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[Accessibility of sulfhydryl groups to 5,5'-dithiobis-2-nitrobenzoic acid and acid-base properties of bovine and walleye pollock rhodopsin preparations].
|
Both the number of exposed SH-groups and the rate of reaction with 5,5'dithiobis-2-nitrobenzoic acid (DTNB) in walleye pollock and bovine rhodopsin depend on a degree of native structure of the preparation to be investigated. The preparations studied can be arranged in the order of increase of these parameters as follows: ROS less than rhodopsin extracted by digitonin less than triton X-100 less than cetyltrimethylammonium bromide (CTAB) less than sodium dodecylsulphate (SDS). After illumination of ROS and digitonin, triton X-100 and CTAB-solubilized rhodopsin, and increase was observed in the number of modified SH-groups. Dark and bleached samples of walleye pollock rhodopsin exhibited a faster rate reaction and a more number of modified SH-groups as compared to bovine preparation. The differences between bovine and walleye pollock preparation disappeared after complete opsin unfolding as a result ROS solubilization in SDS. Six SH-groups per molecule of rhodopsin were modified in both preparation under these conditions. No differences in the number of cysteine residues (10--11), disulfide groups (2), acid (35--40) and base (25--30) titratable groups per rhodopsin molecule were found between bovine and walleye pollock ROS membranes. The isoelectric point of both rhodopsin preparations was within the pH range 5.2--5.6. After proteolysis of ROS with papain, a fragment with molecular weight 24500 +/- 1000 was detected, which contained the same number of SH-groups and cysteine residues as in the case of intact rhodopsin. The results obtained suggest that, in spite of a similar primary structure, the walleye pollock visual pigment has more "loose" and "fluid" space packing in the ROS membrane than the bovine pigment.
| 25,681
|
Purinergic innervation of the guinea-pig urinary bladder.
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1 A number of criteria for considering adenosine 5'-triphosphate (ATP) as a neurotransmitter in the guinea-pig urinary bladder have been examined. In addition, the effect of tachyphylaxis to ATP on the response to non-adrenergic, non-cholinergic nerve stimulation has been re-examined.2 Quinacrine fluorescence histochemistry revealed a population of nerve fibres, ganglion cells, and nerve bundles in the bladder which were not seen in either the iris or vas deferens, where adrenergic and cholinergic nerves predominate. The distribution and morphology of the quinacrine-positive nerves in the bladder were different from those observed with catecholamine fluorescence and cholinesterase histochemistry, and were unaffected by chemical sympathectomy.3 Release of ATP from the bladder during stimulation of intramural excitatory nerves, in the presence of atropine and guanethidine increased to 3-12 times prestimulation levels. Tetrodotoxin abolished both the contractile response and the increase in ATP release resulting from intramural nerve stimulation. There was no increase in ATP release during contraction resulting from direct muscle stimulation following nerve paralysis with tetrodotoxin.4 Sympathectomy with 6-hydroxydopamine did not affect release of ATP in response to intramural nerve stimulation.5 Release of ATP was dependent on the concentration of calcium ion in the medium.6 Contractions in response to non-adrenergic, non-cholinergic intramural nerve stimulation were closely mimicked by ATP, but not by acetylcholine or histamine.7 Adenosine and dipyridamole reduced the contractions to both ATP and non-cholinergic nerve stimulation.8 2-2'-Pyridylisatogen was not a specific blocker of either ATP or intramural nerve stimulation in the guinea-pig bladder. 2-Substituted imidazolines initiated spontaneous activity making it impossible to assess any blocking action that they may have had.9 Prostaglandins (E(1), E(2) and F(2alpha)) gave weak, slow contractions and an increase in spontaneous activity. Both the response to ATP and non-adrenergic, non-cholinergic nerve stimulation were greatly potentiated in the presence of prostaglandins.10 In the presence of indomethacin the response to non-adrenergic, non-cholinergic nerve stimulation was virtually abolished following desensitization to ATP.
| 25,686
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A thermodynamic analysis of the amorphous to crystalline calcium phosphate transformation.
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A thermodynamic analysis of the precipitation of amorphous calcium phosphate (ACP) and its transformation to crystalline apatite had been made. A nearly constant ion product, over a wide variety of conditions, was obtained for a tricalcium phosphate (TCP)-like phase suggesting that the molecular unit which governs the solubility of ACP may be similar in composition to TCP. The introduction of 10% acid phosphate into the formula for the TCP ion product improves the fit of experimental data and results in an invariant ion product. The stability of ACP in solution was found to be dependent upon its thermodynamic instability with respect to an octacalcium phosphate (OCP)-like phase. The dependence of the induction period for the amorphous to crystalline transformation upon the pH and the Ca/P ratio of the solution is best explained by the assumption that an OCP-like phase is initially nucleated on the surfaces of the ACP particles. The events that occur in the immediate post-transition period suggest the hydrolysis of this OCP-like material to an apatitic phase.
| 25,699
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Optimal conditions and comparison of lactate dehydrogenase catalysis of the lactate-to-pyruvate and pyruvate-to-lactate reactions in human serum at 25, 30, and 37 degrees C.
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We report optimal conditions for assaying highly purified human lactate dehydrogenase isoenzymes with the lactate-to-pyruvate and pyruvate-to-lactate reactions, as they apply to human serum. Interconversion of results between reactions is not practicable. Measurements of lactate dehydrogenase in either reaction direction at 25, 30, or 37 degrees C can be equally reliable if the volume fraction and the resulting deltaA/min is small. However, for interinstrument and interlaboratory comparisons, results from the lactate-to-pyruvate reaction are more reliable.
| 25,724
|
Streptococcus pneumoniae isolates relatively insensitive to penicillin G recovered from patients in Switzerland.
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The sensitivity to penicillin G of pneumococci isolated in Switzerland has been determined by the quantitative tube dilution method. 3 out of 100 strains were relatively insensitive to this antibiotic (minimum inhibitory concentration greater than 0.1 microgram/ml), thus confirming observations already made in other countries. These results underline the necessity of routinely testing the sensitivity of pneumococci to penicillin G.
| 25,749
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[Excretory function of the kidney after denervation and the administration of a beta-blockader].
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Osmotic diuresis (15% mannitol, 4.5 ml/hr) was in duced in anesthetized rats. At the end of each of 10 consecutive 10-min clearance periods the following parameters were determined: diuresis, sodium, chlorine and osmotic excretion, GFR (inulin clearance). The animals were divided into three groups: a) controls, b) with bilateral renal denervation (performed one week earlier) and c) with application of beta-adrenergic blocking agent propranolol (Obsidan, Germed DDR) introduced intravenously 0.1 mg/100 g initially and 0.12 mg/100 g sustaining dose during 2 hrs. The experimental results showed an increased sodium excretion in denervated and obsidan--treated animals with no change of the total excreted osmotically active substances. In denervated animals the chlorine excretion was increased as well. The data suggest that, in osmotic diuresis, the renal denervation and beta-adrenergic blocking agents inhibit the tubular sodium transport. The kidney osmoregulatory functions remains unchanged.
| 25,791
|
Clostridial sepsis after abortion with PGF2alpha and intracervical laminaria tents--a case report.
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A case of clostridial endomyometritis and sepsis necessitating total abdominal hysterectomy which occurred 12 hours following abortion induced with intraamniotic administration of prostaglandin F2 alpha and laminaria tent insertion is discussed. Cultures from cervical, blood, and surgical specimens all yielded Clostridium perfringens. Intrauterine contamination with this microorganism most likely followed the insertion of laminaria tents through the cervical os, which was colonized with C. perfringens. Since C. perfringens may be present in the microflora of the lower female genital tract, great care must be taken to cleanse this area prior to intracervical laminaria tent insertion.
| 25,807
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The potential reduction of medical complications from induced abortion.
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Reducing medical complications resulting from induced abortion by identifying the safest and most appropriate procedures(s) for each gestational age is the purpose of this study. Data on all women who had induced abortions at all hospitals in the State of Hawaii where such procedures were performed between March 11, 1970, when the new abortion law went into effect, and June 30, 1974 were analyzed. Study findings show that if the abortion procedure with the least risk of complications at each length of gestation were selected a reduction in the complication rate of nearly 30% could result.
| 25,810
|
A behavioral approach to post-catastrophic illness work phobias.
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Two patients developed work phobias following major catastrophic physical illness. A combined approach to addressing their specific fears of returning to premorbid levels of work function utilized deep muscle relaxation, imagery based desensitization, social reinforcement, and shaping techniques. A significant increase in adaptive function and decrease in depressive symptomatology resulted in both cases within six weeks after initiation of treatment.
| 25,848
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Identity of proline dehydrogenase and delta1-pyrroline-5-carboxylic acid reductase in Clostridium sporogenes.
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Proline dehydrogenase and delta1-pyrroline-5-carboxylic acid (PCA) reductase activities were copurified 60- and 130-fold, respectively, from extracts of Clostridium sporogenes. The primary change in the ratio of activites was the result of a loss of proline dehydrogenase activity during dialysis. Both activities were eluted in single peaks from diethylaminoethyl-cellulose, hydroxylapatite, and Sephadex G-200 columns. They had identical sedimentation coefficients (10.3S), as determined in linear sucrose gradients, and identical isoelectric points (4.95 to 5.12) based on isoelectric focusing. The proline dehydrogenase activity was dependent on nicotinamide adenine dinucleotide and L-proline, and the PCA reductase required L-PCA and reduced nicotinamide adenine dinucleotide. The optimum pH for the assay of proline dehydrogenase was approximately 10.2, whereas that for PCA reductase was 6.5 to 7.5. An increase in pH from 8.0 to 10.2 greatly decreased the apparent Michaelis constant observed for L-proline, and an increase from pH 8.3 to 8.6 resulted in a large shift in the reaction equilibrium toward PCA. Both the dehydrogenase and reductase activities were stabilized to heating at 65 degrees C for 5 min by solutes of high ionic strength and were inactivated in a similar fashion when dissolved in low-ionic-strength buffer. The specific activities for both were reduced by about 50% when glucose was added to the growth medium. The data support the conclusion that L-proline and L-PCA are interconverted by either a single enzyme or an enzyme complex in extracts of C. sporogenes cells.
| 25,881
|
Purification and characterization of a secondary alcohol dehydrogenase from a pseudomonad.
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Growth of Pseudomonas sp. NRRL B3266 in the presence of oleic acid resulted in the induction of two enzymes: oleate hydratase, which produced 10(R)hydroxyoctadecanoate, and hydroxyoctadecanoate dehydrogenase, which catalyzed the oxidized nicotinamide adenine dinucleotide-dependent production of 10-oxooctadecanoate. This latter enzyme was purified to homogeneity and shown to consist of two polypeptide chains of about 29,000 daltons each. The enzyme had a broad substrate specificity, catalyzing the dehydrogenation of a number of 18-carbon hydroxy fatty acids. The kinetic parameters for various 10- and 12-hydroxy fatty acids were similar (Km ca. 5 micron and Vmax ca. 50 to 200 mumol/min per mg of protein). The enzyme also catalyzed the dehydrogenation of unsubstituted secondary alcohols. The effectiveness of these alcohols as substrates was highly dependent on their hydrophobicity, the Km decreasing from 9 mM for 4-heptanol to 7 micron for 6-dodecanol. Inhibition of the enzyme by primary alcohols also showed a dependence on hydrophobicity, the Ki decreasing from 350 mM for methanol to 90 micron for decanol.
| 25,883
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Changes in hepatic levels of tyrosine aminotransferase messenger RNA during induction by hydrocortisone.
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Messenger RNA specific for tyrosine aminotransferase was quantitated by microinjection into oocytes of Xenopus laevis. The heterologously translated enzyme was identified by specific immunoprecipitation and found to be identical with authentic aminotransferase by several criteria. The level of functional message present in rat liver increases during hydrocortisone induction, and this increase is directly proportional to the increased rate of synthesis of the enzyme. Kinetic analysis of the changes in tyrosine aminotransferase mRNA levels during induction and withdrawal indicates that the steroid does not affect the stability of the message, which has a half-life of approximately 1.2 h. Hydrocortisone, therefore, acts to increase the rate of synthesis of the specific messenger by stimulating either its transcription or processing to functional mRNA.
| 25,898
|
The identification of an octopaminergic neurone and the modulation of a myogenic rhythm in the locust.
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An octopaminergic neurone in an insect is demonstrated. This cell (DUMETi) is the dorsal unpaired median neurone which projects to the extensor tibiae muscle of the locust metathoracic leg. Its soma was physiologically identified, isolated and shown to contain about 0.1 pmol of octopamine. Octopamine is about four times more concentrated in the axon than in the soma. The concentration in the soma is at least 800 times more than that in the soma of an identified motoneurone (which controls the fast extensor of the tibia). The effects of DUMETi on a myogenic rhythm in the extensor muscle of the locust metathoracic leg can be mimicked by superfusion with low concentrations of octopamine. The myogenic bundle possesses at least two types of aminergic receptor: one which slows the rhythm (and has a high-affinity for octopamine) and a second which accelerates the rhythm (and has a low-affinity for octopamine but a high-affinity for the indolalkylamine, 5-hydroxytryptamine). The roles of the two receptor types in modulating the rhythm are discussed in relation to the function of the rhythm.
| 25,941
|
Intestinal transport of weak electrolytes: Determinants of influx at the luminal surface.
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The determinants of weak electrolyte influx into everted segments of rat small intestine have been studied. Preliminary experiments showed that the observed influxes could be described as unidirectional, diffusional fluxes of the nonionized compound uncomplicated by a parallel ionic component. It is shown that the determinants of weak electrolyte influx in this situation may be described in terms of the resistance of the unstirred layer to movement from the bulk phase to the cell surface, the degree of ionization of the weak electrolyte at the cell surface, and the cellular permeability to the nonionized weak electrolyte. Quantitative considerations indicated that the unstirred layer was totally rate-limiting in the cases of some poorly ionized, or highly permeant compounds, but the unstirred layer was not totally rate limiting for most of the compounds studied. Calculation of cellular permeabilities for the nonionized forms of weak electrolytes required assumptions to be made concerning the pH value in the surface fluid layer. A uniform set of permeability data including both weak acids and weak bases was obtained only when it was assumed that the pH in the surface fluid layer was equal to that in the bulk phase, and it was concluded that these studies do not support the concept of a microclimate of distinctive pH at the epithelial surface as a determinant of weak electrolyte transport.
| 25,945
|
Chemical and electrochemical oxidation of 7-hydroxychlorpromazine.
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The oxidation of 7-hydroxychlorpromazine, a process associated with several side effects of chlorpromazine therapy, was examined in vitro by electrochemistry and rapid-scanning spectrophotometry. At pH 2, the oxidation results in a quantitative yield of 7,8-dioxochlorpromazine, but several intermediates are observable during the course of the reaction. These include a quinone imine with a half-life of 0.1 s, a monosubstituted benzoquinone with a half-life of approximately 50 s, and a disubstituted benzoquinone with a half-life of approximately 5 min. The concentrations of each intermediate were determined quantitatively as a function of time, and a complete oxidation mechanism is proposed. At pH 7, the yield of 7,8-dioxochlorpromazine is less than at pH 2, and an additional reaction pathway involving direct hydroxylation of the quinone imine is observed. The relationship of these reactions to the pharmacology of the hydroxylated chlorpromazine metabolites is discussed.
| 25,968
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Experience with 425 subfertile male patients.
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Subfertility was evaluated in 425 men. Varicocele were diagnosed in 37.4 per cent of these patients and surgical correction of the varicocele in 68 men resulted in a 65 per cent improvement in semen quality. Idiopathic abnormalities were found in 25.4 per cent of the patients. Since the study group was heterogenous setereotyped or empirical treatment cannot hope to be successful if uniformly applied. Other specific causes of male subfertility are identified and therapeutic options are discussed.
| 25,971
|
[Acidophilic thermotolerant Candida utilis yeast strain obtained by continuous cultivation].
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An acidophilic thermotolerant strain of Candida utilis 1668-3-37 was produced under conditions of continuous cultivation during 128 days. The optimum pH is 3.0-4.5 at 32 degrees C. The strain grows with mumax=0.30 hr(-1) at 37-38 degrees C and the same pH values if dry yeast autolysate (0.05%) is added to the medium.
| 26,012
|
Transcription in the interbands of Drosophila.
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Many interbands of Drosophila contain morphological evidence for transcription. Decondensed band material makes no detectable contribution to certain transcriptionally active interbands.
| 26,090
|
Labilization of brain lysosomes by trichloroethylene metabolites and peroxide anion in vitro.
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Lysosomes were isolated from adult male Wistar rat brain and incubated in vitro with 10 micron trichloroethylene and microsomes or postmicrosomal supernatant with added NADPH. Freezing and incubation with the solvent alone served as controls. The results were compared with the effect of peroxide anion from the xanthine-xanthine oxidase reaction. Mere solvent did not cause an appearance of acid proteinase activity in the incubation medium whereas other treatments induced lysosomal labilization.
| 26,109
|
Graft-versus-host reactions within the thyroid gland may evoke pari passu autoimmune thyroiditis.
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Unilateral, intraorganal injection of parental lymph node cells into thyroid lobes of F1 hybrid rats elicited an intense, local graft-versus-host reaction within the injected lobes containing massive numbers of lymphocytes. Surprisingly, significant mononuclear cell infiltration was also seen within the contralateral (noninjected) thyroid lobes, even when the isthmus had been divided. The local graft-versus-host reaction spread from the injected gland to involve the regional lymph nodes and spleen. Migration of 51-cr-labeled donor lymph node cells was documented in these same tissue sites; lesser numbers of labeled cells were found in distant lymph nodes, including the contralateral cervical nodes. However, no significant label was found in the contralateral thyroid lobes. Microscopic evaluation of noninjected glands revealed intense infiltration of mononuclear cells around and within follicles, reminiscent of lesions induced by immunization with thyroid extract in Freund's complete adjuvant. The absence of donor cells in the inflammatory reactions within noninjected thyroid lobes raises the possibility of an autoimmune rather than graft-versus-host pathogenesis.
| 26,130
|
Myocardial effects of lithium in vitro.
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The myocardial effects of increasing concentrations of ionic lithium were investigated in isolated, spontaneously beating rabbit hearts, which were retrogradely perfused with a modified Krebs-Henseleit solution containing lithium in concentration of 1, 5 or 10 mM. The following functional parameters were continuously recorded: heart rate, amplitude and rate of contraction, coronary flow, myocardial oxygen consumption and ECG. The lowest concentration of 1 mM lithium did not cause any measurable changes in these parameters. A concentration of 5 mM lithium produced a rather slowly developed increase in amplitude and rate of contraction of about 22% without any concomitant increase of oxygen consumption. A delayed increase in the oxygen consumption of about 21%, but accompanied by a significant decrease in contractility however, occurred much later in the experiments, probably as an expression of a decrease in myocardial efficiency. The highest lithium concentration produced similar effects. None of the other parameters measured were markedly influenced by lithium. The positive inotropic effect of lithium on myocardial contractility was very convincingly verified in isolated electrically stimulated rabbit papillary muscles by isometric measurements of the maximum tension produced and the rate of its development. An inhibitory influence of lithium on the positive inotropic effect of increasing frequency of stimulation was observed. Adrenergic beta-receptor blockade did not abolish the positive inotropic effect of lithium. A possible causative influence of lithium on the cellular calcium metabolism is discussed.
| 26,164
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Comparison of beta-adrenoceptors mediating vasodilatation in canine subcutaneous adipose tissue and skeletal muscle.
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Blood flow changes in response to various drugs in simulataneously autoperfused canine subcutaneous adipose tissue and gracilis muscle were compared to study the vascular beta-adrenoceptors. Compared to isoprenaline the beta 2-selective agonist salbutamol was 4--6 times more potent as a vasodilator in the muscle than in adipose tissue. Furthermore two beta 1-selective agonists (Tazolol and H80/62) caused vasodilatation in adipose tissue but not in the gracilis muscle. When given by close i.a. injection after beta-adrenoceptor blockade, adrenaline was a more potent vasoconstrictor than noradrenaline in both tissues. Before beta-blockade, however, noradrenaline was the more potent vasoconstrictor in the gracilis muscle whereas adrenaline was more potent in adipose tissue. Intravenous infusion of adrenaline in doses causing vasodilatation in the muscle caused vasoconstriction in adipose tissue whereas intravenous infusion of noradrenaline caused vasoconstriction in both tissues. The present findings suggest that the beta-adrenoceptors mediating vasodilatation in skeletal muscle are mainly ose tissue. Since adrenaline is a much more potent beta2- than beta1-agonist, these differences point to different roles of intravascular adrenaline in the two sites. In skeletal muscle circulating adrenaline is mainly a vasodilator whereas in subcutaneous adipose tissue it mainly acts as a vasoconstrictor.
| 26,166
|
Attenuated variants of eastern equine encephalomyelitis virus: pathomorphological, immunofluorescence and virological studies of infection in Syrian hamsters.
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A virulent strain of eastern equine encephalomyelitis virus produced in hamsters a lethal infection with severe lesions of nerve cells predominatly in the anterior parts of the brain. Parenchyma necroses occurred in the liver and lymphoid organs. Infectious virus and viral antigen were found in all the organs examined with the greatest accumulation in the brain. Attenuated variants of the virus produced in most hamsters an inapparent infection. In some animals without clinical signs, focal inflammatory-dystrophic lesions were found in the central nervous system (CNS) and the liver, as were immunomorphological changes in the lymphoid tissue. In the latter infectious virus could be detected for 6 days after inoculation (p.i.), whereas in the brain only viral antigen could be found up to 14 days. At 3 and 6 months p.i., no persistence of attenuated virus in the brain and lymphoid tissues could be established by organ culture and co-cultivation methods. Nor was virus antigen detected. No pathomorphological changes or proliferative-hypertrophic astrocyte reaction were found.
| 26,199
|
T lymphocytes as an indicator in influenza vaccination, influenza and acute respiratory diseases.
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Significant differences in T-lymphocyte counts in the peripheral blood of normal subject and volunteers vaccinated with live and inactivated influenza vaccines as well as patients with influenza and viral acute respiratory diseases (ARD) were demonstrated. A laboratory test using T lymphocytes was proposed for the evaluation of the safety of live influenza vaccine.
| 26,203
|
Comparative study of virion transcriptase of some influenza virus strains.
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The activities, the temperature and pH optima of in vitro functioning and stability upon heating of virion transcriptase of 10 human influenza virus A strains differing in reactogenicity and isolated in different epidemiological situations, and of fowl plague virus (FVP) were compared. As compared with virion transcriptase of human influenza virus strains studied, that of FPV had a higher pH optimum, was capable of functioning in vitro at a higher temperature and was more stable on heating. Freshly isolated and vaccine influenza virus strains on the one hand and strains isolated at the peak and in the end of an epidemic did not differ in the virion transcriptase properties. The virion transcriptase of a strain isolated from a local influenza outbreak was much less active than transcriptase of a highly epiedmic strain.
| 26,210
|
[DNA--"rejoining" in lymphycytes of patients with a minifestation of rheumatoid arthritis in older age (author's transl)].
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Relations between the time of manifestation of the disease and the course of the rheumatoid arthritis were found from the clinic frequently. Patients with later first manifestation of rheumatoid arthritis show clear differences against patients with earlier manifestation of the disease at which the late first manifestation a high activity of the process of the disease exhibit. In males first manifestation of rheumatoid arthritis in middle age of 54,5 years was observed, while in a first manifestation of rheumatoid arthritis in middle age of 47 years a normal course of the disease was found. The difference between the both courses was proved as significantly. In former investigations we could prove that in patients with rheumatoid arthritis the 3H-Thymidin-build in the course of not programmed DNA-synthesis in the DNA of lymphocytes after damage with ionizing was retarded. The rate of not programmed DNA synthesis seems to be in old persons equal. The ligase reaction is possibly diminished because the number of DNA-strand breakes with the age is strong increasing.
| 26,226
|
[Interactions of drugs, used in the treatment of rheumatism in the elderly (author's transl)].
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This paper reviews the possibilities of interactions of drugs, used in the treatment of rheumatism in the elderly. Exspecially glycosides, antikoagulants, diuretics, uricosurics, salicylates, barbiturates and corticosteroides are discussed.
| 26,228
|
[Further data on the isolation of the aged (authors transl)].
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Author's studies performed on 100 aged persons over sixty revealed the factors which play a role in the decline of the interpersonal connections. From his results, he suggests two forms of the communication-decrease during senessence. One form is a factor of exogen origin, which comes into existence as a result of deprivation effects, respectively. On the other hand, the second one is of intra-individual origin, whose nature formed by special characteristics of personality. These are typical of the individual during whole life. Both forms verify that in certain cases favourable, compensating components must be taken into account, however, sometimes this effect could be inauspicious. Separating the two forms is of great importance from the point of geriatrics, as well.
| 26,248
|
Influence of methyl xanthine treatment on calcitonin effect.
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The presented results clearly demonstrate that theophylline, caffeine and theobromine have a blocking action on calcitonin effect as determined by the elevation of serum calcium level, although different degree of potency was found with each drugs. There is no difference in respect of the serum calcium elevation after a single dose of methyl xanthines or after a 9-10 day lasting treatment. The castration had no additional enhancing effect of the calcitonin resistance of methyl xanthine treated animals. The administration of androgens simultaneously with the methyl xanthine treatment failed to produce improvement of calcitonin sensitivty preventing the elevation of serum calcium after calcitonin injection. So the calcitonin resistance of methyl xanthine treated animals appears to be different to the calcitonin resistance of sex hormone deprived conditions because the latter could be abolished by androgen administration. Theophylline treatment resulted in a slightly but significantly elevated serum calcium comparing to controls without exogeneous calcitonin. This magnitude of elevation remains between the normocalcaemic limits.
| 26,253
|
[Survived brain infarction in old age - clinical and morphological findings. part I: extracranial stenoses of carotis arteries (author's transl)].
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By clinical and post mortem findings we searched for the risk factors, important for brain infarctions in people of nearly 80 years. We were especially interested in the conditions of the extracranial vessels such as the carotid arteries and the murmurs at this point. The number of arterial stenoses in this region, ascertained in younger people is similar in old age. Besides of others factors, caused by old age, the many cases of multiple extracranial stenoses are probably responsible for the overproportional big brain infarctions in this series. In nearly 50% of all stenoses we heard vascular murmurs, mostly in both of the carotid arteries. Despite of some uncertainly of the clinical importance - just in old age many cardiac murmurs of the ejection type with tendency to transmission have been heard - they should give rise to investigate carefully the region of the neck in symptomatic patients.
| 26,254
|
[Results concerning the sensitivity of old patients against digitalis (author's transl)].
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It could be demonstrated that there was an age-dependent increase of digitalisintoxications in correlation with digitalisconcentrations in blood. This phenomenon can be explained with the frequently observed underweight in the senium. Some patients older than 70 years showed symptoms of intoxication in spite of a normal digitalisconcentration in serum. But the presented results did not demonstrate a significant difference between young and old patients concerning the sensitivity against digitalis. Therefore it is necessary to consider the bodyweight for digitalis therapy in older patients.
| 26,259
|
[The motor activity as an age parameter of the rat (authors transl)].
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The motor activity as an behavioural parameter provides information about the functional state of the organism as a whole. Therefore it is an important age parameter. The results of activity measurements, however, depend strongly on the method of registration. Using 3 groups of male Sprague-Dawley rats aged 9, 15 and 29 months two methods have been tested: 1) An electronic recording: the rats were registrated in their normal cages on the Animex-Activity-Meter during the dark-phase in complete darkness. The activity measured by this method has been regarded as spontaneous activity. 2) A kinematographic method: the rats were registrated in a changed environment at constant light during the dark-phase. The activity assessed by this method has been regarded as reactive activity. Spontaneous and reactive activity show a different age dependence. For the use of the motor activity as an age parameter, both, spontaneous and reactive activity, should be assessed to get a better information about the ageing of the different functional levels of the systems governing the animal's behaviour.
| 26,274
|
Characterization of the papain active centre by using two-protonic-state electrophiles as reactivity probes. Evidence for nucleophilic reactivity in the un-interrupted cysteine-25-histidine-159 interactive system.
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1.2,2'-Dipyridyl disulphide (2-Py-S-S-2-Py) and n-propyl 2-pyridyl disulphide (propyl-S-S-2-Py) were used as two-protonic-state reactivity probes to investigate the active centre of papain (EC 3.4.22.2).2. The existence of a striking rate optimum at pH approx. 4 in the reaction of papain not only with the symmetrical probe but also with the unsymmetrical probe is shown to constitute compelling evidence that the thiolate ion component of the cysteine-25-histidine-159 interactive system of papain possesses appreciable nucleophilic character. It is not a necessary requirement that the probe reagent should engage the imidazolium ion of histidine-159 in hydrogen-bonding for the sulphur atom of the interactive system to display nucleophilic character. The single proton-binding site of propyl-S-S-2-Py cannot simultaneously interrupt the active-centre ion pair and provide for rate enhancement as the pH is lowered towards 4. The possible implication of this for the mechanism of papain-catalysed hydrolysis is discussed. 3. The suspected difference in the active centres of papain and ficin (EC 3.4.22.3), which could be a lack in ficin of a carboxy group conformationally equivalent to that of aspartic acid-158 of papain is confirmed. The reactivity of the papain thiol group towards both probe reagents is controlled by two ionizations with pKa close to 4 that are positively co-operative. 4. In the reaction of papain with 2-Py-S-S-2-Py. the reactivity appears to be controlled also by an addition ionization with pKa approx. 5. Possible origins of this additional ionization are discussed. K. The spectral and ionization characteristics of propyl-S-S-2-Py are reported. 6. The reagent reacts rapidly with thiol groups at the sulphur atom distal from the pyridyl ring to provide, at pH values below 9, stoicheiometric release of 2-thiopyridone. This property, together with the ability of the reagent markedly to increase its electrophilicity consequent on protonation, suggests alkyl-2-pyridyl disulphides in general as valuable two-protonic-state reactivity probes with exceptional specificity for thiol groups.
| 26,335
|
Purification and properties of a manganese-stimulated deoxyribonuclease produced during sporulation of Bacillus subtilis.
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A DNAase (deoxyribonuclease) was isolated from culture supernatants of sporulating Bacillus subtilis 168. The purified enzyme migrated as a single band during polyacrylamide-gel electrophoresis. The enzyme differs from other DNAases of B. subtilis in molecular weight, metal-ion requirement and mode of action. The enzyme was inactive in the absence of metal ions, and exhibited optimum activity with 10 mM-Mn2+, although Mg2+, Cd2+ and Co2+ could also permit some activity. The pH optimum for the enzyme was pH 7.5, and it degraded linear-duplex DNA or closed-circular-duplex DNA to acid-soluble material. There was little or no activity on single-stranded DNA or rRNA. Sucrose-gradient analysis of the products of DNAase action on bacteriophage T7 DNA showed that endonucleolytic cleavage had occurred by the introduction of single-strand breaks in both strands of the duplex. The molecular weight of the enzyme was determined, by gel filtration on Sephadex G-75, to be 12000.
| 26,339
|
Prevention and treatment of premature labour by drugs: review of controlled clinical trials.
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This review sought evidence from 18 controlled clinical trials about the benefits of drugs (hormones, ethanol or beta-sympathomimetic agents) used to prevent premature birth. Of the 16 trials comparing drug with placebo, 13 were judged to be methodologically adequate. In eight trials, drugs were given prophylactically and in five they were given therapeutically. Two of the therapeutic trials found the drug more effective than placebo in postponing delivery. However, only one therapeutic trial and one prophylactic trial found the drug to affect favourably the outcome for the infant. The side effects of the drugs were not systematically studied. Additional clinical trials are needed to justify the use of drugs to inhibit labour.
| 26,374
|
Photosynthetic electron transport and phosphorylation reactions in thylakoid membranes from the blue-green alga Anacystis nidulans.
|
Thylakoid membranes were prepared from the blue-green alga, Anacystis nidulans with lysozyme treatment and a short period of sonic oscillation. The thylakoid membrane preparation was highly active in the electron transport reactions such as the Hill reactions with ferricyanide and with 2,6-dichlorophenolindophenol, the Mehler reaction mediated by methyl viologen and the system 1 reaction with methyl viologen as an electron acceptor and 2,6-dichlorophenolindophenol and ascorbate as an electron donor system. The Hill reaction with ferricyanide and the system 1 reaction was stimulated by the phosphorylating conditions. The cyclic and non-cyclic phosphorylation was also active. These findings suggest that the preparation of thylakoid membranes retained the electron transport system from H2O to reaction center 1, and that the phosphorylation reaction was coupled to the Hill reaction and the system 1 reaction.
| 26,396
|
Role of Bohr group salt bridges in cooperativity in hemoglobin.
|
Possible problems in measuring the first Adair constant, K1, from accurate oxygen equilibrium curves have been investigated. Of these only the presence of small amounts of CO-hemoglobin or hemoglobin dimers had a significant effect. The former can be eliminated by treatment with oxygen, the latter by measuring the concentration-dependence of K1 or working at high protein concentrations. K1 values have been measured for normal hemoglobin at pH 7 and 9, hemoglobin specifically reacted with cyanate at Val 1alpha (alphac2beta2) and des(His 146beta) hemoglobin at pH 7. K1 is equal to KT, the oxygen affinity of the T state of hemoglobin, for all these hemoglobins and was increased in all of them when compared to normal hemoglobin at pH 7. This shows that the breakage of the Bohr group salt bridges by increasing pH or specific modification changes KT. Hence the Bohr group salt bridges break on ligation of the T state and are partially responsible for the free energy of cooperativity.
| 26,416
|
Influence of pH and temperature on behaviour of surfactant from human neonatal lungs.
|
The surface pressures of human surfactant films were measured under static conditions and under dynamic (expansion-compression) conditions. The results from both methods showed that the maximum surface pressures generated by surfactant films in vitro were strongly dependent on temperature throughout the range 29-41 degrees C, higher pressures being achieved at the lower temperatures. In contrast, increasing the pH of the subphase stepwise over the range 7.1-7.7 produced a modest fall in the maximum pressures exerted by the films. The possibility that surfactant films may behave in a similar manner in vivo is discussed.
| 26,432
|
Investigation of the role of histamine in antigen-induced bronchoconstriction in the ascaris-hypersensitive dog.
|
1 Aerosol administration of ascaris antigen to the airways of ascaris-hypersensitive dogs provoked increases in pulmonary resistance (Rp) and decreases in dynamic lung compliance (Cdyn). These changes in pulmonary mechanics were not inhibited by the histamine H1-receptor antagonists, diphenhydramine or mepyramine. 2 Increases in Rp and decreases in Cdyn induced by a histamine aerosol were markedly or totally inhibited by comparable doses of these H1-antihistamines. 3 Doses of antigen which produced pathophysiological pulmonary responses failed to produce a detectable histamine release from the cardiopulmonary system in vivo. Aerosol antigen provocation, equivalent to 5 to 9 times greater than that which produced substantial pathophysiological pulmonary responses, did cause histamine release in vivo. 4 The canine cardiopulmonary system showed only a modest ability to remove and/or degrade circulating histamine. 5 It is concluded that histamine may not play a major role in mediating the acute antigen-induced bronchoconstriction in the ascaris-hypersensitive dog.
| 26,444
|
The treatment of frigidity: a comparative study of group and individual desensitization.
|
Forty patients took part in this study. Twenty patients treated by group desensitization were compared with twenty treated by individual desensitization. Group desensitization appeared the more effective treatment if outcome was measured on the patients' self-rating scale, but the less effective if outcome was measured by the sexual interest questionnaire. Of the two, the group method took longer to administer, but more patients treated in this way completed the course of treatment.
| 26,447
|
Induction of autolysis in Bacillus subtilis by ochratoxin A.
|
Ochratoxin A (OTA) added during the exponential growth phase at a concentration higher than 12 microgram/ml caused autolysis of Bacillus subtilis. Optical density of cultures decreased, and at higher concentrations the cultures became sterile. Optimum OTA-induced lysis was about pH 5. At concentrations below 10 microgram/ml, protein synthesis was inhibited more strongly than RNA synthesis. Cell wall synthesis was also strongly inhibited. A fraction extracted from the lysates had the property of a lysis inhibitor. The relevance of this fraction in respect to autolysis is discussed.
| 26,457
|
Prescribing of psychoactive drugs for chronically ill elderly patients.
|
The prescribing of psychoactive drugs for 1431 chronically ill elderly patients being assessed for long-term institutional or community care was surveyed. Psychoactive drugs had been prescribed for about one quarter of the patients; benzodiazepines were the most frequently prescribed group. Judging from the extensive prescribing of flurazepam and chloral hydrate, commonly used hypnotics, the main reason psychoactive drugs were prescribed was to provide night-time sedation. Antidepressants and drugs promoted as useful in improving cognitive function were infrequently prescribed. Commendable prescribing practices included the infrequent use of "cerebral vasodilators" and barbiturates. Questionable prescribing practices included the infrequent use of tricyclic antidepressants in severely depressed patients and the use of tranquilizers in patients described by their attending physician as markedly or extremely withdrawn.
| 26,459
|
Changes in small vessel blood content of the rat heart induced by hypercapnic, hyperoxic or asphyxic conditions.
|
The small vessel blood content (SVBC) of the ventricular walls of the heart of anesthetized closed chest rats was determined using 59FeC13 to label the plasma siderophilin. SVBC was measured breathing air, 100% O2, 5% CO2 in 21% O2 and during asphyxia. The average SVBC could be ranked: air less than 100% O2 less than 5% CO2 less than asphyxia. Only the '100% O2' values were not significantly above the 'air' values. Under control conditions, SVBC of the rat heart averaged 6.77 +/-(SE) 0.23 ml blood/100 g tissue. Inhalation of 5% CO2 increased this to 8.68 +/- 0.34, while asphyxia produced a maximal response to 14.40 +/- 0.77. Comparison of SVBC were made between various regions of the ventricular walls. The only significant difference was that the right side of the septum had a lower SVBC than the left ventricular subepicardium under all conditions except CO2. These differences in SVBC are related to the number of open capillaries in the myocardium. Thus inhalation of CO2 decreases intercapillary distance while 100% O2 has no effect.
| 26,467
|
Levodopa pharmacokinetics. Alterations after benserazide, a decarboxylase inhibitor.
|
Plasma levodopa decay curves appeared to be triexponential up to 6 hr after single intravenous injections of levodopa in rats, rabbits, and dogs. After pretreatment of each of these three species with benserazide (Ro-4-4602), a decarboxylase inhibitor, plasma levodopa concentrations declined biexponentially. Administration of benserazide decreased both total plasma clearance and apparent volume of distribution of levodopa, but did not change the rate constant of the terminal phase of the plasma levodopa decay curve. Thus, decarboxylase inhibition failed to alter the plasma half-life of levodopa.
| 26,532
|
Chorismate mutase/prephenate dehydratase from Escherichia coli K12. Binding studies with the allosteric effector phenylalanine.
|
The binding of phenylalanine to the allosteric site of chorismate mutase/prephenate dehydratase has been studied by steady-state dialysis. Under most of the experimental conditions examined positive co-operativity was observed for the binding of ligand up to 50% saturation and negative co-operativity above 50% saturation. In the presence of 0.4 M NaCl at pH 8.2 the co-operativity was positive at all phenylalanine concentrations and the maximal stoichiometry of 1 mol of phenylalanine/mol of enzyme subunit was observed. It was concluded that there is a single phenylalanine-binding site per subunit which is associated with the regulation of each of the mutase and dehydratase activities. The effects of enzyme concentration, NaCl, temperature and pH on the binding of phenylalanine have been investigated. Neither tyrosine nor tryptophan bound to the allosteric site of the enzyme. Enzyme that was desensitized to inhibition by phenylalanine following modification of three sulphydryl groups with 5,5'-dithio-bis (2-nitrobenzoic acid) did not bind phenylalanine. The mechanism of co-operativity, the binding of the enzyme to Sepharosyl-phenylalanine and the physiological significance of the inhibition of the enzyme by phenylalanine are discussed in terms of the results obtained.
| 26,562
|
Biphasic effect of chlorpromazine on rat paradoxical sleep: a study of dose-related mechanisms.
|
The experiments reported here investigated the effect of chlorpromazine (CPZ) alone or after inhibition of catecholamine (CA) synthesis on paradoxical sleep (PS) in the rat. The dose--response curve for CPZ was biphasic with enhancement of PS after low doses, and depression of PS after higher doses. In contrast, low doses of CPZ after inhibition of CA synthesis markedly decreased PS. This decrease was greater after tyrosine hydroxylase inhibition than after dopamine-beta-hydroxylase inhibition. These results support the view that low doses of CPZ produce increased activity in brain CA synapses, and that both dopamine and noradrenaline participate in the control of PS in the rat.
| 26,579
|
Positive chronotropic and inotropic responses to guanosine in the isolated dog atrium.
|
The effects of guanosine on chronotropism and inotropism in isolated dog atria were studied in spontaneously beating preparations which were suspended in a bath perfused with arterial blood from a carotid artery of a heparinized support dog. Guanosine administered into the cannulated sinus node artery in a dose range of 30 microgram to 3 mg produced a dose-related positive inotropic and chronotropic effect. The positive responses to guanosine were not inhibited by treatment with propranolol or a non-depressant beta-blocker, carteolol, in doses which blocked responses to norepinephrine. From these results, it is concluded that guanosine has a direct effect on atrial rate and contractility.
| 26,581
|
[On the acute toxicity of labetalol (AH-5158), a combined alpha-and-beta-adrenoceptor-blocking agent (author's transl)].
|
Acute toxicity studies in labetalol were performed using mice, rats and rabbits, An oral administration of labetalol produced an increase in salivary secretion due to local irritation. Death followed convulsions by large doses of labetalol. Pathological examinations suggested that the cause of death by labetalol was circulatory disturbances due to the damage of heart muscles and a subsequent respiratory paralysis. Parenteral LD50 showed almost the same values among mice (50 mg/kg iv, 117 mg/kg ip), rats (66 mg/kg iv, 115 mg/kg ip) and rabbits (43 mg/kg iv). However, species difference was seen in oral LD50 values which were enormously large as compared with iv LD50 values.
| 26,632
|
Aspartokinase of Streptococcus mutans: purification, properties, and regulation.
|
Aspartokinase from Streptococcus mutans BHT was purified to homogeneity and characterized. The molecular weight of the native enzyme was estimated to be 242,000 by gel filtration. Cross-linking of aspartokinase with dimethyl suberimidate and polyacrylamide gel electrophoresis of the amidinated enzyme in the presence of sodium dodecyl sulfate showed the enzyme to be composed of six identical subunits with a molecular wieght of 40,000. The optimal pH range for enzyme activity was 6.5 to 8.5. The apparent Michaelis-Menten constants for aspartate and ATP were 5.5 and 2.2 mM, respectively. The enzyme was stable within the temperature range of 10 to 35 degrees C. Aspartokinase was not feedback inhibited by individual amino acids, but was concertedly inhibited by L-lysine and L-threonine (93.5% inhibition at 10 mM each). The inhibition was noncompetitive with respect to aspartate (Ki = 10 mM) and mixed with respect to ATP. L-Threonine methyl ester and L-threonine amide were able to substitute for L-threonine in feedback inhibition, but the requirement for L-lysine uas strict. The feedback inhibitor pair protected the enzyme against heat denaturation. Aspartokinase synthesis was repressed by L-threonine; this repression was enhanced by L-lysine, but was slightly attenuated by L-methionine.
| 26,656
|
Purification and properties of the inducible nicotinamide adenine dinucleotide phosphate-specific glutamate dehydrogenase from Chlorella sorokiniana.
|
The nicotinamide adenine dinucleotide phosphate-specific glutamate dehydrogenase (NADP-GDH) of Chlorella sorokiniana was purified 260-fold to electrophoretic homogeneity in six steps. Depending on the techniques used, the native enzyme appeared to have a molecular weight of 290,000 or 410,000 and to be composed of five to seven identical subunits with a molecular weight of 58,000. The amino acid composition of this enzyme was shown to differ considerably from that of the NAD-GDH in this organism. The NH2-terminal amino acid was unavailable to dansylation. All six cysteines in the native enzyme were in the free sulfhydryl form. The pH optima for the aminating and deaminating reactions were 7.2 and 9.2, respectively. The Km values for NH4+, alpha-ketoglutarate, NADPH, L-glutamate, and NADP+ were 68, 12, 0.13, and 0.038 mM, respectively. At low substrate concentrations, no cooperativity was seen; however, severe inhibition of enzyme activity was observed at high alpha-ketoglutarate concentrations. Nucleotides did not affect enzyme activity. Antiserum produced in rabbits to the subunits of the enzyme yielded a single precipitin band with the purified enzyme in Ouchterlony double-diffusion analysis. Immunoelectrophoresis was used to confirm the purity of the enzyme and also to quantify the amount of enzyme antigen. These studies indicate that the NADPH-GDH and NAD-GDH isozymes are distinct molecular species in this organism.
| 26,661
|
Mutations that alter the covalent modification of glutamine synthetase in Salmonella typhimurium.
|
glnD and glnE mutant strains of Salmonella typhimurium lack three of the four activities required for reversible covalent modification of glutamine synthetase (GS; EC 6.3.1.2). The glnD strains, which are unable to deadenylylate GS and therefore accumulate the adenylylated or less active form of the enzyme, were isolated as glutamine bradytrophs. They lack the activity of PIIA uridylyl-transferase, one of the proteins required for deadenylylation of GS; in addition, they lack PIID uridylyl-removing activity. Mutations in glnD are suppressed by second-site mutations in glnE that eliminate the activity of GS adenylyltransferase (EC 2.7.7.42) and thus prevent adenylylation of GS. The glnD and glnE strains have one-third to one-half as much total GS as the wild-type strain when they are grown in a medium containing a high concentration of NH4+. The wild-type strain derepresses synthesis of GS fourfold in response to nitrogen limitation; glnD and glnE strains derepress synthesis of the enzyme fourfold and sevenfold, respectively. Thus, mutations that alter covalent modification of GS in Salmonella do not significantly affect derepression of its synthesis. The glnD gene lies at 7 min on the Salmonella chromosome and is 50% linked to pyrH by P22-mediated transduction.
| 26,663
|
Superoxide generation by digitonin-stimulated guinea pig granulocytes. A basis for a continuous assay for monitoring superoxide production and for the study of the activation of the generating system.
|
Stimulation of guinea pig granolocytes by digitonin results in superoxide (O-2) generation. A continuous assay shows that there is a lag between the addition of digitonin and the onset of O-2 production. The rate of activation of the O-2 generating system is dependent upon the concentration of digitonin and the temperature. The final linear rate of O-2 production is affected by the concentration of digitonin, temperature, pH, and the presence of exogenous reduced pyridine nucleotides. Thus, factors which alter either the activation process or the activity of the O-2 generating system can affect O-2 production by stimulated granolocytes.
| 26,695
|
Relationship between phosphorylation of tyrosine aminotransferase and regulation of its synthesis by cyclic AMP and hormones.
|
Tyrosine adminotransferase (EC 2.6.1.5) has been found to be phosphorylated in intact rat hepatoma cells in culture. Incorporation of [32p]i into the enzyme is rapid and is exclusively found as phosphoserine. Cycloheximide treatment reduced phosphorylation of the aminotransferase only slightly and in the presence of three different inducers of this enzyme, dexamethasone, insulin, and dibutyryl cyclic AMP, [32P]I incorporation was increased. It is concluded that [32p]i incorporation into this enzyme probably reflects turnover of phosphate groups associated with pre-existing enzyme molecules catalyzed by a cyclic AMP-independent protein kinase.
| 26,702
|
The mechanism of the hypothermic effect of amantadine in rats and mice.
|
Amantadine (25--100 mg kg-1, i.p.) given to rats at an ambient temperature of 4 degrees, or mice at 21 degrees, caused a marked fall in rectal temperature. Prior administration of pimozide (1--2 mg kg-1, s.c.) did not block hypothermia due to amantadine in rats or mice; in contrast, hypothermia due to apomorphine (2 mg kg-1, i.p.) and piribedil (10--40 mg kg-1, i.p.) in rats was blocked by pimozide pretreatment. Amphetamine (5 mg kg-1, i.p.) given 2 h after reserpine (2 mg kg-1, i.p.) caused a reversal of the hypothermic effect of reserpine in mice, but a reversal was not obtained with amantadine (50 mg kg-1, i.p.). Direct injection of amantadine (4--8 mg kg-1) into the cerebral ventricles (i.c.v.) of mice caused marked hypothermia which was not blocked by pimozide, but intravenous injection of the same dose of amantadine did not cause hypothermia. Rimantadine, a congener of amantadine but without anti-parkinsonian activity, also caused pimozide insensitive hypothermia in mice at doses of 50 mg kg-1, intraperitoneally or 2--4 mg kg-1, intracerebroventricularly. The main conclusion drawn from these results is that in causing hypothermia amantadine acts in the cns but not on dopamine receptors.
| 26,741
|
A mammalian muscle with the pharmacological characteristics of slow tonic muscle.
|
The guinea-pig isolated cremaster muscle gave tetrodotoxin-resistant dose-related contractures with acetylcholine, carbachol and the depolarizing neuromuscular blocking agents. The dose-response curve to suxamethonium in tetrodotoxin 2 X 10(-7)M could be shifted to the right with tubocurarine 10(-6)M. KCl, 0.1M, produced slow sustained contractures of the muscle. With the cremaster nerve-muscle preparation tetanic contractions at 20 Hz were maintained over several minutes. Tetrodotoxin eliminated the twitch response to single shock nerve stimulation but not the sustained increase in tension produced by suxamethonium. The results suggest either that there is a component of slow tonic muscle in the guinea-pig cremaster or that the cremaster consists of a type of focally innervated muscle which has pharmacological responses qualitatively different from those of most focally innervated muscles so far described.
| 26,743
|
On methods of expressing dissolution rate data.
|
The value of the Weibull, logarithmic-logistic, and logarithmic-normal plots in expressing dissolution rate data is considered for the combinations of zero and first-order release with sink and non-sink conditions, and for actual dissolution rate data of diazepam from tablets in a medium of pH2.
| 26,763
|
Investigation of possible interactions between substance P and transmitter mechanisms in the substantia nigra and corpus striatum of the rat.
|
The effect of substnace P (SP) on the uptake and release of radiolabelled dopamine (3H-DA), 5-hydroxytryptamine (3H-5-HT) and y-aminobutyric acid (3H-GABA) was studied in slices of rat substantia nigra and corpus triatum. SP, 10(-9) to 10(-5) m, failed to modify the uptakes of these compounds during incubations (10-90 min) with slices of either brain region. SP, 10(-6)M, had no apparent effect on the spontaneous output of any of these compounds in either substantia nigra or corpus striatum. In the corpus striatum, SP seemed to potentiate the potassium-stimulated outflow of 3H-DA and 3H-5-HT, but not 3H-GABA, while the realeases from substantia nigra were unaffected. Morphine (10(-3)M), but not met-enkephalin (5 X 10(-6)M), weakly antagonized K+- EVOKED RELEASE OF 3/-DA in the corpus striatum. These results are discussed with reference to the possible interaction of SP with transmitter mechanisms at presynaptic sites in the central nervous system.
| 26,766
|
Rat brain and serum lithium concentrations after acute injections of lithium carbonate and orotate.
|
Eight hours after intraperitoneal injections of 1.0, 2.0, and 4.0m equiv Li kg-1, the serum and brain lithium concentrations of rats were significantly greater after lithium orotate than after lithium carbonate. While little serum lithium remained at 24 h after injection of 2.0 m equiv kg-1 lithium carbonate, two-thirds of the 2 h serum lithium concentration was present 24h after lithium orotate. Furthermore, the 24 h brain concentration of lithium after lithium orotate was approximately three times greater than that after lithium carbonate. These data suggest the possibility that lower doses of lithium orotate than lithium carbonate may achieve therapeutic brain lithium concentrations and relatively stable serum concentrations.
| 26,768
|
Antidotal effects of dimethyl sulphoxide against paracetamol-, bromobenzene-, and thioacetamide-induced hepatotoxicity.
|
In mice the hepatotoxic effects of paracetamol (0.5-1.0 g kg-1, orally) as evidenced by increased serum enzyme activities of the aminotransferases and sorbitol dehydrogenase were dose-dependently inhibited by simultaneous treatment with dimethyl sulphoxide (DMSO 0,25-1.0 g kg-1, i.p.). DMSO was also active against bromobenzene- and thioacetamide-induced hepatotoxicity, but failed to protect mice against carbon tetrachloride-induced liver damage. Hepatic glutathione depletion in mice amounting to 94% after paracetamol (0.5 g kg-1, orally) and to 60% after bromobezene (0.25 ml kg-1, orally) was dose-dependently reduced by the simultaneous administration of DMSO(0.25--1.0 G KG-1, I.P.). This indicates less conjugation of the toxic metabolites of paracetamol and bromobenzene to liver glutathione (G-SH) in the presence of DMSO.
| 26,770
|
Interaction of tricyclic antipsychotic and antidepressant drugs with 1-anilino-8-naphthalenesulfonic acid.
|
The binding of 1-anilino-8-naphthalenesulfonic acid to selected tricyclic antipsychotic and antidepressant drugs was studied by fluorescence spectroscopy. The acid exhibited an increase in fluorescence intensity accompanied by a hypsochromic shift of the emission lambdamax in the presence of these drugs. These fluorescence characteristics, in addition to those of acid-drug complexes after addition of potassium chloride or urea, suggested that binding was hydrophobic. The spectra also provided evidence regarding the importance of certain structural features of drugs in determining the nature of binding.
| 26,787
|
Beta adrenergic blockade, regional left ventricular blood flow and ST-segment elevation in canine experimental myocardial ischemia.
|
The effects of dl-propranolol, d-propranolol, dl-pindolol and dl-practolol on regional myocardial blood flow (assessed by means of tracer microspheres) and on ST-segment elevation in ischemic and nonischemic areas of the canine left ventricle have been investigated. dl-Propranolol and dl-pindolol, but not dl-practolol and d-propranolol, induced blood flow redistribution from the epicardium to the endocardium both in ischemic and nonischemic areas. dl-Propranolol-induced redistribution was abolished by atrial pacing at the control heart rate value. These results indicate that the redistribution phenomenon only occurs if both a bradycardia-inducing beta1 adrenoreceptor blockade and a coronary vessels beta2 adrenoceptor blockade are simultaneously achieved. All four drugs significantly decreased ST-segment elevation in ischemic areas. Under atrial pacing, this effect was abolished with dl-practolol but only reduced with dl- and d-propranol, suggesting that, besides bradycardia, membrane stabilization might be involved in protection against ST-segment elevation in ischemic areas.
| 26,795
|
Liberation of cyanide from alpha-aminonitriles relative to amygdalin.
|
A series of aminoitriles have been synthesized and studied whose nonenzymatic dissociation with release of cyanide may be varied by modest alteration of their molecular structure from that obtained with nonenzymatic dissociation of amygdalin to that obtained from enzymatic dissociation of amygdalin by substantial quantities of beta-glucosidase. The relationship between such alterations in molecular structure and nonenzymatic dissociation is discussed. A combination of the results of these studies and studies relating molecular structure to physical localization propensity in tumors has potential in the design of chemotherapeutic agents.
| 26,797
|
A method for the isolation of Bacteroides melaninogenicus from the human mouth.
|
Isolation procedures involving the direct plating of specimens and the use of selective, non-selective, transport and enrichment media were compared in respect of their value for the recovery of Bacteroides melaninogenicus from the gingival sulcus. A selective medium containing kanamycin and vancomycin enhanced the recovery rate of B. melaninogenicus. VMGII transport medium was convenient to use and gave as good a recovery rate as that obtained with plates directly inoculated in the clinic.
| 26,805
|
Intracellular electrolytes in erythrocytes during and after shock: relation to impaired consciousness.
|
Of 32 patients in shock and catabolic state following shock with impaired consciousness 31 exhibited raised sodium content in their erythrocytes. On the assumption that the erythrocyte membrane acts the same as nerve cell membrane, the hypofunction of erythrocyte membrane may result in impaired consciousness. The hypofunction of erythrocyte membrane is assumed by its increased permeability in shock. A positive osmotic discrepancy between measured and calculated levels denotes altered membranous permeability. Subjectively, impaired consciousness was evaluated by clinical grading. Meanwhile, as a trial of quantification of conscious levels, we applied a new technique of analysis of power spectrum obtained by computer on the autocorrelogram of the EEG during intermittent photic stimulation. This new analytic method was useful in evaluating objective changes of cerebral function. There was a good correlation between raised sodium content in erythrocytes and depressed power spectrum. The degree of increased sodium in erythrocytes seems to correlate with patients' clinical prognosis.
| 26,808
|
Helper-independent transformation by unintegrated Harvey sarcoma virus DNA.
|
We have studied the unintegrated infectious DNA of Harvey sarcoma virus (Ha-SV) and Moloney leukemia virus (Mo-MuLV). The source of infectious viral DNA was the Hirt supernatant fraction from cells acutely infected with Ha-SV and Mo-MuLV. To obtain a direct quantitative assay for infectious viral DNA, recipient mouse cells were first exposed to calcium phosphate-precipitated viral DNA and then treated with dimethyl sulfoxide. Infectivity was monitored by focus formation for Ha-SV and XC plaque formation for Mo-MuLV. The viral DNA titration pattern followed single-hit kinetics for both foci and plaques, indicating that a single molecule carried information for each function. Focus-forming and plaque-forming activity were present in different molecules, since these two biological activities could be separated from each other by agarose gel electrophoresis. The focus-forming molecule was linear DNA with a molecular weight of about 4 x 10(6) daltons. The focus-forming activity of the viral DNA was sensitive to EcoRI and resistant to XhoI restriction endonucleases, whereas the plaque-forming activity was resistant to EcoRI and sensitive to XhoI. The generation of helper-independent foci indicates that Ha-SV DNA can transform mouse cells in the absence of helper virus or its proteins.
| 26,810
|
[Hemodynamic effects of antihypertensive drugs].
|
The physiopathology of hypertension is not fully understood, though the haemodynamic pictures accompanying the various arterial forms have been established. Clinical employment of antihypertensive drugs should tend to correct these pictures and the extent to which this is true is examined in the light of the latest evidence with respect to the drugs most commonly used.
| 26,893
|
The metabolic profile of adult Fasciola hepatica obtained from rafoxanide-treated sheep.
|
Sheep infected with adult Fasciola hepatica were drenched with rafoxanide. At 4, 8, 16 and 24 h after drenching the sheep were killed and the flukes removed, washed and rapidly frozen in liquid nitrogen. The content of key metabolites in the fermentation pathway were determined and compared with those in control F. hepatica, whose hosts were not treated with rafoxanide. Rafoxanide decreased glycogen, malate, NADH and ATP levels. The level of other metabolites in the pathway increased for the first 8-16 h after rafoxanide treatment. The marked decrease in ATP and glycogen, and the increase in total [NAD+]/[NADH] and [oxaloacetate]/[malate], together with the changed content of other metabolites, led to the conclusion that the mode of action of rafoxanide against F. hepatica in vivo is by uncoupling oxidative phosphorylation.
| 26,902
|
Heat-stable enterotoxin of Escherichia coli: in vitro effects on guanylate cyclase activity, cyclic GMP concentration, and ion transport in small intestine.
|
A partially purified preparation of the heat-stable enterotoxin of Escherichia coli caused a rapid and persistent increase in electric potential difference and short-circuit current when added in vitro to the luminal surface of isolated rabbit ileal mucosa. As little as 1 ng/ml produced an easily detectable response. Under short-circuit condition, the enterotoxin abolished net Cl- absorption; this change was half that produced by theophylline, which stimulated net secretion. The enterotoxin did not change cyclic AMP concentration but caused large and persistent increases in cyclic GMP concentration. The electrical and nucleotide responses exhibited similar and unusually broad concentration-dependences and maximal effects could not be demonstrated. Theophylline elevated cyclic GMP concentration 3-fold both in the presence and absense of the enterotoxin, suggesting no effect of the toxin on cyclic GMP phosphodiesterase. Guanylate cyclase [GTP pyrophosphatelyase(cyclizing); EC 4.6.1.2] activity in a crude membrane fraction from intestinal epithelial cells was stimulated 7-fold by the enterotoxin. These results suggest that guanylate cyclase stimulation is the basis for the toxin's diarrheagenic effect.
| 26,915
|
Androgen concentration and partial characterization of 5alpha reductase in the epididymis of the rhesus monkey.
|
The 5alpha reductase activity ofthe monkey epididymis was studied. The enzyme was found in particulate subcellular fractions, its distribution closely resembling that of the microsomal marker enzyme NADPH: cytochrome c reductase, suggesting an association of 5alpha reductase with membranes of the endoplasmic reticulum. Maximal enzyme activity was found at pH 5.4 and at 32--37 C. The crude nuclear preparation had a Km: 0.315 x 10(-6)M and Vmax: 168 pmoles/mg protein/h. The microsomal enzyme had a Km: 0.243 x 10(-6)M and Vmax: 828 pmoles/mg protein/h. Neither enzyme preparation was affected by addition to the incubation media of dihydrotestosterone (DHT) or 5alpha-androstane-3alpha,17beta-diol. The endogenous androgen concentration in the epididymides of 2 different monkeys, in ng/g wet weight was: DHT 20.81 +/- 1.98; T: 9.0L +/- 2.83; diol: 3.03 +/- 0.41.
| 26,992
|
Lack of correlation between splenic and marrow hematopoiesis following irradiation or irradiation and transplantation in mice.
|
Differences were seen in the relative importance of spleen and marrow in early erythroid regeneration of lethally irradiated mice given spleen or marrow cell transplants compared with that in sublethally irradiated mice with surviving endogenous hematopoietic cells. Radioactive iron uptake was predominantly in the spleen of mice with transplants and in the marrow of endogenously recovering mice. Visable spleen colony counts increased from day 4 to day 7 and plateaued through day 10 in the transplant system, but shoed a small abortive rise with a 5-day peak, followed by a steady increase from days 6 to 10 in the endogenous system. Comparisons of peroxidase-positive cells (granulocytes) in the marrow of femurs and humeri and iron uptake in marrow and spleen suggested that repopulation of the marrow and spleen were independent, while that of different areas of the marrow was interrelated. The interrelationship of the rate of marrow regeneration was closer in the endogenous than in the transplant system.
| 26,995
|
[Increase in tryptic digestibility of dietary proteins in the stomach].
|
The trypsin assailability of food proteins (bread, dried milk and egg powder pastes) subjected for different periods of time to the action of the gastric juice directly in the stomach was studied by taking account of the specific topography of its content. It is shown that foodstuffs proteins can be increasingly assailable with trypsin as a result of the action exerted upon them in the stomach by the secretion of its glands. For different food proteins and at different time after feeding the animals as well as in different layers of the gastric contents this effect manifests itself dissimilarly. The trypsin assailability of food proteins increases in the layer near the mucosa and in the antral layers of the gastric contents. A higher trypsin assailability of food proteins is directly related to the level of the proteins hydrolysis in the stomach, to the acidity of the gastric contents and, especially, to its proteolytic activity.
| 27,010
|
Acute and long-term salt depletion and beta-blockade: plasma renin activity response and its relation to blood pressure reduction in long-term treatment.
|
The changes in plasma renin activity (PRA) during short-term salt depletion (and peroral furosemide on the first day) and after bolus injection of propranolol were compared to the change during long-term treatment with diuretic and with propranolol in 19 patients with benign primary hypertension. A highly significant correlation was found between PRA on short-term and long-term salt depletion (r=0.02). A highly significant correlation was likewise found between initial PRA and decrement of PRA after bolus injection of or long-term treatment with propranolol. Only a weak inverse correlation was found between PRA reached during short-term salt depletion or long-term diuretic treatment and the fall in diastolic BP during long-term treatment (r=0.60). No significant correlation was found between decrease in PRA on propranolol (bolus/long-term) and diastolic BP reduction. It is concluded that the short-term PRA response to salt depletion and propranolol in the individual patient gives a good prediction of the PRA level on long-term diuretic or propranolol treatment, but is of no value in predicting the BP reduction during treatment.
| 27,064
|
Granulomatous ileocolitis preceded by three years of pauciarticular arthritis.
|
The case of a 12-year old male is presented in whom pauciarticular arthritis preceded the clinical onset of granulomatous ileocolitis by three years. Before the onset of gastrointestinal symptoms, the patients' clinical diagnosis was juvenile rheumatoid arthritis. This case stresses the importance of including inflammatory bowel disease in the differential diagnosis of pauciarticular arthritis in children.
| 27,094
|
The influence of maternal psychological stress on the fetus.
|
The effects of maternal agitation, induced by exposure to bright light, upon fetal well-being were studied in pregnant rhesus monkeys at 139 to 148 days of gestation. Fetuses were classified as "healthy" or "asphyxiated" according to their initial acid-base state. Following variable periods of maternal excitement, a decrease in heart rate and arterial oxygenation was seen in all fetuses. Recovery occurred more rapidly in the healthy group, after maternal sedation was achieved, either by removing the stimulus or by additional administration of pentobarbital, 5 to 20 mg. intravenously. The beneficial effects of meternal sedation on the fetus have thus been demonstrated.
| 27,097
|
[Contribution to wet and dry weights of mesenchymal and parenchymatous organs of humans and rats during the course of life (author's transl)].
|
The wet and dry weights of parenchymatous (lung, heart, liver, kidney) and of mesenchymal organs (aorta, skin, xiphoid cartilage) of humans and rats (both sexes) were investigated during the course of life. Furthermore, these investigations were done on the following rat organs: brain (divided in cerebrum as well as in cerebellum plus pons), spleen, rib cartilage, testis and ovar. The water content of these tissues and organs of both species was calculated by means of their wet and dry weights. The dry weights of the investigated parenchymal and mesenchymal organs of both species remain constant during the whole course of life (pastly until the high senile age)--using freeze-drying. The same is true for the water content: constancy without significant decrease during the investigated life periods and without sex dependent differences.
| 27,108
|
[Measuring nursing needs of older people related to actual nursing time in institutions for the aged (author's transl)].
|
A great many of the elderly people are in need of care. In offering services accordingly it is necessary to acquire relevant data. The following article gives results of a study which determined 1) the real amount of given nursing care and 2) the measured amount of nursing needs of these patients. The research was done at 10 nursing stations with 210 persons. The results make clear 1) that need of care must be seen in a multidemensional perspective and 2) that much of the psychological and social needs of the patients are not yet satisfied.
| 27,117
|
Acid aspiration during laparoscopy.
|
The prophylactic efficacy of pre-operative antacid administration was shown by comparing the pH and volumes of gastric contents in 50 female patients treated with 10 ml of Mist. Magnesium Trisilicate B.P.C. with that of 50 controls. Routine antacid prophylaxis was advocated for all patients undergoing pelvic laparoscopy as intra-operative conditions increase the risk of pulmonary acid aspiration.
| 27,129
|
Chloramphenicol resistance in Streptococcus pneumoniae: enzymatic acetylation and possible plasmid linkage.
|
Clinical isolates of Streptococcus pneumoniae resistant to chloramphenicol were observed in France for the first time in 1973. During a 4-year survey, these strains were found to represent 6% of a total of 564 isolates of S. pneumoniae in a general hospital and to belong to 13 different serotypes. One such strain, referred to as BM 6001, was shown to inactivate chloramphenicol, and the process was found to be inducible. The inactivated products were demonstrated to be O-acetoxy esters of chloramphenicol. The synthesis of an inducible chloramphenicol acetyltransferase was shown to be responsible for the inactivation of the drug. The resistant strain was able to transfer the chloramphenicol marker by transformation to competent strains of pneumococci at a frequency of 1% of that observed for control chromosomal markers. The loss of resistance was enhanced by ethidium bromide treatment, but no chloramphenicol-resistant mutant was isolated by mutagenesis of a "cured" clone or naturally susceptible isolates. All attempts to isolate plasmid deoxyribonucleic acid as covalently closed circular molecules from strain BM 6001 have been unsuccessful, but epidemiological evidence and the fact that the genes specifying chloramphenicol acetyltransferase synthesis are usually located on plasmids suggest that this marker may be plasmid-borne in S. pneumoniae.
| 27,138
|
The action of lecithin monolayers on mosquitoes I. General observations.
|
Monolayers of pure egg-lecithin at maximum equilibrium pressure were tested against eight species of mosquito in the laboratory, Anopheline larvae were prevented from surfacing and died in water of low dissolved oxygen content, but culicine larvae survived. The pupae of all species except Culex p. fatigans were killed. Effects on floating eggs, pupal-adult eclosion and adult behaviour are also reported.
| 27,146
|
An experimental non-invasive animal technique for measuring nasal airway resistance: I. Adrenergic and antihistaminic agents.
|
A non-invasive technically simple and sensitive method is described for the determination of nasal airway resistance (NAR). Aerosolized saline elicited a +/- 7% change in baseline NAR, duration 2 minutes, whereas aerosolized histamine increased NAR, duration is greater than 30 minutes. Aerosolized phenylephrine, norepinephrine, and oxymetrazoline elicited dose related decongestive response in a naris subjected to prior congestion (aerosolized histamine). Both H1 and H2 receptors are involved in the congestive response to intranasal histamine.
| 27,153
|
Stabilization of human fibroblast interferon purified on concanavalin A-agarose.
|
Human fibroblast interferon, obtained by chromatography on concanavalin A-agarose, was stable for at least a month in 30--50 per cent ethylene glycol at 4 degrees, --20 degrees, and --70 degrees C. The succinct point of the present finding is that human fibroblast interferon may be stabilized by ethylene glycol alone without the addition of bovine serum albumin and 'back-contamination' of the interferon preparation.
| 27,163
|
Interaction of fluorinated ether anesthetics with artificial membranes.
|
Fluorine-19 nuclear magnetic resonance spectroscopy is applied to the study of the environment of dipalmitoyl phosphatidylcholine-bound fluorinated ether anesthetics (enflurane, fluoroxene and methoxyflurane) both below and above the lipid gel to liquid crystal phase transition temperature. Line widths and spin-lattice relaxation time (T1) measurements are consistent with substantial immobilization of the lipid-bound anesethetic molecules. Heating anesthetic/lipid mixtures above the lipid transition temperature leads to narrowing of the lipid-bound anesthetic fluorine resonances accompanied by little or no change in anesthetic fluorine-19 chemical shifts, suggesting that although the mobility of the bound anesthetic increases at the higher temperature, the nature of the anesthetic-lipid interaction changes little as a result of this phase change. Differential scanning calorimetric studies of the effects of these anesthetics on the phase transition behavior of the phospholipid indicate that the regions of the bilayer in which volatile anesthetics partition at lower concentrations are different from the regions in which they partition at higher concentrations.
| 27,214
|
Sites of direct and indirect halogenation of albumin.
|
The sites of radiohalogenation in proteins vary with the labeling method and the pH of the labeling reaciton. We have directly halogenated albumin with carrier-free radioiodide by three methods (pH range 2.2--9.3), and with carrier-free radiobromide by the chloroperoxidase method (pH range 2.2--4.6). Albumin was also indirectly halogenated by attaching a radioiodinated acylating agent, N-succinimidyl-3-(4-hydroxyphenyl) propionate (SHPP). The labeled proteins were proteolyzed enzymatically at neutral pH and the labeled amino acids produced were analyzed by liquid chromatography. Iodination at pH 7 yielded predominantly monoiodotyrosine, but at lower pH, fewer tyrosyl residues are labeled and a greater number of unstable sulfur-iodine bonds are formed at cysteinyl residues. Bromination with chloroperoxidase resulted in a high degree of labeling of cysteinyl residues at pH 2.8, the condition for optimum activity of this halogenating enzyme. Indirect halogenation with SHPP resulted in labeling of mid-chain lysyl, histidyl and tyrosyl residues.
| 27,226
|
An evaluation of respiration chain-associated functions during initiation of germination of Bacillus megaterium spores.
|
In Bacillus megaterium QM B1551, spore germination could be initiated by glucose in the absence of detectable oxygen consumption, ATP synthesis or a pH decrease in the external media, suggesting that none of those reactions were mandatory. In addition, initiation of germination was insensitive to a variety of inhibitors of energy production or protonmotive force uncouplers. Therefore the respiratory chain-associated functions are not prerequisites for initiation of germination but these functions may be necessary to drive energy-dependent transport systems and other biosynthetic reactions during outgrowth.
| 27,232
|
[Effect of pH on the permeability and mechanical properties of intercellular contacts in the small intestinal epithelium].
|
It is shown that acid site population controlling ion permeation through cell contacts is localized in the region of tight junction. The isoelectric point of cell surface in the region to tight junction changed from mean pH = 2.37 +/- 0.1 for duodenum to pH =2.80 +/- +/- 0.1 for ileum. The maximum of cell adhesion in the tissue reached at mean pH that corresponding the isoelectric point. It seems possible, that this acid site population take part in interaction of plasma membranes of neighbouring cells.
| 27,238
|
[Pharmacology of azidomorphine].
|
As revealed, in acute experiments on rabbits, cats, and rats, a new morphine-like synthetic analgesic drug azidomorphine exceeded 20--100-fold the morphine ability to inhibit synaptic transmission in the thalamic structures, cerebral cortex, and the spinal cord during the nociceptive stimulation, and also by its analgesic activity.
| 27,263
|
Factors limiting the rate of termination of the neuromuscular blocking action of fazadinium dibromide.
|
1 Reasons for the termination of the neuromuscular blocking action of fazadinium dibromide have been investigated. 2 In the anaesthetized cat, maximum neuromuscular block of tibialis anterior muscle twitches following rapid intravenous injection of fazadinium was obtained as the injection bolus passed through the muscle, indicating the fazadinium very readily crosses capillary membranes. 3. The half-life of plasma clearance of fazadinium was about 1 min in both cat and man, despite a 10 fold difference in duration of action in these species. Plasma samples were bioassayed for neuromuscular blocking activity on an isolated, superfused phrenic nerve-diaphragm preparation of the rat. 4 In the anaesthetized cat, occlusion of the renal or hepatic circulations did not prolong the neuromuscular blocking action of single doses of fazadinium. Repeated doses accumulated slowly when the hepatic circulation was occluded but not when the renal circulation was occluded. 5 Fazadinium is eliminated from the body by both the liver and kidneys but the rates of these processes are insufficient to account for the initial rapid plasma clearance. 6 The rate-limiting step for the termination of the neuromuscular blocking action of fazadinium is most likely to be the rate of drug-receptor dissociation
| 27,272
|
Enhancement by an antagonist of transmitter release from frog motor nerve terminals.
|
1 The effect of Ba2+ on the synchronous release of acetylcholine from frog motor nerve terminals was studied by conventional electrophysiological techniques. 2 When Ca2+ and Ba2+ were the only divalent cations in the bathing fluid, Ba2+ caused a presynaptic reduction in the amplitude of the endplate potential (e.p.p.). This effect was surmountable by increasing the Ca2+ concentration. 3 The affinity constant (KA) for Ba2+, calculated on the assumption that Ba2+ is a competitive inhibitor of the agonist, Ca2+, was 1.1 +/- 0.4 mM-1 (mean +/- s.e. mean, n = 8). 4 When e.p.ps were depressed by the addition of 1 mM Mg2+, addition of Ba2+ (1 to 3 mM) caused either a further presynaptic depression of moderate magnitude or had no additional effect. 5 When e.p.p.s were depressed with [Mg2+] greater than or equal to 2 mM, addition of Ba2+ greater than or equal to 0.9 mM enhanced the e.p.p. amplitude by a presynaptic mechanism. 6 The interaction of the divalent cation antagonists Mg2+ and Ba2+ with the agonist, Ca2+ is discussed. It is demonstrated that a model which considers the nonequilibrium, kinetic properties of binding can be used to describe interactions between divalent cations at the external surface of the motor nerve ending.
| 27,281
|
Guanosine triphosphate catabolism in human and rabbit erythrocytes: role of reductive deamination of guanylate to inosinate.
|
The reductive deamination of guanylate to inosinate was demonstrable but occurred at low rates in human and rabbit erythrocytes incubated in vitro with or without glucose. However, the process was considerably accelerated in erythrocytes incubated with deoxyglucose. In human erythrocytes incubated with deoxyglucose, deamination was the major pathway of catabolism of guanylate; little or no guanylate was dephosphorylated. In rabbit erythrocytes, guanylate was both deaminated and dephosphorylated. Inosinate formed from guanylate was metabolized only by dephosphorylation in human erythrocytes, but in rabbit erythrocytes, it was also converted to xanthylate.
| 27,292
|
The control of pyruvate kinases of Escherichia coli: further studies of the enzyme activated by ribose-5-phosphate.
|
The pyruvate kinase activated by ribose-5-phosphate from Escherichia coli has been purified to homogeneity, taking advantage of the stabilization of the enzyme by its inhibitor phosphate and by thiol reagents. The native enzyme has a tetrameric quaternary structure which, while prone to dissociation under many conditions, remains intact in the presence of the above reagents. The enzyme was found to reactivate on dilution out of 8 M urea. Interestingly, the recovery of activity is greatly increased by phosphate, an allosteric inhibitor, but markedly reduced by the allosteric activator, ribose-5-phosphate, implying that it is harder for the enzyme to refold to a 'relaxed state.' Proteolysis studies indicate a more open structure in the presence of the activator.
| 27,294
|
Reduced nicotinamide adenine dinucleotide phosphate-dependent formation of 2,3-dihydro-2,3-dihydroxyaflatoxin B1 from aflatoxin B1 by hepatic microsomes.
|
2,3-Dihydro-2,3-dihydroxyaflatoxin B1 (dihydrodiol) was formed as a major metabolite in the incubation of aflatoxin B1 with rat and hamster liver microsomes. The yield of the dihydrodiol was maximal at pH 6.5, was reduced nicotinmide adenine dinucleotide phosphate- and cytochrome P-450-dependent, and was increased 2- to 4-fold by pretreatment of the animals with phenobarbital; pretreatment with 3-methylcholanthrene did not alter the activity of rat hepatic microsomes. Inhibitors of epoxide hydrase did not lower the yield of the dihydrodiol in these systems. Negligible yields of the dihydrodiol were formed from aflatoxin B1 and rat liver microsomes in the presence of DNA. Little or no formation of the dihydrodiol was noted with microsomes from rat intestinal mucosa, kidney, or lung. These results further support the formation of aflatoxin B1 2,3-oxide as a major electrophilic metabolite of aflatoxin B1 in rat and hamster liver microsomal systems, since this highly reactive epoxide would be expected to hydrolyze readily to form the dihydrodiol.
| 27,299
|
Quantitative characteristics of the Feyrter cells and neuroepithelial bodies of the fetal rabbit lung in normoxia and short term chronic hypoxia.
|
We report here quantitative data on the Feyrter (single) cells (APUD cells) and neuroepithelial bodies (grouped Feyrter cells), in the lungs of rabbit fetuses at 26, 27.5 and 29 days gestational age, during normoxia and short term chronic hypoxia. The apparent number of these cells declines during this period; we suggest that this might be due to increased hypoxemia. Moreover, the number of cells in the lungs of fetuses from short term chronically hypoxic mothers is lower than in the normoxic animals. These findings are in agreement with our previous studies in short term chronically hypoxic neonatal rabbits, and suggest that the increased hypoxemia in the fetus, caused by the induction of hypoxia in the mother, constitutes a stimulus for secretory activity of the Feyrter cells and neuroepithelial bodies (NEBs). This in turn could be part of the mechanism responsible for maintaining the pulmonary vasoconstriction due to hypoxemia. Our results from fetuses of normoxic does provide base line data on the chronological importance of the Feyrter cells and NEBs.
| 27,304
|
Erythrocyte organic phosphates in the anemia of renal failure in childhood.
|
Erythrocyte 2,3-diphosphoglycerate (2,3-DPG ) and adenosinetriphosphate (ATP) levels were determined in 43 children with chronic renal failure on conservative treatment (CT), and 12 children on regular hemodialysis (HD) immediately before and after a HD session. The results were compared to non-anemic and anemic controls. In spite of anemia, erythrocyte 2,3-DPG in renal failure was similar to non-anemic controls at normal blood pH, but rose during dialysis as a result of alkalosis. In contrast, ATP levels were high already at a normal blood pH. 2,3-DPG correlated with packed cell volume (PCV) in children with renal failure but at lower concentrations compared to controls. Both organic phosphates in the erythrocytes showed a significant correlation with blood pH. The poor increase of 2,3-DPG, in combination with elevated ATP levels, suggests uremia-induced inhibition of 2,3-DPG synthesis.
| 27,366
|
[Influence of isolanide and trasicor on the content of nicotinamide coenzymes in the myocardium of growing rats in hemic hypoxia].
|
Hemic hypoxia was produced in 7,30-day and 3--5-month old (adult) rats through introduction of sodium nitrite (100 mg/kg) with subsequent determination of the nicotinamide co-enzymes content in the myocardium. The effect of combined and separate application of the cardiac glycoside isolanide and beta-adrenoblocking agent trasicor under hypoxia at early stages of post-natal ontogenesis is shown.
| 27,378
|
Relationship between site of peptic ulceration and gastric acid-peptic activity: new evaluation of gastric analysis in patients with acute gastric bleeding and chronic peptic ulcer.
|
In an attempt to elucidate the etiology of acute gastric bleeding and/or erosion and chronic peptic ulcer, a measurement of gastric juice and mucosal pepsin was carried out in surgically-treated patients. Patients with massive gastric mucosal bleeding in the fundic gland area showed high levels of fundic mucosal pepsin without acid-pepsin appearance in the gastric contents. In these patients, a significantly high value of the peptic activity ratio of gastric mucosa to gastric juice (MJPR, 36.4 +/- 6.7) was observed. It can be suggested that transient blockage of pepsin output from peptic cells with occur in the course of the acute mucosal bleeding, while acid-peptic digestion could be carried out within the fundic gland mucosa. On the other hand, a close correlation between relatively high acid-and-pepsin concentration of the gastric contents and a low level of MJPR (5.6 +/- 1.2) was observed in patients with chronic gastric ulcer. Patients who had a gastric ulcer within the pyloric gland mucosa had a highest acid-peptic activity among three groups with ulcers in fundic gland area, border zone and pyloric gland area. There is a rule that acid-peptic activity becomes low when the site of gastric ulcer moves from pylorus to fundus. A marked increase in acid-and-pepsin secretion into the gastric cavity was observed in patients suffering from chronic duodenal ulcer showing the lowest level of MJPR (3.40 +/- 0.50).
| 27,412
|
Food sensitivity in reflux esophagitis.
|
We examined 66 patients with pain of possible esophageal origin for sensitivity to intraesophageal infusions of coffee, orange juice, spicy tomato drink, or HCl of varying concentrations as an addendum to their acid infusion (Bernstein) tests. Compared to Berstein-negative subjects, acid-sensitive patients were sensitive to infusion of coffee (P less than 0.01), orange juice (P less than 0.001), and tomato drink (P less than 0.001). Patients were largely insensitive to HCl solutions with a titratable acidity of 1 mEq per liter or less, less than the least acidic food solution tested. However, Berstein-positive patients were still highly sensitive to infusions of coffee, orange juice, and tomato drink adjusted to pH 7 (P less than 0.001). Patients were unable to differentiate symptoms caused by acid or food infusions, and solutions did not differ in the duration of infusion needed either to cause symptoms or to relieve them by saline. We conclude that the pain of esophagitis is nonspecific and can be precipitated by variety of seemingly unrelated substances.
| 27,414
|
[Acid-base equilibrium in the cerebrospinal fluid in diseases of the central nervous parenchyma].
|
A number of case studies reveal and dynamic changes of the acid-base balance in the blood and cerebrospinal fluid, such as the increasing decompensation of the metabolic lactate acidosis in the cerebrospinal fluid in lethal cases or the gradual regression in patients who were cured. Individual metabolic cerebrospinal parameters are correlated with the disturbance of consciousness. The cerebrospinal fluid parameters of patients with clouded consiciousness constitute prognostically critical values: lactate 3.6 mmol/l, pyruvate 0.19 mmol/l, pH 7.249 and bicarbonate 18.1 mmol/l. Affections of the central nervous parenchyma are better reflected in the cerebrospinal fluid than in the blood. The determination of the CSF/blood relationship of individual parameters shows a significant increase of the lactate quotient as well as a decrease of the pH quotient and of bicarbonate quotient. Respiratory parameters do not show any statistically significant changes. Statistically significant correlations show that, in the case of primary central nervous diseases, the increased hydrogen ion supply in the cerebrospinal fluid is quickly intercepted by the bicarbonate buffer and that, with a corresponding pH decrease, there is a rapid decompensation of the acid-base balance.
| 27,438
|
Unilateral cryptorchidism with compensatory hypertrophy of descended testicle in prepubertal boys.
|
5 prepubertal boys with unilateral cryptorchidism and compensatory hypertrophy of the descended testicle, 22 prepubertal boys with unilateral cryptorchidism and without CTH, and 14 prepubertal normal boys were submitted to LH-RH and to HCG tests in order to study the hormonal behaviour in CTH phenomenon before puberty. High but normal peaks of plasma LH and FSH were observed after LH-RH in CTH boys who showed a significant increase of testosterone after HCG stimulation. On the contrary the LH response to LH-RH and the testosterone response to HCG of the boys with unilateral cryptorchidism and without CTH were, as expected, significantly lower than in the control ones.
| 27,440
|
Cell envelope of Neisseria gonorrhoeae: phospholipase activity and its relationship to autolysis.
|
The relationship between conditions which permit or inhibit cell lysis and those which promote phospholipid hydrolysis in Neisseria gonorrhoeae was investigated. Suspension of exponential-phase gonococci in buffer in the absence of divalent cations resulted in autolysis but not in phosphlipid hydrolysis. The addition of Ca2+ or Mg2+ to the buffer inhibited autolysis and markedly stimulated the hydrolysis of phosphatidylethanolamine. Incubation of cells in buffer at pH 6 inhibited both autolysis and phospholipid hydrolysis.
| 27,458
|
Red cell oxygen affinity in fetal sheep: role of 2,3-DPG and adult hemoglobin.
|
Studies were carried out during fetal life in sheep to determine the relationship of 2,3-diphosphoglycerate (DPG), the intracellular red cell and extracellular pH, and the switchover to adult hemoglobin synthesis in regulating the position of the fetal red cell oxygen-affinity curve in utero. Adult hemoglobin first appeared near 120 days of gestation. The mean oxygen tension at which hemoglobin is half saturated (P50) prior to 120 days of gestation remained constant at 13.9 +/- 0.3 (SD) Torr and then increased gradually as gestation continued, reaching 19 Torr at term. During the interval of fetal life studied, the level of DPG was 4.43 +/- 1.63 (SD) micromol/g Hb and the deltapH between plasma and red blood cells was 0.227 +/- 0.038 (SD); neither was affected by gestational age. The decrease in the red cell oxygen affinity after 120 days of gestation ocrrelated with the amount of adult hemoglobin present in the fetus (r = 0.78; P less than 0.001). This decrease can be attributed only to the amount of the adult-type hemoglobin present, and not to DPG, or to changes in the deltapH between plasma and red blood cells, because both remained stable during the last trimester.
| 27,486
|
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