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Synthesis of stereospecifically deuterated phenylalamines and determination of their configuration.
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1. Starting from trans-cinnamic acid a chiral (-)3-phenyl-[2,3-2H]propionic acid has been synthesized using Clostridium kiuyveri cells as catalyst. 2. The chiral dideuterated acid has been converted by chemical methods to a mixture of (2R) and (2S)-phenyl[2,3-2H]-alanine. 3. By means of 1H nuclear magnetic resonance spectroscopy and the action of D and L-amino acid oxidase the configuration of the phenylalamine has been shown to be (2R, 3S) and (2S, 3S), respectively. The labelled phenylalanine is thus sterically and isotopically homogenous at position 3 but heterogenous at position 2.
| 13,996
|
Carcinoembryonic character of gamma-glutamyltranspeptidase in primary hepatocellular carcinoma.
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As a characteristic isoenzyme of gamma-glutamyl transpeptidase (gamma-GTP) has been detected in sera of patients with primary hepatocellular carcinoma, which migrates to alpha-globulin region on polyacrylamide-gel electrophoresis, biochemical studies on human fetal liver, Morris hepatoma (7316-A, 7794-A), and human hepatoma was carried out to elucidate its carcinoembryonic character. The highest distribution of the enzyme was found in particle fraction of human fetal liver as well as of Morris hepatoma, and an isoenzyme of gamma-GTP with the same electrophoretic mobility as detected in human hepatoma was obtained, which reflected to the pattern of the serum zymograms. Histochemically, the enzyme was distributed in plasma membrane of the fetal hepatocytes and Morris hepatoma cells, while it was distributed diffusely throughout the cytoplasm of human hepatoma cells. These findings may strongly suggest that gamma-GTP in hepatoma has a carcinoembryonic character and the detection of a serum isoenzyme in the alpha-globulin region is a quite diagnostic as well as the detection of alpha-fetoprotein in the field of neoplasma of the liver. The physicochemical and kinetic properties of the enzyme in human hepatoma were also discussed.
| 14,048
|
Heartburn of pregnancy.
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Lower esophageal sphincter pressure, basal gastric pH, fasting plasma gastrin, and plasma concentrations of estrone, estradiol, and progesterone were measured in pregnant volunteers at 12, 24, and 36 weeks of gestation, and again at 1 to 4 weeks postpartum. In addition, basal and pentagastrin-stimulated acid secretory responses at each time were measured. No differences in basal gastric pH, basal, and peak acid outputs were observed during pregnancy when compared to the postpartum values. In contrast, lower esophageal sphincter pressure was reduced at all times during pregnancy, reaching a nadir at 36 weeks. Postpartum lower esophageal pressures were normal. As expected, plasma concentrations of progesterone and both estrogens increased progressively during pregnancy. These data are consistent with earlier studies in women ingesting oral contraceptives. Moreover, they provide support for the thesis that the progressive increase in plasma progesterone alone or in combination with estrogens that occurs during pregnancy is responsible for the reduction of lower esophageal sphincter pressure which allows esophageal reflux to occur with the resultant development of symptomatic heartburn.
| 14,050
|
[Synthesis of norepinephrine from 3,4-dihydroxyphenylserine by L-aromatic amino acid decarboxylase of the rat brain and kidneys].
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The enzymic decarboxylation of stereoisomers of DOPS was examined using rat brain and kidney decarboxylase. Optimal assay conditions for racemic threo- and racemic erythro-DOPS decarboxylation were determined by the experiments concerning 1) time course, linear for 20 min, 2) optimal pH, pH 8.2, 3) optimal temperature, 37 degrees C except racemic L-threo-DOPS decarboxylation by kidney enzyme and 4) protein concentration, 1 to 5 mg in incubation medium. Under the optimal assay condition, Km of brain enzyme for L-threo-DOPS was 1.43 X 10(-3)M and Vmax, 2.22 nmoles NE/mg/15min, and Km for racemic erythro-DOPS was 10(-3)M and Vmas, 4.3 nmoles NE/mg/15min. Km of kidney enzyme for L-threo-DOPS was 1.37 X 10(-3)M and Vmax 21 nmoles NE/mg/15min, and Km for racemic erythro-DOPS was 8.7 X 10(-4)M and Vmax, 16.7 nmoles NE/mg/15min. On the other hand, D-threo and D-erythro-DOPS were scarcely decarboxylated. Decarboxylation of L-threo-DOPS in kidney enzyme was markedly inhibited by D-threo-DOPS. Kinetic analysis revealed that the type of inhibition was non-competitive. In helically-cut strips of isolated rabbit aorta, the contractile response to NE (10(-8)g/ml) formed from L-threo-DOPS was 95% that of 1-NE (10(-8)g/ml) while the response to NE (10(-8)g/ml) formed from racemic erythro-DOPS was not detectable. These results suggest that L-threo-DOPS is a more effective precursor of natural 1-NE than racemic threo-DOPS.
| 14,060
|
[Paroxysmal alveolar hypoventilation syndrome (author's transl)].
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The case of a 42-year-old female patient with central disturbance of respiration was reported which, contrary to the previously described forms of central alveolar hypoventilation, could be characterized by paroxysmal-like apnoic conditions without any feeling of suffocation. Clinically, initial cardiopulmonary complications were primary in this central disturbance of respiration. The possibility of isolated apnoic paroxysms as an expression of a true cerebro-organic nature of the attacks was described. In addition, the attempt was made to localize the morphological or functional disturbance at the basis of the observed pathological process in the bulbopontine area of the brain stem on the ventral side of the medulla in the area of the point of exit of the seventh to the twelfth cranial nerves. With anticonvulsive and analeptic treatment, a distinct improvement could be observed in the disease after the cardiopulmonary complications had subsided.
| 14,066
|
Isolation of an Escherichia coli mutant deficient in thioredoxin reductase.
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A mutant of Escherichia coli defective in thioredoxin reductase has been isolated and partially characterized. This mutant has no detectable thioredoxin reductase activity in vitro and yet it exhibits no in vivo defect in reduction of ribonucleotides. Evidence is presented that indicates that, in cells permeabilized via ether treatment, ribonucleoside diphosphate reduction can utilize glutathione as an alternate reducing system.
| 14,115
|
Dog renal kallikrein: purification and some properties.
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The contents of kallikrein [EC 3.4.21.8] in the kidneys of various animals were estimated and the activity was found to be most potent in dogs. The dog renal kallikrein (DRK) was located mainly in the kidney cortex. Following the activation of a dog kidney cortex homogenate with acetone, kallikrein was purified about 2,000-fold with an overall yield of 18% by diethylaminoethyl (DEAE)-cellulose adsorption, acetone fractionation, and chromatography on Sephadex G-75 and DEAE-Sephadex A-50. The final purified preparation of dog renal kallikrein had a vasodilator activity of 65.5 KU per A280, and appeared to be homogeneous both in disc electrophoresis and ultracentrifugal analysis. Its molecular weight was estimated to be approximately 3.8 X 10(4) from the sedimentation coefficient obtained by ultracentrifugation, and by Sephadex gel filtration. However, isoelectric fractionation of the purified DRK preparation gave three isoelectric point, 3.9, 4.1, and 4.3. The DRK had an optimum pH of about 8.6 and was stable at pH 8. This enzyme was hardly inhibited by Trasylol, soybean trypsin inhibitor, ovomucoid trypsin inhibitor or potato kallikrein inhibitors. These properties were compared with those of kallikrein from other sources; DRK appeared to be similar to urinary kallikrein.
| 14,121
|
A novel neutral protease(s) from monkey liver.
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A novel neutral protease(s), which is presumably membrane-bound, was found in monkey liver using heat-denatured casein as a substrate and was separated from other major catheptic proteases by successive procedures of gel filtration on Ultrogel AcA 22, solubilization by deoxycholate and gel filtration on Sepharose 6B. The enzyme(s) showed maximal activity at pH 8.0, and was strongly inhibited by DFP and PMSF. Many other reagents tested, including TPCK, TLCK, pCMB, iodoacetic acid, and EDTA, were without marked effect on the activity. Activation of the enzyme(s) by NaCl was not observed.
| 14,127
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A new large form of transcarboxylase with six outer subunits and twelve biotinyl carboxyl carrier subunits.
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A new form of transcarboxylase has been isolated which has a molecular weight of 1,200,000, an s20,w of 26 S, and contains 12 biotinyl groups. Transcarboxylase as isolated previously has a molecular weight of 790,000, an s20,w of 18 S, and contains six biotinyl groups. The larger species of enzyme consists of a central hexameric subunit with six dimeric outer subunits attached to it by biotinyl carboxyl carrier proteins, three each at the opposite faces of the central subunits. This larger species is stable at pH 5.5, but dissociates to the 18 S species at pH values near neutrality with loss of a set of three of the outer subunits with two of the biotinyl carboxyl carrier proteins still attached to each of these subunits. The dissociation to the 18 S form occurs by several rapidly reversible steps and under certain conditions of centrifugation multiple peaks are observed as a consequence of the occurrence of different forms of enzyme with variable numbers of the outer subunits attached to the 18 S enzyme. The s20,w value of the so-called 26 S enzyme varies with conditions. Isolated 18 S enzyme has been combined with isolated outer subunits to form active 26 S enzyme. The newly enzyme is a normal form but has not been isolated previously because of its dissociation to the 18 S form at neutral pH. A procedure is described for the isolation of the 26 S form in a highly purified state. The molecular weight of the enzyme has been determined by high speed meniscus depletion. In addition, a procedure is described for dissociation of the 26 S form of the enzyme and isolation of the resulting outer subunits with the biotinyl subunits still attached to it. Evidence is presented that all six outer subunits participate in the enzymatic reaction which includes the demonstration that; (a) all 12 biotins of the 26 S form of the enzyme can be carboxylated with [3-14C]methylmalonyl coenzyme A; (b) there is an increase in enzymatic activity when the outer subunits are combined with the normal 18 S enzyme with formation of the 26 S enzyme; and (c) a 26 S form of the enzyme is active which is prepared by combination of inactive 18 S trypsin-treated transcarboxylase with the outer subunits. The trypsin-treated 18 S enzyme is inactive because trypsin removes the biotin as biotinyl peptides and the 26 S enzyme is active because of the second set of active outer subunits.
| 14,153
|
Surface localization of 5'-nucleotidase on the mouse lymphocyte.
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The optimal conditions for the cytochemical localization of 5'-nucleotidase (AMPase) in the mouse lymphocyte have been established. Quantitative monitoring of the effects of fixation and the components of the cytochemical medium showed that the cytochemistry can be performed under conditions that do not lead to loss of AMPase activity, and also under conditions where penetration of the substrate into the cell has occurred. The cytochemical reaction product was seen only on the surface of a proportion of splenic lymphocytes, regardless of the fixative used. Biochemical data confirmed that AMPase is an ectoenzyme and is the only protein in splenic lymphocytes capable of catalysing the hydrolysis of AMP. The activity of 5'-nucleotidase was studied also by harvesting cells either from thymus or spleen of A/ST or Cd-1 mouse strains. The enzymatic activity in splenic lymphocytes was more than six time higher than the activity of intact thymus cells. Cytochemically it was evident that within splenic lymphocytes there was a distinct population of lymphocytes with readily demonstrable AMPase activity, and another with no cytochemically demonstrable AMPase activity. It was concluded that murine lymphocytes vary in their activity of AMPase, and that the enzyme is exclusively confined to the cell surface.
| 14,210
|
Delayed initiation of SS1 pulses in the sea anemone Calliactis parasitica: evidence for a fourth conducting system.
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1. Single electrical shocks to the column sometimes elicit a series of 1-6 pulses in the SS1 (ectodermal slow system) but the first pulse does not appear until 5-28 s after stimulation. These pulses occur in addition to the early SS1 pulse which follows every shock and which has a conduction delay of less than 1 s. 2. The threshold of the delayed SS1 response is different from the thresholds of the three known conducting systems (through-conducting nerve net, SS1, and SS2). 3. In the case of stimulation of the column, the delayed SS1 pulses do not arise at the point of stimulation but probably originate in the tentacles or upper column. The pulse origin can shift during a single burst. 4. The pathway from the point of stimulation to the site of origin of delayed SS1 pulses is endodermal. We propose that this pathway represents a fourth conducting system (Delayed Initiation System--DIS). The DIS must connect, across the mesogloea, with the ectodermal SS1. The long pulse delay and repetitive firing may derive from pacemaker activity in the DIS. The DIS pacemakers closely resemble the pacemakers connected to the through-conducting nerve net. The DIS may be neuronal. 5. Delayed SS1 pulse bursts from unattached anemones showed an earlier onset, and more pulses/burst, than those from attached anemones. 6. Delayed SS1 pulses can also be evoked by electrical, and in some cases mechanical, stimulation of the pedal disc, tentacles, and pharynx, but there are regional differences in the number of pulses evoked, in their delay, and in their site of origin.
| 14,219
|
Correlation of structural transitions in coliphage R17 with its loss of infectivity.
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A circular dichroism comparative study of isolated and in situ phage R17 RNA reveals in both cases the same degree of base pairing. However, thermal circular dichroism melting profiles exhibit the presence of free energy of interaction between RNA and capsid protein. It is apparent that the capsid stabilizes the RNA structure with and without the addition of Mg2+. A close RNA capsid association is also derived from pH titration circular dichroism studies. The pH melting of the RNA in situ starts to occur about 0-5 pH unit higher with and without the addition of Mg2+ than the acid denaturation of isolated RNA. A direct correlation between bathochromic CD peak shift to the main position band and loss of survivors is noted for the thermal melting as well as pH titration experiments. It is suggested that the heat and pH induced conformational alterations of R17 RNA in situ coinciding with loss of infectivity occur after an in situ alteration of nucleic acid-capsid protein interaction.
| 14,222
|
The use of tris-HCl buffer for inoculation of tomato protoplasts with tobacco mosaic virus.
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When tris-HCL was used as the buffer for inoculation of tomato protoplasts with tobacco mosaic virus, a greater proportion became infected than when phosphate was used. Using 0-05 M-tris-HCl buffer, pH 8-0, in the presence of poly-L-ornithine or poly-D-lysine, 50 to 80 % infection was obtained.
| 14,223
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Traditional versus individualized nursing instruction: comparison of State Board Examination scores as a result of these two methods of nursing instruction.
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There is no evidence as a result of this study to preclude that the LEGS Program is not worthwhile. Achievement of State Board Examination Scores have not suffered as a result of this method of instruction, at least in the three schools studied. Statistically, there is no significant difference in mean achievement of State Board Examination Scores as a result of the two methods of nursing instruction. Efforts should be made to improve upon the further investigate this new method of nursing instruction.
| 14,227
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The effects of feeding on arterial blood gases and lung mechanics in newborn infants recovering from respiratory disease.
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Fifteen infants recovering from neonatal respiratory disease had arterial blood gases and lung mechanics measured 5 minutes before bolus feeds and at 5, 10, 20, and 30 minutes after feeding to determine physiologic effects of feeding. PaO2 fell significantly from prefeeding values at 5, 10, and 20 minutes after feeds. Mean prefeeding pH and base excess values were significantly different from mean postfeeding values at 5, 10, 20, and 30 minutes, respectively. PaCO2 remained unchanged before and after feeding. Heart rate and systolic and diastolic blood pressure did not change throughout the study. Dynamic lung compliance, respiratory, rate, and tidal volume did not change significantly but there was a trend toward increase in tidal volume. Mean minute volume rose with time as a consequence of the increased tidal volume. Work of breathing remained unchanged at 10 and 20 minutes postfeed and increased slightly at 30 minutes; this was due to a small increase in both elastic and viscous work components at this time.
| 14,240
|
[Perspectives of use of genetic methods of control of bloodsucking Diptera - vectors of the diseases of man].
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This paper presents genetic methods of control of bloodsucking Diptera, mosquitoes. The perspective of the use of various control methods, first of all those tested under field conditions in application for bloodsuckers which are of medical importance throughout the USSR, is regarded. The opinion is suggested that the method of X-ray sterilization of pupae taken from nature and the translocation and chemical sterilization methods can be successfully used for the control of An. m. sacharovi, malaria vectors resistant to DDT. The male sterilization method and the use of males cytoplasmatically incompatible with translocations are suggested for the control of synanthropic populations of C. pipiens.
| 14,323
|
High-dose treatment with neuroleptics in the acute phase of mental disease.
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More than 300 patients have been observed during treatment with either flupenthixol, haloperidol, fluphenazine enanthate or perphenazine enanthate in high doses, whilst suffering from severe mental disease, usually of psychotic nature. Used correctly, high-dose treatment gives a rapid control of psychotic symptoms, an earlier discharge from the ward, and (when using long-acting neuroleptics) pharmacological control even during a follow up period. This means a social availability gain of 30-50%. We have not seen any severe somatic effects except those of parkinsonian type which can be treated successfully by the well trained psychiatrist and a skilled staff.
| 14,332
|
Analgesic, heart rate, and temperature effects of delta8-THC during acute and chronic administration to conscious rats.
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Acute and chronic effects of delta8-THC on tail-flick, heart rate, and rectal temperature responses in conscious, unrestrained male rats were studied. In the acute experiment unidirectional dose-dependent analgesic, hypothermic, and negative chronotropic cardiac effects were observed within the dose range employed. Of the three variables, heart-rate decreases were most sensitive to the effects of THC, reaching significance at 2 mg/kg. Rapid development of tolerance occurred for all three measures, with complete tolerance developing within 13 days only to the heart-rate decreases. The results discussed in the context of previous data.
| 14,347
|
The role of brief hypocapnia in the ventilatory response to CO2 with hypoxia.
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In conscious cats the ventilatory response curve to physiological range of CO2 is displaced upward by hypoxia (about 45 torr), but it rises, either parallel with, or convergent on, the normoxic curve. Thus, a positive interaction of hypoxia and hypercapnic stimuli is not observed under these circumstances. However, if during the hypoxic exposure, hypocapnia is allowed to develop, the subsequently determined CO2 ventilatory response curve will shift to the left, rise steeply, particularly in the early phase, and demonstrate a positive hypoxic hypercapnic interaction. A demonstrable interactive effect was dependent on a conditioning period of hypocapnia, and this was shown to be associated with an elevated level of lactic acid to a greater degree in cerebral venous blood than in CSF or arterial blood. The interpretation is discussed without reaching a firm conclusion of mechanism, but the results emphasize how a minor change of experimental protocol affects a basic phenomenon in the chemical control of breathing.
| 14,364
|
The CSF HCO3 increase in hypercapnia relationshp to HCO3, glutamate, glutamine and NH3 in brain.
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To study the role of carbonic anhydrase in the CSF [HCO3] increase in respiratory acidosis and its effect on brain ammonia, anesthetized rats were subjected to hypercapnia (7% CO2) for 2 hours. The animals received periodic intraventricular injections of either 'mock' CSF or 'mock' CSF and acetazolamide for 45 minutes prior and during hypercapnia when: (a) plasma [HCO3-] was allowed to increase normally and (2) plasma [HCO3] increase was prevented by i.v. HC1 infusion, CSF [HCO3] increased 8.5 mM/L after 2 hours of hypercapnia (delta PCO2 40) in the rats with intraventricular 'mock' CSF injections, and only 6 mM/L in the animals with acetazolamide injections. CSF [HCO3-] increased 7 mM/L during hypercapnia and HCl infusion with intraventricular 'mock' CSF injections, but only 2 mM/L with acetazolamide injections. Changes in total brain CO2 (increase) and brain glutamic acid (decrease) in hypercapnia were not affected by intraventricular acetazolamide and i.v. HCl. The increase of brain NH4+ and glutamine in hypercapnia was reduced in these conditions. It is concluded that there are at least two sources for the CSF [HCO3-] increase in hypercapnia; one formed in the CNS and dependent on carbonic anhydrase, and the other derived from plasma [HCO3-] increase.
| 14,366
|
Oral complications in anorexia nervosa.
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Anorexia nervosa (AN), a psychosomatic disease mainly affecting young women, is characterized by conscious starvation, periods of excessive carbohydrate intake and often deliberate vomiting. Medical history, dental examination, and saliva tests of 39 patients aged 14 to 42 years, having suffered from AN for periods of 1 to 20 years, showed dental caries, due to excessive carbohydrate consumption, in all subjects, often in a rampant form. In patients with a history of intense vomiting (27 cases) severe lingual-occlusal erosion (perimylolysis) was nearly always present. Buccal erosion, mainly due to high consumption of acid fruits and drinks to relieve thirst caused by dehydration, was more frequent in vomiting than in non-vomiting patients. Subnormal values of saliva properties, owing to dehydration or xerostomia-inducing medication, were present in the majority of cases; the lowest values occurred in those vomiting. The association AN - vomiting - perimylolysis is discussed, as well as prophylactic and therapeutic measures. A medical, psychiatric, and dental survey of AN is presented.
| 14,394
|
Massive skeletal trauma in renal transplant patients.
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A review of 251 renal transplants done at the Vanderbilt University Medical Center since October 1962 revealed three patients who had suffered subsequent skeletal injuries sufficient to cause hospitalization. In a 37-year-old woman, a closed fracture of the pelvis healed satisfactorily in the usual period of time. In a 30-year-old man, closed fractures healed well, but there was prolonged delay in the healing of massive open wounds resulting from crushing injuries of the lower extremities. He required prolonged hospitalization, but satisfactory result was achieved after early amputation and close cooperation between orthopedic and renal teams. No significant alterations in the function of either patient's transplanted kidney occurred. It is postulated that severe trauma in transplantation patients may become more common in the future, and certain guidelines for its management are set forth. With close cooperation between the orthopedic surgical and medical renal teams, a successful outcome can be expected.
| 14,401
|
[Gamma-glutamyltranspeptidase in chronic polyarthritis. II. Influence of drugs].
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Thirty outpatients with active RA were treated with Sudoxicam, a nonsteroidal antirheumatic drug, for periods of 6-10 months. Gamma-GT, alkaline phosphatase and transaminase were estimated at 2 week intervals. During treatment, the frequently elevated values showed a significant tendency towards normality (time trend analysis). During a second drug trial with Piroxicam in 32 RA outpatients over a period of 18 months, the mean value of gamma-GT and alkaline phosphatase did not decrease significantly. With regards to liver function tests, there was no significant difference between 19 patients receiving and 13 patients not receiving simultaneous gold therapy. During gold treatment periods of 26 patients with a total dose of 3.8 g Fosfocrisolo (0.8 g Au) the mean value of gamma-GT decreased from 26 to IU/l. Cyclophosphamide treatment of 13 patients, with daily doses of 50-150 mg to a total dose auf 48 g, had no significant influence on gamma-GT and alkaline phosphatase. Our results indicate that the very frequent elevations of gamma-GT and of other liver data in RA are caused by the rheumatoid process itself and not induced by drugs.
| 14,456
|
Infantile periarteritis nodosa or mucocutaneous lymph node syndrome. A report on four cases and diagnostic considerations.
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Coronary artery aneurysm in childhood is a rare disease and has in most cases been ascribed to infantile periarteritis nodosa (IPN). In recent years a mucocutaneous lymph node syndrom (MLNS) has been found almost exclusively in Japan first described by Kawasaki 1967; this disease frequently involves the coronary arteries and myocardium. Four cases with coronary aneurysms are presented from Sweden and seem to be first described from Scandinavia. Three of these patients died a sudden death with cardiac arrest. Since MLNS and IPN have identical clinical and pathological features, we suggest that MLNS and IPN constitute a pathologic entity and that to separate them on a clinical or histological basis is nonsensical. The risk of coronary aneurysm and possible sudden death must be considered in patients with uncharacteristic symptoms including prolonged fever, conjunctivitis, exanthema, lesions in the oral mucosa, elevated sedimintation rate, and leukocytosis.
| 14,473
|
Salivary Secretion in wild Glossina pallidipes Austen. (Diptera, Glossinidae).
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The salivation behaviour of wild G. pallidipes obtained from Lambwe Valley and Kbwezi was studied. Salivation was measured by counting the number of salivary drops secreted per minute and measuring the sizes of the stained saliva after drawing them with a camera lucida. The results confirmed observations obtained from laboratory bred flies. The quantity of saliva secreted by tsetse flies was significantly increased as the flies became hungrier. The proportion of flies salivating also increased with intensity of hunger. Female G. pallidipes secreted significantly more saliva than the males. There was no significant difference between the quantities of saliva secreted by infected and free tsetse flies; thus there is no evidence to support the suggestion that the presence of trypanosomes in the tsetse fly stimulated it to salivate copiously. Flies having trypanosome infection in their salivary glands discharge large numbers of mature parasites in their saliva. Flies with trypanosomes in their proboscis discharged relatively few mature and immature parasites in their saliva.
| 14,492
|
The essential action of propranolol in hypertension.
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The unique action of propranolol and other beta blockers in lowering raised arterial pressure is discussed. Although the onset of the antihypertensive effect is not immediate, many trials have confirmed the efficacy of these drugs. Animal experiments have thrown little light on the mechanism of action of beta blockers in hypertension: this may be because in animals, especially the rat, peripheral beta adrenoceptor vasodilatation is relatively more important than in man. Five principal theories have been advanced to explain the antihypertensive effect. None of these, the renin, central nervous system, cardiac, baroceptor or metabolite theory, is totally satisfactory. A new theory is proposed suggesting that the essential action is to diminish sympathetic nerve output by damping sensory input to the central nervous system from a heart whose capacity to respond to exercise and stress is blunted by beta adrenoceptor blockade.
| 14,498
|
Renin and aldosterone secretion in pheochromocytoma. Effect of chronic alpha-adrenergic receptor blockade.
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Patients suffering from pheochromocytoma characterized by an exclusive or almost exclusive excess of norepinephrine showed no (one patient) or only a moderate increase (two patients) in renin and aldosterone secretion. In those three patients with concomitant distinct hypersecretion of epinephrine, renin release (and aldosterone secretion except in one patient) was markedly enhanced. Similar results were obtained in a patient with excess norepinephrine and dopamine secretion. Renin release was markedly reduced in all patients during preoperative long-term alpha-adrenergic receptor blockade. With the exception of one patient, increased renin and aldosterone secretion was abolished. The results indicate that augmentation in renin release depends on the ratio of the different catecholamines secreted by the pheochromocytoma and their different effe-tiveness in stimulating beta-adrenergic receptors. Even in the presence of excess catecholamine secretion, there is evidence that renin secretion is predominantly mediated by beta receptors rather than by renal vascular alpha-adrenergic receptors. Normalization of catecholamine-induced enhanced renin release in patients with pheochromocytoma during chronic alpha-adrenergic receptor blockade supports the assumption that (alpha-) adrenergic blocking agents inhibit renin secretion distal to their blockade of specific adrenergic receptors. However, contrary to beta-adrenergic blockade, circadian rhythm of renin release seems to remain intact during alpha-adrenergic blockade.
| 14,500
|
Different antihypertensive effect of beta-blocking drugs in low and normal-high renin hypertension.
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The treatment response to beta-adrenoceptor blocking drugs was compared in two groups of patients with primary (essential) hypertension and different renin levels. Each group consisted of 25 patients and was equally distributed regarding age, severity and stage of hypertension. In the first group (group 1), the mean upright plasma renin activity was 0.8 ng ml-1h-1 (range 0.3 to 1.5) and the patients were considered to have low renin hypertension. In the other group (group 2) the patients had a mean plasma renin activity of 2.1 ng ml-1h-1 (range 1.1 to 5.1) and were considered to have normal to high renin hypertension. In both groups the patients were initially treated with beta-blocking drugs; in group 1 with a beta-blocker corresponding to an average dose of 311 mg propranolol a day for at least eight weeks and in group 2 with propranolol 320 mg a day in a fixed dose for eight weeks. The hypotensive response differed significantly between the two groups (p less than 0.001). In group 1 the pretreatment blood pressure was 197/117 mm Hg supine and 198/120 mm Hg standing. During treatment blood pressure decreased only 5/3 mm Hg supine and 9/5 mm Hg standing. The pretreatment blood pressure in group 2 was 187/114 mm Hg supine and 186/117 mm Hg standing. Beta-blocking therapy reduced blood pressure 36/23 and 34/18 mm Hg, respectively (both p less than 0.001). Pulse rates fell significantly in the two groups, both in the lying and standing positions. In 17 patients with low renin hypertension (group 1), a volume-depleting drug was added (spironolactone, 14 patients; thiazides, 3 patients) and this achieved a marked fall in blood pressure levels of 38/16 mm Hg supine and 37/19 mm Hg standing (both p less than 0.001). These results suggest the following: (1) Most patients with normal to high plasma renin activity respond well to moderate doses of propranolol. (2) Propranolol given in the same doses is almost without antihypertensive effect in patients with low renin hypertension. (3) A volume factor may be operating in patients with low renin hypertension since a hypotensive effect is demonstrated after the addition of volume-depleting drugs. (4) Determination of plasma renin activity with adequate methods can predict the treatment response to hypotensive agents.
| 14,504
|
A smooth muscle active factor isolated from renal cortex of the rabbit.
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Homogenates of rabbit renal cortex contained a water-soluble material with striking activity on smooth muscle derived from the rabbit aorta, rat stomach, and guinea pig ileum--but not rat colon or chick rectum. Evidence derived from the spectrum of its pharmacologic activity, the influence of specific competitive antagonists on the smooth muscle responses to the factor, the influence of proteolytic enzymes and its elution position during molecular sieve filtration on Sephadex G-10 made it unlikely that the factor was a prostaglandin, renin, angiotensin, a catecholamine, serotonin, bradykinin, a nucleotide, a small organic product of local metabolism, or a small ion. The agent was not found in extracts of renal medulla, spleen, myocardium, or lung. The smooth muscle response to the factor was blocked by phenoxybenzamine. The renal cortical factor in subthreshold concentration also potentiated responses of the rabbit aorta to angiotensin and norepinephrine. The factor's intrinsic activity and ability to potentiate the smooth muscle actions of endogenous vasoconstrictors make it a candidate as a mediator of smooth muscle responses in a number of states.
| 14,508
|
[Effect of run-training and run-stress on glucose assimilation and insulin release in rats of different age (author's transl)].
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82 male rats of different age have been investigated after a definitive run-training, after a run-training with subsequent run-stress and after a run-stress without run-training. An intravenous glucose tolerance test has been done measuring glucose and insulin serum levels before and after i.v. glucose application. Data obtained in this study demonstrate that: 1. adult rats have a better glucose assimilation and higher insulin serum levels after i.v. glucose than older ones. 2. run-stress leads to a deterioration of glucose assimilation and diminution of insulin release in rats of any age. 3. run-training improves glucose tolerance and saves insulin at the same time. 4. in old rats, which have never done any training before, run-training improves glucose assimilation, too. 5. run-stress after run-training has a different effect on adult and old rats: In adult rats there is nearly no effect on glucose assimilation and insulin release in comparison to control animals, while old rats show a significant deterioration of glucose assimilation in comparison to control rats of the same age. Obviously the effect of run-training is less distinct in old rats despite of similar running work.
| 14,518
|
[Geriatric change of thyroid function and thyroid diseases (author's transl)].
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The geriatric changes of thyroid function in healthy individuals are relatively low; therefore it is not necessary to take it into consideration for routine diagnostic work. Thyroid diseases show an increase with age and also a change of the clinical picture. Therefore, and because of being superimposed by symptoms of simulatneous second disease, it is necessary to start with the specific diagnostic earlier than in younger patients.
| 14,521
|
[Paranoid syndromes in the involution (author's transl)].
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Conditions of outbreak and chronification of paranoid syndromes, including the existence of an "axial syndrome" and behaviour theories are hypothetically summarized. The individual characteristics of patients with the first paranoid symptoms during involution appear to depend mainly on three factors: the theme of the delusion seems to be connected with the age at the onset, in more than half of the male patients exogenous psychoorganic symptoms were observed, and in females however predominantly manic-depressive syndroms could be found.
| 14,525
|
[Patients and their diseases in a geriatric hospital (author's transl)].
|
Report on patients and their problems of a hospital of chronic diseases. Geriatric departments, part of clinics of acute diseases should treat not only patients without real chance for rehabilitation or discharge. Most of the diseases of elder persons are such of the arterial system, especially of the cerebral and coronary vessels. Although patients suffered of partial or complete dementia and had to stay long in the hospital visitors came more often. Generally must be postulated, that all institutions for medical care or nursing of old people should cooperate better than today.
| 14,542
|
[Indications for orthopedic procedures in old people (author's transl)].
|
Advancements in general medicine and anesthesiology have enabled surgical procedures in old people with diminished risks. With reference to special problems the absolute indication for orthopedic procedures particularly for the old can be demonstrated.
| 14,544
|
[Chromosomal investigations in two age groups of human females].
|
Chromosomal analysis was performed in cultured lymphocytes from 32 old (ages 76-85, abbr. A) and 31 young (ages 15-20, abbr. J) patients, who were representative for a great part of the "normal" female population of the same age. In regard to culture time (48 and 72 hours) each age group was divided into two halves; 1500 cells were examined in each of the resulting four sub-units (A 48, A 72; J 48, J 72). Whereas the frequency of "spontaneous" gaps showed no dependency from age or culture time, single chromatid breaks were predominantly observed in A 72 and dicentric chromosomes in A 48. The mean breakage rates in the two age groups (A 48 2,4% A 72 3,0%; J 48 1,3%, J 72 1,7%) differed significantly for both culture times (Chi2 -test: A 48/J 48 p less than 0,01; A 72/J 72 p approximately 0,01). After karyotyping and additional application of a trypsin-Giemsa-branding-technique large, acentric "fragments," which could only be detected in metaphases of old females (A 48 1,0%, A 72 0,5%), proved to be X-chromosomes with premature centromere division and a high tendency to non-disjunction. These results are in agreement with those published by Fitzgerald (8).
| 14,549
|
[Place of neuroleptics in geriatric anesthesia].
|
The elderly show changes in various parenchymas linked to the process of ageing. Pathological abnormalities may be added to this picture leading to physiopathology peculiar to the aged. In relation to special problems raised by this background, the advantages and disadvantages of N.L.A. are discussed. The authors refer to an experiment in the Department of Anesthetics and Intensive Care in Créteil.
| 14,566
|
[Place of neuroleptics in neurosurgical anesthesia-resuscitation].
|
The interest of neuroleptics in neurosurgery should be examined in the light of physiopathological and pharmacological data concerning cerebral circulatory autoregulation and intracranial pressure. The fairly favourable conclusions permit one to consider their wide use justified, especially, by the feeble hypnogenic effects, without any marked disturbance of the E.E.G., associated with an anticatecholaminergic and stabilizing effect on the autonomic nervous system. They therefore occupy a place of choice, in particular during induction of anesthesia in high risk patients, during operations requiring neurological or continuous E.E.G. investigations, in surgery of intracranial aneurysm and, finally, to obtain sedation and post-operative autonomic control.
| 14,570
|
[Very-high-dose droperidol and brain stem injuries].
|
Treating four comatose children with severe injuries of the brain stem, suffering from severe autonomic disorders without any indications for neurosurgery, we were led to increase gradually the doses of neuroleptics used as basis of treatment, the main one being Droperidol. The increase in dosage, often reaching very high doses, was rendered necessary owing to a phenomenon comparable to that of addiction, a steadily increasing dose was necessary each day to obtain the same beneficial effects of autonomic stabilization. A complete cure was obtained on each occasion, at the end of a coma varying between 20 days and two and a half months. The extreme case was the last case in which we were led to give in a single day, 7 grams of the drug to a 12 years old child, who completely recovered his motor and intellectual functions after a coma lasting thirty five days. Comparison of the four cases led us to suppose that the result is all the better when treatment with neuroleptics is started soon after the accident, in low dosage but regularly increased without fixing any other ceiling than the effect obtained, the toxicity of Droperidol seemed to us very low, even in very high dosage, provided the conditions of gradualness are respected. Although it is classical to say that the prognosis of trauma of the brain stem is more favourable in children than in adults, we are certain that such treatment contributed considerably to avoid a fatal issue or chronic invalidism.
| 14,571
|
Comparison of thiopentone versus althesin for caesarean section.
|
Thiopentone and Althesin were compared in 50 patients undergoing general anaesthesia for Caesarean section. The patients were divided into group A (24 mothers) were thiopentone (3.5 mg/kg) was used for induction and group B (26 mothers) where Althesin (80 mu1/kg) was employed. Blood samples for estimating the maternal and umbilical venous and arterial blood pH, pCO2, BD and pO2 were taken at the time of delivery. The clinical condition of the newborn were estimated by the Apgar score. Postoperatively the mothers were interviewed about thei subjective opinion concerning the anaesthesia. The interview showed equal acceptance of both induction agents. The umbilical venous and arterial pH, pCO2 and BD were well within the normal physiological range and there was no significant intergroup difference. The only significant differences were the lower umbilical venous and arterial pO2 values in the Althesin group. The clinical condition of the newborn (Apgar score) showed no significant difference between the two groups.
| 14,588
|
An experimental and clinical pharmacological study of the influence of triamterene on the diuretic and saluretic properties of furosemide xantinol.
|
The diuretic and saluretic effect of furosemide xantinol administered alone and mixed with different amounts of 2,4,7-triamino-6-phenylpteridine (triamterene) have been investigated in rat and man. The presence of triamterene resulted in a dose dependent inhibition of furosemide xantinol induced diuresis in both species. It was necessary to reduce the amount of triamterene present in the mixture to approximately half that of the one theoretically required according to considerations of the recommended therapeutic doses of the two diuretics before significant inhibition was avoided. Nevertheless, this reduced amount of triamterene proved sufficient to inhibit the distal tubular exchange of Na+ for K+ and H+ and a mixture formulated to give the ratio of 40 mg furosemide xantinol (as base) plus 25 mg triamterene (Salidur) was shown to produce a smooth but efficient loss of water and Na+ in the absence of detectable kaliuresis or reduction in urinary pH, thereby reducing the usual risk of inducing hypokalaemic alkalosis.
| 14,648
|
Biosynthesis of spin-labeled peptidoglycan: spin-spin interactions.
|
Membrane preparations from Gaffkya homari catalyzed the in vitro biosynthesis of soluble uncross-linked spin-labeled peptidoglycan, a uniformly labeled polynitroxide, from the spin-labeled nucleotide UDP-MurNAc-Ala-DGlu-Lys(Nepsilon-2,2,5,5-tetramethyl-1-pyrrolin-1-oxyl-3-carbonyl)-DAla-DAla (I) and UDP-GlcNAc. Soluble spin-labeled peptidoglycan was separated from membrane fragments and its spin-labeled precursor by centrifugation and gel filtration. The molecular weight distribution of the polymer was examined by agarose gel filtration. Spin-labeled [14C]peptidoglycan was polydisperse with a peak of radioactivity corresponding to a molecular weight of 5.0 X 10(5). The electron spin resonance spectrum of spin-labeled peptidoglycan was extensively broadened by spin-spin exchange interactions. These interactions were modified by changes in temperature, reduction by ascorbate, hydrolysis by lysozyme, and complexation with the antibiotic, vancomycin. Spin-spin exchange was reduced or eliminated in spin-labeled peptidoglycan by the random reduction of free radicals by ascorbate. A rotational correlation time of 0.37 ns was calculated for the probe in partially reduced spin-labeled peptidoglycan. This compares to a correlation time of 0.13 ns for the substrate (I). Raising the temperature increases spin-spin exchange line broadening. No transition points were observed for spin-labeled peptidoglycan as measured by this method. Degradati on of spin-labeled peptidoglycan by lysozyme eliminated the observed spin-spin exchange and yielded products with a mobility similar to I. Complexation of spin-labeled peptidoglycan with vancomycin resulted in both pronounced free-radical immobilization and a decrease in spin-spin exchange. The exchange effects are consistent with distance measurements in molecular models for peptidoglycan.
| 14,677
|
Selective chemical modification of Escherichia coli elongation factor G: butanedione modification of an arginine essential for nucleotide binding.
|
Treatment of Escherichia coli elongation factor G with the arginine reagent, 2,3-butanedione, leads to the inactivation of the enzyme when performed in sodium borate buffers. The inhibition follows pseudo-first-order kinetics until 95% of the activity has been lost and further incubation results in complete inhibiton. Removal of the borate by exhaustive dialysis results in the restoration of approximately 85% of the original activity. The pH dependence of the reaction suggests that the ionization of a group in the protein with a pKa of approximately 8.8 facilitates the reaction with butanedione. A reaction order of 1.01 +/- 0.13 was calculated for the inhibition reaction, indicating that the incorporation of one butanedione per elongation factor G results in the inactivation of the enzyme. The kinetics of inhibition in the presence of GTP indicate that the elongation factor G-GTP complex is refractory to butanedione inhibiton. Elongation factor G which has been partially inactivated by butanedione has the same apparent Km for GTP as does the native enzyme. These results indicate that elongation factor G contains only one essential arginine residue which is reactive with butanedione and that this residue is located at its nucleotide binding site.
| 14,679
|
Separation of DNA-dependent DNA polymerase activities in Micrococcus radiodurans.
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DNA polymerase activities in Micrococcus radiodurans were separated into two fractions after purification more than 2000 fold. They differ in pH optimum and residual activities in the absence of a full deoxyribonucleoside triphosphates complement. NAD partly inhibited one of the activities. Both activities were eluted as a single peak on gel filtration and sedimented at the same rate on glycerol gradient centrifugation. Molecular weight 140000 was calculated from Stokes radius and sedimentation constant. Deoxyribonuclease activity was detected on one of the polymerase activities which preferentially degraded double-stranded DNA. Priming activity of nicked DNA was reduced by gamma-irradiation. These results have been related to the possible rolls in repair synthesis in vivo or DNA synthesis in permeable cells of M. radiodurans.
| 14,686
|
Iodination-deiodination. A radiochemical method for detection of structure and changes in structure in RNA.
|
Bound iodine is released from radioiodinated nucleotides in polymers exposed to sodium bisulfite. The rate of bisulfite-catalyzed deiodination of pyrimidines can be controlled both by change of temperature of pH and is also dependent on the molecular association of the nucleotide. The rate of release of iodine from iodocytidine in polycytidylate is greater than the rate of elimination from RNA. Experiments testing the influence of base-pairing of the iodopyrimidines in synthetic polynucleotides showed that pairing of the substituted nucleotide protected the iodine bond. The rates of bisulfite-catalyzed deiodination of several radioiodinated RNAs were measured. The action of bisulfite on all single stranded RNAs tested was multiphasic consisting of a rapid early deiodination reaction supplanted by a slower phase which was followed by reacceleration of release. The release of iodine from double stranded RNA and DNA-RNA duplexes was retarded in comparison with the release from ribosomal and messenger RNA fractions. The deiodination profiles of single and double stranded RNA suggested that the intermediate stage iodine release is governed by melting of paired zones of low stability. Late release may result from destablization of the molecule through the addition of bisulfite to the pyrimidine ring or deamination. The effect of several substances expected to complex with polynucleotides was tested. Acridine orange and ethidium bromide increased loss of iodine from ribosomal RNA but slightly decreased elimination from double stranded viral RNA. A basic protein fraction isolated from ribosomal particles accelerated the deiodination of ribosomal RNA. While the destabilization caused by this protein fraction was greater than that caused by an equal amount of albumin, as tested the effect was non-specific. The results show that a change in sensitivity to chemical deiodination may folow the interaction of small amounts of protein with polynucleotides.
| 14,687
|
Sulphur metabolism in Paracoccus denitrificans. Purification, properties and regulation of serine transacetylase, O-acetylserine sulphydrylase and beta-cystathionase.
|
1. Serine transacetylase, O-acetylserine sulphydrylase and beta-cystathionase were purified from Paracoccus denitrificans strain 8944. 2. Serin transacetylase was purified 150-fold. The enzyme has a pH optimum between 7.5 and 8.0, is specific for L-serine and is inhibited by sulphydryl-group reagents. The apparent Km values for serine and acetyl-CoA are 4.0 - 10(-4) and 1.0 - 10(-4) M, respectively. Serine transacetylase is strongly inhibited by cysteine. 3. O-Acetylserine sulphydrylase was purified 450-fold. The enzymes has a sharp pH optimum at pH 7.5. In addition to catalysing the synthesis of cysteine, O-acetylserine sulphydrylase catalyses the synthesis of selenocysteine from O-acetylserine and selenide. The Km values for sulphide and O-acetylserine are 2.7 - 10(-3) and 1.25 - 10(-3) M, respectively. The enzyme was stimulated by pyridoxal phosphate and was inhibited by cystathionine, homocysteine and methionine. 4. beta-Cystathionase was purified approx. 50-fold. beta-Cystathionase has a pH optimum between pH 9.0 and 9.5, is sensitive to sulphydryl-group reagents, required pyridoxal phosphate for maximum activity and has an apparent Km for cystathionine of 4.2 - 10 (-3) M. beta-Cystathionase also catalyses the release of keto acid from lanthionine, djenkolic acid and cystine. Cysteine, O-acetylserine, homocysteine and glutathione strongly inhibit beta-cystathionase activity and homocysteine and methionine represses enzyme activity. 5. O-Acetylserine lyase was identified in crude extracts of Paracoccus denitrificans. The enzyme is specific for O-acetyl-L-serine, requires pyridoxal phosphate and is inhibied by KCN and hydroxylamine. The enzyme has a high Km value for O-acetylserine (50--100 mM).
| 14,692
|
Sulphur metabolism in Paracoccus denitrificans. Purification, properties and regulation of cysteinyl-and methionyl-tRNA synthetase.
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Cysteinyl- and methionyl-tRNA synthetases (EC 6.11.-) were purified 1200- and 1000-fold, respectively, from sonic extracts of Paracoccus denitrificans strain 8944, and kinetics, substrate specificity and regulatory properties were determined using the ATP-PPi exchange reaction. Both enzymes had pH optima of approx. 8 and were inhibited by sulphydryl-group reagents. Cysteinyl-tRNA synthetase catalysed L-selenocysteine- and alpha-aminobutyric acid-dependent ATP-PPi exchange and methionyl-tRNA synthetase catalysed L-homocysteine-, L-selenomethionine- and norleucine-dependent ATP-PPi exchange. Both enzymes were inhibited by O-acetylserine. Cysteinyl-tRNA synthetase activity was stimulated by methionine and methionyl-tRNA synthetase activity was stimulated by sulphide, cysteine, and cysteic acid.
| 14,693
|
The rate of reaction between cytochrome C peroxidase and hydrogen peroxide is not diffusion limited.
|
The apparent biomolecular rate constant for the cytochrome C peroxidase (EC 1.11.1.5)-hydrogen peroxide reaction has been measured as a function of temperature between 5 and 25 degree C at pH 4,5.5, and 7 and as a function of viscosity over a fifteen-fold range. From the independence of the rate constant on the viscosity, it is concluded that the reaction is not diffusion limited.
| 14,694
|
[Isolation and some properties of Ca2+-, Mg2+-dependent deoxyribonuclease from sea urchin (Strongylocentrotus intermedius) embryos].
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Ca2+-Mg2+-dependent deoxyribonuclease (deoxyribonucleate-5'-oligonucleotidehydrolase E. C. 3.1.4.5). Molecular weight of the enzyme is found to be 40 000 daltons isoelectric point--4.4. The enzyme degraded DNA only in the presence of bivalent cations. It hydrolyses preferentially native DNA with pH optimum 7.0-7.2 in the presence of Mg2+ ions. Ca2+ ions shift the pH optimum to 8.0-8.5. Combined addition of Ca2+ and Mg2+ ions results in a sinergic effect and changes the enzyme specificity to the secondary DNA structure. The enzyme hydrolyses both native and denatured DNA by the endonucleolytic type to form oligonucleotides with 5' terminal phosphate the content of tetra-octanucleotides being 80-85%.
| 14,721
|
Isolation and properties of a ferredoxin from leaves of Sambucus racemosa L.
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Ferredoxin was isolated in good yield from leaves of Sambucus racemosa L. by the following procedure: (1) homogenization in buffered acetone-water (1:1v/v); (2) ion-exchange chromatography on several columns of DEAE-cellulose; and (3) purification by gel filtration with Sephadex G-75. The ultraviolet and visible spectrum showed maxima at 277, 331, 423, and 466 nm. The electron paramagnetic resonance spectrum was centered around g = 1.957. The protein sustained an initial photoreduction rate of 86 mumol NADP per milligram chlorophyll per hour. The amino acid composition was found to be Lys 5, His 2, Arg1, Asx11, Thr5, Ser7, Glx17, Pro6, Gly7, Ala6-7, Cys4, Val8, Ile5, Leu7, Tyr3, Phe2, and Trp1. The molecule had a molecular weight of 10 700 and contained two atoms of iron. The amino-terminal residue was alanine. These properties are highly similar to those of other angiosperm ferredoxins. Sambucus ferredoxin was found to be most closely related to that of Leucaena.
| 14,775
|
Evoked release from guinea pig cerebral cortex slices of endogenous 14C-labelled amino acids, labelled via D-[U-14C]glucose.
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Release of endogenous amino acids labelled via D-[U-14C]glucose was compared with that of several exogenous labelled amino acids using slices of guinea pig cerebral cortex. Electrical field stimulation evoked a selective release of endogenous [14C]glutamate, [14C]aspartate, and gamma-amino[14C]butyrate (14C-labelled GABA). The selectivity of release correlated well with 14C incorporation into endogenous amino acids. Calculations of the fraction of the tissue radioactivity released indicated that the selectivity was not an artifact due to differential incorporation. Because glucose in mammalian brain is metabolized almost entirely by the so-called 'large compartment', it is tentatively concluded that the releasable 'transmitter pool' of glutamate, aspartate, and GABA is located in this 'large compartment'.
| 14,778
|
Coprecipitation of active uridine kinase and phosphomonoesterase from rat kidney by Zn2+-ions. III. Enzymes relevant to cancer chemotherapy.
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Partially purified enzyme fraction from rat kidney possessing high uridine kinase and phosphomonoesterase activity was insolubilized by means of zinc precipitation without substantial loss of the activity. While uridine kinase in a soluble and Zn-precipitated form was inhibited by low concentrations (0.5-1.0 mM) of Zn2+-ions, phosphomonoesterase was fully active. In contrast to the soluble fraction, the two enzymes in zinc-precipitated and lyophilized preparations were stable on heating at 100 degrees C. Metal complexed proteins catalyze the dephosphorylation of 5'-UMP, 6-AzaUMP as well as of 2'(3')-UMP or 2,4-dinitrophenyl phosphate indicating thus the presence of several phosphomonoesterases in the complex.
| 14,785
|
Baroreflex sensitivity in patients with Takayasu's aortitis.
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Takayasu's aortitis is an arterial inflammatory disease of arteries of unknown etiology. Fainting is a common symptom and has been attributed to ypersensitivity of the baroreflex. We studied baroreflex sensitivity in 11 patients with Takayasu's aortitis and compared it with that of eight control subjects of comparable age. Baroreflex sensitivity was assessed by determining the slope of a regression line relating the rise of systolic arterial pressure to the prolongation of the R-R interval of the electrocardiogram during a transient rise of arterial pressure induced by an intravenous injection of phenylephrine. The average baroreflex slope of patients with Takayasu's arteritis (4.0 +/- 0.8 msec/mm Hg) was significantly less than that of control subjects (10.7 +/- 0.8 msec/mm Hg, P less than 0.001). Reduced baroreflex sensitivity in patients with Takayasu's aortitis may be due to the hardening of the arteries where baroreceptors lie, or to hypertension and/or cardiac disease which was present in most of the patients included in this study. Patients with Takayasu's aortitis who complained of fainting also showed the reduced baroreflex sensitivity. This indicates that fainting in this disease is not likely to be caused by the hyperreactivity of the baroreceptors as is commonly postulated.
| 14,792
|
Three types of paranoid processes.
|
In classical descriptive psychiatry the term 'paranoid' is often used ambiguously -- referring to a variety of clinical processes which should be more clearly differentiated. Specifically, in this paper, we have differentiated three distinct sets of clinical phenomena all usually lumped together as 'paranoid': 1. Paranoid from a Sense of Guilt, 2. Paranoid from a sense of Low Self-Esteem, and 3. Paranoid from a Sense of Persecution. These three processes are distinct descriptively, dynamically and genetically. Further, this differentiation is most significant pragmatically as the treatment is different for each type.
| 14,813
|
Characterization of the pH 4.0 endonuclease from adenovirus-type-2-infected KB cells.
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The properties of the pH 4.0 endonuclease from adenovirus-type-2-infected KB cells were determined. The enzyme has a molecular weight of approximately 40000. Its pH optimum is at pH 4.0, it is not inhibited by ethylenediaminetetraacetate (EDTA), and it is active at temperatures up to 60 degree C. The enzyme cleaves adenovirus DNA in a stepwise manner. The limit digestion product has a molecular weight of 120000-200000. There is evidence that the cleavage reaction proceeds via an initial single-strand nick. Under the conditions tested the endonuclease did not seem to reveal a high degree of specificity as to the recognition of cleavage sites, or else the sites recognized occurred very frequently.
| 14,826
|
New developments in our knowledge of the chemistry of renin.
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Although the role of renin in hypertension continues to be incompletely defined, recent progress in the chemistry of renin has been considerable. Extensive purifications of hog kidney renin and the renin-like mouse submaxillary gland enzyme have been achieved. Various inhibitory peptides based on tetradecapeptide renin substrate have been useful in renin kinetic studies and in renin affinity chromatography. Classification of renin as an acid protease results from its marked inhibition by pepstatin and from the discovery that free carboxyl at the active site is essential for activity in human and hog kidney and mouse submaxillary gland enzymes. The presence of pseudorenin in all tissues has limited the use of model peptides as renin substrates in plasma and crude tissue extracts, since the proteolytic properties of the two enzymes are nearly identical. The existence of renin in multiple, chromatographically separable forms has been known. More recently inactive forms have been found in plasma, amniotic fluid, and hog and rabbit kidneys. Prolonged storage or treatment with acid, trypsin, or pepsin causes activation; in some instances the conversion is from a higher than normal molecular weight. The implications of these findings with respect to the renin-angiotensin system need much further investigation.
| 14,850
|
Reproduction of the eosinopenia of acute infection by passive transfer of a material obtained from inflammatory exudate.
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Studies of the eosinopenic effect of acute inflammation were conducted in mice previously rendered eosinophilic with trichinosis. Exudate removed from a pneumococcal abscess contained material (eosinopenic factor [EF]) capable of causing eosinopenia of 4- to 24-h duration when injected intraperitoneally into eosinophilic mice. The material passed through a 0.45-micronm filter, but was retained by a dialysis membrane capable of retaining protein molecules of greater than approximately 30,000 molecular weight. EF was soluble in 7% perchloric acid, was not destroyed by pneumococcal proteolytic enzymes in the presence of Trasylol, but was inactivated by heating to 56 degrees C for 30 min. EF was detectable in the exudate after 10 h and had reached its highest concentration after 20 h. When the effect of EF was expressed as a percent suppression of control eosinophil levels, there was a geometric dose response. Eosinopenia could not be ascribed to steroids present in the preparation, and the EF was effective in adrenalectomized animals. Eosinopenia was not induced by transfer of similarly treated heat-killed pneumococci, pneumococcal culture filtrate, or normal serum. The eosinopenia of acute infection may be the direct effect of a substance present at the site of acute inflammation.
| 14,891
|
Purification of several proteolytic enzymes by tosyl- and carbobenzoxy-triethylene-tetramine-sepharoses.
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Tosyl-triethylenetetramine-Sepharose (Tos-T-Sepharose) and carbenzoxytriethylenetetramine-Sepharose (Z-T-Sepharose) were found to be adsorbents utilizable in the purification of several microbial and animal proteases. The former Sepharose derivative adsorbed alpha-chymotrypsin, trypsin, subtilisin, thermolysin and neutral subtilopeptidase at neutral pH range, and acid proteases such as pepsin and Rhizopus niveus protease at pH 3.5-6.5. alpha-Chymotrypsin and trypsin were eluted with 0.1 N acetic acid and Rhizopus protease with 0.5 N acetic acid, thermolysin with 1 M guanidine-HCl or 33% ethyleneglycol, whilst pepsin was recovered by elution with 2 M guanidine-HCl at pH 3.5. The binding of neutral subtilopeptidase and subtilisin to this adsorbent was comparatively weak and both the enzymes were recovered by elution with 0.5 M NaCl at neutral pH. On the other hand, Z-T-Sepharose was found to bind tightly to these proteolytic enzymes except neutral subtilopeptidase. Trypsin and alpha-chymotrypsin were released from the adsorbent column with 1 M p-toluenesulfonate, and subtilisin with 1 M guanidine-HCl or 33% ethyleneglycol at neutral pH region. By these chromatographic procedures, the specific activities of these proteolytic enzymes increased effectively. Comparison of the binding abilities of acetyl-, benzoyl-, tosyl- and carbobenzoxy-T-Sepharoses to these enzymes suggests that hydrophobicity of tosyl and carbobenzoxy groups plays an important role in the enzyme-adsorbent interaction.
| 14,898
|
Subcellular distribution of pyridoxal kinase in ox retina.
|
PL kinase activity has been determined in primary and secondary subcellular fractions of ox retina. Enzymic activity is predominantly located in the soluble fraction (S3). About 65% of the recovered PL kinase activity of crude mitochondria is released from synaptosomal fraction after hypoosmotic treatment. PL kinase activity in supernatant fraction (S3) does not exceed the enzyme activity measured in the homogenate, excluding the presence of a particulate-bound inhibitor to PL kinase in the homogenate. The possible physiological significance of PL kinase cellular compartmentation has been considered.
| 14,904
|
Sterol 24(28) methylene reductase in Saccharomyces cerevisiae.
|
Optimal conditions for the 24(28)methylene reductase were obtained. The enzyme assay provided for unusually high activity; the Km was determined to be 10.8 mum. The enzyme activity was increased in cells grown with ethanol as the substrate.
| 14,922
|
Purification and some properties of an extracellular alpha-amylase from Bacteroides amylophilus.
|
A medium was developed to obtain maximum yields of extracellular amylase from Bacteroides amylophilus 70. Crude enzyme preparation, obtained by ammonium sulfate precipitation of cell-free broth, contained six amylolytic isoenzymes that were detected by isoelectric focusing and polyacrylamide gel electrophoresis. One of these amylases was purified by diethylaminoethyl-Sephadex A-50 ion-exchange chromatography and Sephadex G-200 gel filtration techniques. Some properties of the purified extracellular alpha-amylase were: optimum pH, 6.3; optimum temperature, 43 degrees C: PH stability range, 5.8 to 7.5; isoelectric point, pH 4.6; molecular weight, 92,000 (by sodium dodecyl sulfatedisc gel electrophoresis); and sugars causing inhibition, cyclomaltoheptaose, cyclomaltohexaose, and alpha-d-phenylglucoside. In addition, Ca2+ and Co2+ were strong activators,and Hg2+ was a strong inhibitior; all other cations were slightly stimulatory. Dialysis against 0.01 M ethylenediaminetetraacetic acid caused a 58% loss of activity that was restored to 92% of the original by the addition of 0.04 M Ca2+. The enzyme affected a blue-value-reducing-value curve characteristic of alpha-type amylases. The relative rates of hydrolysis of amylose, soluble starch, amylopectin, and dextrin were 100, 97, 92, and 60%, respectively; Michaelis constants for these substrates were 18.2, 18.7, 18.2, and 16.7 mumol of d-glucosidic bond/liter, respectively. The enzyme degraded maize (corn) starch granules to some extent and had relatively little activity on potato starch granules.
| 14,926
|
Kallikrein inhibitors in rat plasma.
|
The kallikrein inhibitor contents of human and animal plasma were determined with glandular kallikreins [EC 3.4.21.8]. One ml of plasma could inactivate 20-700 kallikrein units (KU). Rat plasma was the most potent and inactivated 230-700 KU. However, no enzyme capable of inactivating kallikrein could be found in this plasma. Two fractions which inhibited hog pancreatic kallikrein, a fraction corresponding to alpha2-macroglobulin and a fraction which was eluted prior to albumin, were separated from rat plasma by Sephadex G-200 gel filtration. The former inhibitor could inhibit hog pancreatic kallikrein action on Nalpha-benzoyl-L-arginine ethyl ester (BAEE) as well as in the dog vasodilator assay. The other inhibitor was partially purified from rat plasma. One mg of the preparation inhibited 67 KU and the hydrolysis of 5.8 micronmoles/min of BAEE by hog pancreatic kallikrein [EC 3.4.21.8]. The inhibitor also inhibited other glandular and plasma kallikreins, trypsin [EC 3.4.21.4], alpha-chymotrypsin [EC 3.4.21.1], etc. The optimal pH of the inhibitor was 7.5-8. The inhibitor was unstable below pH 5, and was destroyed by heating at temperature above 60 degrees. The isoelectric point of the inhibitor was determined by Ampholine focusing to be 4.4, and its molecular weight was estimated to be 73,000 by Sephadex G-100 and G-150 filtrations. Several experimental results suggested that this inhibitor differed from alpha1-antitrypsin.
| 14,935
|
Kinetics of conformational change of troponin-C induced by proton binding or removal in the absence of calcium ions.
|
The kinetics of the conformational change of troponin-C induced by binding or removal of protons was studied by a stopped-flow pH-jump spectrofluorometric method. In the pH-down experiment (to investigate the kinetics of conformational change from the deprotonated state to the protonated state), a single first-order reaction with a rate constant and amplitude of 1.75-2.4 sec-1 and around 10% respectively, was observed. On the other hand, two first-order reactions with rate constants of 0.84-1.6 sec-1 and 0.08-0.4 sec-1 were observed in the pH-up experiment, the total amplitudes of these reactions being around 10-20%. The pH dependences of the rate constants of these reactions were analyzed in terms of a three-species mechanism.
| 14,938
|
Tryptic cleavage of rat liver sulfite oxidase. Isolation and characterization of molybdenum and heme domains.
|
Treatment of rat liver sulfite oxidase with trypsin leads to loss of ability to oxidize sulfite in the presence of cytochrome c as electron acceptor. Ability to oxidize sulfite with ferricyanide as acceptor is undiminished, while sulfite leads to O2 activity is partially retained. Gel filtration of the proteolytic products has led to the isolation of two major fragments of dissimilar size derived from sulfite oxidase. The smaller fragment has a molecular weight of 9500 and appears to be monomeric when detached from sulfite oxidase. It contains the heme in its cytochrome b5 structure, has no sulfite oxidase activity, and is reducible with dithionite but not with sulfite. The heme fragment can mediate electron transfer between pig liver microsomal NADH cytochrome b5 reductase and cytochrome c. The larger fragment has a molecular weight of 47,400 under denaturing conditions but elutes from Sephadex G-200 as a dimer. It contains no heme but retains all of the molybdenum and the modified sulfite-oxidizing capacity present in the proteolytic mixture. All of the EPR properties of the molybdenum center of native sulfite oxidase are retained in the molybdenum fragment. The molybdenum center is a weak chromophore with an absorption sectrum suggestive of coordination with sulfur ligands. Reduction by sulfite generates a spectrum attributable to molybdenum (V). Spectra of oxidized and sulfite-reduced preparations are sensitive to anions and pH. NH2-terminal analysis of native sulfite oxidase and the two tryptic fragments has permitted the conclusion that the sequence represented by the heme fragment is the NH2 terminus of native enzyme. These studies have demonstrated that the two cofactor moieties of sulfite oxidase are contained in distinct domains which are covalently held in contiguity by means of an exposed hinge region. Isolation of functional heme and molybdenum domains of sulfite oxidase after tryptic cleavage has demonstrated conclusively that the cytochrome b5 region of the molecule is required for electron transfer to the physiological acceptor, cytochrome c.
| 14,956
|
Proton magnetic relaxation of aspartate transcarbamylase - succinate complexes.
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Nuclear magnetic relaxation methods were used to investigate the interaction of the inhibitor succinate with aspartate transcarbamylase from Escherichia coli. Over the pH range 7 to 9, the dissociation constant for succinate remains less than the inhibitor concentration used for most of this work (0.05 M). As a result, the enzyme predominantly exists in a single "gross" conformational state. Succinate binding to this enzyme state (generally known as the R form) parallels the behavior seen previously with the isolated catalytic subunit (Beard, C. B., and Schmidt, P.G. (1973) Biochemistry 12, 2255-2264). The pH and temperature dependence of succinate proton relaxation rates, 1/T2 - 1/T1, in the presence of carbamyl phosphate, is interpreted in terms of a binding mechanism involving three forms of the enzyme, differing by their states of protonation. The least protonated form of the enzyme does not interact with succinate, the singly protonated species binds succinate to form a rapidly dissociating complex, and the doubly protonated species undergoes a conformational isomerization upon succinate binding, yielding a slow exchange complex. Relaxation data provide sufficient information to determine pKa values of 7.2 and 8.9 for two ionizing groups, as well as the dissociation constant for succinate in the fast exchange complex, Kd =1.6 X 10(-2) M. Rate constants for the forward and reverse steps of the isomerization, 1.3 X 10(3) s-1 and 33 s-1, respectively, indicate a significantly slower reverse rate from that obtained in the earlier NMR study of the isolated catalytic subunit. In experiments where the succinate concentration was varied, the relaxation rates showed sigmoidal binding of that ligand to the fast exchange complex above pH 9.1, (a) indicating cooperative binding of succinate, and (b) suggesting that above pH 9.1, the system cannot be characterized by a single dissociation constant, ionization constant, or relaxation effect. CTP and ATP were tested for their ability to affect succinate binding to the fast exchange complex. Heterotropic interactions were observed for CTP but not for ATP. Addition of low concentrations of the transition state analog N-(phosphonacetyl)-L-aspartate to the enzyme-carbamyl phosphate-succinate complex sharply decreased the relaxation rate, indicating that the measurements are sensitive only to succinate bound specifically to the active site.
| 14,960
|
Cell lines from old immunodeficient donors give normal responses in young recipients.
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Two different immune responses were compared in spleen cells obtained from old and young CBA/HT6J mice. Spleen cells from old mice (23 to 33 months) responded about half as well as did spleen cells from young mice (4 to 10 months) in the adoptive transfer anti-sheep red blood cell (SRBC) plague-forming assay, and caused slightly less than half the uptake of tritiated thymidine in response to phytohemagglutinin (PHA) in vitro. Marrow stem cell from some of the old and young mice whose splenic immune responses were tested were transplanted into irradiated young CBA/CaJ recipients. Seven to 17 weeks later these same immune responses were tested in the spleen cells of these young recipients, and the T6 chromosome marker was used to identify donor cells. Old animals' responses varied greatly, perhaps due to suppressing cells or factors in some individuals. Therefore, cells were never pooled and the responses of receipients were compared to the responses of the donor whose marrow had populated them. The response for a particular old donor, or for the recipients of its stem cells, was divided by the response for the young control used with that donor, or for its stem cell recipients. This was called the old/young ratio. With original donors with an old/young ratio for the SRBC response of (mean +/- S.D.) 0.35 +/- 0.14, The old/young ratio for that same response in the recipients was significantly improved to 1.26 +/- 0.71. In original donors with an old/young ratio for the PHA response of 0.44 +/- 0.17, the old/young ratio in the recipients improved significantly to 0.86 +/- 0.27. Thus, little or none of the decline with age in these immune responses was intrinsic to the old lymphoid stem cells.
| 15,033
|
Mouse lymphocytes with and without surface immunoglobulin: preparative scale separation in polystyrene tissue culture dishes coated with specifically purified anti-immunoglobulin.
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Mouse spleen cells could be preparatively separated into immunoglobulin positive (Ig+) and immunoglobulin-netative (Ig-)populations by incubating as many as 2 X 10(8) cells per 100 mm diameter petri plate coated with specifically purified goat anti-mouse immunoglobulin. The non-adherent population was 95% or more Ig-, and possessed graft versus host and cytotoxic effector activities, as would be expected for T cells. They could also give a mixed lymphocyte reaction and generate cytotoxic effector activity on culture in vitro. The adherent cells could not be released undamaged from plates coated with undiluted anti-Ig, but they could be released from plates coated with a 1/4 or 1/10 dilution of anti-Ig in an irrelevant antibody. The released cells were over 90% viable by trypan-blue staining, and 94% or more of the viable cells were Ig+.
| 15,036
|
Blood and brain concentrations of imipramine, clomipramine and their monomethylated metabolites after oral and intramuscular administration in rats.
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Imipramine and clomipramine were administered to rats by the oral and intramuscular routes as single and multiple doses. The concentrations of both drugs and their active demethylated metabolites desipramine and desmethylclomipramine were measured in blood plasma, blood cells and brain. The concentrations of the metabolites were higher and the concentrations of the parent substances lower after oral than after parenteral administration, both in blood and in brain. In brain imipramine, despiramine and clomipramine during continuous treatment exceeded their plasma concentrations by six to ten times. The corresponding figure for desmethylclomipramine was 1-7. The extent of accumulation of the investigated substances in the brain was independent of the route of administration.
| 15,053
|
Dimensional changes of compacts after compression.
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A non-contact optical technique has been used to measure changes in the heights and diameters of compacts prepared from sodium chloride, spray dried lactose, two samples of methylcellulose powder and two spray-dried lactose-maize starch granulations. Both sodium chloride and spray dried lactose exhibited relatively small dimensional changes whilst the methylcellulose powders showed up to 30% axial and 3% radial expansion. The results are discussed in terms of the inherent properties of the materials. When the lactose was granulated with maize starch, the ratio of axial; radial strain recovery was reduced from 5-9:1 to approximately 1:1, suggesting an improved distribution of forces during compression of the granulations,
| 15,067
|
Cathepsin D activity in bovine articular cartilage, synovial membrane and fluid: degradation of cartilage proteoglycans from same joint.
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Cathepsin D type proteases were extracted from articular cartilage, synovial membrane, and synovial fluid from normal, adult bovine knee joints. A sensitive enzyme assay made it possible to measure protease activity in the different tissues from individual joints. Highest activity was found in the synovial membrane, while cell free synovial fluids contained comparatively low activity. The degrading effect on articular cartilage proteoglycans (PGC and PGS), isolated from the same joints, was demonstrated by gelfiltration on Sepharose columns and by viscometry. Gelfiltration profiles of incubation mixtures indicated a proteolytic effect on PGC and on PGS), at pH 3.5, in concentrations of enzyme and proteoglycans found in cartilage tissue. No effect at neutral pH was obtained despite a 100-fold increase of enzyme concentration. These findings were supported by viscometry data. The degrading effect of enzymes from all sources was completely inhibited by pepstatin.
| 15,110
|
[Intestinal autoflora of the test subjects in a 6-month biological engineering experiment].
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During a 6-month bioengineering experiment the intestinal microflora of four test subjects was examined. Changes in the composition of different groups of intestinal microflora (bifidobacteria, lactic-acid bacteria, sporogenous anaerobes, proteus, etc) were found. In spite of the unstable pattern of the intestinal microflora and its tendency for simplification, the total number of microorganisms in 1 g of feces remained relatively unchanged in all the test subjects.
| 15,161
|
Involvement of cytochrome b5 in the oxidative desaturation of linoleic acid to gamma-linolenic acid in rat liver microsomes.
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The effects of antibodies against microsomal electron-transport components on the in vitro activity of delta6-desaturation of linoleic acid to gamma-linolenic acid have been studied in intact microsomal membranes of rat liver. Reduced nicotinamide adenine dinucleotide (NADH) or reduced nicotinamide adenine dinucleotide phosphate (NADPH) (0.87 mM) served as electron donors, and effectively prompted the delta6-desaturase activities with yields of about 1.1 to 1.3 nmol per mg of protein in 10 min. Of the two antibodies studied under the same in vitro conditions, i.e., rabbit antisera preparations against rat liver microsomal hydrophilic parts of cytochrome b5 and NADPH-cytochrome c reductase, only the antibody against cytochrome b5 demonstrated a marked ability to inhibit the delta6-desaturase activity. This evidence supports a participation of cytochrome b5 in the delta6-desaturation of linoleic acid and suggests a pathway analogous to the delta9-desaturation of stearyl-CoA.
| 15,177
|
Physicochemical properties of Sendai virus RNA. II. Effect of ionic strength on thermostability of RNA.
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The dependence of the melting point (Tm) and width of the melting range (deltaTm) on the ionic strength and pH of the medium was investigated for the double-stranded RNA formed through self-hybridization during the isolation of RNA from Sendai virus. It was shown that Tm is a linear function of the logarithm of the sodium ion concentration in the range of concentrations from 10(-1) to 10(-4) M, with a slope of 11.5 degrees toward the abscissa for each order of magnitude. The width of the melting range increased slightly with a decrease in the ionic strength. A change in the pH of the solutions from 5 to 8 had almost no effect on the melting point or the width of the melting range. The degree of purification of the preparations of RNA and the presence of EDTA in the solutions affected the form of the dependence of the mp on the logarithm of the sodium ion concentration very strongly, especially in the region of low ionic strengths.
| 15,210
|
Affinity labeling of gamma-glutamyl transpeptidase and location of the gamma-glutamyl binding site on the light subunit.
|
Gamma-Glutamyl transpeptidase, which consists of two nonidentical subunits, is rapidly inactivated with respect to its transpeptidase and hydrolase activities by the gamma-glutamyl analogs 6-diazo-5-oxo-L-norleucine and L-azaserine. Inactivation, which is prevented by gamma-glutamyl substrates (but not by acceptor substrates), is accelerated by maleate, which was previously shown to enhance utilization of glutamine by transpeptidase. 6-Diazo-5-oxo--norleucine reacts specifically, covalently, and stoichiometrically at the gamma-glutamyl site of the enzyme, which was localized through studies with 6-diazo-5-OXO-[14C]norleucine to the light subunits of both the transpeptidase of rat kidney (which has subunits of molecular weights 22,000 and 46,000) and the transpeptidase of human kidney (which has subunits of molecular weights 22,000 and 62,000). The findings, which indicate that these enzymes have similar gamma-glutamyl binding subunits, are relevant to the structure-function relationships of this membrane-bound enzyme and its physiological role.
| 15,260
|
[Electrolyte-water balance and acid-base equilibrium in brain tumor patients].
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Electrolyte variations, water-balance disturbances, and acid-base equilibrium disorders observed in patients with brain tumors are due, in the majority of cases, to increases in intracranial pressure and, in a relatively small number of cases, to the particular location of the tumor. Severe pathological pictures are not, in general, observed until the ailment has advanced to a critical state. The authors, after describing the clinical pictures of the various forms of acid-base equilibrium disorders, also discuss methods of treatment. Disturbances of water balance are closely associated with the electrolyte metabolism. Consequently, it is necessary that, if a dehydrating form of therapy is used, careful attention should be given to the corresponding parameters. Disturbances of iatrogenic origin tend to produce particularly adverse effects in brain tumor patients.
| 15,294
|
The influence of hypoxia and acidity on the hyperthermic response of malignant cells in vitro.
|
Colony formation of JB-1-E tumor cells was studied after hyperthermic treatment (42.5 degrees C) at a pH of 6.4 or 7.2 under hypoxic and euoxic conditions. At a pH of 7.2 and normal oxygen tension, there was a moderate decrease in colony formation with increasing duration of hyperthermic treatment (To = 65 min.). This effect was slightly enhanced under hypoxic conditions (To = 36 min.). The hyperthermic effect was enhanced to a considerably greater degree when treatment was performed at a pH of 6.4 (To = 19 min.), with no observable difference between hypoxia and euoxia. These findings indicate that environmental acidity is a determining factor in the hyperthermic effect. The hypoxic effect at a pH of 7.2 is probably due to a slight decrease in the intracellular pH caused by increased production of lactic acid.
| 15,300
|
Postnatal changes in blood respiratory characteristics in an American opossum (Didelphis virginiana).
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The oxygen affinity of opossum blood changes in the postnatal period. The youngest opossums studied were 53 days of age (dated from the day of transit from vagina to pouch) and still confined to the maternal pouch: they had a blood P50 of 32.6 +/- 2.9 mm Hg. The blood P50 value then increased significantly, in two steps. First, while the young were still in the pouch, blood P50 rose secondary to a rise in the concentration of 2,3-diphosphoglycerate (DPG). Blood P50 and DPG concentration then remained stable until the animals left the maternal pouch, when DPG rose again, causing a further increment in the blood P50 which peaked at 48.7 +/- 4.5 mm Hg in animals 148 days old. Blood P50 subsequently decreased significantly, reaching the adult value (42.0 +/- 1.9 mm Hg) at about 250 days.
| 15,307
|
Tris buffer attenuates acetylcholine responses in Aplysia neurons.
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The commonly used buffering agent tris(hydroxymethyl)methylamine (tris) antagonizes the action of iontophoretically applied acetylcholine on neurons of Aplysia californica. Concentrations of 5 to 10 millimolar tris markedly reduced both excitatory and inhibitory responses.
| 15,317
|
Medical treatment of hypertension.
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The management of hypertension with current hypotensive drugs on the South African pharmaceutical market is reviewed. The advent of the use of beta-adrenergic blocking agents and vasodilators in the treatment of hypertension is promising.
| 15,323
|
Local mechanism of CO2 action of cat pial arterioles.
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The effect of local hypercapnic acidosis or local hypocapnic alkalosis on pial arterioles were studied in anesthetized cats equipped with a cranial window for the direct observation of the pial microcirculation of the parietal cortex. Changes in PCO2 and pH of the extracellular fluid were induced by perfusing the space under the cranial window with artificial cerebrospinal fluid equilibrated with different concentrations of CO2, while PaCO2 was maintained constant. Hypercapnic acidosis dilated and hypocapnic alkalosis constricted pial arteioles markedly. The results indicate that a basis exists for considering CO2 as a mediator for local regulation of brain blood flow. The vasodilation associated with arterial hypercapnia was abolished by a reduction in CSF PCO2 equal in magnitude to the rise in arterial blood PCO2, suggesting that the action of CO2 is entirely local.
| 15,334
|
Changes in agglomeration of human red blood cells in liquid storage in CPD media.
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A procedure which may distinguish between old and new CPD blood units in liquid state is described. It is based on the observation of increased tendency to reversible agglomeration in old erythrocytes in liquid preservation. Erythrocytes clump together when they are mixed with low ionic strength solutions in pH range of 5.2 to 6.5. We found that liquid-stored erythrocytes show an augmented tendency to agglomerate in 0.24M sucrose, pH 7.2. The tendency increases with storage so that in the fourth week, more than 70% of the units show agglomeration under these conditions. The addition of minute amounts of sodium chloride may prevent agglomeration. As the cells age, higher salt concentration is required to prevent agglomeration. A short incubation of washed cells with adenosine may reverse the tendency of outdated erythrocytes to agglomerate, concomitantly with reestablishment of initial ATP level. However, depletion of the ATP of fresh cells with fluoride does not induce agglomeration. A 20 hour incubation of units at 37 C with CPD revealed an increased sensitivity of older units, with low ATP and positive agglomeration. This test may help in distinguishing between outdated and younger units in the blood bank.
| 15,336
|
[Fetal heart rate, dip area and acid base observations in breech and vertex deliveries (author's transl)].
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Fetal heart rate (FHR), dip area (DA) and the acid base status (AB) were investigated in breech deliveries (BD) (N= 167) and in group of spontaneously delivered vertex presentations (VP) (NFHR, DA=50; NAB=109). 90 minutes prior to delivery fetal heart rate and dip area were in both groups not significantly different. However as labor progressed the fetal heart rate as well as dip area increased in breech deliveries much more (FHR 163 (SD 16.2) beats/min, DA 1,07 (SD 0,80) cm2/min) than in VP (FHR 136 (SD 14,8) beats/min, DA 0,65 (SD 0,39) cm2/min) (2p less than 0,001). The base excess of the umbilical arterial blood was correlated to the DA measured from 10 minutes prior to birth till the delivery of the baby: BE = -8,2 --0,3 (DA) (2alpha less than 0,01). The frequency of acidotic babies was more in vaginally delivered breech presentations (pH less than 7,20 = 30, 2%, BE greater than -10 meq/l = 43,7%) than in breech deliveries by caesarean section (pH less than 7,20 = 19,1%, BE greater than -10 meq/l = 24,4%) and vertex presentations (pH less than 7,20 - 5,5%, BE greater than -10 meq/l = 14,6%), respectively. The distance between the vertex and the umbilicus was 28 cm and between the breech and the umbilicus 9,4 cm. From this anatomical observation it is concluded that umbilical cord compression, preferentially umbilicai vein occlusion takes place in breech presentation at an earlier point on than in vertex presentation. The rise of fetal heart rate and the increase in dip area are showing in addition that the fetal buffer base in breech presentation will be reduced during the last time course of the second stage of labor.
| 15,354
|
[Hemodynamic effects of Etomidate].
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Hemodynamic variations due to Etomidate administration were studies in 10 patients submitted to artificial ventilation. Etomidate was given at a 0.37 mg/kg B.W. dosage. Cardiac rate, mean arterial B.P., C.V.P., mean arteial pulmonary pressure, mean pulmonary capillary pressure and cardiac output were investigated. From values found, systolic output, systemic vascular resistance, and pulmonary arteriolar resistance were calculated. Results show that Etomidate has little effect on hemodynamics. There is only a 5 p. 100 increase in cardiac rate, a 16p. 100 decrease in cardiac output, 1 18 p. 100 decrease in systolic output and a 12p. 100 decrease in mean arterial B.P. Variations of mean capillary pressure, of systemic vascular resistance and of pulmonary arteriolar resistance are not significant.
| 15,477
|
[Continuous measurement of arterial pressure by means of an arterial catheter. Its value in secondary transport].
|
It is of no much use to try to assess the cardiovascular condition of patients with impending or confirmed shock by taking the blood pressure with the classical arm cuff, especially if arterfacts such as noise, vibrations, shaking etc... are interfering. Instant continuous measurement of blood pressure by means of arterial cannulation avoids those drawbacks and is a sure and efficient method of assessment of an often unstable, precarious and sometimes aggravated cardio-vascular condition by the very transportation. The S.A.M.U. of Montpellier used this technique in 15 cases. The authors are reporting their experience and also are evoking some technical problems that may occur.
| 15,482
|
[Macrokinetic equations of pH effect on the growth of Actinomyces aureofaciens and biosynthesis of tetracycline].
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The effect of pH on the culture respiration rate at different concentrations of glucose in the medium was studied. It was found that the hydrogen ions showed their effect irrespective of the subsrate concentration in the medium. In this connection a type of macrokinetic equations of the effect of pH on the growth and antibiotic biosynthesis was chosen. The constants of the model were determined.
| 15,502
|
Effect of culture conditions on synthesis of L-asparaginase by Escherichia coli A-1.
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The nutritional requirements and culture conditions affecting biosynthesis of L-asparaginase in a mutant of Escherichia coli HAP designated strain A-1 were studied. Asparaginase activity was increased by the addition of L-glutamic acid, L-glutamine, or commercial-grade monosodium glutamate. The rate of enzyme synthesis was dependent on the interaction between the pH of the culture and the amount of oxygen dissolved in the medium. A critical oxygen transfer rate essential for asparaginase formation was identified, and a fermentation procedure is described in which enzyme synthesis is controlled by aeration rate. Enhancement of L-asparaginase activity by monosodium glutamate was inhibited by the presence of glucose, culture pH, chloramphenicol, and oxygen dissolved in the fermentation medium.
| 15,509
|
Acidostability of speroplasts prepared from Thiobacillus thiooxidans.
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Thiobacillus thiooxidans was acidostable even in the absence of its respiratory substrate, elementary sulfur. This suggests that the acidostability of the bacterium was enery-independent. The organism was subjected to osmotic shock with 0.75 M sucrose at 0 degrees C and then treated with snail intestinal juice in the presence of 0.3 M sucrose. The decrease in the optical density of the sample thus prepared on dilution with deionized water and electron microscopic observation of the sample showed that spheroplasts were formed from the bacterium by this procedure. Spheroplasts were able to respire sulfur and their respiratory activity was acidostable. Spheroplasts, when treated with Nagase, proteolytic enzyme, lost their acidostability, and some protein components disappeared from the membrane fraction. This suggests that the acidostability of the bacterium may be related to protein conponents of the membrane.
| 15,528
|
Penicillinase (beta-lactamase) formation by blue-green algae.
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Beta-Lactamase (penicillinase) activity was found in a number of strains of blue-green algea. In some cases, this enzyme permitted algae to overcome the inhibitory effects of penicillin. Production and localization of beta-lactamase were studied in a unicellular species, Coccochloris elabens (strain 7003), and in a filamentous, nitrogen-fixing Anabaena species (strain 7120). When cells were grown in a neutral medium with NaNO3 as N source, the pH rose during growth; at a pH of about 10, most of the enzyme was expressed equally well in intact or disrupted cells. If the pH was kept near neutrality during growth by gassing with CO2 in N2 or by growth under conditions of N2 fixation, the enzyme remained cell-bound and cryptic for most of the growth phase, being measurable only after cells were disrupted. The enzymes from strains 7003 and 7120 had greater activity on benzyl penicillin and other penicillins than on cephalosporins. Some differences were observed in the "substrate proliles" of penicillinases from the two strains against different penicillins.
| 15,530
|
Fluorine-19 nuclear magnetic resonance studies of effects of ligands on trifluoroacetonylated supernatant aspartate transaminase.
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The selective reaction of Cys-45 and -82, on the one hand, and Cys-390, on the other, with 3-bromo-1,1,1-trifluoropropanone allows for the probing of these regions of aspartate transaminase in the absence and in the presence of enzymatic ligands by 19F nuclear magnetic resonance (NMR). The 19F chemical shifts of the resonance lines differ for the three cysteines and so does their behavior with pH changes. The resonance signals with chemical shifts at 615 and 800 Hz upfield from trifluoroacetic acid correspond to modified cysteine-82 and -45 and have tentatively been assigned in this order. The 615-Hz resonance is affected by pH changes that fit best the influence of a single ionizing residue. On the 800-Hz line, the pH changes appear to be the influence of a minimum of two ionizing residues. The 19F resonance from modified Cys-390 is pH independent in the pH range 5-9 for the pyridoxal phosphate, pyridoxamine phosphate, and apoenzyme forms of the enzyme. Occupation of the active site by a quasi-enzyme-substrate complex, trifluoromethionine pyridoxyl phosphate, affects the 19F chemical shift of modified Cys-390, making it pH dependent with a pK value of 8.4. The 19F NMR properties of the pyridoxal form of Cys-390-modified enzyme can be used to monitor some ligand interactions with the active-center region. Addition of alpha-ketoglutarate or succinate to the ketone labeled enzyme causes a decrease in the resonance line width, and titrations show that this procedure is a good method with which to study the affinity of the enzyme for these ligands. The interpretation of the chemical shift and line-width characteristics of the 19F resonance arising from Cys-390 are most consistent with a model in which the region around this residue seems to be affected by conformational changes arising from substrate binding to the active-center subsites in productive (covalent) manner. Nonproductive complexes which possess fast ligand-protein exchange, such as those between alpha-ketoglutarate or succinate with the pyridoxal phosphate form of the enzyme, may result only in a greater degree of freedom for Cys-390.
| 15,584
|
Phosphate transport in Micrococcus lysodeikticus.
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Phosphate accumulates in Micrococcus lysodeikticus cells against a concentration gradient, by an energy-dependent process. The phosphate transport is derepressed during phosphate deprivation. The depression process is inhibited by chloramphenicol. The apparent Km of phosphate transport is 4.3 micronM. The activation energy of the transport is 21 kcal per mol in the temperature range of 0-29degrees C, and 4.9 kcal per mol between 29 and 40degrees C. The rate of the transport increases in presence of K+ and Mg2+. Arsenate is a competitive inhibitor of phosphate transport, having an apparent Ki of 6.0 micronM. Sulfhydryl reagents, respiratory inhibitors and uncouplers of oxidative phosphorylation inhibit phosphate transport.
| 15,596
|
Physicochemical properties of alpha- and beta-fibrinogenases of Trimeresurus mucrosquamatus venom.
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alpha- and beta-Fibrinogenases (EC 3.4.21.5) were purified from Trimeresurus mucrosquamatus venom by the technique of recycling chromatography. Both enzymes were single polypeptide chains and homogeneous as judged by sodium dodecyl sulfate (SDS) polyacrylamide gel electrophoresis and ultracentrifugation. The sedimentation constants of alpha- and beta-fibrinogenases were 2.52 and 3.04 respectively. The molecular weight of alpha-fibrinogenase was 21 500--23 400, and that of beta-fibrinogenase was 25 000--26 000. The contents of proline, glycine and tryptophan were higher in beta-fibrinogenase than in alpha-fibrinogenase. The isoelectric points of alpha- and beta-fibrinogenases were pH 8.1 and 5.7 respectively. The optimal pH of alpha-fibrinogenase was about 7.4 and that of beta-fibrinogenase was around 8.5. The activity of alpha-fibrinogenase was completely destroyed after 30 min at 60 degrees C, pH 5.6, 7.4 and 9.0, while that of beta-fibrinogenase was not significantly affected by the same treatment. Both enzymes showed proteolytic activities toward fibrinogen and casein, but were devoid of phospholipase A, alkaline phosphomonoesterase and phosphodiesterase activities of the crude venom. The tosyl-L-arginine methylester esterase activity of beta-fibrinogenase was about 17 times that of the crude venom, while alpha-fibrinogenase was completely devoid of this activity. The fibrinogenolytic activity of alpha-fibrinogenase was markedly inhibited by EDTA and cysteine, while that of beta-fibrinogenase was inhibited markedly by phenylmethane sulfonylfluoride and slightly by tosyl-L-lysine chloromethylketone and cysteine.
| 15,616
|
Activation of liver guanylate cyclase by bile salts and contaminants in crude secretin and pancreozymin preparations.
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Crude preparations of secretin or pancreozymin increased and at higher concentrations decreased guanylate cyclase (GTP pyophosphate-lyase, EC 4.6.1.2) activity from soluble and particulate fractions of rat liver homogenates. Partially purified and synthetic secretin were without effect as was the biologically active octapeptide fragment of pancreozymin. The active contaminants in these preparations survived boiling, saponification, and treatment with phospholipase A, trypsin and neuraminidase C. The activity was extractable with chloroform/methanol and did not survive ashing. Eight bile salt contaminants in crude secretin were obtained with thin-layer chromatography. Two of the contaminating bile salts that increased liver particulate guanylate cyclase activity were identified as taurodeoxycholate and either glycochenodeoxycholate or glycodeoxycholate; taurocholate was inhibitory. The sodium salts of cholate, deoxycholate, chenodeoxycholate and their glycine-or taurine-conjugated forms either increased or decreased particulate and soluble rat liver guanylate cyclase activity depending upon their concentration. Thus, the previously reported stimulatory and inhibitory effects of secretin and pancreozymin preparations on guanylate cyclase activity are probable attributable to their bile salt contaminants.
| 15,619
|
Structural studies by proton magnetic relaxation of stereochemical probes. II. Allosteric effects in human methaemoglobin.
|
The haem-iron accessibility to solvent molecules in human aquomet- and fluoromethaemoglobin was studied by the magnetic relaxation of protons from a stereochemical probe (methanol in deuterated solutions) in its dependence on allosteric effects induced by inositol hexaphosphate and pH between 5.5 and 8.5. The exchange of methanol with bulk solvent was observed only when inositol hexaphosphate was bound to aquomethaemoglobin, which is consistent with a widening of the haemcrevice compared to the conformation in the absence of inositol hexaphosphate. An increase in alkalinity in the physiological range of the Bohr effect results in a gradual impedence of the solvent dynamics inside the haem-pocket. The fast-relaxation phase of methyl protons indicates that a large number of methanol molecules are under the strong influence of the protein; this effect is considerably smaller with inositol hexaphosphate bound to aquomethaemoglobin. The hypothesis which implies a proton from the coordinated water molecule is responsible for the observed relaxation rates has been critically discussed. The model with a water molecule exchanging between a position next to the sixth-ligand site of the haem-iron and the bulk solvent is further substantiated experimentally. This model has been found to be the simplest and most self consistent in the interpretation of all these proton magnetic relaxation data.
| 15,624
|
[Glutamine metabolism regulation in Chlorella pyrenoidosa. Regulation of Chlorella glutamine synthetase activity by amino acids].
|
Effect of glutamine and its metabolites (amino acids) on Chlorella glutamine synthetase (GS) (E.C.6.3.1.2) in the presence of Mg or Mn was studied. Purified GS preparation was used, isolated from Chlorella grown in the presence of NH as a sole nitrogen source. Glutamate, aspartate, alanine and glycine inhibit GS activity in the presence of both Mg and Mn. Tryptophane and valine (up to 15 mM) activate GS in the presence of Mn. Tryptophane inhibits GS in the system with Mg. Sinergistic inhibition was observed under the combined effect of amino acids on GS in the presence of Mn and aspartate or alanine. The change of GS activity observed is supposed to be due to the inhibitory effect of glutamine and amino acids studied, since the glutamine content is increased (in 2.5 times for 5 min) and that of alanine and dicarbonic amino acids (for the following 15 min) under NH assimilation in Chlorella cells.
| 15,647
|
[Adenine uptake in Neurospora crassa mycelium].
|
The uptake of 8-C14-adenine in N. crassa strain Lindegren (+) was studied. The ability of N. crassa cells to uptake adenine from the medium reaches maximum at the very beginning of the logarithmic stage of growth. Adenine enters the mycelium against the concentration gradient. The uptake of adenine is maximal at 25-30 degrees C, pH 4,6-4,8, and adenine concentration in the medium about 2-15X10(-6) M. The entry of adenine into the cells follows normal Michaelis-Menten kinetics, the apparent Km=0.83+/-0.02 micron. The uptake is inhibited at higher concentrations (10(-3)-10(-4) M) of adenine. 2,6-Diaminopurine, hypoxanthine, guanine, 8-azaadenine and 8-azaguanine inhibit the transport of adenine into the cell. Xanthine and cytosine do not affect the uptake of adenine. Adenine taken up into the cell is rapidly metabolized to AMP, ADP and ATP.
| 15,650
|
[Purification, properties and quaternary structure of glutamine synthetase from Chlorella].
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A highly purified preparation of glutamine synthetase from chlorella grown on a medium containing nitrate as a sole source of nitrogen, was isolated and characterized by disc-electrophoresis and analytical ultracentrifugation. The N-terminal amino acid of glutamine synthetase is glycine. The molecular weight of glutamine synthetase is 32.000; its activity in the presence of Mg2+ was 150 mkmol o-phosphate per min per mg protein. The molecular weight of subunits of the enzyme, equal to 53.000 was determined by disc-electrophoresis in polyacrylamide gel in the presence of sodium dodecyl sulfate. Electron microscopy of negatively contrasted enzyme preparations revealed 6 subunits in the enzyme molecule, arranged in a point symmetry group 32.
| 15,657
|
[Some physicochemical properties of modified trypsin].
|
Physico-chemical properties of trypsin covalently bound with human serum albumin by glutaric aldehyde have been studied. The modification of the enzyme practically caused no changes in the pH optimum of trypsin. The inhibition of modified trypsin by inhibitors from soy beans and human blood serum has been also studied. The apparent inhibition constants have been calculated. The modification has been shown to result in a deceleration of autolytic degradation. The autolysis rate constants have been calculated at 50 degrees C.
| 15,658
|
[Effect of abrogating hybrid resistance on the survival of radiation chimeras].
|
A study was made of the effect of the hybrid resistance abrogation by means of the lymphoid cell administration on the survival of the lethally irradiated mice protected by the transplantation of the semiallogeneic bone marrow. Injection to the C57BLxCBA recipients of the C57BL lymphoid cells one day before the irradiation and the transplantation of the bone marrow of the same genotype (C57BL) increased the chimera survival in comparison with the untreated recipients; such pretreatment 7 days before the irradiation decreased the chimera survival. Parental spleen lymphocytes administration produced but an insignificant effect on the radioresistance both of the stem hemopoietic cells (by the endocolonisation test) and of the organism as a whole (by the 30-day survival test) of the F1 hybrid. On this basis a conclusion was drawn that the differences in the splenocyte efficacy, when they were injected at different periods before the irradiation, could not be attributed to the changes in radioresistance.
| 15,680
|
[Immunocompetent lymphoi- cells from pregnant mice studied in the graft-versus-host reaction].
|
The capacity of lymphoid cells taken from C57BL/6 mice gravid from the CBA males (the second trimester) to induce the graft-versus-host reaction in the hybrids (CBA X C57B/6) F1 was reduced as compared with the cells of the virgin donors and syngeneic gravid mice. This was expressed by the prolonged survival of the experimental recipients and reduced inhibition of endogenous colony formation in the spleen of the sublethally irradiated (500 r) hybrids. At the end of gravidity this capacity was restored, in some instances even exceeding control figures.
| 15,684
|
[Quantitative changes in gastric juice proteases in dogs during ulcer formation in the stomach].
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Disc-electrophoretic investigation of proteases of the gastric juice of dogs under normal conditions and in experimental atophan ulcer of the stomach demonstrated that in fasting dogs ulceration was accompanied by marked quantitative changes in the protease spectrum. Fraction No. 6 showed a significant elevation against the background of total reduction of proteolytic fraction of the gastric juice in sham feeding of ulcerated dogs. Sham feeding replete ulcerated dogs indicated a marked increase of fractions No.1 and No.2. The noted changes of the gastric juice protease spectrum may be of ulcerogenic significance.
| 15,686
|
Thrombin-induced vasodilation in the hindlimb (dog).
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The objective of this study is to test the hypothesis that the vasodilation produced by intra-arterial injection of thrombin to the hindlimb of a dog may be caused by the secondary release or production of some vasodilating substance. The vasodilator response to thrombin was compared with the vasodilator response to acetylcholine, isoproterenol, histamine and serotonin before and after blockade with atropine, propranolol, phenergan or methyl-D-lysergic acid butanolamide (UML-491), respectively. Though the appropriate blocking agent blocked the vasodilator response to the respective drug, the thrombin-induced vasodilation was not blocked. These data support the hypothesis that thrombin-induced vasodilation is a response to the thrombin moiety.
| 15,689
|
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