triphtazine or haloperidol with the same doses of lithium carbonate, chloride or hydroxybutyrate, the lethal dose exceeded the total lethal dose in the event the drugs were administered alone. Non-lethal doses of the lithium salts produced no effect on LD16, LD50 and LD84 of triphtazine and haloperidol, but non-lethal doses of these neuroleptics potentiated the action of lethal doses of the lithium salts. Haloperidol is an exception to the rule since it did not exert such action with respect to lithium chloride. Aminazin and lithium salts increased also each other's toxicity in instances where one of the drugs was administered in a non-lethal dose, whereas the other in a lethal one.
| 38,997
|
A double-blind comparison of prazepam with diazepam, chlorazepate dipotassium and placebo in anxious out-patients.
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The study compared prazepam with diazepam, chlorazepate dipotassium, and placebo in the treatment of anxious out-patients. Patients were screened for participation in the study to be sure they met the criteria for inclusion. Patients were excluded if they had complicating physical or mental problems. All patients signed an informed consent. Seventy-three patients entered the study, thirteen did not complete at least two weeks of treatment and were not used in the data analysis. Of these thirteen, ten did not return and were lost to follow-up, tow entered the hospital for reasons unrelated to the drug study, and one patient on diazepam was terminated because of increased anxiety. Six patients were used in the data analysis, thirty-six males and twenty-four females with an age range of 21-61 years. Side-effects were minimal. Drowsiness was reported by two people in the placebo group, one taking chlorazepate dipotassium, three on prazepam and one on diazepam. One diazepam patient reported nausea and vomitting. Scores on the Zung Self-Rating Scale for Anxiety showed all three drug groups to be superior to placebo. The Hopkins Symptom Check-list found prazepam and diazepam to be superior to placebo and chlorazepate. No differences among the groups were found in the Hamilton Anxiety Scale. Prazepam may offer advantages over the other available benzodiazepines since it may be more readily absorbed than chlorazepate and has less side-effects than diazepam.
| 39,012
|
Lactoperoxidase binding to streptococci.
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There have been conflicting reports regarding the binding of lactoperoxidase to bacterial cell surfaces. We describe here the effects of cell-bound lactoperoxidase on acid production by suspensions of Streptococcus mutans (NCTC 10449) in the presence of hydrogen peroxide and thiocyanate. Saline suspensions of log-phase bacteria were treated with 0.1 mg of lactoperoxidase per ml and were then washed thoroughly. The addition of hydrogen peroxide and thiocyanate markedly reduced the acid production of these lactoperoxidase-treated bacteria but had no effect on the acid production of untreated controls. After a 3-h incubation in saline, the lactoperoxidase-treated bacteria produced acid in the presence of hydrogen peroxide and thiocyanate at the same rate as untreated bacteria. These observations suggest that lactoperoxidase is initially bound to the cell surface in an enzymatically active form at a concentration sufficient to inhibit acid production. The lactoperoxidase is slowly degraded or desorbed as the bacteria stand in saline suspension.
| 39,032
|
Conformational stability of ribonuclease T1. I. Thermal denaturation and effects of salts.
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The thermal transition of RNase T1 was studied by two different methods; tryptophan residue fluorescence and circular dichroism. The fluorescence measurements provide information about the environment of the indole group and CD measurements on the gross conformation of the polypeptide chain. Both measurements at pH 5 gave the same transition temperature of 56 degrees C and the same thermodynamic quantities, delta Htr (= 120 kcal/mol) and delta Str (= 360 eu/mol), for the transition from the native state to the thermally denatured state, indicating simultaneous melting of the whole molecule including the hydrophobic region where the tryptophan residue is buried. Stabilization by salts was observed in the pH range from 2 to 10, since the presence of 0.5 m NaCL caused an increase of about 5 degrees C to 10 degrees C in the transition temperature, depending on the pH. The fluorescence measurements on the RNase T1 complexed with 2'-GMP showed a transition with delta Htr =167 kcal/mol and delta Str =497 eu/mol at a transition temperature about 6 degrees C higher than that for the free enzyme. The large value of delta Htr for RNase T1 indicates the highly cooperative nature of the thermal transition; this value is much higher than those of other globular proteins. Analysis of the CD spectrum of thermally denatured RNase T1 suggests that the denatured state is not completely random but retains some ordered structures.
| 39,067
|
Improved procedure for transport of dental plaque samples and other clinical specimens containing anaerobic bacteria.
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An improved transport system for samples containing anaerobic bacteria was developed. This system increased the recovery rate of anaerobic bacteria up to 28.8% as compared to a commonly used method.
| 39,087
|
Kinetics and mechanism of chlorambucil hydrolysis.
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The kinetics and mechanism of hydrolysis of the cytotoxic drug chlorambucil were investigated. A study of the reaction order and of the pH, dielectric constant, and ionic strength effects on the reaction rate revealed that the hydrolysis was a limiting unimolecular nucleophilic substitution, the rate-determining step being the ionization of the first 2-chloroethylamine chlorine. The hydrolysis rate was markedly dependent on the protonation degree of the chlorambucil basic group. indicating that a cyclic ethyleneimmonium ion may be involved in the rate-determining step.
| 39,159
|
Nucleoside phosphotransferase of chick embryo.
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This paper describes a purification procedure and some properties of a nonspecific nucleoside phosphotransferase of chick embryo, an activity which catalyzes the transfer of chick embryo, an activity which catalyzes the transfer of the phosphate ester from a deoxyribonucleotide or a pyrimidine ribonucleotide to a deoxyribonucleoside acceptor. The enzyme is very unstable to heat, dilution and dialysis and it is almost entirely inactivated by DEAE-cellulose chromatography or gel filtration. A marked enhancement in its stability is caused by numerous nucleotides. In these experiments at least 920-fold purification was obtained by using dTTP (50 microM) as nucleotide protector. The enzyme, purified in presence of dTTP, has a molecular weight about 270,000, an isoelectric point of 6.27, a pH optimum of 8.8 and is stable at 37 degrees C at least for 10 min. In absence of nucleotide protector, nucleoside phosphofranserferase is connected at 37 degrees C or by gel filtration in a very small active form with a lower molecular weight (about 30,000) and a pH optimum of 7.6.
| 39,250
|
The effect of vanadate on human kidney potassium dependent phosphatase.
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This study examined the effects of vanadate on the potassium dependent phosphatase activity present in purified human kidney microsomal (Na+ + K+)-adenosine triphosphatase. Vanadate anion inhibited the K+-dependent phosphatase at a K1 of 35 nM. This inhibition was noncompetitive with the substrate, p-nitrophenylphosphate. The inhibition by vanadate at 1 mM K+ was only 45% of the inhibition that was observed at 10 mM K+. Neither preincubation of the enzyme with vanadate, nor changing the pH of the assay from 8.2 to 7.2 had any effect on the K1 for vanadate. The inclusion of 2.5 mM isoproterenol, to complex the yanadate, reversed the inhibition, as did diluting the enzymatic reaction. Vanadate also inhibited the overall (Na+ + K+)-ATPase reaction at a K1 of 1.91 microM. This inhibition was also reversible upon inclusion of isoproterenol in the assay. Increasing the level of magnesium from 6 mM to 30 mM lowered the K1 of vanadate to 0.25 microM. The possible role of vanadate as a physiological mediator of (Na+ + k+)-atpase activity is discussed.
| 39,261
|
Excitation-contraction coupling in frog sartorius and the role of the surface charge due to the carboxyl group of sialic acid.
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Frog sartorius muscle fibres were incubated with the enzyme neuraminidase which is known to remove surface-bound sialic acids. The sialic acid content of the incubation media was analysed, and the relationship between the threshold of contraction and the altered pH and divalent cation concentration was investigated. The threshold potential of fibres treated with 3.3, 5 or 6.7 units of neuraminidase (at pH 5.5 and 30 degrees C for 2 h) was more positive than that of the control muscle fibres incubated under the same conditions, but without the enzyme. The potential shift is positively correlated with the enzyme concentration and with the amount of sialic acid released. After incubation with 5 units of neuraminidase the potential shift rose to +8.5 mV, depending on [Ca2+]0, [Mg2+]0 and pH. The threshold shift is greatest at low divalent cation concentration (0.5 mM), and not significant at high concentrations of divalent cations (50 mM). In both neuraminidase-treated and control muscles, the effectiveness of Mg2+ is half of that of Ca2+. The dependence of the contraction threshold on pH in the range 5.5--10 is even more pronounced in enzyme-treated than in control muscle fibres. Resting potential, time-course and overshoot of action potential are not affected by treatment with neuraminidase. Threshold shifts are explained by shifts of an external surface potential upon variation of [Ca2+]0, [Mg2+]0 and pH. Treating the muscles with neuraminidase diminishes the net negative charge density, and hence shifts the surface potential to more positive values, by release of negatively charged sialic acid. The different effectiveness of Ca2+ and Mg2+ is ascribed to their different effectiveness of Ca2+ Mg2+ is ascribed to their different binding behaviour towards the negative surface charges.
| 39,290
|
Induction by thymic fractions of T cell subsets capable of modulating GVHR intensity.
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Two thymic stromal fractions previously shown to have specific enhancing effects on anatomically distinct T cell populations were tested for their capacity to induce functionally distinct T cell subsets. Parental mice were injected with either soluble thymic fraction (STF) or insoluble thymic fraction (ITF), and their lymphoid cells were harvested 11 days later. It was shown that ITF elicited a splenic corticosensitive T cell subset endowed with enhanced graft-versus-host reaction (GVHR)-inducing capacity. On the other hand, STF increased, mainly in lymph nodes, the number of corticoresistant T cells significantly less active in GVHR. Furthermore, lymphocytes from ITF-treated parental donors could become corticoresistant with reduced GVHR activity after a 1-hr in vitro incubation with STF. We have thus shown that two different elements of the thymic microenvironment could modulate the intensity of the GVHR by modifying the equilibrium between two T cell subsets. These are believed to represent two consecutive differentiation stages.
| 39,373
|
Fructose-1,6-bisphosphate aldolase from Vibrio marinus, a psychrophilic marine bacterium.
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Fructose-1,6-bisphosphate aldolase (Fru-P2A) from a psychrophilic marine bacterium was found to be Class II aldolase based on activation by K+, activation by divalent cations, inactivation by EDTA, low molecular weight, and similar values for Km, Vmax, and Arrhenius activation energy. This enzyme was not markedly different in amino acid composition from the enzymes from mesophilic and thermophilic organisms, yet it has unusual thermal properties.
| 39,385
|
Disseminated intravascular coagulation related to outcome in head injury.
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In 46 head-injured patients coagulation studies were performed immediately after admission. In 76% of all cases signs of disseminated intravascular coagulation (DIC) were found. DIC was related to the severity of the injury and outcome. It is suggested that DIC may be used as an important parameter in assessing craniocerebral trauma. In a previous report it was stated that disseminated intravascular coagulation (DIC) is met frequently in head-injured patients (2.5--15.3%), and is associated with a more severe grade of injury and an increased mortality. This paper explores in more detail the relationship between outcome after head-injury and signs of DIC, as detected by laboratory studies performed in the first few hours after injury.
| 39,428
|
Fentanyl concentrations in brain and serum during respiratory acid--base changes in the dog.
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It is a clinical impression that less fentanyl is needed for anesthesia during hyperventilation and hypocarbia. If true, it might be due to both increased penetration of fentanyl, a highly lipid-soluble agent, into the brain and increased brain tissue binding. Serum and brain concentrations of fentanyl were determined in dogs anesthetized with halothane during normocarbia, hypocarbia by hyperventilation, and hypercarbia by addition of CO2 to the inspired mixture. Fentanyl, 12.5 micrograms/kg, was injected iv, and serum and brain samples were taken for fentanyl analysis by radioimmunoassay. Brain fentanyl values peaked latest (15--20 min) and were highest during hypocarbia; brain fentanyl values peaked earliest (0--5 min) and were lowest during hypercarbia; values during normocarbia were intermediate in time to peak (10--15 min) and concentration. Thereafter, brain levels declined, but during hypocarbia were significantly higher and during hypercarbia were significantly lower than during normocarbia. Interestingly, serum fentanyl levels were also significantly higher during hypocarbia. The brain--blood fentanyl ratios for each of the three CO2 levels increased for 30 min and thereafter stayed relatively constant. The brain--blood ratios were highest with hypocarbia and lowest with hypercarbia. At 35 min, when clinical analgesia may be considered terminated, hypocarbic brain levels were double those of normocarbia. The authors feel this reflects, to a large extent, higher serum fentanyl concentrations and delayed cerebral wash-out because of decreased blood flow. To a small but unknown extent the higher brain fentanyl levels result from increased brain--blood penetration due to increased lipid solubility, and increased brain tissue binding of fentanyl during respiratory alkalosis.
| 39,475
|
Pneumonia and pneumococcal infections, with special reference to pneumococcal pneumonia. The 1979 J. Burns Amberson lecture.
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An etiologic classification of acute pneumonia was presented and the relative importance of some of the causative agents was briefly reviewed. The early developments of the therapy of pneumococcal pneumonia with type-specific antisera, sulfonamide drugs, and antimicrobial drugs were reviewed, mostly from the experiences of the author at Boston City Hospital. Changes in the occurrence and relative importance of the pneumococcus as a cause of infections associated with bacteremia, empyema, and meningitis were demonstrated, based on cases observed at Boston City Hospital during 12 selected years between 1935 and 1972. These findings, among others, indicate that the pneumococcus is still one of the most important causes of serious bacterial infections and of mortality from such infections, particularly in the elderly. Some possible indications for polyvalent pneumococcal capsular polysaccharide vaccine were discussed, and the need for further extensive clinical and field trials to demonstrate its range of effectiveness was stressed.
| 39,481
|
Effects of pH of the medium on flagellation of Vibrio parahaemolyticus.
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Formation of the lateral flagella by Vibrio parahaemolyticus was inhibited under an alkaline condition of the medium. However, flagellation of the polar monotrichous flagellum was not affected in the same condition. Flagellation of the lateral flagella depended on the pH of the medium.
| 39,500
|
[Noisy circulation syndrome. Study of 28 cases].
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Twenty eight subjects with noisy circulation sindrome (NCS) defined as cases at least, with 4 murmurs in different arteries were studied. They were divided in groups A, B, C formed by 9 normal children, 9 peripheral vascular atherosclerosis adults and 10 Takayasu's arteritis cases, respectively. In the whole population a complete chronometric arterial auscultation and in groups B and C an arteriography of at least 3 arteries with murmurs, were performed. Groups A, B and C had 40, 50 and 37 arterial murmurs, respectively, which were predominantly localized in supraortic trunks, pelvic and phemoral arteries, and supraortic and abdominal regions, respectively. 100, 19.1 and 21.1% of
| 39,522
|
Interactions of small molecules with phospholipid bilayers. Binding to egg phosphatidylcholine of some organic anions (bromosulphophthalein, oestrone sulphate, haem and bilirubin) that bind to ligandin and aminoazo-dye-binding protein A.
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1. To assess the possible involvement of ligandin and aminoazo-dye-binding protein A in intracellular transport it is necessary to know how their ligands, most of which are molecules with hydrophobic moieties, interact with cellular membranes. To obtain such information we examined the interactions of bromosulphophthalein, oestrone sulphate, haem and bilirubin with aqueous dispersions of egg phosphatidylcholine and egg phosphatidylchone/cholesterol (1:1, molar ratio) by equilibrium dialysis and spectrophotometry. 2. In all four cases, saturation effects were observed. Values of Vmax (v = mol of compound bound/mol of lipid phosphorus) at 25 degrees C were: for bromosulphophthalein, approximately 0.1; for oestrone sulphate, approximately 0.25; for haem, approximately 0.25 (all at pH 7.4); and for bilirubin 0.1--0.2 (at pH 8.2). 3. Limiting values of v/c (c = unbound concentration) as v leads to 0 at 25 degrees C and pH 7.4 are: for bromosulphophthalein, 6.25 x 10(4) litre-mol-1; for oestrone sulphate, 7.8 x 10(2) litre-mol-1; for haem, 4.5 x 10(5) litre-mol-1; and for bilirubin, approximately 1.2 x 10(4) litre-mol-1. For haem the result depends on the assumption that only the monomeric form binds to the lipid. 4. The binding of each compound was decreased by cholesterol; bromosulphophthalein and oestrone sulphate were affected more than haem and bilirubin. 5. Bromosulphophthalein at saturating concentration decreased the limiting values of v/c of the other three compounds by approximately one order of magnitude. 6. By assuming that the interactions with egg phosphatidylcholine resemble those with the phospholipid components of mammalian intracellular membranes the binding data for phosphyatidylcholine, together with data for binding to the intracellular proteins ligandin and aminoazo-dye-binding protein A, enable the subcellular distributions of the four compounds to be estimated. For the rat hepatocyte up to 92, 51, 98 and 47% of the total bromosulphophthalein, oestrone sulphate, haem and bilirubin respectively may be membrane-bound.
| 39,548
|
The effects of calcium ions and adenine nucleotides on the activity of pig heart 2-oxoglutarate dehydrogenase complex.
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1. The effects of Ca2+ (mainly by using EGTA buffers), pH, ATP and ADP on the activity of the 2-oxoglutarate dehydrogenase complex from pig heart were explored. 2. Ca2+ (about 30 micrometer) resulted in a decrease in the apparent Km for 2-oxoglutarate from 2.1 to 0.16 mM (at pH 7) without altering the maximal velocity. At 0.1 mM-oxoglutarate there was a 4--5-fold activation by Ca2+, with an apparent Km for Ca2+ of 1.2 micrometer. A similar activation was also observed with Sr2+ (Km 15.1 micrometer), but not wised markedly from pH 7.4 TO 6.6. The effects of Ca2+ remained evident over this pH range. 4. In the presence of Mg2+, ATP resulted in a marked increase in the apparent Km for oxoglutarate, whereas ADP greatly decreased thisp arameter. The concentrations of adenine nucleotide required for half-maximal effects were about 10 micrometer in each case. 5. The effects of the adenine nucleotides and Ca2+ on the apparent Km for oxoglutarate appeared to be essentially independent of each other, reversible, and demonstrable in the presence of end product inhibition by NADH and obtained. 6. Effects similar to those described above were also observed on the activity of 2-oxoglutarate dehydrogenase from rat heart and brown adipose tissue. 7. We discuss the mechanisms controlling this enzyme's activity and compare these regulatory features with those of NAD-isocitrate dehydrogenase and the pyruvate dehydrogenase system, which are also sensitive to Ca2+ and adenine nucleotides.
| 39,549
|
The assay and partial characterization of macromolecular heparin depolymerase activity in rat small intestine.
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Homogenates of rat small intestine can depolymerize macromolecular rat skin heparin (RS heparin) to products similar in size to commercial heparin [Horner (1972) Proc. Natl. Acad. Sci. U.S.A. 69, 3469--3473]. This activity is attributed to an enzyme provisionally named 'macromolecular heparin depolymerase'. An assay for macromolecular heparin depolymerase activity in rat small intestine has been developed, based on the action of the enzyme on 35S-labelled macromolecular RS heparin. The depolymerized products are separated into two peaks by gel chromatography through columns of Bio-Gel A-15m. The amount of label in the second peak, expressed as a percentage of the total radioactivity, is the index of enzyme activity. The pH optimum was found to be 6.0 and the temperature optimum 45 degrees C. The enzyme was shown to be most stable in 50mM-Tris/maleate buffer containing 1 mM-EDTA. Macromolecular heparin depolymerase activity measured as a function of time and substrate concentration produced curves typical of an enzymic reaction. Evidence was obtained demonstrating that the activity did not originate from bacteria in the intestine. Macromolecular heparin depolymerase activity was increased by dilution and storage at 7 degrees C for 24 h. This suggests that homogenates of rat small intestine contain an unstable inhibitor of the enzyme.
| 39,552
|
Partial purification and properties of L-asparagine synthetase from mouse pancreas.
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l-Asparagine synthetase was partially purified from mouse pancreas to a final mean specific activity of 0.10 unit/mg of protein. The enzyme exhibited an l-glutaminase activity which was not affected by l-asparate, NH(4)Cl, ATP-MgCl(2), l-glutamate, AMP (sodium salt) or sodium pyrophosphate. The l-glutamine-dependent l-asparagine synthetase activity of the partially purified enzyme from mouse pancreas was markedly decreased by freezing for 7 days at -87 degrees C in the presence of 1mm-dithiothreitol, but effectively protected from inactivation by high concentrations (10mm) of the thiol reagent. The l-glutaminase activity of the enzyme was inhibited by antagonists of l-glutamine (e.g. 6-diazo-5-oxo-l-norleucine, 5-chloro-4-oxo-l-norvaline, 5-diazo-4-oxo-l-norvaline and NSC-163501) and thiol-reactive compounds (e.g. 2-amino-4-arsenophenol hydrochloride, maleimide, mucochloric acid and ZnCl(2)), but not by aminomalonic acid, the next lower homologue of l-aspartate, nor by l-homoserine beta-adenylate, an analogue of the presumed transitory covalent intermediate. The complete forward reaction catalysed by l-asparagine synthetase from mouse pancreas appears to be irreversible and essentially stoicheiometric under the conditions examined. Mouse pancreas contains a proteolytic inhibitor of l-asparagine synthetase separable from the enzyme by ion-exchange column chromatography. The inhibitor is activated by incubation at 4 degrees C for 110h and inactivated by soya-bean trypsin inhibitor, di-isopropyl phosphorofluoridate and boiling.
| 39,555
|
Microbiological activity of cefazedone as compared to cefazolin and cephalothin.
|
In a comparison of the antibacterial activity of (6R,7R)-7-(2-[3,5-dichloro-4-oxo-1(4H)-pyridyl]-acetamido)-3-([5-methyl-1,3,4-thiadiazol-2-yl)-thio]methyl)-8-oxo-5-thia-1-azabicyclo[4,2,0]oct-2-ene-2-carboxylic acid (cefazedone, Refosporen) as compared to other cephalosporins it can be seen that cefazedone possesses good activity against gram-positive bacteria; as regards activity against Enterobacteriaceae, in particular strains of E. coli, Klebsiella species and Proteus mirabilis, they fall within the spectrum of activity of the substance.
| 39,575
|
[Synthesis of several phenoxymethylphenyl derivatives with local-anesthetic activity (author's transl)].
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1. Several 4-phenoxymethyl-procaine derivatives (IV) were synthetised in order to investigate the influence of the intermediate chain on the activity. 2. By replacing the CH2-CH2-group in fomocain by a COO-group we succeeded in doubling the efficacy of this local anesthetic. 3. The type and position of the hetero atoms, N,S and O in the intermediate chain of the procaine (I), xylocaine (II), cinchocaine (III) and phenoxymethyl-procaine (IV) series have in each of these series quite a different effect due to the structural specificity of the remaining part of the molecule. 4. Other examples confirm the significance of the ester group in the intermediate chain for the liposolubility and reactivity. In ketones these properties are altered unfavourably.
| 39,578
|
[Synthesis and H2-antihistaminic activity of ring methylated metiamide analogues. 4th communication: H2-antihistaminic agents (author's transl)].
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In studies on structure-activity relationships of histamine H2-receptor antagonists, the influence of different imidazole ring methylation on the H2-antagonist activity was investigated. 2-Methyl-, 5-methyl-, 2,5-dimethyl- and unsubstituted analogues of metiamide were prepared and tested. While 5-methyl- and unmethylated analogues with a thiourea group proved to be quite active, the 2-methyl- and 2,5-dimethyl-derivatives, as well as those with a urea group, had only low H2-antihistaminic activity.
| 39,579
|
A comparative study of the effects of prostaglandins and H2-receptor antagonists on gastric acid secretion, mucosal blood flow and ulcer formation.
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The prostaglandins E2 and 16,16-dimethyl-PGE2 methyl ester were compared with the H2-receptor antagonists burimamide and metiamide for their effects on gastric acid secretion (GAS) and gastric mucosal blood flow (MBF) in rats and dogs, and on ulcer formation in rats. Orally, both 16,16-dimethyl-PGE2 methyl ester (20 microgram/kg) and metiamide (6 mg/kg) were markedly effective inhibitors of GAS stimulated by histamine acid phosphate or pentagastrin in Heidenhain pouch dogs, producing a reduction both in volume of gastric juice and in the concentration of titratable acid. In anaesthetised rats, however, the H2-receptor antagonists, when perfused into the gastric lumen, did not consistently inhibit the increased GAS caused by various secretagogues. In contrast, the prostaglandins, under the same conditions, caused marked inhibition of GAS provoked by all secretagogues. Intravenously, both burimamide and metiamide were effective in inhibiting GAS in rats but were less potent than the prostaglandins. The order of potency was: 16,16-dimethyl-PGE2 methyl ester greater than PGE2 greater than metiamide greater than burimamide. By the oral route, the H2-receptor antagonists were found to be very weak inhibitors of indometacin-induced gastric ulcer in rats, as compared to the prostaglandins. MBF studies in rats and in Heidenhain dogs showed that i.v. or p.o. administration inhibited both GAS and MBF in most cases. The ratio r = [MBF (ml/min)/GAS (mumol H+/min)] was generally increased by both types of compounds, suggesting a preferential effect on GAS.
| 39,581
|
Dermatitis as a side-effect of long-term topical treatment with certain beta-blocking agents.
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Three groups of glaucoma patients, treated topically with various beta-blocking agents, were studied for mucocutaneous side-effects of long-term therapy. In five of eleven patients with ocular and/or periocular dermatitis as an adverse reaction to long-term treatment with metoprolol eye drops a dermatitis, reproducible by patch tests with pure metoprolol 3%, was demonstrable. Histopathological examination of positive patch tests examined in three cases showed a picture compatible with a delayed type of hypersensitivity. Four atenolol treated patients showed adverse reactions, but negative patch tests to atenolol were found. In addition new data are reported in favour of cross-reactivity between certain beta-blocking agents.
| 39,586
|
Differential effects of pH and inositol hexaphosphate on the spectroscopic properties of the alpha and beta subunits in methemoglobins M Milwaukee and A.
|
The effect of pH and inositol hexaphosphate on the electron spin resonance spectra of the alpha-hemes (g = 6.0) and the beta-hemes (g = 6.7) has been measured in methemoglobin M Milwaukee and compared with that of methemoglobin A (g = 6.0). The beta-hemes are found to be comparatively insensitive to both effectors while the alpha-hemes behave in a manner similar to the heme groups of methemoglobin A. Binding of inositol hexaphosphate enhances the high spin ESR signal of the alpha-hemes in both methemoglobins. Comparison of the optical properties of methemoglobins A and M Milwaukee over the pH range from 5.0 to 8.1 shows that inositol hexaphosphate has a differential effect on the subunit types in these two methemoglobins. At low pH the spectral changes observed upon inositol hexaphosphate binding arise primarily from the beta-hemes, while at neutral and alkaline pH these changes arise from both subunit types. The beta-heme spectral changes appear to be pH independent while those arising from the alpha-hemes are strongly pH dependent. It is concluded that it is the hydroxymet form of the alpha-hemes which undergoes spectral change upon inositol hexaphosphate binding to the beta-subunits. In methemoglobin A the spin state and paramagnetic susceptibility increase only in the neutral and alkaline pH ranges upon inositol hexaphosphate binding (Gupta, R.K. and Mildvan, R.S. (1975) J. Biol. Chem. 250, 246; Perutz, M.F., Sanders, J.K.M., Chenery, D.H., Noble, R.W., Penelly, R.R., Fung, L.W.-M., Ho, C., Giannini, I., Porschke, D. and Winkler, H. (1978) Biochemistry 17, 3640). Therefore the hydroxymet form of the alpha-hemes which is responsible for the observed spectral changes must also be responsible for these increases in the magnetic properties of methemoglobin A. Inositol hexaphosphate can bind to methemoglobin at alkaline pH if the beta-hemes are in the high spin form.
| 39,622
|
The relationship between pH and the amount of calcium bound to glycerinated muscle fibers.
|
Variation of pH over the range 6.2--7.4 had no effect on the Ca2+ titration curve of glycerinated rabbit psoas muscle fibers. Thus the effect of H+ on muscle contraction is not due to a simple H+-Ca2+ competition for binding sites.
| 39,630
|
[Allosteric regulation in the open futile cycle fructose-6-P--fructose-1,6-P2].
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The effect of fructosebisphosphatase inhibition and phosphofructokinase activation by fructose-1,6-bisphosphate on a parasite recirculation of substrates in the futile (energy-dissipating) cycle fructose-6-P in equilibrium fructose-1,6-P2 has been studied. Both the inhibition and activation have been shown to produce self-oscillations in the cycle under flow-through conditions. The common recirculation with both regulatory mechanisms present is about half as high as with only one of them. The analysis fulfilled resulted in a conclusion of the importance of the concerted action of substrate inhibition and product activation both in the cycle fructose-6-P in equilibrium fructose-1,6-P2 and in the cycles glutamine in equilibrium glutamate and acetyl-CoA in equilibrium fatty acids playing an important part in the amino acid and lipid metabolism regulation.
| 39,635
|
Phosphoester specificity of purified human liver alkaline phosphatase.
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Kinetic parameters for the hydrolysis of a number of physiologically important phosphoesters by purified human liver alkaline phosphatase have been determined. The enzyme was studied at pH values of 7.0 to 10.0. The affinity of the enzyme for the compounds was determined by competition experiments and by their direct employment as substrates. Phosphodiesters and phosphonates were not hydrolysed but the latter were inhibitors. Calcium and magnesium ions inhibited the hydrolysis of ATP and PP1 and evidence is presented to show that the metal complexes of these substrates are not hydrolysed by alkaline phosphatase. A calcium-stimulated ATPase activity could not be demonstrated for the purified enzyme or the enzyme in the presence of a calcium-dependent regulator protein. Nevertheless, the influence of magnesium and calcium ions on the ATPase activity of alkaline phosphatase means that precautions must be taken when assaying for Ca2+-ATPase in the presence of alkaline phosphatase. The low substrate Km values and the hydrolysis which occurs at pH 7.4 mean that the enzyme could have a significant phosphohydrolytic role. However, liver cell phosphate concentrations, if accessible to the enzyme, are sufficient to strongly inhibit this activity.
| 39,670
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The stoichiometry and stability of the NADP complexes with manganese(II) ions as studied by electron paramagnetic resonance.
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Magnetic resonance techniques have been applied to study the stability of the complexes formed between Mn(II) ions and NADP in aqueous solutions at a pH of 7.5 and 20 degrees C. The electron paramagnetic resonance (epr) data indicate that at low Mn(II) ion concentrations ([Mn(II)] less than 1 mM; [NADP] approximately 5 mM), a 1:1 complex is formed with an apparent stability constant K1 = 370 +/- 50 M-1 at an ionic strength of 0.22 in the presence of 0.20 M Cl-. At high Mn(II) ion concentrations, a Mn(II)2-NADP species, with an apparent stability constant K2 = 54 +/- 17 M-1, is present in significant amounts. When the epr data are corrected for the presence of the MnCl+ ion, the analysis of the new Scatchard plot yields stability constants for the two sites of K1 = 640 +/- 90 M-1 and K2 = 88 +/- 13 M-1, respectively. The presence of two metal ion binding sites on the NADP molecule has not been observed previously, and previous workers have always analyzed their data in terms of the 1:1 Mn(II)-NADP complex. An epr temperature study of K1 yields a value of delta H equal to 1.3 +/- 0.2 kcal/mol (1 cal = 4.187 J).
| 39,671
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The effects of temperature, local anaesthetics, pH, divalent cations, and group-specific reagents on repriming and repolarization-induced contractures in frog skeletal muscle.
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Contractures appear during repolarization of frog toe muscles in media containing perchlorate in place of chloride. These contractures were suppressed or delayed by certain procedures which retard the repriming of K contractures, i.e., by sufficient reduction in temperature or by alkaline pH in solutions lacking divalent cations. They also were greatly reduced without interference with repriming after treatment with a reagent which selectively modifies free amino groups. In the presence of appropriate concentrations of procaine, repriming was markedly impaired with only a small reduction in the amplitude of repolarization-induced contractures. Small contractures were produced during repolarization in chloride solutions in the presence of 10 mM procaine at pH 8.0. None of these procedures affected the changes produced by perchlorate solutions in the potential dependence and the time course of K contractures. The results support the view that activation and inactivation of contraction following depolarization are separate potential dependent processes. Tension appears to develop during repolarization when the reversal of inactivation occurs before the reversal of activation is completed, both steps being necessary to recover the reprimed resting state.
| 39,672
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Cardiotonic activity of amrinone--Win 40680 [5-amino-3,4'-bipyridine-6(1H)-one].
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The cardiotonic activity of a new, noncatechol, nonglycoside agent, amrinone, was investigated in vitro and in anesthestized and unanesthetized dogs. Amrinone (3-100 microgram/ml) caused a dose-dependent increase in papillary muscle developed tension and df/dt without significant changes in duration of the contractile cycle or time-to-peak tension. Amrinone induced slight increases in right atrial rate with no changes in electrophysiological properties of the cat papillary muscle or dog Purkinje fibers. In anesthetized dogs, intravenous bolus injections of amrinone at doses ranging from 1 to 10 mg/kg caused increases in cardiac contractile force and left ventricular dp/dt max with relatively small changes in heart rate and blood pressure. No significant changes in lead II ECG were observed. In unanesthetized dogs, intravenous infusion of amrinone (10-100 microgram/kg per min) caused increases in left ventricular dp/dt max and only small changes in heart rate and blood pressure. Amrinone, tested orally in this model at doses of 2-10 mg/kg, produced a positive inotropic effect with a rapid onset and long duration of action. The inotropic response to amrinone was not blocked by propranolol, dibenzyline, chlorisondamine, atropine, metiamide, or reserpine. Amrinone's inotropic response was not associated with significant alterations in cardiac norepinephrine, phosphodiesterase, cyclic AMP, or Na+, K+-activated ATPase.
| 39,684
|
Primary amniotic fluid cell, skin fibroblast and liver alpha-L-fucosidase and its relation to cystic fibrosis.
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Cultured skin fibroblast and primary amniotic fluid cell alpha-L-fucosidase had a double optimum of pH 5.0 and 6.0. Alpha-L-fucosidase was largely bound as a single peak to DEAE-cellulose at pH 6.6. Sucrose density isoelectric focusing revealed up to seven components with pI values of 4.9, 5.2, 5.4, 5.8, 6.1, 6.5 and 7.1 with their apparent KM values (77--500 mumol/l) being higher than that (57 mumol/l) of the unfocused enzyme. Liver, skin fibroblast and amniotic fluid cell alpha-L-fucosidase was separated into two peaks by gel filtration. Peak one was more active and stable at low pH and more thermostable at 50 degrees C than peak two, while both peaks had an apparent KM of 52 mumol/l. Apart from the different proportions of the peaks separated by gel filtration, the results for the three tissues were similar. The properties of alpha-L-fucosidase studied were similar for control and cystic fibrosis liver or skin fibroblasts.
| 39,687
|
Plasma gamma-glutamyl transpeptidase in heroin addicts.
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Plasma gamma-glutamyl transpeptidase was measured in 25 heroin addicts. The purpose was to find out if the long term administration of heroin would lead to a stimulation of GGTP due to the detoxication of this drug in the endoplasmatic reticulum of the liver. In 10 patients the elevation of GGTP could be attributed to liver damage, since other liver enzymes were also increased. 15 patients had normal GGTP activities, in 4 of them accompanied by minor elevations of single other hepatic enzymes. In 11 patients the GGTP activity as weel as that of the other enzymes was normal despite heavy chronic herioin abuse. It is therefore improbable that GGTP can be used to diagnose abuse of this drug and to evaluate the progress of drug detoxication treatments and drug abstention as has been proposed in chronic alcoholism.
| 39,692
|
Interaction of alpha- and beta-adrenergic receptor blocking agents: circulatory effects in the conscious rat.
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The alpha-receptor blockers phenoxybenzamine and phentolamine produced similar circulatory effects, e.g. hypotension and tachycardia in the conscious rat. The hypotension was more pronounced than that seen after an acute cervical transection of the spinal cord or after hexamethonium treatment. The tachycardia was blocked by drugs with beta 1-receptor blocking capacity while the hypotensive response was blocked by drugs with beta 2-receptor blocking capacity. The pronounced hypotension and tachycardia was absent after spinal transection, hexamethonium pretreatment or adrenal demedullation. In adrenal demedullated rats substitution with adrenaline after alpha-receptor blockade produced tachycardia and hypotension of the same degree as seen in intact rats after alpha-receptor blockade. There was no correlation between the degree of beta-blocker induced decrease in heart frequency and increase in blood pressure after alpha-receptor blockade, while a significant correlation was found between the alpha-blocker induced decrease in blood pressure and the subsequent beta 2-blocker induced increase in blood pressure. In spinal rats, pretreated with phentolamine, adrenaline caused a depressor response. This depressor response was converted into a pressor response by administration of beta-blockers at doses which seemed to correlate well with the doses of beta-blockers needed to effectively block the alpha-blocker induced hypotension in intact animals. It is concluded that acute administration of phentolamine or phenoxybenzamine, by blocking alpha-receptors causes a reflex increase in adrenaline output, which subsequently further decreases the blood pressure and increases the heart frequency by stimulation of beta-receptors.
| 39,712
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Biotransformation of azapetine to oxazapetine in rat and rabbit liver fractions.
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The biotransformation of azapetine (I) to a lactam metabolite, oxazapetine (II), has been investigated in rat and rabbit hepatic subcellular fractions. In the presence of NADPH, II was produced from I in incubation mixtures containing 9000 g supernatant fraction or combined microsomes and cytosol, but not in mixtures containing microsomes or cytosol alone. Production of II was also observed when dehydrozapetine (III) was incubated with rabbit 9000 g supernatant fraction or cytosol. In washed rabbit microsomes II was not produced from III, but I was converted to III in the presence of NADPH. These results suggested that the biotransformation is initiated by microsomal enzymatic oxidation of I to III, followed by further oxidation of III to II by a soluble enzyme.
| 39,720
|
[Neuropharmacological data on the striatum].
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The striatum constitutes the most voluminous basal ganglia in man. It is issued from ganglionic eminences which are very early bound by limbic kernels. If the cortical and reticulo-spinal projections have been first described the existence of anatomical connexions with the limbic system offers a large number of functional possibilities. The knowledge of the distribution of the different chemical substances which are present within this structure as well as the enzymes necessary for their synthesis and destruction permits to establish a chemical mapping, the dopaminergic one being the best known. The dopaminergic synaptic function in the striatum helps to understand the respective roles of the pre and post-synaptic receptors as well as the mechanisms by which the other neuromediators can modulate the dopaminergic activity, the cyclic nucleotides being often necessary for this action. These fundamental data subtend the mechanism of action of most of the drugs which are involved in extrapyramidal phenomenons (neuroleptics, dopaminergic agonists) and allows to put forth physiopathological hypothesis on Parkinson disease, Huntington chorea, as well as certain induced or spontaneous dyskinetic states. The functions of the striatum are then evoked: if the role of this structure in motor control is critical, its involvement in complex behaviours is strongly suggested.
| 39,737
|
Intrauterine devices: medicated and nonmedicated.
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The main benefits of intrauterine devices (IUDs) are a lack of adverse systemic effects, excellent effectiveness, high continuation rates and the single act of motivation required for use. First year failure rates range from 2% to 3%, but decline steadily thereafter to a cumulative annual failure rate of less than 1% after six years. The risks of IUDs include increased blood loss, uterine perforation, pelvic infection and pregnancy-related complications. The incidence of perforation of the uterine fundus ranges from 1:1000 to 1:2500 insertions, while that of cervical perforation with the copper devices ranges from 1:600 to 1:1000. IUD use is associated with about a three-fold increased incidence of developing acute salpingitis in comparison with use of oral contraceptives and diaphragms. If pregnancy occurs with an IUD in place, there is a three-fold increased risk of spontaneous abortion, a ten-fold increased risk of ectopic pregnancy (5% of all IUD pregnancies) and a possible increased incidence of sepsis during the pregnancy.
| 39,813
|
Teenagers and contraception.
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Early sexual activity in young women has created new problems in contraception and gynecologic pathology for physicians. None of the existing birth control methods seems ideally adapted to the young: oran contraceptives, the only infallible method, may present adverse effects. Intrauterine devices may result in expulsion or infection. Diaphragms or spermicides are less effective and not always well accepted by young girls. The physician, however, must bear in mind that whatever inconvenience may result, birth control is always preferable to an unwanted pregnancy or to abortion. Given the seemingly growing incidence of veneral disease and of abnormalities of cervical cytology, physicians must exercise the utmost care and consider a birth control consultation by a young girl as a full medical act.
| 39,828
|
Aerobic and anaerobic cervical flora of healthy Thai women.
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The bacteriologic study of the cervical flora in 50 healthy women revealed that 70% harbored mixed aerobic and anaerobic organisms. Aerobic organisms alone were recovered in 15 women (30%). Polymicrobial organisms were found in all but five women (in these only one aerobe was isolated per patient). The majority of patients had 1-2 anaerobes, with more than two aerobes. The common aerobes were alpha-hemolytic streptococci, Staphylococcus epidermidis and lactobacilli. The most common anaerobes were Peptococcus asaccharolyticus isolated in 21 women (42%), P prevotii in 13 (26%) and Bacteroides in 10 (20%). These organisms are frequently found in pelvic infection, suggesting the pathogenic potential of the normal flora of the cervix.
| 39,833
|
Rheumatic heart disease diagnosed during pregnancy: a 30-year follow-up.
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One hundred one patients originally diagnosed as having rheumatic heart disease (RHD) during the years 1945-1948 were reevaluated in 1975 to determine the natural history of the disease. Twenty patients (19.8%) showed no sign of RHD. Of the patients with confirmed RHD, 56 (70.0%) had their original lesion confirmed, while 23 (28.8%) had developed additional valvular involvement. Pure mitral stenosis resulted in significantly lower mortality than all other valvular lesions, and congestive heart failure was the leading cause of death. Nineteen patients underwent cardiac surgery; the mortality in this group (52.6%) was not significantly higher than that in the overall RHD group (38.8%). False diagnosis of RHD during pregnancy is common. A more thorough evaluation of the "cardiac murmur of pregnancy" is advocated.
| 39,838
|
Euhypnos Forte (temazepam) in insomniac patients: a clinical trial in general practice.
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In an open evaluation, soft gelatin capsules containing 20 mg temazepam (Euhypnos Forte) were administrated in doses of 40--60 mg to 134 patients from twenty-two general practices. The patients selected by the general practitioners werethose known to require hypnotics but in whom conventional doses had proven unsatisfactory. Of the 134 patients who entered the trial, 104 preferred the higher doses of two or three capsules. Eighty-eight per cent of these patients found Euhypnos Forte to be 'very good' or 'good' and 69% expressed preference for Euhypnos over their customary medication. Eighty-eight per cent of these patients experinces no hangover effect.
| 39,856
|
[Risk of incompatibility reactions in the repeated use of contrast media in urography].
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In a prospective study 260 urographies were evaluated regarding clinical compatibility. In altogether 11% of the patients mild incompatibility reactions were observed (heat sensation, urticaria, nausea, vomiting). 29% of the patients with known prior contrast agent incompatibility suffered from anaphylactoid symptoms mostly of a subjective type (heat sensation, nausea). There was no statistically significant difference in the frequency of objective symptoms (urticaria, vomiting) between patients with prior contrast media incompatibility (3%) and patients who had tolerated previous contrast media applications without symptoms (2%).
| 39,885
|
Production of heat-stable, methanol-soluble enterotoxin by Yersinia enterocolitica.
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Seven isolates of Yersinia enterocolitica serotype 0:8, recovered during an outbreak of gastrointestinal illness, were examined for enterotoxin production. All seven strains were enterotoxigenic in the suckling mouse model, and three of five isolates tested produced keratoconjunctivitis in the guinea pig eye model (Sereny test). Enterotoxin was detected in broth supernatant fluid after 12 h of incubation at 25 degrees C. The toxin was not inactivated by exposure to 121 degrees C for 30 min or by storage at 4 or -40 degrees C for at least 5 months. The enterotoxin was also acid stable and methanol soluble. Methanol extraction did not affect its heat stability or enterotoxic activity in suckling mice. These physical characteristics plus limited ultrafiltration studies suggest that the enterotoxin is a low-molecular-weight substance. Y. enterocolitica enterotoxin resembles Escherichia coli heat-stable enterotoxin in heat and pH stability, methanol solubility, and enterotoxic activity in suckling mice. However, its role in the pathogenesis of human diarrhea has not been established.
| 39,891
|
Evidence for pili-mediated adherence of Klebsiella pneumoniae to rat bladder epithelial cells in vitro.
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The possible role of pili in the pathogenesis of urinary tract infections caused by Klebsiella pneumoniae was studied in an in vitro mixture of a phosphate-buffered saline suspension of rat bladder epithelial cells and phosphate-buffered saline-washed K. pneumoniae. Nonpiliated and piliated populations derived from a single K. pneumoniae strain were obtained by controlling the total time of growth in broth medium. The piliated phase demonstrated a significant increase in adherence when compared to the nonpiliated phase. Incubation of the bacteria and epithelial cell mixture at 4 and 37 degrees C resulted in no differences in adherence; optimal adherence occurred at pH 5. Pretreatment of the bacteria with enzymes to destroy the pili resulted in a decrease in adherence, as did killing the bacteria by various means before adherence testing. Pretreatment of the epithelial cells with certain saccharides inhibited bacterial adherence. Finally, a 96% decrease in adherence was observed after coincubation of bacteria and epithelial cells with papain-treated antipili antibodies. Thus, it appears that pili on the surface of K. pneumoniae mediate attachment of the bacteria to rat bladder epithelial cells.
| 39,895
|
Murine lymphoma alkaline phosphatase: a cell membrane carcinofetal enzyme.
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Alkaline phosphatase (APase) has been shown to have a membrane-bound localization in the murine fetal thymus, in murine thymic lymphoma and in adult spleen. Since it was suggested from these previous experiments that the lymphoma APase might represent an embryonic function, a detailed biochemical comparison of the lymphoma APase with the fetal thymus, placenta, fetus and spleen APases was performed. The parameters investigated were pH optimum, activation, inhibition, heat inactivation, substrate ratios, Michaelis constant, and electrophoretic analysis in the presence and absence of neuraminidase with the substrates alpha-naphthyl phosphate, beta-glycerophosphate, and p-nitrophenyl phosphate. The results indicate that the lymphoma APase is very similar to the fetal thymus, placenta and spleen APases. Furthermore, these results lend support to the hypothesis that the APase activity which appears in thymic lymphoma might represent a derepressed embryonic function. Thus, the murine lymphoma APase may be termed a cell membrane carcinofetal enzyme.
| 39,898
|
Variable pH dependence of the myosin-ATPase in different muscles of the rat.
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For the histochemical demosntration of the Myosin-ATPase (EC 3.6.1.3) the pH of both the preincubation and the incubation medium was varied in steps of 1 within a range: 10.2 to 10.5 and 9.3 to 9.9, respectively. The optimum combinations of both pH values, defined as the ones providing most consistent contrast among the three major types of muscle fibers were determined in 9 different muscles of the rat. The spectrum of optimum combinations differs considerably from muscle to muscle. The reduction of the incubation pH by only 0.1 may drastically change the staining pattern. This probably reflects the unspecificity of the histochemical procedure as well as the plasticity of the ATPase systems. To cope with the lability of the myosin-ATPase the optimum pH values of both media should be determined for each muscle separately.
| 39,907
|
Enzyme-linked immunosorbent assay for detection of Streptococcus pneumoniae antigen.
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An enzyme-linked immunosorbent assay (ELISA) was developed for the detection of Streptococcus pneumoniae polysaccharide antigen in cerebrospinal fluid and serum. Sensitivity and specificity were determined for purified antigen preparations. Specificity was also evaluated in the rabbit meningitis model, and the sensitivity was compared to counterimmunoelectrophoresis, using the infected rabbits' cerebrospinal fluid and serum. The ELISA was a specific technique for detecting S. pneumoniae antigen. ELISA was 25 times more sensitive than counterimmunoelectrophoresis for purified antigen and resulted in an increased positivity of the cerebrospinal fluid and serum from infected rabbits. ELISA should prove very useful in the diagnosis of pneumococcal infections.
| 39,946
|
Inheritance of lysozyme deficiency in rabbits.
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The phenotypes of 273 offspring of 56 matings of various genotypes of lysozyme-deficient and normal New Zealand white rabbits were analyzed. It was determined that lysozyme deficiency of rabbits is inherited as an autosomal recessive with complete penetrance. The symbol ld is suggested for the gene for lysozyme deficiency. Further studies on the nature of the condition revealed that the lysozyme deficiency was not due to a lysozyme that was cold labile, or to a lysozyme that was so tightly bound it was unavailable for enzymatic assay, or to a lysozyme with a variant pH optimum. It was demonstrated, however, that the pH profile of the lysozyme remaining in the ld/ld rabbits was different from that found in normal rabbits.
| 39,955
|
On the possible mode of action of serotonin in neurotransmission and brain dysfunction.
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Criteria necessary to classify a substance as neurotransmitter are used to determine whether disturbances in neurotransmitter function are involved in brain disorders. Six rather stringent criteria for a neurotransmitter are satisfied by the biogenic amine 5-hydroxytryptamine (5-HT): 1. the availability of 5-HT within the CNS is proved by its synthesis and transport, 2. it is stored within the presynaptic bouton, 3. presynaptic stimulation releases 5-HT, 4. it reacts with receptors of the synaptic membranes. 5. a functional equivalence of presynaptic stimulation and subsynaptic 5-HT action can be demonstrated, 6. the transmission is terminated by a retrieval mechanism.--On the basis of this transmitter concept brain dysfunctions as described in the literature are discussed in the light of results obtained using in vitro techniques with isolated synaptic structures. In renal and hepatic insufficiency the transport of the 5-HT precursor tryptophan is affected at the site of the blood-brain barrier. Tryptophan-5-hydroxylase, the rate-limiting enzyme in 5-HT synthesis, is inhibited in hypoxia. The antiparkinson drug 1-aminoadamantane and its 3.5-dimethyl derivative, D 145, inhibit 5-HT catabolism as well as 5-HT storage in synaptic vesicles and reuptake into isolated nerve endings. Since 1-aminoadamantanes enhance the electrically stimulated 5-HT and DA release from nerve endings spatial shifts of transmitter substances within the synaptic area as well as direct receptor stimulation by the drugs may be the cause for the ameliorating effect.
| 39,972
|
Tripeptide analogues of melanocyte-stimulating hormone release-inhibiting hormone (Pro-Leu-Gly-NH2) as inhibitors of oxotremorine-induced tremor.
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Fourteen di- and tripeptide analogues of MIF, Pro-Leu-Gly-NH2, have been synthesized and assayed for inhibition of oxotremorine-induced tremor. Replacement of Pro by HCO-Pro or cyclopentanecarboxylic acid gave inactive analogues, while some peptides of the general structure less than Glu-Leu-Gly-NR1R2 were highly active. Thus, R1 = C3H8 and R2 = H gave 4 times the activity of MIF, R1 = I-C3H8 and R2 = H gave 13 times the activity of MIF, and R1 = R2 = CH3 gave 29 times the activity of MIF. cyclo(-Pro-Leu-), Pro-Lys-Gly-NH2, and Pro-Arg-Gly-NH2 had no activity. Apparently, small modifications in the structure of MIF can yield highly active analogues with potential clinical value, e.g., in the treatment of Parkinson's disease or mental depression.
| 40,028
|
On two-dimensional passive random walk in lipid bilayers and fluid pathways in biomembranes.
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The lateral mobility of pyrene, pyrene decanoic acid, and 1-palmitoyl-2-pyrene decanoyl-phosphatidyl choline (pyrene lecithin) in lipid bilayers is determined by the excimer formation technique. This method is applied to vesicles of lecithins differing in chain length and in the degree of saturation of the hydrocarbon chains. These values are compared with results in cephalins of different chain length and in dipalmitoyl phosphatidic acid at variable pH. The influence of cholesterol is investigated. The results are analyzed in terms of the Montroll model of two-dimensional random walk. The jump frequency of the probe molecule within the lipid lattice is obtained. The advantage of this measure of transport in lipid layers is that it does not involve lipid lattice parameters. The main results of the present work are: (i) The lateral mobility of a given solute molecule in lamellae of saturated lecithins is independent of hydrocarbon chain length and rather a universal function of temperature. (ii) In unsaturated dioleyl lecithin the amphiphatic molecules have lateral mobilities of the same size as in saturated lipids. The jump frequency of pyrene, however, is by a factor of two larger in the unsaturated lecithin. (iii) The jump frequencies in phosphatidyl ethanolamines are about equal to those in lecithins. (iv) In phosphatidic acid layers the hopping frequencies depend on the charges of the head groups of both the lipids and the probes. (v) Cholesterol strongly reduces the jump frequency in fluid layers. (vi) The lateral mobility in biological membranes is comparable to that in artificial lipid bilayers. The experimental results are discussed in terms of the free volume model of diffusion in fluids. Good agreement with the predictions made from this model is found. A striking result is the observation of a tilt in dioleyl-lecithin bilayer membranes from the hopping frequencies of pyrene and pyrene lecithin. A tilt angle of phi = 17 degrees is estimated.
| 40,032
|
Specificity and mode of cleavage of the pH 4.0 endonuclease from adenovirus type 2 - infected KB cells.
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Adenovirus type 2 or lambda DNA was digested with the pH 4.0 endonuclease, purified from adenovirus 2-infected KB cells. The enzyme produces a limit digest of approximate size in the range of 140-210 base pairs long. The termini of the DNA fragments generated by the endonuclease digestion had 3'-P and 5'-OH groups. The 3' and 5' end groups of the products were analyzed. Our data indicate that 3' end group was a purine (68-76%), dA occuring about twice the frequency of dG. The 5' end group was either dG or dC with equal frequency. Data obtained by treatment of the 5' labeled endonuclease product of lambda DNA with single-strand specific S1 nuclease from Asperigillus oryzae or exonuclease VII from Escherichia coli indicated that the majority of the products had a short 5' protruding ends. The mode of cleavage of this endonuclease seems to be through initial formation of several single-strand breaks with some base specificity. If these breaks are at close proximity on opposite strands, double-stranded fragments with protruding ends are generated.
| 40,209
|
Oral complications of bone marrow transplantation in adults with acute leukemia.
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In recent years bone marrow transplantation has become increasingly feasible for treating adult acute leukemia unresponsive to chemotherapy. However, the technique is not without significant intrinsic morbidity. The mouth is a singularly sensitive reflector of the cytotoxic, infectious, and hemorrhagic complications and of the graft-vs-host reactions associated with bone marrow transplantation in refractory acute leukemia.
| 40,210
|
The laminar organization of optic nerve fibres in the tectum of goldfish.
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Potentials in the tectum of large (12--20 cm) goldfish, evoked by stimulation of the optic nerve, were recorded extracellularly with double-barrelled electrodes (d.c., saline and a.c., Woods metal--Pt). Four fibre groups (E, M1, M2, M3) were recorded at latencies of approximately 2, 3, 5 and 8 ms after stimulation (conduction velocities of approximately 7, 5, 3 and 2 m/s). The same four groups were recorded from the optic nerve when the tectum was stimulated. The fastest fibre groups (E) did not give rise to a postsynaptic wave. Fibre groups M1, M2 and M3 gave rise to postsynaptic potentials which, following computation of their second spatial derivatives with depth, were found to have current sinks at depths of approximately 100-150 micrometers, 150--200 micrometers and 250--350 micrometers respectively. Thus the fastest conducting retinotectal fibres make their synapses most superficially, the opposite of the arrangement in the frog tectum. These postsynaptic waves fatigued at repetitive stimulus rates of 20--50 per second, and in twin pulses at interstimulus intervals of 10--15 ms; and they were reversibly blocked by topical application of pentobarbitol. The fibre potentials, however, were virtually undecremented under these conditions. To compare these electrophysiological findings with the anatomy, the cobalt procedure was used to visualize the profiles of the optic fibres in the various tectal laminae. A thick dense projection filled the superficial grey and white (s.g.w.) layer, and there was a thin satellite band just superficial to it. In addition, there were two deeper bands of sparse innervation, in the middle of the central grey zone (c.g.) and in the deep white (d.w.) layer. These bands were associated with the field potential sinks through lesions made with recording electrodes. The two deep bands correspond to the M3 fibre group. The dense s.g.w. innervation contains both the M1 and M2 fibre groups, the M1 just superficial to the M2. The fastest fibre group, E, which had no postsynaptic wave associated with it, persisted at least six weeks after retinal removal, and probably represents efferent cells with fibres projecting back through the optic nerve to the retina. Filled cell profiles could not be positively identified with the cobalt technique, but could be seen with the HRP technique, when the optic afferents were first allowed to degenerate. The filled cells were the pyramidals of the s.g.w. layer.
| 40,252
|
The need for sublethal studies.
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In problems of waste management, the preoccupation of the would-be manager is the means whereby waste may be released to the environment without impairing the health of the biota inhabiting the receiving waters. In such a situation, measurements based upon acute poisoning are unhelpful since they tell nothing of the impact that the much lower concentrations found at some distance from the waste source have upon the ability of the affected organisms to undertake the responses necessary to ensure survival and more particularly to reproduce successfully. Such responses can only be investigated with organisms not at the point of death, i.e. in truly sublethal studies.
| 40,270
|
Biological variables, especially skeletal deformities in fish, for monitoring marine pollution.
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When considering principles for selection of indicators, i.e. biological variables, for monitoring marine pollution, it must be regarded as important to search for effects on the highest possible level of organization. For a global monitoring programme there are, however, many practical limitations in the number of useful indicators. The paper suggests skeletal deformities in fish as one possible indicator for this purpose in the future and gives a review on the occurrence, effects, causative factors and possible mechanisms of skeletal deformities in fish.
| 40,272
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Pollution-induced changes in populations.
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The effects of pollution by organic matter, oil or industrial waste on marine communities are remarkably similar. Diversity values fall, biomass and numbers of organisms initially rise and then fall as the pollution load is increased. Diversity indices are, however, insensitive to pollution-induced changes and have to be assessed subjectively. Departure from a log-normal distribution of individuals among species offers a sensitive and objective method of assessing perturbation effects on communities. Under severe pollution stress, the dominant species are those which have a flexible life-history ranging from direct development to a planktonic larva and the ability to undergo short-term genetic selection. Species have a somewhat less flexible life-history strategy show increased abundance under conditions of slight pollution. The increase in abundance of seven or eight neither rare nor common species, which gives the departure from a log-normal distribution, is suggested as being the most significant and the earliest detectable change caused by pollution in a community. Thus the presence of a species in a polluted area may be more a question of life-history strategy than the tolerance of adverse environmental conditions. If this hypothesis is correct, considerable doubt must beplaced on the ecological relevance of data from toxicity tests.
| 40,277
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The osmotic fragility of red blood cells: a re-evaluation of technical conditions.
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The osmotic fragility of red blood cells is influenced by even modest environmental changes. Consequently, the technical procedure must be strictly standardized. This implies that temperature equilibrium of the buffered salt solutions should be reached prior to the addition of blood. Furthermore, since erroneous statements concerning the composition of phosphate buffers regularly used to secure correct pH of the salt solutions have repeatedly appeared in the literature, pH control of such solutions prior to use becomes essential.
| 40,304
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Significance of antral pH for gastrin release by insulin hypoglycemia in duodenal ulcer patients.
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The significance of antral pH for the basal serum level of immunoreactive gastrin and for the release of gastrin during insulin hypoglycemia has been studied in duodenal ulcer (DU) patients. To permit paired comparisons, 14 DU patients underwent two or three tests with insulin. Venous blood samples were collected at fixed intervals for determination of gastrin (radioimmunoassay). In the first insulin test, the gastric juice was aspirated; in the second test, the stomach was perfused with citrate-phosphate buffer, pH 7.0; and in the third test the stomach was perfused with 0.1M HCl, pH 1.0. The rate of buffer or acid perfusion was adjusted, and the pH of the perfusate was kept above 5.0 and below 1.3, respectively. Gastric perfusion with buffer or acid for 1 hour did not affect the basal serum gastrin level, nor did perfusion with buffer for 3 hours. Insulin hypoglycemia stimulated acid secretion and produced a significant integrated serum gastrin response during gastric aspiration, but the gastrin response was four times greater during buffer perfusion. Acid perfusion abolished the gastrin response. From our previous and present findings, it is concluded that the gastrin in serum during basal conditions is of extra-antral origin and is independent of antral pH. Insulin hypoglycemia releases antral gastrin by a pH-sensitive mechanism in DU patients; the release is suppressed at pH 1.3 or less and also is markedly inhibited when the gastric juice is aspirated.
| 40,312
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[The effect of large burns in ruminants on the edibility of meat].
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The effect of non-contact burns was studied on a model of a slaughter ruminant. The study included the examination of the penetration of germs into the blood stream and into the meat and of the main changes characterizing the ripening of the obtained meat. The tests were conducted with two groups of animals, killed 1) at the beginning of the development of the infection process in the burn, 2) in a health state in which the prognosis was unfavourable quo ad vitam. It was found on the basis of haemocultivation, microbiological examination of the samples of organs and meat, and examination of pH values in the meat that the natural body barriers were destructed and the biochemistry of the muscular tissue was impaired. The penetration of the germs through the natural barriers of the organism was recorded also before the initiation of the development of the infection in the burn. The acidification of the meat worsened post mortem. It is possible, on the basis of the facts which were revealed, to present the following recommendations for the practical use of the results in the veterinary inspection of meat in ruminants with large burns: to take samples for microbial examination, even though the animal has been slaughtered in the earliest stage of the disease; to determine the pH in the meat obtained from the slaughtered animals and to expect worse acidification and imperfect ripening of the meat.
| 40,336
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Developments in understanding the physiology and pharmacology of parkinsonism.
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While the era of major advances in understanding and treating parkinsonism seems to be over, steady progress is being made in elucidating physiological and pharmacological aspects of extrapyramidal function. The dramatic impact of levodopa therapy has been followed by the recognition of serious limitations to its long-term use, which provides a continuing stimulus for efforts to analyze the physiological and pharmacological properties of the basal ganglia and substantia nigra. There are reasonable grounds for the hope that this research will lead to significant developments in therapy.
| 40,381
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Uptake of putative neurotransmitters in the organ of Corti.
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In vitro uptake of putative neurotransmitters into the organ of Corti of the guinea pig was studied by autoradiography. After incubation in 3H-glycine the label was heaviest over the inner hair cell, but was not confined to the synaptic region of the cell. After incubation in 3H-GABA, 3H-glutamate and 3H-aspartate, heavy labeling was seen over the fibers and terminals of the efferent olivocochlear bundle. Leucine, an amino acid not thought to be a neurotransmitter, was uniformly taken up by all cochlear structures. The fact that GABA, glutamate and aspartate are taken up into efferents, which are almost certainly cholinergic, suggests that high affinity uptake of these substances is not restricted to terminals in which these substances are released as neurotransmitters.
| 40,384
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[Institutional and personnel obstacles to the realisation of co-determination by old-age home inhabitants (author's transl)].
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Following the intentions of the "Heimgesetz" partizipation of the residents does not only concern a better protection of their interests, but also a change in the traditional, hierachical structure of organization of the homes for the aged. A realization of this aim is not only faced by the position of power of the management. On the one hand the law itself restricts the nature and the range of the partizipation of the residents concerning decisionmaking in the institution. On the other hand the residents' committee got too little power to carry through the interests of the residents against the interests of the institution. So a considerable change in the traditional structure of the organisation is not very likely.
| 40,445
|
[Therapy groups with patients and nursing staff in a geriatric hospital (author's transl)].
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Within a very short time the non-demented, chronically hospitalized old person turns into a hospital-activity-oriented patient. He thereby gives up a considerablle part of his personality. In order to understand this process, special attention has to be paid to the intertwining of the dynamics of the chronic geriatric patient with the dynamics of the nursing staff. As a therapy experiment we have been conducting parallel talk-groups with patients and with their nursing staff for one year. As a result, the patients showed increased activity, increased dynamism, improved contact ability, increased interest in the outside world, and improved affect. The nursing staff also reported improvement of the group-patients' condition on the floor. With the nursing staff we found a reduction of the defensive mechanisms, a separation from old nursing-role definitions, acceptance and encouragement of the patients in their new role, and improved satisfaction with patient contact. On the other hand, the nursing staff expects more personal contact to come from the patients. The groups have shown to be useful and have to a large extent reached the therapy goals.
| 40,446
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Sexual development and activity of men with disturbances of somatic development.
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By means of Questionnaires HTDM and SAM the heterosexual development and sexual activity were investigated in the following groups of males: 1. the control group consists of 345 married men from sterile marriages, who were adequately developed somatosexually, had normozoospermia in the ejaculate and a good potency; 2. in 48 unilateral and 57 bilateral adult cryptorchids; 3. in 101 married men with a distinct testicular hypoplasia, the long axis of both sexual glands being shorter than 30 mm; 4. in 110 patients with a Klinefelter's syndrome; 5. in 14 patients with hypogonadotropic hypogonadism. Whereas the retardation of heterosexual development was found only in two groups (group 4 and 5), a distinctly lowered activity in sex life was ascertained in all four pathological samples.
| 40,461
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[Postoperative analgesia by constant flow injection of lignocaine in obstetrical and gynecologic surgery].
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154 surgical patients were given post-operative analgesia by peridural injection at a constant flow in the post-operative period after obstetric or gynecological surgery. These patients received 536.2 +/- 105.3 mu mol.h-1 (145.2 +/- 28.5 mg.h-1) of lignocaine for 46.97 +/- 15.56 h through a catheter omserted between L1-L2. The drug was given in concentrations which varied between: 27.7 to 18.5 m mol.l-1 (0.75 to 0.50 p. 100) depending on the age; and the volume varied between 17.5 to 30 ml.h-1 depending on the height. Satisfactory analgesia in 87 p. 100 of cases allowed all supplementary analgesia to be stopped. The only significant hemodynamic effect was a slight tachycardia (+ 15 p. 100). Two undesirable side effects were noted: a transitory but well-defined (type 2 or 3) motor paralysis, and an accumulation of plasma lignocaine (40 mu mol.l-1 (1.1 microgram.ml-1) at 48 h).
| 40,489
|
Effect of socio-environmental isolation on brain biochemistry, behaviour and psychoactive drug activity.
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Isolation has been widely described to induce a strong aggressive behaviour in many animal species and especially in rodents. A deeper analysis of this altered behaviour induced by isolation, allows for the identification of several other changes involving numerous peripheral, behavioural and neurochemical functions. As a consequence of the manifold aspects involved in this experimental situation, the definition "isolation syndrome" seems to be much more adequate than the simplest definition of "aggressiveness by isolation". On this framework, some similarities with psychoneurosis in men are also suggested.
| 40,500
|
[Acute toxoplasmosis with necrotizing vasculitis (author's transl)].
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Acute toxoplasmosis was diagnosed in a Japanese woman aged 31 years after the discovery of a raised lysis titre and agglutinins resistant to 2-ME, as well as early increases in specific IgM followed later by increases in specific IgG. A high fever was present and signs of mainly distal polymyositis. The muscle lesion was confirmed by EMG examination. No increase in muscle enzyme levels was noted at any stage of the disease. Muscle biopsy demonstrated inflammatory lesions in interstitial tissue and perimysium, and, more particularly, segmental necrotizing arteritis in several arterioles. All the arteriolar lesions were at the same stage of development. After prednisolone (60 mg/day) had failed to produce improvement, spiramycin was given and caused apyrexia in 48 hours and definite disappearance of all muscle signs within several days. Recovery was complete and there was no return of symptoms 18 months later. The authors discuss the association of acute toxoplasmosis, polymyositis, and necrotizing vasculitis, and suggest a possible pathogenic role for the immune complexes deposited on the arterial walls.
| 40,506
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Isolation, characterization and the role of rabbit testicular arysulphatase A in fertilization.
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Arysulphatase A was purified from rabbit testis. The purification was accomplished by a four-step procedure involving (NH4)2SO4 fractionation, chromatography on DEAE-cellulose, SP(sulphopropyl)-Sephadex and affinity chromatography on concanavalin A-Sepharose. The specific activity of purified preparation was 135 mumol/min per mg of protein, which represented an increase of 900-fold above that of the crude homogenate. The purified enzyme (20-50 micrograms) was found to move electrophoretically as a single band on polyacrylamide gel at pH 7.2 and 8.4. The homogeneous enzyme was shown to be a glycoprotein with 0.8% (w/w) of N-acetylneuraminic acid and 20% neutral sugar. The treatment of purified enzyme with bacterial neuraminidase had no effect on enzyme activity or kinetic properties, but it changed the elution prolife of rabbit testis arylsulphatase A through DEAE-Sephadex. The purified enzyme was strongly inhibited by Cu2+, Fe3+ and Ag+. It hydrolysed several sulphate esters including cerebroside 3-sulphate, ascorbic acid 2-sulphate and steroid sulphates. Pure arysulphatase was effective in dispersing the cumulus cells of rabbit ova.
| 40,545
|
Limited-turnover studies on proton translocation in reconstituted cytochrome c oxidase-containing vesicles.
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We have investigated ferrocytochrome c-induced proton ejection from reconstituted cytochrome c oxidase-containing vesicles using careful control of the number of enzyme turnovers. Ferrocytochrome c caused the appearance of protons at the vesicle exterior, and this could be abolished by using a protonophore. In addition, its decay was dependent on the permeability of the vesicle membranes to protons and the number of turnovers of the oxidase. These observations indicate that the ejection of protons was the result of genuine translocation. The possibility of this translocation occurring via a Mitchellian loop as a result of the presence of a reduced hydrogen carrier contaminating the enzyme was considered and excluded. Proton-translocating activity in this reconstituted system depended critically on the ratio of enzyme to lipid used in the reconstitution process and we propose a rationale to account for this. We conclude that our data provide strong support for the proposal that cytochrome c oxidase acts as a proton pump and that approx. 0.9 H+ is excluded per ferrocytochrome c molecule oxidized.
| 40,547
|
Antianginal and haemodynamic effects of a new beta-blocking agent, SD 1601.
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Seventeen patients suffering from angina pectoris were submitted to bicycle ergometer test until an ST ischemic segment of typical pain occurred. Before and during the effort the ECG was recorded: before and after the exercise, the systolic intervals were calculated and arterial pressure measured. The T.P. index, namely the product of systolic arterial pressure by the heart rate and ejection time was calculated. The recordings and the effort test were repeated 5 min after treatment with the beta-blocking drug 1-(o-methoxyphenoxy)-3-isopropylamino-2-propanol hydrochloride (SD 1601). After treatment with the blocker, patients were able to prolong the duration of exercise or perform a higher mean total external work. SD 1601 significantly diminished O2 myocardial consumption at rest, expressed as T.P. During physical exercise, work and thus O2 consumption rise; given equal external work, SD 1601 rduces significantly O2 consumption. Acutely given, SD 1601 did not affect systolic intervals nor did it exert any negative inotropic effect.
| 40,567
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Proestrus and metestrus rat uterus, a rapid and simple in vitro method for detecting histamine H2-receptor antagonism.
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The antagonism caused by metiamide and cimetidine on histamine-induced inhibition of spontaneous and electrically stimulated isometric contractions of superfused rat uterine horns from proestrus and metestrus stages was studied in vitro. Histamine depressed smooth muscle "twitch" responses of spontaneously contracting or electrically stimulated uterine preparations of both stages in the same dose-dependent manner. The typical effects of organ relaxation, inhibition of contraction height and reduction of resting tension generated by histamine, could both be antagonized by the histamine H2-receptor blockers metiamide and cimetidine, while both compounds failed to reverse orciprenaline- or isoproterenol-induced inhibition of uterine contractility. Diphenhydramine, a histamine H1-receptor antagonist, was not able to reduce histamine-induced inhibition of uterine contractions, thereby confirming that the histamine receptors of the rat uterine tissue are H2 in type. Furthermore, beta-adrenergic blockers, like propranolol and dichloroisoproterenol, failed to antagonize the decrease in contraction amplitude but prevented fall in resting tension induced by histamine. Tyramine, cAMP or dibutyryl-cAMP produced no inhibition of motility of the isolated uterine tissue. Possible mechanisms of these findings are discussed. The findings show that the isolated non-estrus rat uterus is useful as a rapid method for investigating specific effects of drugs designated for potential histamine H2-receptor antagonism. This preparation offers the additional advantage that no interference with beta-blockers occurs.
| 40,581
|
Studies on the nature of the catalytically essential ionizing group of plasmin with pK 8.4.
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A fully carbamylated derivative of plasminogen having no free amino groups has been prepared and converted by urokinase to an active enzyme, called carbamyl plasmin A, with a single free NH2-terminal amino group (Val-561). Carbamyl plasmin A was shown to possess a catalytically essential ionizing group having pK 8.6. Carbamylation of the free NH2-terminal amino group of carbamyl plasmin A led to complete loss of catalytic activity. The results of solvent perturbation studies of normal plasmin (EC 3.4.21.7) indicate that the group with pK 8.4 is a neutral acid group. It is suggested that the catalytically essential ionizing group of plasmin having a pK of 8.4 is the alpha-ammonium group of the NH2-terminal Val-561 or the light chain of plasmin, forming an ion pair with a COO- group of an aspartate or glutamate residue.
| 40,605
|
Purification and properties of a proteinaceous metallo-proteinase inhibitor from Streptomyces nigrescens TK-23.
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A novel metallo-proteinase inhibitor which is capable of inhibiting the activities of metallo-proteinases such as the thermolysin, was isolated from the culture filtrates of Streptomyces nigrescens TK-23. The inhibitor was purified batch-wise from the culture filtrate by Amberlite IRC-50 and column chromatographies on CM-Sephadex C-50 and Sephadex G-50. The purified inhibitor showed a single band on 15% polyacrylamide gel electrophoresis at pH 4.3, and at pH 7.5 on SDS-gels. The inhibitor retained 80% of its original activity after treatment of 100 degrees C for 5 min between pH and 7. The molecular weight was estimated to be 12 000 by gel filtration and SDS-polyacrylamide gel electrophoresis, and calcuated as 11 950 from its amino acid composition. The isoelectric point was pH 10.3. The inhibitor showed a high content of hydrophobic amino acids, did not contain tryptophan, and had two disulfide bridges. It also showed specific inhibitory activity for metallo-proteinases but not for serine-, thio- and carboxyl-proteinases.
| 40,611
|
The effects of histamine on responses of the rabbit ear artery to electrical stimulation and to exogenous noradrenaline.
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1 The effects of a subconstrictor dose of histamine (9 x 10(-7) mol/l) on the responses of the isolated perfused ear artery of the rabbit to electrical stimulation (E.S.) and to exogenous noradrenaline (NA) were investigated.2 Both intraluminal (I/L) and extraluminal (E/L) histamine potentiated responses to E.S. and to I/L NA to the same extent.3 Mepyramine alone (2.5 x 10(-6) mol/l) had no effect on the response of the ear artery to either stimulus, but in the presence of this concentration of mepyramine, the potentiation by histamine of the response to I/L NA was significantly decreased and that to E.S. was replaced by inhibition.4 The H(1)-receptor agonist, 2(2-pyridyl) ethylamine, applied I/L potentiated responses to I/L NA at both concentrations used (5.1 and 51 x 10(-7) mol/l), but only potentiated the effects of E.S. at the higher concentration.5 The H(2)-receptor antagonist, metiamide (4 x 10(-6) mol/l), alone did not alter the extent of potentiation of responses to either E.S. or I/L NA by histamine. This suggests relatively weak H(2)-receptor activity in the rabbit ear artery. In the presence, but not the absence of metiamide, the potentiation by histamine of the I/L NA response was reversible, an observation suggesting an interaction between metiamide and the non-reversible component of the potentiating effect of histamine.6 These results are interpreted in terms of postsynaptic H(1)-receptors which potentiate and presynaptic H(2)-receptors which inhibit contractile responses in the ear artery.
| 40,650
|
A comparison of the effects of gamma-hydroxybutyrate and gamma-butyrolactone on cerebral carbohydrate metabolism.
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The metabolic effects of 60-min exposure to 250-2000 mg gamma-hydroxybutyrate (GHB) per kilogram or 150-1200 mg gamma-butyrolactone (GBL) per kilogram were studied in rats by measurement of the cerebral hemisphere contents of energy phosphates and glycolytic-Krebs' cycle metabolites. A general pattern of increased glycogen and glucose with decreased pyruvate, lactate, alpha-ketoglutarate, and malate was observed. This pattern in association with unchanged adenylates and decreased energy phosphate utilization was consistent with a metabolic adaptation to a state of cerebral depression. The major qualitative difference between the two drugs was that higher doses of GBL were associated with additional decreases of citrate and glutamate. Since these doses of GBL were also associated with acute increases of arterial CO2 tension, it is proposed that these differences were secondary to hypercapnia and not due to a distinctive primary action of GBL. Derivation of the cytoplasmic NAD(P)H:NAD(P)+ ratios indicated that GHB and GBL were not associated with consistent alterations of the cytoplasmic redox state.
| 40,677
|
Fine-needle aspiration of the breast: diagnoses and pitfalls. A review of 3545 cases.
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Fine-needle aspiration is now a recognized diagnostic tool. In the past eight years we have studied 3545 aspirates from the breast, including both cystic and solid masses. All were prepared according to the method of Papanicalaou. The cellular findings are described and discussed. Abnormal cells were found in the aspirates from 90% of the 368 malignancies. Reliable criteria for diagnosis are emphasized and diagnostic pitfalls discussed. Aspiration biopsy was helpful in the management of all patients with breast lesions. The method is rapid, accurate, and essentially complication-free. It should be used with the idea of complementing, not competing with, routine histologic biopsy.
| 40,687
|
Characterization of an established cell line from human renal carcinoma.
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A cell line, designated as OUR-10, has been established from a renal carcinoma in a Japanese woman. This cell line forms monolayers of polygonal epithelial cells with scattered round or dendritic cells and exhibits multilayering. With electron microscopy, differentiated surface structures that resemble the microvilli characteristic of renal carcinomas can be seen even at the 60th transfer. The cells have a hypodiploid karyotype with modal numbers of 39 and 40. No marker chromosomes were seen, but definite nonrandom loss of three chromosomes in Group D and one in Group E were recognized. The doubling time was estimated as approximately 32 hr in exponentially growing cultures, and the cells formed colonies in soft agar with an average efficiency of 25%. Heterotransplantation into the cheek pouch of immunosuppressed hamsters produced tumors that were histologically similar to the original cancerous tissue. The electrophoretic mobility of gamma-glutamyl transpeptidase extracted from the cells coincided with that of a novel isozyme found in human renal carcinoma tissue, and the genetic phenotype of the glucose-6-phosphate dehydrogenase was proved to be the B phenotype. The antigenic structure of HLA was determined as HLA-A2, 11; B5, 40, which was the same as that of peripheral blood lymphocytes of the woman with renal carcinoma.
| 40,693
|
A controlled study on the preventive effect of ketotifen, an antiallergic agent, on methacholine-induced bronchoconstriction in asthmatics.
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We studied the preventive effect of ketotifen, an oral drug with antianaphylactic and antihistaminic properties on methacholine-induced bronchoconstriction in controlled cross-over experiments in twenty-six adult patients with extrinsic asthma. Both a single dose of 1 mg ketotifen and 4 weeks treatment of ketotifen, 1 mg twice daily, failed to reduce the methacholine-induced drop in peak expiratory flow. The spirometric findings remained unchanged during ketotifen treatment. There was no difference between treatments with ketotifen and placebo with regard to the patients assessment of the severity of asthma or airway sensitivity to tobacco smoke, fumes or dusts, or exercise. The results suggest that treatment during 4 weeks with ketotifen does not reduce unspecific broncial hyperreactivity in patients with extrinsic asthma.
| 40,709
|
Human erythrocyte thiol methyltransferase: radiochemical microassay and biochemical properties.
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A radiochemical microassay for the measurement of thiol methyltransferase (TMT) activity in human red blood cell (RBC) membranes has been developed. Both 2-mercaptoethanol and dithiothreitol were used as substrates for the enzyme. The pH optimum of the reaction was approximately 9.0 when glycine NaOH was used as a buffer. The apparent Michaelis-Menten (KM) value for the methyl donor for the reaction, S-adenosyl-L-methionine, was 43 mumol/l. Human RBC TMT activity was neither activated nor inhibited by Ca2+, Mg2+, or tropolone, but the enzyme was inhibited by SKF 525A and by reagents that react with sulfhydryl groups. The mean TMT activity in blood from 289 randomly selected adult white subjects was 10.93 +/- 3.22 units per mg protein (mean +/- S.D.). The activity was the same in samples from men and women. The results of experiments in which TMT activity was measured in mextures of RBC membranes with relatively "low" and relatively "high" activities provided no evidence that individual variations in the enzyme activity were due to variations in endogenous TMT activators or inhibitors.
| 40,715
|
A rare cause of ischemic colitis: polyarteritis nodosa.
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This paper details the first case report of a patient with fulminant, gangrenous, ischemic colitis caused by polyarteritis nodosa which was successfully treated surgically. Ischemic colitis is a rare complication of polyarteritis nodosa. It should be suspected in patients with a past history of polyarteritis nodosa who develop abdominal pain and rectal bleeding. The identification of cutaneous lesions preoperatively and or mesenteric or serosal vascular beading at operation are helpful in establishing this diagnosis. Prognosis is generally determined by the extent of systemic involvement by polyarteritis nodosa, and death is generally associated with renal failure.
| 40,759
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Role of enterohepatic circulation in the analgesic action of 1-alpha-acetylmethadol in the rat.
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The enterohepatic circulation of 1-alpha-acetylmethadol (LAAM) was investigated in the rat. Bile containing 3H-LAAM metabolites was collected from a biliary cannulated donor rat after administration of 3H-LAAM (5 mg/kg, 15 muCi/kg, sc) and infused into the intestine of a double biliary-cannulated recipient rat for 1 hr, and tritium excreted into the bile of the recipient rat was monitored. Within 1 hr after the end of infusion significant radioactivity was found in the bile of the recipient rat and by 10 hr 50% of the infused dose of 3H had been re-excreted into bile. The contribution of enterohepatic circulation of LAAM metabolites to the analgesic action of LAAM was also assessed. Pretreatment of rats with neomycin sulfate was used as a method of decreasing enterohepatic circulation of biliary glucuronide conjugates of LAAM metabolites, and such pretreatment had no effect on LAAM analgesia (6 mg/kg) measured by the hot-plate method. In rats with a biliary fistula, a situation in which enterohepatic circulation was completely eliminated, the analgesic response to a dose of LAAM (6 mg/kg, sc) was not different from sham-operated control group. The above findings indicate that enterohepatic circulation of LAAM metabolites does not contribute to the intensity or duration of LAAM analgesia.
| 40,771
|
Metabolic fate of phenobarbital in man. N-Glucoside formation.
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1-(beta-D-Glucopyranosyl)phenobarbital was identified as the major metabolite of phenobarbital in man. Proof of structure was based on the comparison of the UV, NMR, and mass spectrometry and TLC data for the acetylated metabolite with an authentic compound. The previous erroneous structure assignment of this metabolite as N-hydroxyphenobarbital was based on insufficient data. After oral administration of 14C-labeled phenobarbital to two healthy male subjects, most of the radioactivity (87 and 78% of the dose) was recovered in urine over a period of 16 days. The N-glucopyranoside, p-hydroxyphenobarbital, and unchanged phenobarbital accounted for 30 and 24%, 18 and 19%, and 33 and 25% of the dose, respectively.
| 40,773
|
Blood pressure and plasma noradrenaline during single high-dose beta adrenoceptor blockade.
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The acute effects upon blood pressure and sympathetic outflow of two beta adrenoceptor blocking drugs, propranolol and atenolol, are described in five healthy normotensive subjects. Supine blood pressure, heart rate, plasma noradrenaline, and urinary catecholamine excretion were measured before and at intervals for 24 h after a single oral dose of either propranolol 200 mg, atenolol 100 mg, or placebo. Propranolol caused a fall in blood pressure and heart rate of 17.2/14.1 mm Hg and 20.4 beats/min respectively two hours after dose. Atenolol caused a fall in blood pressure of 11.4/18.6 mm Hg within 7 h of the dose, and a fall in heart rate of 13.8 beats/min after 2 h. The reduction in blood pressure after single high dose beta adrenoceptor blockade is established. The synchronous reduction in blood pressure and heart rate after propranolol was not associated with an increase in peripheral sympathietic activity as assessed by the biochemical indices. It is conceivable that the reduction in blood pressure during beta adrenoceptor blockade may be due in part to inappropriately low sympathetic activity but this cannot be the main mechanism of pressure reduction.
| 40,797
|
Consultation evaluation: I. Psychotropic drug recommendations.
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A follow-up chart review was undertaken of 100 consecutive patients seen in psychiatric consultation for whom psychotropic medication was recommended. Significant differences in implementation (P less than 0.01) by class of drugs (neuroleptics, tricyclics, benzodiazepines) were found. Most often no discernible reason for consultee disagreement could be found or inferred. The importance of such follow-up studies for consultation work is stressed.
| 40,844
|
Prostaglandin synthetase activity in acute ulcerative colitis: effects of treatment with sulphasalazine, codeine phosphate and prednisolone.
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Prostaglandin synthetase activity in rectal biopsy specimens from patients with ulcerative colitis has been shown to fall on treatment with sulphasalazine, local steroids, and codeine phosphate. In vitro studies have shown that sulphasalazine is an inhibitor of prostaglandin synthetase, although less potent than indomethacin, whereas prednisolone and codeine phosphate were inactive. It is suggested that the therapeutic action of sulphasalazine may be related in part to its action in inhibiting prostaglandin biosynthesis.
| 40,848
|
Human platelet arylsulphatases: identification and capacity to destroy SRS-A.
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Arylsulphatases IIA and IIB have been separately identified in human platelets by use of anion exchange chromatography and gel filtration. Arylsulphatase IIA had a molecular weight of 160,000 and a pH optimum of 4.5. Arylsulphatase IIB had a molecular weight of 60,000 and a pH optimum of 5.5. Both arylsulphatases IIA and IIB were inhibited by phosphate and sulphate ions characteristic of this enzyme class. Platelets, upon exposure to ionophore A-23187 or thrombin, discharged arylsulphatase coincident with beta-glcuronidase release. Partially purified platelet arylsulphatase IIB inactivated rat SRS-A.
| 40,872
|
Immunochemical cross-reactions between type III group B Streptococcus and type 14 Streptococcus pneumoniae.
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Serological cross-reactions between certain streptococci and some serotypes of Streptococcus pneumoniae have been reported. These studies detail the serological cross-reactivity observed between hot HCl-extracted group b streptococcus type III (GBS III) antigens and S. pneumoniae type 14 (Pn 14) polysaccharide. Similar electrophoretic migration patterns of GBS III and Pn 14 were observed when either type-specific BGS III antisera or pneumococcal omniserum was utilized to precipitate these antigens. Both the GBS III antigen and the Pn 14 polysaccharide migrated toward the cathode, whereas all other pneumococcal polysaccharides migrated toward the anode. No cross-reactions were observed between GBS III antisera and the 11 other types of pneumococcal polysaccharides. Lines of identity were observed between type-specific GBS III antisera and monospecific Pn 14 antiserum with either GBS III antigens or purified Pn 14 polysaccharide. The cross-reacting antigens of GBS III and Pn 14 appear to be identical by immunodiffusion and immunoelectrophoresis.
| 40,876
|
Large-scale production and physicochemical characterization of human immune interferon.
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Large-scale production of crude high-titered (10(2.3) to 10(4) U/ml) human immune interferon (type II) was carried out in roller bottle cultures of human peripheral lymphocytes by using the T-cell mitogen staphylococcal enterotoxin A. Over 99% of human immune interferon was destroyed by pH 2 or heat at 56 degrees C for 1 h. The interferon was not neutralized by antibody to human leukocyte interferon. The kinetics of development of the antiviral state were slow for immune interferon relative to those for leukocyte interferon. Ultrogel AcA 54 chromatography of crude or the concentrated interferon resulted in two peaks of activity, a major one (87% of recovered activity) with a molecular weight of 40,000 to 46,000 and a minor peak of molecular weight 65,000 to 70,000. The column elution buffer consisting of 18% ethylene glycol and 1 M NaCl in phosphate-buffered saline resulted in at least 100% recovery of added interferon. The data suggest, then, that the interferon produced under large-scale conditions was immune (type II). The efficiency of the production was comparable to that described for large-scale production of human leukocyte interferon. Our large-scale production system for human immune interferon offers a feasible approach to preparation of large quantities of purified immune interferon for structure studies, antibody production, and clinical application.
| 40,881
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Attachment pili from enterotoxigenic Escherichia coli pathogenic for humans.
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Pili from enterotoxigenic Escherichia coli pathogenic for humans have been isolated by adsorption to the surface of erythrocytes followed by thermal elution. The pili are composed of two protein subunits with molecular weights of 13,100 and 12,500 as determined by sodium dodecyl sulfate-gel electrophoresis. These pili also bind to human buccal cells under temperature conditions (37 degrees C) which prevent the binding of these pili to the erythrocytes. Analogous temperature effects on binding have previously been observed with whole bacterial cells. This binding can be inhibited by antiserum prepared against the isolated pili.
| 40,882
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A calorimetric study of the interaction of ATP with rabbit muscle phosphofructokinase.
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The heat of interaction of ATP with phosphofructokinase from rabbit muscle was determined at 25 degrees C in 0.1 M potassium phosphate, pH 7.0 and 8.0. The limiting value of the enthalpy change at high ATP concentrations was found to be -11.5 kcal mol of enzyme polypeptide chains. Since phosphate and imidazole have very different heats of ionization (+0.8 and +7.5 kcal/mol, respectively), this suggests that the binding of at least two protons to the enzyme occurs concomitantly with the binding of ATP at the regulatory site.
| 40,994
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Precise spectrophotometry of small quantities of drugs in the presence of irreproducible quantities of impurities.
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A variety of methods of spectrophotometric assay of compounds in the presence of one or more irrelevant impurities have been recently described, employing, for example, the use of Legendre polynomials and trigonometric functions. The use of least-squares solutions of overdetermined systems (Scheid 1968) in spectrophotometry is outlined, with conditions under which simplified overdetermined systems have been used for precise spectrophotometric assay of small quantities of drug substances in the presence of largely irreproducible quantities of irrelevant impurities.
| 41,037
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The use of phospholipid liposomes for lithium administration. Polydipsic effect and tissue distribution of lithium.
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Administration of lithium entrapped in phospholipid liposomes increased the lithium-induced polydipsia, but did not accelerate the onset of this effect. It also resulted in a larger accumulation of lithium in the liver, kidney and spleen, but not in the brain. The time course of polydipsia suggests that it depends on the intracellular lithium concentration. However, the rate of development of this effect depends on some additional factor.
| 41,065
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