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Kinetics and equilibrium studies on autologous and heterologous recombinations of heavy and light chains of myeloma proteins.
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1. The kinetics of the heterologous recombination reaction of alkylated H chains of a myeloma protein (Jo) with alkylated L chains of another myeloma protein (Ita) were studied by following changes with time in the circular dichroism at 235 nm and the results were compared with those for the autologous recombination of Jo-H chains with Jo-H chains reported previously (T. Azuma et al.(1975) J. Biochem. 77, 473-479 and the preceding paper). The heterologous reaction also followed second-order kinetics. The second-order rate constant (kapp) for heterologous recombination was about seven times smaller than that for autologous recombination at pH 5.5, while they were similar between pH 4.2 and 4.7. 2. The apparent association constants (Kapp) for the reaction, H2+L2=H2L2, were determined by measuring the ellipticities at 235 nm of mixtures of H and L chains in various ratios. The values of Kapp for the autologous and heterologous recombinations were both pH-dependent and changed from 10(6) M-1 at pH 3.9 to 108 M-1 at pH 4.3. Using these values of kapp and Kapp, the half-time for the dissociation of autologous H2L2 to H2 and L2 at pH 4.3 was estimated to be 80 hr.
| 6,439
|
Trinitrophenylation of nucleic acids and their constituents.
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1. Under relatively mild conditions, nucleic acids and their constituents were trinitrophenylated with 2,4,6-trinitrobenzenesulfonate (TNBS) in aqueous solution (pH 8-11), yielding reddish-orange trinitrophenyl (TNP) derivatives. Guanine residues were trinitrophenylated on the base residues at the 2-amino group (N2-TNP derivatives), and in addition, 2'- and 3'-hydroxyl groups of the ribose moieties of nucleosides or nucleotides were trinitrophenylated to form Meisenheimer complexes. 2. The preparation of TNP derivatives (N2-TNP-guanine, -guanosine, N2, O-bis-TNP-guanosine, O-TNP-guanosine, -adenosine, -cytidine , and -uridine), their rates of formation, absorption spectra (UV, visible, and infrared), molar extinction coefficients, Rf value, electrophoretic mobilities, and stability in acid or alkaline solution, are presented. 3. Trinitrophenylation of several kinds of nucleic acid was investigated. Calf thymus DNA and yeast transfer RNA showed a resistance to trinitrophenylation compared to guanosine 3'(2')-phosphate, yeast RNA or denatured calf thymus DNA. TNP-RNA showed resistance to the action of ribonucleases T1 and T2 [EC 3.1.4.8 and 3.1.4.23]. 4. Trinitrophenylation reactions using 2,4,6-trinitrochlorobenzene and 2,4,6-trinitrofluorobenzene were compared with that using TNBS as regards specificity and reaction rate.
| 6,442
|
Cytochrome P-450 of bovine adrenal mitochondria. Ligand binding to two forms resolved by EPR spectroscopy.
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The binding of cholest-5-ene-3beta,20alpha-diol (20alpha-hydroxycholesterol), 11-deoxycorticosterone, and aminoglutethimide to cytochrome P-450 in bovine adrenal mitochondria was measured by changes in optical spectra at room temperature and by EPR spectra at 14 K. The two methods provided nearly identical quantitation of these interactions with cytochrome P-450. Two distinct high spin forms of cytochrome P-450 were revealed by EPR spectra. The predominant high spin species (g = 8.2) was decreased by addition of 20alpha-hydroxycholesterol and elevated pH but was increased by addition of cholesterol. The minor high spin species (g = 8.1) was incrreased by addition of deoxycorticosterone but decreased by low concentrations of metyrapone. The two forms were evidently not in equilibrium and have been assigned to distinct forms of cytochrome P-450 involved in, respectively, cholesterol side chain cleavage (P-450scc) and steroid 11beta hydroxylation (P-450(11)beta). The high spin states are derived from complexes of these P-450 cytochromes with endogenous substrates, which are, respectively, cholesterol and deoxycorticoids. A high to low spin transition was observed when these complexes were turned over by initiating hydroxylation with malate. The contributions of cytochromes P-450(11)beta and P-450scc to the low spin spectrum were also resolved by similar means. At least 20% of P-450scc is in the low spin state while about 90% of P-450(11)beta is low spin in isolated beef adrenal mitochondria. Low spin complexes of cytochrome P-450scc with 20alpha-hydroxycholesterol and 3beta-hydroxypregn-5-ene-20-one (pregnenolone) gave distinct EPR spectra. Aminoglutethimide interacted with the total cytochrome P-450 content of the bovine adrenal mitochondria forming low spin complexes. Both optical and EPR data indicated binding to two forms of cytochrome P-450. These results suggest a detailed correlation between the spin state and absorbance changes seen at room temperature, illustrate that EPR allows the distinction of two principal forms of P-450, and suggest that there is no appreciable change in the spin state of either cytochrome between 14 K and 300 K.
| 6,460
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Re-evaluation of the kinetics of lactate dehydrogenase-catalyzed chain oxidation of nicotinamide adenine dinucleotide by superoxide radicals in the presence of ethylenediaminetetraacetate.
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The chain oxidation of lactate dehydrogenase-bound NADH initiated by superoxide radicals and propagated by oxygen was studied with pulse radiolysis. The kinetic parameters were re-evaluated in a system with carefully purified reagents (water and other chemicals) and in the presence of EDTA. The rate constant for the oxidation of the enzyme-bound NADH by O2- is calculated from the observed pseudo-first order disappearance of NADH and the chain length (molecules of NADH oxidized per O2- anion generated in the pulse). It is (1.0 +/- 0.2) X 10(5) M-1 S-1, consistent within a 13-fold variation in lactate dehydrogenase. NADH complex concentration and with varying chain length up to 6.1. Based on experiments with varying pH values from 4.5 to 9.0, the rate constant for oxidation of enzyme-bound NADH by HO2 is estimated to be 2.0 X 10(6) M-1 S-1.
| 6,464
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Description of a polyvalent conjugate and a new serogroup of Bacteroides melaninogenicus by fluorescent antibody staining.
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A polyvalent conjugate (fluorescein isothiocyanate-labeled antibody reagent) containing serogroups A, B, and C conjugates was prepared. This polyvalent conjugate gave a positive fluorescent antibody (FA) stain with 49 stains of Bacteroides melaninogenicus representing serogroups A, B, and C. When additional strains (92 strains) of the three subspecies of B. melaninogenicus were examined by the FA stain, with A, B, and C, and polyvalent conjugates, nine strains of B. melaninogenicus subsp. intermedius failed to give a positive stain with any conjugate. Therefore, an FA conjugate was prepared with the antiserum to one of these strains (532-70A); all nine strains stained positively with this conjugate. These nine strains were biochemically characteristic of B. melaninogenicus subsp. intermedius; thus, these strains were designated as a new serogroup, serogroup C-1. A new polyvalent conjugate containing serogroups A, B, C, and C-1 was prepared. This polyvalent conjugate stained positively with 23 representative strains from serogroups A, B, C, and C-1. The new conjugates failed to stain positively with other anaerobes and aerobes tested. The four individual conjugates, as well as the polyvalent conjugate, may be used for a more rapid identification of B. melaninogenicus than is possible by biochemical testing.
| 6,487
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beta-Adrenergic receptors in rat brain.
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125I-Iodohydroxybenzylpindolol ([125I] IHYP), a potent beta-adrenergic receptor antagonist, has been used to study beta-adrenergic receptors in rat brain. Binding of [125I] IHYP (30 pM) to a membrane fraction min and dissociation took place with a half time of about 16 min. Phentolamine (10(-4) M) decreased non-receptor binding but it had no effect on the binding of [125I] IHYP to beta-adrenergic receptors in cortex, cerebellum or caudate. In the presence of phentolamine specific binding (defined as binding which was blocked by 0.3 muM dl-propranolol) represented 70-85% of total binding. The binding of [125I] IHYP was inhibited by beta-adrenergic agonists and antagonists. d-Stereoisomers were 2-3 orders of magnitude less potent than the corresponding 1-isomers. The denstiy of [125I] IHYP binding sites was studied in membrane fractions from cerebral cortex, cerebellum, and caudate nucleus by means of Scatchard analysis. The K(D) of [125I] IHYP was similar in the three regions studied, and the density of [125I] IHYP binding sites was approximately 50% greater in the cortex and caudate than in the cerebellum. The Hill coefficient for the binding of [125I] IHYP to membranes from cerebral cortex was 1.02. The properties of the binding of [125I] IHYP are similar to those which would be expected of binding to beta-adrenergic receptors in vitro.
| 6,494
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[Study of fetal heart rate in deliveries complicated by fetal acidosis].
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A study has been carried out on the parameters of the graph of the fetal heart rate (the basal rate and dips) in 44 cases of acute fetal distress with a pH lower than 7.2 in the blood and in 30 normal deliveries. The statistical analysis confirms that there is a significant rise in the number of heart rate abnormalities such as persistent bradycardia or persistent tachycardia and with dips during deliveries with fetal acidosis. The frequency of these abnormalities increases with the degree of acidosis. Sometimes the abnormalities in the fetal heart rate precede the appearance of the acidosis. All the same the discovery of these abnormalities does not by itself make a precise diagnosis of fetal distress because we do find these abnormalities in a certain number of cases even in normal deliveries. Only measuring fetal pH at a definite time can establish the diagnosis of fetal distress and the severity of the condition.
| 6,505
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The cleaning and disinfection by heat of bedpans in automatic and semi-automatic machines.
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This work is concerned with the cleaning and disinfection by heat of stainless-steel and polypropylene bedpans, which had been soiled with either a biological contaminant, human serum albumin (HSA) labelled with technetium-99m 99m(Tc), or a bacteriological contaminant, streptococcus faecalis mixed with Tc-labelled HSA. Results of cleaning and disinfection achieved with a Test Machine and those achieved by procedures adopted in eight different wards of a general hospital are reported. Bedpan washers installed in wards were found to be less efficient than the Test Machine, at least partly because of inadequate maintenance. Stainless-steel and polypropylene bedpans gave essentially the same results.
| 6,591
|
On the interaction of NH+4 and Na+ fluxes in the isolated trout gill.
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1. Sodium influx was measured in isolated, previously perfused gill arches of rainbow trout, Salmo gairdneri, by measuring incorporation of 22Na into gill tissue following timed exposure to a 1 mM 22NaCl medium. Transport rates approximated those estimated for intact fish and were linear for at least one min. 2. NH4Cl-containing perfusates at pH 7 and 8 stimulated Na+ influx equally, indicating that only ionized ammonia is important in the transport process. A Na+/NH4+ exchange at basal and/or lateral membranes of the transporting cells is suggested. 3. Low-sodium Ringer perfusate augmented Na+ influx; in one group of gills the transport rate was more than double that of NaCl Ringer controls. The increase in transport induced by internal NH4+ was not additive with the low sodium augmentation. A reduction in intracellular (Na+) is postulated as the mechanism operating in both cases. 4. Ouabain had no appreciable effect on Na+ influx, either with or without NH4+ in the perfusate. Diamox partially blocked the augmented Na+ influx induced by NH4+. Amiloride completely inhibited Na+ influx, both with and without NH4+ in the perfusate.
| 6,610
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The persistence of dextran 70 in blood plasma following its infusion, during surgery, for prophylaxis against thromboembolism.
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An infusion of dextran (mean molecular weight 70000) in normal saline (either 1 litre or 500 ml) was given to patients undergoing hysterectomy. The infusion was started at induction of anaesthesia and continued throughout the operation and for up to 5 h thereafter. The rate of elimination of dextran was independent of the dose given. The time to eliminate half the dose was nearly two days and up to 10% was still present in the circulation after one week. The persistence of dextran in the plasma in these amounts and for this length of time may have considerable implications in the prophylaxis of postoperative deep venous thrombosis.
| 6,646
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The absorption and elimination of metoclopramide in three animal species.
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The absorption and elimination of metoclopramide have been studied in the rat, rabbit and dog. Thin-layer chromatography followed by photodensitometry was used for the analysis of the unchanged drug and its metabolites. N-De-ethylation is an important Phase I metabolic reaction and conjugation with glucoronic acid and sulphate is a major route of metabolism, particularly in the rabbit. The pharmacokinetic parameters after intravenous administration showed little interspecies variation. First order elimination kinetics with short half-lives and high apparent volumes of distribution (greater than 1.1 kg(-1)) were observed. Major interspecies variations were seen after oral administration of high doses of the drug. Metoclopramide was eliminated slowly after oral administration to rats. The findings in the rabbit and in the dog suggest that the liver plays an active role reducing the systemic availability of unchanged metoclopramide after oral administration.
| 6,647
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The isolated cremaster muscle preparation and (external) spermatic nerve-cremaster muscle preparation of the guinea-pig.
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The isolated cremaster muscle preparation and spermatic nerve-cremaster muscle preparation of the guinea-pig were studied in vitro to determine their suitability as pharmacological test models. The preparation was contracted by acetylcholine, carbachol, succinylcholine and decamethonium (pD2 values, 4-2, 5-3, 7-3 and 7-4, respectively) through an action on a curare-sensitive cholinoceptor. Lobeline and DMPP were ineffective. Nicotine contracted the muscle, but there was tachyphylaxis. Tubocurarine and hexamethonium presumably competitively antagonized acetylcholine (pA2 values, 7-3 and 5-8); lobeline was a non-competitive antagonist (pD'2 value, 6-4). Atropine and mecamylamine exerted a dualistic action against acetylcholine (final pD'2 values, 5-3 and 6-7, respectively). Tubocurarine, succinylcholine and decamethonium exhibited their typical action when tested with spermatic nerve-cremaster muscle preparation; the latter two drugs also produced muscle spasm. Hexamethonium was a weak blocker of neuromuscular transmission. Atropine, mecamylamine, lobeline and DMPP exhibited neuromuscular blocking activity; however, directly evoked muscle twitches were also notably affected. The cremaster muscle preparations seem to add usefully to the list of currently used in vitro tests, with the added advantage that a mammalian skeletal muscle model is used for simultaneous quantitative studies.
| 6,717
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Aggregation of antiacetylcholine drugs in aqueous solution: micellar properties of some diphenylmethane derivatives.
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Light scattering methods have been used to examine the aggregation in aqueous solution of a series of antiacetylcholine drugs based on the diphenylmethane nucleus. The drugs investigated included adiphenine hydrochloride, piperidolate hydrochloride, benztropine mesylate, orphenadrine hydrochloride, chlorphenoxamine hydrochloride, lachesine hydrochloride, poldine methylsulphate, pipenzolate bromide, clidinium bromide, benzilonium bromide and ambutonium bromide. A micellar pattern of association was established for all compounds and critical micellar concentrations and aggregation numbers have been determined.
| 6,747
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Anomalies in some properties of powder mixtures.
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Mixtures of lactose and paracetamol and of lactose and oxytetracycline exhibit anomalous properties. The mean particle sizes, tensile strengths and flow properties of the mixtures are not proportionally intermediate between those of the constituents. The results are ascribed to changes that occur in the packing arrangements of the particles. These changes could have practical consequences in monitoring the progress of a mixing operation by measuring apparent particle size and in controlling the properties of granules, capsules and tablets prepared from the mixtures.
| 6,749
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Preliminary investigations of the metabolism and pharmacological activity of beta-hydroxytryptamines in mammals.
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beta-Hydroxytryptamine and beta-hydroxy-5-hydroxytryptamine were incubated with rat liver slices and oxidative deamination was established as the main route of metabolism: in both instances the corresponding indole-3-glycollic acids and indole-3-ethane diols were the major metabolites. However, the rates of deamination of beta-hydroxylated tryptamines, as measured manometrically, were found to be much slower than those of tryptamines nonhydroxylated in the side chain. The pharmacological activities of beta-hydroxylated tryptamines were tested in guinea-pigs on resistance of respiratory pathways, spontaneous respiration, electrocardiogram, blood pressure and isolated ileum, using tryptamine and 5-HT as reference substances. The effects of tryptamines hydroxylated in the side chain were in general similar to those of corresponding tryptamines but of much lower intensities; only in increasing the blood pressure was beta-hydroxytryptamine as active as tryptamine. The different reactions of these two groups of substances in the presence of some antagonists indicate that the receptors are probably not the same.
| 6,751
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The influence of growth medium on the interactions between Bordetella pertussis and Staphylococcus aureus.
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Previous observers showed that many strains of Staphylococcus aureus stimulated the growth of Bordetella pertussis but we have found the reverse: the growth of all available strains of B. pertussis on charcoal-agar medium was inhibited by a standard strain of S. aureus; and 17 of 18 strains of S. aureus (as well as several other organisms) inhibited the growth of a standard strain of B. pertussis. All inhibiting colonies had an unusual brown colouration on the charcoal agar used in the investigation. Both the brown colouration and the inhibitory property were caused by acid production, probably from the starch in the medium. We therefore suggest that media containing starch and blood should not be used in studies of bacterial interference.
| 6,798
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Monitoring of midmyocardial and subendocardial pH in normal and ischemic ventricles.
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Midmyocardial and subendocardial pH monitoring was used as an indirect method for continuous evaluation of regional canine myocardial ischemia. Left ventricular midmyocardial pH (pHm) at 4 mm. depth was monitored in 10 dogs, under resting conditions, by means of a 5 mm. Beckman pH probe. pHm was 6.96 +/- 0.03, recorded at myocardial temperatures of 35 to 37 degrees C. Ischemia was then produced by snare occlusion of the proximal left main coronary artery for 2 minutes. pHm decreased to 6.87 +/- 0.03 (p less than 0.01) at 1 minute and 6.80 +/- 0.04 (p less than 0.005) in 2 minutes. When flow was restored, pHm returned toward normal within 2 minutes (pH 6.86 +/- 0.03) and at 5 minutes had returned to control values (pH 6.93 +/- 0.03). In another 5 dogs under similar conditions, pHm at 4 mm. and subendocardial pH (pHe at 8 mm.) were measured. Baseline pHm (6.97 +/- 0.01) and pHe (6.84 +/- 0.02) levels were significantly different (p less than 0.0005). After 2 minutes of ischemia, pHm was 6.82 +/- 0.03, whereas pHe decreased to 6.78 +/- 0.04 (p less than 0.1). Five minutes after snare release, pHe remained at 6.73 +/- 0.07; pHm (6.93 +/- 0.03) returned to control values. Both pHm (6.93 +/- 0.02) and pHe (6.84 +/- 0.09) levels were normal 15 minutes after release of the snare. The midmyocardium and subendocardium have different pH levels which can be monitored. Ischemia produces different pH patterns in these layers. pHm returns to control values within 5 minutes after 2 minutes of ischemia, whereas pHe remains depressed for at least 5 minutes. pH monitoring provides an accurate and simple method for on-line evaluation of endocardial ischemia.
| 6,826
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[The use of "mesh graft" in traumatology].
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Vandeput and J. Tanner's method for the reconstruction of the reticular grafting skin has been used and is recommended by the authors for the treatment of not only the thermic--, but of the mechanis lesions. The author has obtained very good results. The method is discussed and its advantages are pointed out.
| 6,827
|
[Solitary tuberculoma in the tendonous section of the m. quadriceps].
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A case of isolated tuberculosis observed in the tensinous part of the quadriceps muscle is reported by the authors. The rarity of the case is pointed out. A few possibilities of the development of this tuberculoma are dealt with. In the authors' case the focus developed probably after haematogenous generalization. One year after the operation the patient is symptomfree and has no complaints.
| 6,828
|
[Incidence of blood aspiration in fatal fractures of the base of the skull].
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The frequency of blood inhalation has been examined by the authors in the 15 years' material of the Institute of Forensic Medicine of the "Semmelweis" University Medical School. Out of 51.308 post mortem examinations 487 cases of isolated basicranial fractures were found. Out of them in 265 cases (=54%) blood inhalation as cause of death was verified. Attention is called to the importance of prompt blood aspiration in patients with basicranial fracture.
| 6,831
|
[Takayasu-Onishi arteritis. Current etiopathogenetic aspects].
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By Takayasu-Onishi's arteritis is meant an arteritic process with unknown aetiology which electively affects young women, seemingly of prevalently Asiatic stock. The disease concerns almost exclusively large elastic arteries and presents clinically with early preocclusive symptomatology followed, after a varying period, by a picture of obstructive angiopathy. Here, the most recent aetiopathogenetic findings are considered. The disease's predilection for the young female, together with certain clinical and experimental observations, suggest that a dysendocrine condition may have some pathogenetic responsibility, at least in a favourable sense; this responsibility is documented by the finding of high levels of oestrogenuria during the entire cycle in patients suffering from the disease. On the other hand, the angiopathy localization in the large elastic arteries and in certain segments of the aortic arch and epiaortic trunks means that the role of topographic moments whould not be underestimated. As regards infectious factors, the tubercular and streptococcic continue to be of great importance even today. Neither acts directly, however, but by way of an abnormal immunitary reaction which they seem able to trigger off. The infectious moment would thus appear to be related to the immunitary moment, and the latter would seem to play the part of perpetuating the pathological vascular involvement promoted by contact of the organism with the aetiological agent.
| 6,924
|
Dibenzepin and amitriptyline in depressive states: comparative double-blind trial.
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Dibenzepin and amitriptyline appeared to be equally efficacious in controlling target symptoms of depressive reactions. These results appear to be consistent with pharmacological profiles of the two drugs which are both tricylic compounds. Control of target symptoms occurred in an undulating and non-progressive manner in both groups. Aggravation of depressive symptomatology in the third week of treatment was noted in both groups and appeared to be clinically very important in the management of depressed patients. Dibenzepin caused relatively fewer side effects which appears to be an advantage over amitriptyline. Dibenzepin appeared to be a suitable alternative for amitriptyline intolerant patients, with moderately severe depression associated with anxiety, especially patients who demonstrated emotional sensitivity or passive dependent personality, and psychosomatic symptoms.
| 6,928
|
[The effect of ACTH and several antimetabolites of vitamin B6 on the activity of tyrosine aminotransferase in the liver of intact and hypophysectomized rats].
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ACTH injected intraperitoneally in a dose of 140 Units per 1 kg of body weight to intact rats or to rats subjected to hypophysectomy 24 hours before the experiment produced an increase in the activity of tyrosine-aminotrasferase in the liver (4.5 or 2.5 times, respectively) in comparison with the normal. D-cycloserine and its dimere injected intraperitoneally to the intact starving rats in a dose of 2.0-2.5 g per 1 kg of body weight produced in 4 hours a sharp elevation in the liver of the activity of tyrosine-amino transferase, whose induction constituted 75 and 180%, respectively. 24 hours after hypophysectomy D-cycloserine produced no induction of this enzyme in the rat liver; in difference from this, the D-cycloserine dimere produced an induced formation of tyrosine-aminotransferase (comparable with ACTH) in the liver of hypophysectomized rats. This indicated that the induction mechanism of tyrosine-aminotransferase in the liver of rats under the effect of D-cycloserine and its dimere differed.
| 6,954
|
Acute renal effects of new beta-adrenergic receptor site blocking agents on renal function.
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The effects of two new beta blockers on renal function have been studied. There were significant decreases in urine flow, urea clearance, sodium and chloride excretion rates after acute administration. Fractional excretion of sodium (FeNa) fell significantly but did not continue to fall during chronic administration. Blood pressure and plasma renin activity decreased significantly after two months' therapy. These findings suggest that beta blockers in patients with unstable cardiovascular function increase the need for concomitant diuretic therapy.
| 6,959
|
Nucleation of microbiologic calcification by proteolipid.
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The component of crude phospholipid responsible for B. matruchotii calcification was isolated. Crude phospholipid, extracted from the microorganism, was separated into five fractions by column chromatography. A single, protein-containing fraction catalyzed apatite formation in a metastable calcium phosphate solution. The nucleating fraction was identified as a proteolipid.
| 6,970
|
Prevention of memory loss following puromycin treatment.
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Female C57BL/6J mice were trained on a one trial passive avoidance response. Twenty-four hours later, they were treated with puromycin in combination with either 2.0 or 10.0 mg/kg of amphetamine, 0.3 mg/kg of strychnine, or 20.0 or 50.0 mg/kg of pentylenetetrazol. Tests one week after training revealed that treatment with these stimulant drugs prevented the memory loss characteristic of puromycin; an exception being those animals injected with the low dose of amphetamine. Biochemical determination of amino acid incorporation into protein revealed that none of the stimulant drugs used significantly altered the extent or the duration of protein synthesis inhibition induced by puromycin. These results are interpreted as showing that the amnesic effects of puromycin can be counteracted by a state of heightened nervous system excitation.
| 6,975
|
Exposure in vivo of agoraphobics: contributions of diazepam, group exposure, and anxiety evocation.
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Fifty-seven chronic agoraphobic outpatients were treated by 12 hours of exposure in vivo on four days over two weeks to check the effects of oral diazepam versus placebo during group exposure, group versus individual exposure, and high versus medium anxiety arousal during individual exposure. The controlled parallel design allowed comparative evaluation of each treatment condition to six months follow-up. Assessment was blind with respect to drug and psychological treatment. Patients in all treatment conditions improved significantly in phobias and in related life areas. Outcome to group exposure on phobias and other measures was similar in all three drug conditions (placebo, waning diazepam, peak diazepam) with no significant differences between them. Diazepam patients had significantly less discomfort than placebo patients during group exposure treatment. Group exposure patients improved slightly but significantly more than individual exposure patients on non-phobic measures, though group exposure was accompanied by more panics during treatment yet was easier to run by the therapist. Individual exposure under high anxiety arousal was no more therapeutic than with lower anxiety. Diazepam is a mild palliative during group exposure but does not facilitate outcome to treatment. Group exposure in vivo is mildly facilitatory for outcome compared with individual exposure. Anxiety evocation during treatment was not therapeutically helpful.
| 6,985
|
Avoidance of graft versus host reactions in cured W-anemic mice.
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Graft-versus-host reactions of parental cells in F1 hybrids were studied with two unrelated inbred strains of mice that differed at the mouse histocompatibility locus. W-anemic F1 recipients were compared with lethally irradiated normal F1 recipients. Both sets of recipients were populated by marrow and spleen cell grafts from parental and F1 donors. Most W-anemic F1 recipients were cured by parental and F1 cell grafts (except B6 spleen). Even after 13 to 18 months, they showed little or no effect from GVH reactions. Lethally irradiated normal F1 recipients tolerated parental marrow grafts almost as well, but gave dramatically different results with parental spleen grafts. Seventy-nine of 80 irradiated F1 recipients of parental spleen grafts died within 1 month. Unlike lethally irradiated recipients, W-anemic recipients have substantial numbers of their own cells along with the donor cells in their lymphoid tissues. These F1 lymphocytes may interact with parental lymphocytes in vivo to restrain reactions against F1 allogeneic antigens.
| 7,035
|
[Transparency of analytical results found by different methods of electrophoresis studies on casein (author's transl)].
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The electrophoretic mobility of the major casein components has been studied on different carriers. Besides free electrophoresis and paper electrophoresis starch gel, polyacrylamide gel and cellulose acetate gel have compared. With urea buffer mixtures of neutral to alkaline pH a mobility scale on all gels was found corresponding the order alphas-, beta-, kappa-, gamma-casein in the sense of decreasing mobility. The application of commercially available cellulose acetate strips for the investigation of genetic material in large numbers has been found to be sufficient. The transparency of polyacrylamide gel, starch gel and cellulose acetate gel results is guaranteed.
| 7,057
|
[Examinations to phenomenon of shock-lung (author's transl)].
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The pathogenesis of shock lung as well as the success of therapy in this condition was studied in 79 cases of extrathoracic trauma. The water-, hemoglobin-, and DNA contents of the lungs were measured in order to determine the extent of edema, the rate of perfusion, and proliferation. The cases were divided into two groups according to whether they had or had not received medical therapy before death. The data from these two groups were compared using statistical methods in which time of survival was especially taken into account. The fluid balance, pO2, pCO2, central venous pressure, pH of the serum, total serum protein and serum creatinine were also studied in these cases. Results of the study are as follows. Three phases of the posttraumatic syndrome of shock-lung could be distinguished: phase I (initial phase): blood perfusion is increased, edema is beginning to form, and medical treatment has not yet begun. Phase II (early phase = sydrome of early respiratory failure): pulmonary edema is developing rapidly while perfusion is decreasing. Phase III (late phase = syndrome of late respiratory failure): proliferative changes predominante and the edema is still increasing. The mean weight of the lungs was 397 g (s = 170) in phase I, 774 G (S = 361) In phase II, and 1124 g (s = 310) in phase III. The survival times correlated significantly and positively with the amount of water and DNS in the lungs and significantly and negatively to the amount of hemoglobin in the lungs. Thus, increasing pulmonary edema and increasing proliferative changes occurred with decreasing pulmonary perfusion. This correlation was even noted in groups of patients who had not received medical treatment and whose survival times were short. In treated cases, the fluid balance was significantly and negatively correlated to the total serum protein.
| 7,060
|
The synthesis and properties of N6-substituted 2-amino-purine derivatives.
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1. The synthesis, ultraviolet absorption spectra, and behaviour in alkali of N6-methoxy-, N6-methyl, hydroxy-, and N6-hydroxy-2-aminopurines have been described 2. N6-Methoxy-2-aminopurine riboside 5'-pyrophosphate has been prepared and used for polymerization with polynucleotide phosphorylase. 3. The copolymer containing N6-methoxy-2-aminopurine riboside and adenosine residues has been obtained; attempts to synthesize the homopolymer have not been successful. 4. All the purine analogues synthesized have been tested and shown to act mutagenically on Salmonella typhimurium TA1530.
| 7,092
|
[Vegetation analysis used for the detection of exophile tick populations in the south-east of France: the example Ixodes ricinus (Linne 1758) (acarina, ixodoidea)].
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The cross-linking relation between the evidence of outside living tick populations and specific vegetation units allows for efficiently using the vegetation maps, and more especially the medium scale maps. Ixodes ricinus is referred to here as an example. The limitations of this data derived from such maps are evaluated by the authors. They suggest some means aiding in improving their efficiency through the knowledge of the ecological variables playing a role in the species settlement.
| 7,119
|
[An abnormally formed Ctenophthalmus assimilis assimilis (siphonapteres hystrichosyllidae)].
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A female flea is described the body of which is abnormally formed and compressed. It is characterized by a split along its back, raised up abdominal segments and by a shortening of its head. These anomalies might be explained by longitudinal compression of the body during pupation. The possibility of a mutation is not excluded.
| 7,121
|
[Epidemic of autochthonous hepatic and intestinal amebiasis in a place near Grenoble].
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We had the opportunity of studying an epidemic of autochthonous amoebiasis occurring in the autumn of 1974 in a small town of 4000 inhabitants 30 km from Grenoble. Attention was originally attracted by the occurrence in this town of two cases of hepatic amoebiasis and one of intestinal amoebiasis identified by rectoscopy. Systematic investigations (coproctic examinations and serological tests for amoebiasis by indirect antibody fluorescence) were then carried out on everyone in the locality with digestive disorders which were possibly referable to amoebiasis, and on the other members of their families. A total number of 148 coproctic examinations were made and in two cases revealed the presence of vegetative forms of Entamoeba histolytica. In both cases the infestation provoked few symptoms (asthenia, vague abdominal discomfort, intermittent and apparently banal diarrhoea). On the other hand 20 out of 94 serological tests revealed positive results, 14 of which were equal to or greater than a titre of 1/100, a level at which all risks of non-specificity are virtually ruled out under our experimental conditions. Material reasons made it impossible to subject these cases to repeated faecal checks, but in two of them at least the rectoscopic appearances were very suggestive of subacute intestinal amoebiasis. Moreover, amoebic disease appears to be well confirmed by the results obtained among the patients as a whole by treatment with Metroinidazole. A variety of hypotheses on the origin of this epidemic have been put forward and then abandoned (market garden produce, receipt by certain families of exotic frut from overseas). In actual fact water seems to be the point of departure, for, although specimens of water taken at 7 different levels in the water supply system failed to reveal the presence of a single amoeba, bacteriological analyses during autumn 1974 showed signs of faecal contamination. The locality, which is situated at the foot of the Chartreuse massif, receives its water solely from springs but there is a holiday camp for the staff of an international airline situated above the main water catchment.
| 7,124
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Mucocutaneous lymph node syndrome in the United States.
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Sixteen patients with an unusual and distinct symptom complex were encountered during a four-year period. Principal features of this syndrome are (1) fever lasting more than seven days; (2) conjunctival injection; (3) changes in the mouth consisting of erythema of the oropharynx, "strawberry tongue", and erythema of the lips; (4) indurative edema of hands and feet with palm and sole erythema followed by desquamation of the fingertips; and (5) an erythematous rash. Associated features were lymphadenopathy, pyuria, aseptic meningitis, diarrhea, arthritis, and arthralgia. Although usually a self-limited illness, one patient died with massive coronary artery thrombosis on the 19th day of illness. This syndrome appears to be clinically and pathologically similar to mucocutaneous lymph node syndrome, an illness prevalent in Japan but previously unrecognized by American clinicians. Pathologic features suggest a relationship to infantile periarteritis nodosa.
| 7,134
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A decrease in cell-mediated immunity in uremia associated with an increase in activity of suppressor cells.
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The graft-versus-host (GVH) reactivity of uremic and control spleen cells was studied by popliteal lymph node assay in the rat. The reaction evoked by cells from animals with severe uremia was conspicuously weaker than that evoked by control cells. The magnitude of the GVH reaction induced by control cells was directly proportional to dose, while with the uremic cells the same increases in dose led only to insignificant increases in the strength of the GVH reaction. When mixtures of syngeneic control and uremic cells were used, the GVH reactivity of the control cells was suppressed. The activity of uremic spleen cells can be enhanced (restored) by removal of the sub-population of cells adherent to glass wool. The GVH reaction induced by uremic cells so treated became directly proportional to dose. The removal of the adherent cell population from the uremic spleen cell suspension also led to the disappearance of the suppressor effect in mixtures of control and uremic cells. These results indicate that a decrease in GVH activity of rat uremic spleen cells is due to an increase in suppressor cell activity in the uremic spleen cell population.
| 7,140
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Respiratory effects of 'lissive" anaesthesia using gallamine.
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'Lissive anaesthesia', the administration of a small dose of a non-depolarising muscle relaxant to a patient breathing nitrous oxide, oxygen and an anaesthetic vapour, is a technique popularly employed for minor procedures. In this study, the effects of intravenous gallamine triethiodide (40 mg) on the blood-gas status of 20 patients under general anaesthesia with oxygen, nitrous oxide and halothane after pethidine and atropine premedication, were assessed. The results are compared with those obtained from a control group of 10 patients anaesthetised in an identical manner, but omitting the muscle relaxant drug. All patients in both the relaxant and control groups in this study developed respiratory acidaemia. The rise in mean arterial carbon dioxide tension was, however, greater after injection of gallamine. Significant hypoxia or metabolic acidaemia was not encountered, except in one grossly obese patient in the gallamine group. The implications of these findings are discussed.
| 7,150
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Psychomotor skills during subacute treatment with thioridazine and bromazepam, and their combined effects with alcohol.
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Twenty paid healthy students volunteered for a doubleblind cross-over trial on the effects of two weeks' treatment with placebo, thioridazine and bromazepam on psychomotor skills. The doses used were thioridazine 10 mg t.i.d. during the first week and 20 mg t.i.d. during the second week, or 6 mg of bromazepam t.i.d. during two weeks choice reaction test, two co-ordination tests, a divided attention test, flicker fusion, and proprioception tests were used. The psychomotor skills were measured in the afternoon of the 7th and 14th day of each treatment, 30, 90 and 150 minutes after the second daily administration of the drug in combination with either an alcoholic or a placebo drink. There were no significant differences between the test weeks. Thioridazine alone resembled placebo and had no major combined effect with alcohol. Bromazepam impaired reactive and co-ordinative skills and attention deteriorated. The combination of bromazepam and alcohol potentiated the deterious effects of the single agents, and this effect was most remarkable at 30 minutes. The subjects also gave exaggerated responses in the proprioceptive tests. No significant alterations were recorded in the flicker fusion frequency after any treatment.
| 7,178
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Cultivation of mycoplasmas in a modified tissue culture medium.
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A new medium, which contained a chemically defined tissue culture base ("medium 199"), was developed for the cultivation of mycoplasmas. When supplemented with albumin, glucose, serum, and yeast extract, the new medium adequately supported the growth of Mycoplasma and Acholeplasma species.
| 7,199
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[Studies on the properties of acid erythrocyte phosphatase in sheep and the isoenzymes of sheep and goat acid erythrocyte phosphatase].
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Ovine erythrocytic acid phosphatase showed two peaks of activity at pH 5.0 and 5.7 in acetate buffer with p-nitrophenylphosphate as substrate. The enzyme was only slightly inhibited by fluoride and L-phenylalanine, but high concentrations of urea strongly inhibited it. Activity of the enzyme was greater in goat erythrocytes than in sheep. By means of starch electrophoresis, three isoenzymes belonging to nine types were separated from the ovine enzymes, while three isoenzymes of five types were present in goats. Electrophoresis in polyacrylamide gel was suitable for detecting the rapidly migrating isoenzymes.
| 7,216
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[Origination and importance of glycolysis for malignomas and utilization of this property in the chemotherapy of cancer (author's transl)].
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Glycolysis is not of importance for the process of carcinogenesis. It is very likely, however, that certain molecular-biological and genetic changes are produced which enable the malignant cell to develop an intensive glycolysis, for instance, to form specialized glycolytic isoenzymes already during oncogenesis, and may possible become effective in the primary tumour. As soon as the capacity of the cancer cell to intensive aerobic and anaerobic glycolysis has become manifest, this process is an irreversible one. The extent of glycolysis of a malignoma is greatly dependent on the degree of its dedifferentiation and vascularization (glucose supply), although a direct correlation between growth and the amount of lactic acid formed does not seem to exist. However, a certain utilization of glucose is essential for cell proliferation (supply of basic substances). In many cases there is a correlation between the extent of glycolysis measurable under optimal conditions in vitro (glycolytic power) in a malignant tumour and its growth rate recognizable in vivo. The formation of a strong capacity for glucose degradation via the Embden-Meyerhof pathway that cannot be fully utilized by the whole tumour in vivo is first of all designed to ensure survival and proliferation of cells even at extremely low levels of glucose supply. This process can be regarded as an adaptation of cancer cells to a situation of unsufficient supply. This circumstance endows the cancer cell with an essential advantage over the normal cell which enables or even promotes its invasive and destructive growth and metastatic dissemination. In this respect they differ, for instance, from benignant neoplasms. The possibility is discussed to control neoplastic growth by adjusting an optimal pH difference between normal and tumour tissue by combined administration of detoxicated drugs which are converted to their toxic forms only in the tumour by means of strongly pH-dependent exogenous enzymes.
| 7,218
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Isolation, by partial pepsin digestion, of the three collagen-like regions present in subcomponent Clq of the first component of human complement.
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1. Digestion of human subcomponent C1q with pepsin at pH4.45 for 20h at 37 degrees C fragmented most of the non-collagen-like amino acid sequences in the molecule to small peptides, whereas the entire regions of collagen-like sequence that comprised 38% by weight of the subcomponent C1q were left intact. 2. The collagen-like fraction of the digest was eluted in the void volume of a Sephadex G-200 column, was was showm to be composed of two major fragments when examined by electrophoresis on polyacrylamide gels run in buffers containing sodium dodecyl sulphate. These fragments were separated on CM-cellulose at pH4.9 in buffers containing 7.5M-urea. 3. Human subcomponent C1q on reduction and alkylation yields equimolar amounnts of three chains, which have been designated A, B and C [Reid et al. (1972) Biochem. J. 130, 749-763]. One of the pepsin fragments was shown to be composed of the N-terminal 95 residues of the A chain linked, via residue A4, by a single disulphide bond to a residue in the sequence B2-B6 in the N-terminal 91 residues of the B chain. The second pepsin fragment was shown to be composed of a disulphide-linked dimer of the N-terminal 94 residues of the C chain, the only disulphide bond being located at residue C4.4. The mol. wts. of the unoxidized and oxidized pepsin fragments were estimated from their amino acid compositions to be 20 000 and 18 200 for the A-B and C-C dimers and 11 400, 8800 and 9600 for the collagen-like fragments of the A, B and C chains respectively. Estimation of the molecular weights of the peptic fragments by polyacrylamide-gel electrophoresis run in the presence of sodium dodecyl sulphate gave values that were approx. 50% higher than expected from the amino acid sequence data. This is probably due to the high collagen-like sequence content of these fragments.
| 7,240
|
Polar-group behaviour in mixed monolayers of phospholipids and fusogenic lipids.
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1. The surface potentials of mixed monolayers of synthetic phospholipids with lipids that are fusogenic for hen erythrocytes were investigated. 2. At pH 5.6 and 10, but not at pH2, mixed monolayers of the fusogenic lipid, glycerol mono-oleate, with phosphatidylcholine exhibited negative deviations from the ideality rule in surface potential per molecule which were accompanied by negative deviations in mean molecular area. 3. Interactions of this type were not seen with chemically related but non-fusogenic lipids, nor were they found in mixed monolayers of any of the lipids with phosphatidylethanolamine. 4. Experiments with dihexadecyl phosphate and hexadecyltrimethyl-ammonium indicated that the complete head group of phosphatidylcholine is required for its observed behaviour with fusogenic lipids. 5. Bivalent cations (Ca2+, UO2(2+) or Zn2+) in the subphase at pH 5.6 significantly modified the behaviour of mixed monolayers of fusogenic lipids with phospholipids; there was a parallel perturbing effect of fusogenic lipids on interactions between monolayers of phospholipids and bivalent cations. 6. Possible molecular interactions of fusogenic lipids with membrane phospholipids, and the role of Ca2+, are discussed which may be relevant to cell fusion in erythrocytes induced by low-melting lipids in the presence of Ca2+.
| 7,246
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[MASCA-model of biochemical-pharmacological drug research/Part VIII: Examples (author's transl)].
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In this report two examples (inhibition of alcohol dehydrogenase by pyridine and benzamide derivates) are given for the interpretation of the MASCA-model.
| 7,279
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Guanylate cyclase. Existence of different forms and their regulation by nucleotides in calf uterus.
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The activity of calf uterus guanylate cyclase (EC 4.6.1.2) exists in at least two and most probably three distinct forms. The cytosolic enzyme exhibits hyperbolic substrate curves with respect to GTP and Mn2+, while the particulate cyclases (nuclear and microsomal)display sigmoidal (GTP) and hyperbolic (Mn2+) relationships. The Hill coefficient for the GTP dependence is 0.9 for the cytosolic, 1.5 for the nuclear, and 1.4 for the microsomal enzyme. The cytosolic enzyme has a Km for GTP of 70 muM while half maximal velocity occurs at 90 and 100 muM GTP for the nuclear and microsomal enzymes, respectively. The Ka for Mn2+ is 0.57, 0.71 or 0.75 mM for the cytosolic, nuclear, or microsomal enzyme, respectively.
| 7,317
|
Ca++ binding properties of human prothrombin.
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The binding of Ca++ to human prothrombin has been investigated by equilibrium dialysis. The protein exhibited a positive cooperativity phenomenon for the first three Ca++ bound. Eleven to twelve Ca++ binding sites have been found. They could be differentiated in terms of two classes of sites with respect to their Ca++ affinity: 5 strong binding sites (log Kassoc = 3.9) and 7 weak binding sites (log Kassoc = 2.9). We attempted to determine the Hill coefficient of the strong binding sites responsible for cooperativity. Results have been compared to data previously reported for bovine prothrombin.
| 7,324
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[A method of continuous recording on microsamples of the Hb-O2 association curve. II. A study of Bohr effect and carbamino-formation (author's transl)].
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The authors have worked out an adaptation to microsamples (200-400 mul) of the DUVELLEROY et al. method, allowing the continous registration of the O2-Hb association curve. The microsample being diluted in buffer solution, it is possible to predetermine its pH and PCO2. The prefixed conditions are maintained during the initial deoxygenation phase, and all along the curve registration. Moreover, the adjustment to the desired values of the pH and PCO2 allows the quantification of total BOHR effect, proton BOHR effect and carbamino-formation, during the course of oxygenation.
| 7,333
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Pain as a major cause of postoperative nausea.
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The incidence of nausea in relation to pain was recorded in 104 patients after abdominal operations. Ten per cent of the patients had episodes of nausea not related to pain. One hundred and fourteen episodes of concomitant pain and nausea were recorded in 61 patients (58.6 per cent). The intravenous injection of morphine or ketobemidone relieved nausea as well as pain in 80 per cent of the episodes. Relief of pain with persistence of nausea was uncommon and if pain relief was inadequate nausea was unabated. Nausea was provoked by 3.4 per cent of the morphine injections, but all patients tolerated similar doses of morphine on other occasions without nausea. Nausea often accompanies pain in the early postoperative period and can be relieved concomitant with the pain by the intravenous use of opiates in adequate doses in a high proportion of cases.
| 7,347
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Influence of DNA acidification on DNA premelting and template properties.
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Acidification of a T7 DNA sample was found to be partly irreversible as ultraviolet difference spectra measured at various sub-melting temperatures were different from those observed for a 'normal' DNA sample. This implies some subtle conformational change which is not reversed by return to neutral pH. In the same conditions, only poly(purine)-poly(pyrimidine) polymers behaved in a different manner, during premelting, according to whether they were previously acidified or not. The properties of acidified and reneutralized T7 DNA were also investigated for Escherichia coli RNA polymerase binding and transcription. An inhibition of RNA synthesis and chain initiation was observed. The results suggest that the binding of the enzyme is affected. RNA synthesized is specific but there is a decrease in the number and in the stability of the RNA-polymerase-DNA complexes.
| 7,456
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A new type of fluorocarbon liquid oxygenator.
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A new oxygenator based on gas transfer across liquid-liquid interfaces (liquid oxygenator) is introduced. Perfluorinated chemicals are used as gas carriers. This liquid oxygenator differs from others in its concept basing on the dispersion of the blood droplets in an inert liquid by means of shear forces. This method allows high efficiency both with respect to saturation and to required blood flow. The results of gas transfer experiments in vitro and in vivo are satisfactory.
| 7,460
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Purification and some properties of NADP+ -specific isocitrate dehydrogenase from an extreme thermophile, Thermus flavus AT-62.
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Thermostable NADP+ -specific isocitrate dehydrogenase (EC 1.1.1.42) was purified from crude extract of an extremely thermophilic bacterium Thermus flavus AT-62 through DEAE-cellulose column, acetone fractionation, DEAE-Sephadex A-50 column and isoelectric focussing. The enzyme was purified about 500-folds in its specific activity and purity was found to be about 96%. The enzyme was not inactivated after 60 min at 70 degrees C, but 20 and 80% of the activity were lost after 60 min at 80 degrees and 90 degrees C, respectively. Oxalacetate plus glyoxylate (each 1 nM) demonstrated 75% inhibition of the activity in concerted manner. The degree of the inhibition and the affinity of the enzyme for isocitrate and NADP+ decreased with the rise of temperature, especially above 60 degrees C. The activation energy below and above 60 degrees C were 14,500 and 8,000 cal per mole respectively. In CD spectra negative bands at 210 and 220nm were observed and alpha-helix content was calculated to be about 26%. In the course of heating up to 60 degrees practically no change in CD bands are observed, but above 60 degrees the depth of CD bands decreased gradually and remarkably above 80 degrees C. The effect of temperature on kinetic parameters and secondary structures of the enzyme was discussed in relation to the temperature adaptation of the organism.
| 7,466
|
Studies on the inhibition of thermolysin.
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Thei nhibition of the thermolysin catalyzed hydrolysis of FA-Gly-Leu-NH2 and FA-Gly-Phe-NH2 has been reported. The results suggest a model for substrate and inhibitor binding involving the hydrophobic specificity pocket, Arg-203 and Glu-143.
| 7,470
|
Hemoglobin function in stored blood. XIII. A citrate-adenine preservative with optimal pH to maintain red cell 2,3-DPG (function) and ATP (viability).
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Increasing pH by a 0.5 increment over the commonly used preservative, acid-citrate-dextrose with adenine (ACD-Ad), results in a significant improvement in 2,3-DPG, with no significant loss in concentrations of ATP. The intermediate pH preservative, 6.0, also had ATP concentrations which equaled those of the low pH preservatives, 5.0 and 5.5, from the 21st to the 42nd day of storage. A citrate-adenine preservative, with a pH between 5.5 and 6.0, would seem to be optimal for maintenance of hemoglobin function and red cell viability, as determined by measurements of 2,3-DPG and ATP concentrations.
| 7,517
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An analysis of the relationships among obesity, plasma insulin and hepatic lipogenic enzymes in "viable yellow obese" mice (Avy/a).
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The development of obesity, hyperinsulinemia and six hepatic lipogenic enzymes in Avy/a mice were compared to that in a/a mice. Correlation between body weight, liver weight, plasma insulin concentration and activities of hepatic enzymes was analyzed. In the Avy/a mice, body weight, liver weight and plasma insulin level increased steadily as the mice aged. In the a/a mice, the change of these three parameters was much slower. Plasma insulin concentration in a/a mice did not increase until eight months of age. Compared with a/a mice, Avy/a mice had higher 6-phosphogluconate dehydrogenase and fatty acid synthetase activities at two months of age; lower citrate cleavage enzyme, glucose-6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase activities at three months of age; lower citrate cleavage enzyme and glucose-6-phosphate dehydrogenase and higher acetyl CoA carboxylase activities at five months of age; and higher malic enzyme, citrate cleavage enzyme and 6-phosphogluconate dehydrogenase activities at eight months of age. There were significant correlations between plasma insulin level and body weight and between plasma insulin level and the activities of malic enzyme and citrate cleavage enzyme in Avy/a mice. The correlation between body weight and malic enzyme and citrate cleavage enzyme activities disappeared after the analysis was adjusted for plasma insulin level.
| 7,520
|
Potentiometric studies on benzeneboronic acid-alpha-chymotrypsin interactions.
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When the competitive inhibitor benzeneboronic acid (BBA) forms a complex with alpha-chymotrypsin [EC 3.4.21.1] protons are released in the acidic pH region. The proton release can be measured by a difference potentiometric technique. The proton release is also observed in chymotrypsinogen A but not in TRCK-, DIP-, and anhydrochymotrypsins. Based on these observations, a simple procedure to estimate the equilibrium constants of the trigonal-tetrahedral interconversion of BBA is proposed. Thermodynamic parameters of the ionization of His 57 and of each step involved in BBA binding can be estimated from the temperature dependence of the proton release. Those of His 57 are essentially the same as those of imidazole in water. Regarding the interconversion of BBA on the enzyme, the value of delta S is similar to delta S not equal to of the deacylation step of nonspecific substrates, and delta H is remarkably reduced from that for the ionization of BBA in water. The enthalpic gain of enzymic process is suggested to be due to the change of the proton acceptor, which is water in the case of the ionization of BBA in water, to imidazole on the enzyme.
| 7,550
|
Comparative studies on polyguanylate polymerase and polyadenylate polymerase activities in the DNA-dependent RNA polymerase I fraction from cauliflower.
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The properties of poly(G) polymerase and poly(A) polymerase activities in the DNA-dependent RNA polymerase [nucleosidetriphosphate: RNA nucleotidyltransferase EC 2.7.7.6] I fraction from cauliflower (Brassica oleracea var. botrytis) were comparatively investigated. The pH optimum, the effect of ionic strength, the effect of substrate concentration on the rate of synthesis, the effect of divalent metal ion concentration, and the time course of synthesis at different temperatures were all different for the three polymerase activities. The enzyme fraction preferentially utilized denatured DNA. Synthetic poly(C) and poly(U) were more effectively utillized for the synthesis of polyguanylate and polyadenylate, respectively. Further, it was found that poly(G) and poly(A) formed in vitro by the enzyme fraction had chain length of 25-28 and 84-89 nucleotides, respectively, and that poly (adenylate-gluanylate) chain was hardly formed when ATP and GTP were added together as substrates in the same reaction medium.
| 7,554
|
Studies on the molecular species of DNA polymerase extracted from rat ascites hepatoma cells.
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DNA polymerase [EC 2.7.7.7] activities present in hypotonic extract from rat ascites hepatoma AH130 cells were eluted in three separable peaks on DEAE-cellulose column chromatography. Peak I activity had an alkaline pH optimum, and was relatively resistant to SH-blocking reagents and salt concentration. These properties of DEAE peak I are typical of low molecular weight DNA polymerase. DEAE peak II and peak III activities possessed properties corresponding to high molecular weight (6-8 S) polymerase; they showed maximal activity at neutral pH, and were sensitive to SH-blocking reagents and salt. No low molecular weight polymerase activity was released from DEAE peak II or peak III by salt treatment, though partial conversion from DEAE peak II to peak III was observed on the same treatment.
| 7,555
|
Duodenal immunoglobulin deficiency in graft versus host disease (GVHD) mice.
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The small intestine is a well documented target organ in mouse and human GVHD, and diarrhea is a prominent part of the clinical GVHD syndrome. Although a plethora of systemic immune deficits has been documented in GVHD, the integrity of the small intestinal immune system has not been investigated. A correlation has not been demonstrated between systemic immune dysfuction and the incidence of lymphomas in mouse GVHD survivors. If gastrointestinal immune deficiency exists in mouse GVHD, its possible relationship to GVHD lymphomas, frequently abdominal. should be investigated. GVHD was produced in newborn BLA (C57 BL/Ka females x BALB-C males) mice house in a specific pathogen-free environment by the i.p. inoculation of 10(7) male BALB-C spleen cells. Control mice received syngeneic spleen cells. Twenty GVHD and 16 control mice were sacrificed at 3 weeks and specimens of duodenum were removed for routine histologic and immunofluorescent examination. All but one GVHD mouse (95%) had virtually absent duodenal IgA and IgM. Duodenal cellular fluorescence was demonstrated in all controls. A significant duodenal immunoglobulin deficit has been demonstrated in 3-week-old GVHD mice. The relationship of this finding to GVHD diarrhea, wasting, and neoplasia remains to be determined.
| 7,629
|
Comparison of uptake and binding of disodium cromoglycate and phenol red in rat lung.
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In rat lung slices 3H-disodium cromoglycate (3H-DSCG) (0.001 mM) was taken up rapidly and 3H-DSCG tissue spaces, which equilibrated by 30 minutes, remained constant over a 4-hour incubation period. In contrast, 35S-phenol red (0.001 mM) accumulated in lung slices to a much greater extent than did DSCG, and the measured tissue spaces continued to increase over a 3-hour incubation period. In the presence of either phenol red (1 mM) or the metabolic inhibitors, iodoacetic acid (10(-4) M) and dinitrophenol (10(-4) M), 3H-DSCG uptake was significantly decreased. Accumulation of 3H-DSCG in lung slices and binding to tissue homogenates (pH 7.4) was also decreased when Ca and Mg ions were omitted from the bathing solution. Although DSCG and phenol red mutually inhibited the accumulation of one another over time in lung slices and 3H-DSCG (0.001 mM) binding to lung homogenates was decreased in the presence of 1 mM phenol red, 35S-phenol red efflux was not altered by the addition of 1 mM DSCG during the washout. Thus, it appears that, in rat lung, DSCG and phenol red share a common binding site(s) for uptake, possible on the transport "carrier." Also, there appear to be additional pulmonary binding sites for phenol red. These sites are not occupied by DSCG and their presence could account for the differences observed in the extent of accumulation of the two compounds in lung slices.
| 7,666
|
Permeability parameters of the toad isolated stratum corneum.
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A technique for isolating the stratum corneum from the subjacent layers of the epithelium was developed which permits studying the stratum corneum as an isolated membrane mounted between half-chambers. The method basically consists of an osmotic shock induced by immersing a piece of skin in distilled water at 50 degrees C for 2 min. When the membrane is bathed on each surface by NaCl-Ringer's solution, its electrical resistance is 14.1 +/- 1.3 omega cm2 (n=10). This value is about 1/100 of the whole skin resistance in the presence of the same solution. The hydraulic filtration coefficient (Lp) measured by a hydrostatic pressure method, with identical solutions on each side of the membrane, is 8.8 X 10(-5) +/- 1.5 X 10(-5) cm sec-1 atm-1 (n=10) in distilled water and 9.2 X 10(-5) +/- 1.4 X 10(-5) cm sec-1 atm-1 (n=10) in NaCl-Ringer's solution. These values are not statistically different and are within the range of 1/80 to 1/120 of the whole skin Lp. The stratum corneum shows an amphoteric character when studied by KCl diffusion potentials at different pH'S. The membrane presents an isoelectric pH of 4.6 +/- 0.3 (n=10). Above the isoelectric pH the potassium transport number is higher than the chloride transport number; below it, the reverse situation is valid. Divalent cations (Ca++ or Cu++) reduce membrane ionic discrimination when the membrane is negatively charged and are ineffective when the membrane fixed charges are protonated at low pH.
| 7,676
|
Hemodynamic effects of beta-adrenergic blockade with pindolol, oxprenolol, propranolol and bufetolol hydrochloride in essential hypertension.
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Hemodynamic studies (using (131)I-labeled albumin [RISA]) Were performed before and 5 and 42 weeks after the oral administration of pindolol (av. 30 mg/day), oxprenolol (av. 216 mg/day), propranolol (av. 75 mg/day) or bufetolol hydrochloride (av. 30 mg/day) in 40 patients with essential hypertension. Responders to the antihypertensive actions of short-term (5 weeks) pindolol or bufetolol showed a reduction in total peripheral resistance (pindolol, from av. 2622 to 2022 dyne-sec-cm-5-m2; befetolol, from av. 3301 to 2620, p less than 0.05), without significant changes in cardiac index, while hypotensive actions of propranolol or oxprenolol appeared to be due mainly to a decrease in cardiac output (propranolol, from av. 4.03 to 2.99 L/min/m2; oxprenolol, from av. 3.97 to 3.29 L/min/m2), although the decrease in cardiac output was not significant. In long-term (42 weeks) oxprenolol therapy, antihypertensive effects seemed to be related to reduced cardiac output and a readaptation of peripheral resistance to chronic reduction of cardiac output was not always observed. Circulation time was determined in 9 patients with oxprenolol therapy and 8 with pindolol therapy by the measurement of the arrival time in the cerebral hemisphere of the intravenously injected radioisotope. The patients with oxprenolol therapy showed significant prolongation in circulation time (short-term administration, av. 6.6 to 8.4 sec; long-term administration av. 6.6 to 9.2 sec, p less than 0.05), while no prolongation was observed in pindolol therapy. These results suggest that hemodynamic responses to beta-blocking agents are not uniform and that the antihypertensive actions of beta-blockers depend on the effects on both cardiac output and peripheral vascular resistance.
| 7,688
|
[Arterial hypertension and chronic hemodialysis].
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Basing on the literature data and their own observations of patients with chronic hemodialysis the authors have analysed the pathogenesis, course, hemodynamic shifts and possibilities of purposeful treatment in terminal uremia. Besides two variants of the hypertension course (controlled and noncontrolled), a third type has been revealed--hypertension difficult to control, in the pathogenesis of which, as well as in the noncontrolled variant, an important role is played by the activization of the renin-angiotensin system. Hemodynamic mechanizms of an abrupt change in the arterial pressure (acute hypotension and hypertensive crisis) in the process of hemodialysis are analysed.
| 7,700
|
[Use of beta-blockader visken in children with primary arterial hypertension].
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The effect of Visken was analysed in children with primary arterial hypertension, Stage IB, with reference to their general state, dynamics of cardiac contractions, arterial pressure, cardiac output, and vascular peripheral resistance. The treatment was undertaken in 28 children lasting from 6 to 8 weeks. A multiformity of the drug's effect upon the state of the children with early hypertension was noted. The response of different parameters of the circulatory system to Visken is individual. Side effects may develop against the background of even low doses.
| 7,701
|
[Effect of actinomycin D on transformation of the planulae of Obelia loveni (Allman)].
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The incubation of planulae Obelia loveni in the actinomycin D solution (40 mug/ml) for 3 hrs at 17--20 degrees resulted in the marked inhibition of the process of attachment of planulae to the substrate and their transformation in polyps. A suggestion is put forward that at the final phase of larval development a special RNA is synthesized which participates in the genetically determined control of the complicated morphogenetic phenomenon of attachment and transformation of the planula in polyp.
| 7,762
|
Pneumothorax in the respiratory distress syndrome: incidence and effect on vital signs, blood gases, and pH.
|
We determined the incidence of pneumothorax in 295 infants (mean birthweight, 1,917 gm) with the respiratory distress syndrome (RDS) treated according to the same protocol. Fifty-five infants (mean birthweight, 1,594 gm) developed pneumothorax (incidence, 19%); incidence varied with severity of RDS and intensity of respiratory assistance. Pneumothorax occurred in 3.5% (2 of 58) of infants who received no assisted ventilation and in 11% (14 of 124) of infants who received continuous positive airway pressure (CPAP) as the only form of assisted ventilation; the difference between these two groups is not significant. Forty-nine infants initially treated with CPAP later required mechanical ventilation with positive end-expiratory pressure (PEEP). Pneumothorax occurred in 12 of the 49 (24%) and in 21 of 64 (33%) of those infants initially treated with PEEP; the incidence of pneumothorax for both these groups was significantly higher than for those treated with no assisted ventilation or CPAP only. To assess the value of frequent measurement of vital signs, blood gas tensions, and pH in the recognition of pneumothorax, we analyzed these variables by the cumulative sum statistical technique. We noted the following significant changes associated with pneumothorax: arterial blood pressure, heart rate, and respiratory rate decreased in 77% of cases; pulse pressure narrowed in 51% of cases; Po2 decreased in 17 of 20 cases in which ventilatory settings were constant for at least three hours prior to pneumothorax. However, pH and Pco2 showed consistent changes. Frequent measurements of vital signs and Po2 aid in the early diagnosis of pneumothorax.
| 7,768
|
Purification, characterization, and quantitation of the antigen employed in the immunodiffusion test for diagnosis of equine infectious anemia.
|
Equine infectious anemia (EIA) antigen extracted from the spleen of horses infected with EIA virus was purified by pH treatment, (NH4)2SO4 fractionation and affinity chromatography. The homogeneity of the antigen was indicated by sedimentation rate and sedimentation equilibrium experiments. A S20,w of 0.51 was determined and a molecular weight of 7600 was calculated from sedimentation equilibrium analysis. The amino acid composition of the pure antigen indicated the antigen is an acidic protein. Employing radical immunodiffusion (RID) and pure antigen a method for quantitating antigen content of antigen containing preparations was developed.
| 7,782
|
Dietary and hormonal regulation of the content of acetyl coenzyme A carboxylase-synthesizing polysomes in rat liver.
|
Specific polysomes involved the the synthesis of acetyl-CoA carboxylase [acetyl-CoA: carbon-dioxide ligase (ADP-forming), EC 6.4.1.2] have been identified by the binding of 125I-labeled antiacetyl-CoA carboxylase to rat liver polysomes. The binding is highly specific and occurs through the recognition of the nascent peptide chains on polysomes. With the use of the 125I-labeled antibody binding technique, it has been demonstrated that the relative content of acetyl-CoA carboxylase-synthesizing polysomes in the liver correlates well with the rate of hepatic synthesis of the enzyme in rats subjected to different dietary conditions as well as in alloxan-diabetic rats with or without insulin treatment.
| 7,784
|
Economizing with psychotropic drugs.
|
Every health practitioner can reduce the cost of his treatments without compromising their quality. A review of the magnitude of the cost problem with regard to psychotropic drugs, variables which affect cost, the methods by which the clinician can manipulate the variables to reduce costs, and the application of these methods to the major classes of psychotropic drugs will show that substantial savings can be achieved easily and with no sacrifice in efficacy.
| 7,793
|
Drug inhibition of ecto-ATPase and of phagocytosis in leukocytes.
|
Substituted phenothiazines and tricyclic antidepressants which inhibited the ecto-ATPase in leukocytes also markedly decreased the phagocytic activity of these cells. In affecting either the enzyme or phagocytosis the order of potency of the drugs was similar. Various other CNS drugs were ineffective. The results suggest possible involvement of ecto-ATPase in the phagocytic process, and indicate adverse effects of the aforelisted drugs on the host defense system against foreign materials, including microbes.
| 7,807
|
Alpha-N-Benzoylarginine-2-naphthylamide hydrolase (cathepsin BI?) from rat skin. III. Substrate specificity, modifier characteristics, and transformation of the enzyme at acidic pH.
|
Some properties of rat skin benzoylarginine-2-naphthylamide hydrolase types I (preparations I and AI) and II (preparations II and NII) were studied. Both types were activated by dithiothreitol and EDTA, but responded differently to 1 mM KCN, when benzoylarginine-2-naphthylamide (BANA) was used as a substrate: type I was inhibited, while type II was activated. When leucine-2-naphthylamide was used as a substrate, both types were activated by KCN. Thiol proteinase inhibiting substances, like heavy metals, iodoacetic acid, 4-chloromercuribenzoic acid, and tosyllysine chloromethylketone, inhibited the enzymes. Diisopropylfluorophosphate, phenylmethylsulfonyfluoride, 4-aminobenzamidine, and high-molecular-weight trypsin inhibitors were without effect. The substrate specificity of rat skin BANA hydrolase resembled that of an amino acid naphthylamidase, naphthylamides of methionine, lysine, arginine, and alanine being hydrolyzed most rapidly. The rate of hydrolysis of BANA was only 11% of that of methionine naphthylamide. Amino acid esters with a free alpha-amino group were also good substrates. The transformation of type II to type I at acidic pH was studied. During the transformation amino acids or peptides were formed and probably some inhibitor present in type II was destroyed proteolytically.
| 7,911
|
[Physical and mental fatigue of probable hyperuricemia origin].
|
A blood uric acid analysis has been effected on 193 Iranians of the intellectual group aged from 25 to 60, of which the normal average rate for 99 women and 94 men of a normal state are (47.5 +/- 2.73) and (53.62 +/- 2.73) respectively. After having controlled the uricemia of these subjects during a period of three years in the three states of healthiness, fatigue or physical strains and sickness, we have been able to note that during physical fatigue and intellectual strains the uricemia presents an augmentation notable as in the case of the sicknesses. Taking into consideration the hyperuricemia resulting from fatigue and strains, it may be noteworthy to be taken into consideration by the clinical laboratories and the physicians as well.
| 7,923
|
Electrophoretic separation and characterization of subunits released from influenza virus by detergents.
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Subunits released from influenza A/Singapore/1/57 (H2N2) virus by either Triton-X-100 (T-X-100); or sodium lauryl sarcosinate (SLS) or ether were separated by electrophoresis in agarose suspension into a rapidly migrating fraction (I) and a slowly migrating fraction (II). Fraction I obtained after T-X-100 treatment contained the viral ribonucleoprotein (RNP) in a form indistinguishable from the obtained after ether treatment. SLS treatment of the virus resulted in a rapidly migrating fraction containing only the protein part of the viral RNP. Fraction II obtained after T-X-100 or SLS treatment contained both haemagglutinin (HA) and neuraminidase (NA), mostly dissociated from each other, in contrast to fraction II obtained after ether treatment which contained mixed aggregates of HA and NA. The yields of electrophoretically isolated RNP and HA-NA were essentially the same irrespective of whether T-X-100 or ether was used for virus disruption. Treatment of virus by T-X-100 and subsequent removal of the latter resulted in a 10-20-fold increase of the HA activity. After sodium dodecyl sulphate (SDS) treatment of the virus, the NA activity was found in a heterogeneous fraction with surprisingly high migration rate towards the anode, indicating that NA remained active despite its extensive SDS binding.
| 7,935
|
[Resistance test to streptokinase. Its value in the establishing of a thrombolytic treatment using this enzyme].
|
The reckoning of the rate of serous anti-streptokinase (ASK) evidenced that 8 p. 100 of the test-sample presented a distinct resistance to Streptokinase (SK), and that this percentage could be more important under certain pathological circumstances. On account of this fact and also because SK injectable preparations may offer a variation in activity, the writers advocate a "preliminary control in vitro" by means of the resistance test to streptokinase that enables one to make sure, for each patient, of the biological efficacy of the drug and to specify the starting posology.
| 7,980
|
[Nitric oxide production in rice soils (author's transl)].
|
Nitric oxide gas evolution from nitrite was studied in vitro in three rice soils by gas chromatography. Autoclaved soils showed an NO evolution when supplemented with nitrite. Yet, when temperature of incubation, soil pH, soil moisture content and nitrite concentration were varied in the three soils, and with addition of nitrite reductase inhibitors, it appeared in one soil that NO production was partially a biological process. Thus, NO formation was two times as high in non-sterile soil as in sterile soil, and decreased when the temperature increased. Optimal NO production occurred at about neutrality and increased with increasing soil moisture content; moreover, this NO formation increased much less than in the other two soils with increasing nitrite concentration. Finally, the first soil contained three times more denitrifying bacteria tolerating a high nitrite concentration (5 g/1) that the other soils.
| 7,989
|
Autolysis of high-GC isolates of Pseudomonas putrefaciens.
|
High-GC isolates of P. putrefaciens undergo extensive autolysis after growth, resulting in a marked decrease in turbidity and the release of high-molecular-weight DNA which imparts a high viscosity to culture broths. The native DNA released is resistant to attack by the exocellular DNase activity of the culture broths. Autolysis is inhibited by a pH of 6.0 and the presence of 0.001 M Mg++ or Ca++, and is enhanced by elevated pH values and temperatures. This autolytic phenomenon in broth cultures readily distinguishes high- from low-GC isolates. The latter do not exhibit autolysis.
| 7,999
|
Inhibition of Clostridium perfringens by heated combinations of nitrite, sulfur, and ferrous or ferric ions.
|
Heating mixtures of sodium nitrite, cysteine, and either ferrous sulfate or ferric chloride at 121 C for 20 min at pH 6.5 or 6.3 produced a potent inhibitor of Clostridium perfringens vegetative cells and spores when added to previously heat-sterilized fluid thioglycolate medium. When the mixtures containing FeSO4 at pH 5.2 or FeCl3 at pH 2.7 were heated, the inhibitory effect was not produced. These responses seem to eliminate the possibility that cysteine nitrosothiol is the agent responsible for the heated-nitrite inhibition known as the Perigo effect. The variable pH responses also cast doubt upon the role of the black Roussin salt as the agent of the Perigo effect.
| 8,004
|
Hypotensive action of propranolol and a new beta-blocking agent, D-32 in conscious normotensive and renal hypertensive dogs.
|
The hypotensive actions of dl-propranolol and a new beta-blocking agent, dl-tert-butylamino-3-(2', 3'-dimethylphenoxy)-2-propanol hydrochloride (D-32) were studied in conscious normotensive and renal hypertensive dogs, using a cross-over design. The effects were compared with that of placebo (lactose 200 mg/head, p.o.) administered in a blind fashion. A marked reduction in systolic blood pressure, from 158 +/- 2.9 to 124 +/- 2.3 (mean +/- S.E.) mm Hg, was observed at 3 hr after administration of 50 mg/kg, p.o. of D-32 in renal hypertensive dogs but not in normotensive ones. In both normotensive and renal hypertensive dogs, 10 and 50 mg/kg, p.o. of D-32 caused a marked increase in heart rate. Intravenous infusion of p-OH D-32, a main metabolite of D-32 in dogs, at a rate of 1 mg/kg per min for 5 min into renal hypertensive dogs caused a significant, long-lasting fall in blood pressure and a sustained increase in heart rate, whereas that of D-32 (1 mg/kg per min for 5 min) failed to do so. Propranolol (10 and/or 50 mg/kg, p.o.) produced no significant changes in blood pressure and heart rate in both preparations. These results indicate that D-32 causes a fall in blood pressure in conscious renal hypertensive dogs mainly by a metabolite of D-32, p-OH D-32.
| 8,021
|
The effects of proteolytic digestion by trypsin on the structure and catalytic properties of reduced nicotinamide-adenine dinucleotide dehydrogenase from bovine heart mitochondria.
|
1. At 21 degrees C incubation of NADH-ubiquinone-1 reductase (Complex 1) with trypsin caused selective inhibition of nicotinamide nucleotide transhydrogenase activity. The reduction of K3Fe(CN)6 by NADH or NADPH was unaffected, but a slow decrease in the rate of reduction of ubiquinone-1 by NADH was observed. 2. The pH-dependence of nicotinamide nucleotide transhydrogenase activity differed in Complex I and trypsin-treated Complex I. The trypsin-labile activity had a pH optimum of approx. 6.5, whereas the trypsin-resistant activity had a pH optimum of approx. 5.5 or less. 3. The trypsinlabile transhydrogenase activity was specifically inhibited by butanedione or phenylglyoxal and was identified with the enzyme catalysing energy-linked transhydrogenase activity in submitochondrial particles. 4. Polyacrylamide-gel electrophoresis in the presence of sodium dodecyl sulphate revealed that trypsin caused degradation of a polypeptide of mol.wt 20500 in parallel with the loss of transhydrogenase activity. 5. At 30 degrees C and higher trypsin concentrations, the rate of reduction of K3Fe(CN)6 by NADH or NADPH slowly decreased. Increased lability of NADH-K3Fe(CN)6 reductase activity to trypsin was observed when the endogenous phospholipid of Complex I was depleted by detergent or phospholipase A treatment. 6. Polyacrylamide-gel electrophoresis indicated that removal of phospholipid allowed much more extensive degradation of constituent polypeptides by trypsin. The subunits of the low-molecular-weight (type II) dehydrogenase (53000 and 26000 mol.wt.) were, however, relatively resistant to trypsin even in phospholipid-depleted preparations.
| 8,040
|
The regulation of rat liver tryptophan pyrrolase activity by reduced nicotinamide-adenine dinucleotide (phosphate). Experiments with glucose and nicotinamide.
|
1. Chronic administration of glucose or nicotinamide in drinking water inhibits the activity of rat liver tryptophan pyrrolase, and subsequent withdrawal causes an enhancement. The enzyme activity is also inhibited by administration in drinking water of sucrose, but not fructose, which is capable of preventing the glucose effect. 2. The inhibition by glucose or nictinamide is not due to a defective apoenzyme synthesis nor a decreased cofactor availability. 3. The inhibition by nicotinamide is reversed by regeneration of liver NAD+ and NADP+ in vivo by administration of fructose, pyruvate or phenazine methosulphate. Inhibition by glucose is also reversed by the above agents and by NH4Cl. Reversal of inhibition by glucose or nicotinamide is also achieved in vitro by addition of NAD+ or NADP+. 4. Glucose or nicotinamide increases liver [NADPH]. [NADP+] is also increased by nicotinamide. [NADPH] is also increased by sucrose, but not by fructose, which prevents the glucose effect. Phenazine methosulphate prevents the increase in [NADPH] caused by both glucose and nicotinamide. 5. It is suggested that the inhibition of tryptophan pyrrolase activity by glucose or nicotinamide is mediated by both NADPH and NADH.
| 8,041
|
Basic ethers of cyclohexylphenols with beta-blocking activity: synthesis and pharmacological study of exaprolol.
|
The paper describes the preparation and study of the pharmacological properties of a series of derivatives with the general formula. (see article) where R is a cyclohexyl or cyclohexenyl radical and R1 is a hydrogen, methyl or cyclohexyl. The compounds with a single cycloaliphatic radical ortho to the basic chain, and in particular the one with a cyclohexyl (exaprolol), were found to be particularly active in blocking the beta-adrenergic receptors, as antiarrhythmics and local anesthetics, while the introduction of a second radical or the shift of the cycloaliphatic radical to meta or para position caused the said pharmacological activities to disappear almost entirely, with the exception of the local anesthetic action.
| 8,056
|
General pharmacological properties of a new non-opiate antitussive: zipeprol (3024 CERM). I. Action on respiratory function and acute toxicity.
|
1-(2-Methoxy-2-phenyl)-ethyl-4-(2-hydroxy-3-methoxy-3-phenyl)-propyl-iperazine-dihydrochloride (zipeprol, Respilene) is a substance of non-phenanthrenic chemical structure. In the cat, it antagonised cough induced by stimulation of the superior laryngeal nerve or by direct mechanical excitation of the sensitive tracheo-bronchial receptors. The efficacy of zipeprol after enteral administration made it possible both to establish good intestinal absorption and to rank it favourably in relation to several major antitussive reference products; codeine, codethyline, dextromethorphan, diphenhydramine and pentoxyverine. The activity of zipeprol was superior or equal to that of all these substances, excdept codeine. The antitussive properties appeared to be due to a central action. Other properties have been demonstrated which suggest at least a supplementary mechanism in the inhibition of cough, in addition to the central action. These consisted of slight antihistamine and anticholinergic properties, marked local-anesthetic potency and bronchospasmolytic activity. This latter property was demonstrated by the inhibition of histamine and serotonin induced bronchospasm in the guinea-pig. In vitro, using human sputum, zipeprol had a mucolytic action, shown by a decrease in sputum vis viscosity and lysis of DNA and AMPS fibrils. In the dog, at high doses, zipeprol unlike codeine, did not inhibit central stimulation of respiration by hypercapnia, in addition no modification of ventilatory dynamics or blood gases was seen. On the basis of these results, zipeprol can be considered as possessing no respiratory depressant effect even in the upper ranges of its antitussive doses.
| 8,057
|
Actions of narcotics on brain dopamine metabolism and their relevance for "psychomotor" effects.
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A review is given about the effects of narcotic analgesics, particularly of morphine, on the dopamine metabolism in the corpus striatum and about the relations of these effects to motility and "psychomotor" phenomena. In rats, acute doses of morphine decrease the dopaminergic neurotransmission in brain, without blocking postsynaptic dopamine receptors. Chronic treatment of rats with morphine reverses these acute effects of morphine and induces symptoms of an increased dopaminergic neurotransmission in brain. In mice and cats on the other hand, acute doses of morphine apparently increase dopaminergic neurotransmission. The effects of morphine on striatal dopamine metabolism seem to be a model well suited to study opioid-specific effects on a cellular level. Furthermore, they might also be responsible for some narcotic-specific effects on behaviour observed in animals and man.
| 8,059
|
Structural elucidation and properties of 8alpha-(N1-histidyl)riboflavin: the flavin component of thiamine dehydrogenase and beta-cyclopiazonate oxidocyclase.
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In addition to 8alpha-(N3-histidyl)riboflavin, 8alpha-(N1-histidyl)riboflavin is also formed during the reaction of Nalpha-blocked histidine with 8alpha-bromotetraacetylriboflavin in a yield of 20-25% of the total histidylflavin fraction. The properties of 8alpha-(N1-histidyl)riboflavin are inditical with those of the histidylflavin isolated from thiamine dehydrogenase and beta-cyclopiazonate oxidocyclase but differ from those of 8alpha-(N3-histidyl)riboflavin. These properties include pKa of fluorescence quenching, electrophoretic mobility at pH 5.0, stability to storage, and reduction by NaBH4. Proof for 8alpha substitution is shown by the electron paramagnetic resonance and electron-nuclear double resonance spectra of the cationic semiquinone form, as well as by the proton magnetic resonance spectrum of the oxidized form. The site of histidine substitution by the 8alpha-methylene of the flavin moiety was shown by methylation of the imidazole ring with methyl iodide, cleavage of the methylhistidine-flavin bond by acid hydrolysis at 150 degrees C, and identification of the methylhistidine isomer by electrophoresis. 3-Methylhistidine is the product from the N1-histidylflavin isomer, while 1-methylhistidine is produced from the N3 isomer. The flavin product from reductive Zn cleavage of either isomer has been identified as riboflavin. The compound obtained on acid treatment of 8alpha-(N3-histidyl)riboflavin (previously thought to be the N1 isomer) differs from the parent compound only in the ribityl side chain, since chemical degradation studies show 1-methylhistidine as a product and a flavin product which differs from riboflavin only in mobility in thin-layer chromatography, but not in absorption, fluorescence, and electron paramagnetic resonance spectral properties. Proof that acid modification involves only the ribityl chain has come from the observations that alkaline irradiation of this flavin yields lumiflavin, that the proton magnetic resonance spectrum of the compound differs from that of riboflavin in the region of the ribityl proton resonance, and that its periodate titer is lower than that of authentic riboflavin. The identity of 8alpha-(N1-histidyl)riboflavin with the histidylflavin from thiamine dehydrogenase and beta-cyclopiazonate oxidocyclase shows that both isomeric forms of 8alpha-histidylflavin occur in nature.
| 8,076
|
Histone interactions in solution and susceptibility to denaturation.
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Histone interactions in solution may depend upon treatments used for purification. Optical rotatory dispersion and sedimentation-velocity measurements have been made in a reference solvent, before and after exposure to various treatments, to investigate histone susceptibility to irreversible denaturation. Some acid conditions and urea and guanidine solutions may denature. Interaction studies performed on nondenatured histones indicate that the dimer, (H4)(H3), and tetramer, (H4)2(H3)2, dissociate to monomers at low ionic strength. Sedimentation-velocity experiments suggest a model for the (H4)2(H3)2 tetramer, with a compact semispherical center and four protruding amino-terminal regions. Fractions H2a and H2b interact to form the mixed dimer in equilibrium with monomers. Fraction H2a self-associates readily to dimers, tetramers, and octamers, while fraction H1 associates only weakly to form dimers.
| 8,079
|
Mechanism of inhibition of Chromatium D growth by L-methionine. Regulation of L-threonine biosynthesis by the intracellular level of S-adenosylmethionine.
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(1) An unusual accumulation of S-adenosyl-L-methionine in Chromatium D was associated with a marked growth inhibition by L-methionine. The inhibition was overcome by L-isoleucine, L-leucine, L-phyenylalanine, L-threonine, L-valine and putrescien. Based on their effects, these compounds are classified into 3 types. (2) L-Isoleucine, L-leucine, L-phyenylalanine and L-valine (Type I) inhibited the L-methionine uptake and consequently prevented the bacterium from the unusual accumulation of S-adenosyl-L-methionine even in the presence of L-methionine in the medium. Putrescine (Type II) stimulated the consumption of S-adenosyl-L-methionine, but did not influence the L-methionine uptake. Hence, the effect of putrescine would be explained by the action to diminish the intracellular level of S-adenosyl-L-methionine. L-Threonine (Type III) neither inhibited the L-methionine uptake nor affected the content of S-adenoxyl-L-methionine due to the addition of L-methionine. (3) The specific activity of homoserine kinase (EC 2.7.1.39) was greatly lowered by the addition of L-methionine under conditions in which Chromatium D unusually accumulates S-adenoxyl-L-methionine. Homoserine dehydrogenase (EC 1.1.1.3) activity was inhbitied by S-adenosyl-L-methionine (50% inhibition index, 3.5 mM). These facts strongly suggest that the growth inhibition by L-methionine is associated with the L-threonine deficiency caused by the unusual accumulation of S-adenosyl-L-methionine.
| 8,102
|
Purification and some properties of a neutral protease from human leukocyte granules and its comparison with pancreatic elastase.
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1. A cationic protease has been purified from the granule fraction of blood-donor leukocytes by a preparative method including precipitation by acetone and chromatography on Bio-Gel A 1.5 m, CM-Sephadex C-50 and Sephadex G-G-75. 2. The pH optimum against denatured bovine hemoglobin is 7.4. Gel chromatography indicated a molecular weight close to 23 000. 3. This neutral protease (EC 3.4.-.-) is able to split the synthetic esters Z-Ala-NPh and AcAla3OMe, its activity on the former substrate being 2.2 times greater than that of pancreatic elastase, on the latter the same. It differs crucially from pancreatic elastase in having small elastinolytic activity. 4. In cationic disk electrophoresis, neutral protease resolves into three protein bands with lower mobility than lysozyme: all bands exhibit esterolytic activity against 2-acetoxy-3-naphthoic acid o-toluidide, strongly suggesting that they represent isoenzymes. 5. The enzyme is completely inhibited by iPr2P-F, partially so by soybean trypsin inhibitor and Trasylol. Cysteine, EDTA and TosLysCH2Cl have no effect. 6. During chromatography on CM-Sephadex C-50 a more positively charged enzyme(s) was identified. This had hemoglobinolytic activity at pH 7.4 but only a small esterolytic effect on Z-Ala-NPh; it showed only traces of activity against AcAla3OMe.
| 8,109
|
Redox potential of plastoquinone A in spinach chloroplasts.
|
The redox potential of plastoquinone A in spinach chloroplasts was determined. The midpoint potential of the quinone is about +80 mV at pH 7.0 with an n value of 2. The pH-dependence of the potential is -30 mV per pH between pH 4.0 and 5.7, and -60 mV per pH between pH 5.7 and 8.0. The change of the slope at pH 5.7 is interpreted as the protonation of the oxidized plastoquinone A.
| 8,122
|
Effect of portacaval anastomosis on the activities of hepatic enzymes related to cholesterol and bile acid metabolism in rats.
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1. The effect of a portacaval anastomosis on the activities of hepatic enzymes related to cholesterol metabolism was investigated in rats. 2. Portacaval anastomosis led to a fall in body weight and liver weight/body weight ratio, and to a rise in the activities of hydroxymethylglutaryl-CoA reductase and cholesterol 7alpha-hydroxylase per g of liver. The net effect was to maintain a normal activity of both enzymes per 100 g of rat. Diurnal rhythm in the activities of both enzymes was maintained after portacaval anastomosis. 3. The rate of excretion of total bile acids, per 100 g of rat, in bile fistula rats was not significantly decreased by portacaval anastomosis.
| 8,128
|
HCO-3-activated adenosine triphosphatase in intestinal mucosa of the eel.
|
An HCO-3-activated and SCN--inhibited ATPase (ATP phosphohydrolase, EC 3.6.1.3) found in homogenates of intestinal mucosa of the eel was solubilized by Triton X-100. Optimal HCO-3-concentration and pH for the enzyme were 25 mM and 8.7, respectively. HCO-3-ATPase activity in both homogenate and solubilized preparations increased after seawater adaptation. This adaptive increase in enzyme activity was also observed in the gills and the kidney. The HCO-3-ATPase seems to be related to transport mechanisms, especially for Cl-, in osmoregulatory surfaces of the eel.
| 8,150
|
Electrostatic interactions at charged lipid membranes. I. Effects of pH and univalent cations on membrane structure.
|
Electrostatic interactions at charged lipid membranes make a significant contribution to the free energy of the system, and can be varied within a wide range by alteration either of the membrane's surface charge density or of the concentration of electrolytes in the surrounding medium. Changes in the charged membrane's structure, such as the ordered in equilibrium fluid phase transition, can thus be induced at constant temperature by variations in pH and salt concentration. An adequate quantitative description of these phenomena is obtained from the Gouy--Chapman theory. The good agreement between theory and experiment confirms that the expression derived for the electrostatic free energy especially in respect of its positive sign is correct. The classical expression derived for the electrostatic free energy, especially in respect of its positive sign, is correct. The classical expression for the "free energy of the double layer" derived by Verwey and Overbeek, which has a negative sign, is not applicable to lipid membranes with ionizable polar groups.
| 8,167
|
Successful bone marrow transplantation against mixed lymphocyte culture barrier.
|
If bone marrow transplantation is to become widely applicable in the treatment of patients with leukemia and aplastic anemia, the necessity to have a perfectly histocompatible donor must be overcome. In an effort to define the roles of HL-A type and mixed lymphocyte culture (MLC) reactivity in the determination of successful engraftment and the occurrence of graftversus-host disease (GVHD), we have attempted transplantation of a child with acute myeloblastic leukemia (AML) using an HL-A identical, MLC-reactive sibling donor. Successful engraftment has been accomplished, as documented by the appearance of multiple donor genetic markers in the recipient. There is no evidence of severe GVHD. The recipient is alive, without evidence of leukemia, and has returned to full activities 9 mo after transplantation. The recipient now produces lymphocytes, which have the MLC reactivity that characterize the donor's lymphocytes, rather than that of her own pretransplant lymphocytes. This experience demonstrates that successful bone marrow transplantation in patients with leukemia can be accomplished in the face of MLC reactivity.
| 8,180
|
Comparison of propranolol, metoprolol, and acebutolol on insulin-induced hypoglycaemia.
|
Metoprolol and acebutolol, two supposedly cardio-selective beta-adrenergic recptor blocking agents, were tested in healthy volunteers against propranolol, a non-selective drug, for their effect on blood glucose levels during insulin-induced hypoglycaemia. There was not significant difference between propranolol and metoprolol, which both potentiated the initial hypoglycaemic action of the insulin and delayed the return to normoglycaemia. Acebutolol, even though potentiating the initial hypoglycaemia, did not possess a significant delaying effect. A similar trial should be undertaken in diabetics to determine with certainty the safety of such drugs in diabetes mellitus.
| 8,187
|
Malignant germ cell tumor in situ in a cryptorchid testis.
|
A case of a malignant undifferentiated germ cell tumor in situ of an undescended testis diagnosed by needle biopsy is described. Four similar cases have been so far recorded in the literature, all of them in the infertile men with normally descended descended testes. Two of them developed embryonal carcinoma of testis 4 1/2 later and one had a concomitant seminoma. In a high-risk group of patients (atrophic testis, cryptorchidism), a needle biopsy of a testicle may discover malignancy in its very early phase of development (Stage 0), at which time an orchiectomy alone may be a curative treatment.
| 8,206
|
Fine structure of complex ocelli of a cubomedusan, Tamoya bursaria Haeckel.
|
The retina of the distal and proximal lens-bearing complex ocelli are composed of pigmented sensory cells and long pigmented cells. A ciliary sheath from each sensory cell, together with the processes of long pigmented cells, extends through the vitreous layer as far as the capsule that envelops the lens. Each ciliary sheath has several ballon-like swellings and the ciliary microtubules, arranged in the 9+2 pattern in the proximal part, are markedly disorganized distally in the swollen parts, out of which extends most of the microvilli in the vitreous layer. It is suggested that some of the microvilli may originate in vesicles that are constricted off from the surface of the pigmented sensory cells. Closely packed microvilli run in parallel in short bundles. In addition to characteristic junctions between sensory cells, junctions that are presumably synaptic and, of a new type in coelenterates, are observed between sensory cells and nerve endings.
| 8,210
|
Intracellular acid-base heterogeneity in nucleated avian erythrocytes.
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1. Intracellular hydrogen ion activity, [H+]i, was extimated in human erythrocytes and in nucleated avian erythrocytes from measurements of the distribution of ammonia and 5,5'-dimethyloxazolidine-2,4'-dione (DMO) between intracellular and extracellular fluid. 2. In human erythrocytes there was no difference between values for [H+]i derived from measurements of either DMO or ammonia. 3. In avian erythrocytes, [H+]i(ammonia) was consistently greater than [H+]i(DMO), indicating significant acid-base heterogeneity of the intracellular water. The degree of heterogeneity was assessed by reference to a theoretical model of two compartments of equal size. 4. Experiments with nuclei isolated from avian erythrocytes suggested that DMO is not bound to nucleoproteins, and that the nucleus may be more acidic than the cytoplasm.
| 8,234
|
Telephone management of poisonings using syrup of ipecac.
|
Seven hundred and seventy-six cases were studied during a six-month period to see if induction of emesis could be successfully managed at home by telephone. Emesis was successful in 98.8% of cases. In 6.7% of all cases, symptoms were found at 4-hour follow-up that were referrable to the ingestion, but all were considered to be of minor consequence. No complications of vomiting occurred. Twenty-four hour follow-up investigation indicated no significant complications of induction of emesis or complications from managing the patient by telephone. It is our conclusion that, with appropriate telephone supervision, home-induced emesis of ingestions expected to produce mild to moderate symptoms is as effective as emergency room or physician office management of cases. Furthermore, the absence of adverse affects of complications arising from the induction of emesis at home in our cases confirms that this form of management is quite safe.
| 8,236
|
Metabolism of 2,4,5,2',5'-pentachlorobiphenyl in the rat. Qualitative and quantitative aspects.
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The metabolism of 2,4,5,2',5'-pentachloro [14C] biphenyl (5-CB) was studied in the male rat. Following iv administration of 5-CB (0.6 mg/kg), 84% of the total dose was excreted within 7 days and 89% of the radioactivity excreted was in the form of 5-CB metabolites. Mass spectral and proton nuclear magnetic resonance analysis or chemical methods in conjunction with mass spectral analysis were used to identify the metabolites. The major metabolite was identified as 3'-hydroxy 5-CB. One minor metabolite was identified as the 3',4'-dihydrodiol of 5-CB and a second minor metabolite was tentatively identified as 3',4'-dihydroxy-5-CB. The relative amounts of 5-CB and its metabolites excreted in the urine and feces were also determined.
| 8,291
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Inactivation of porcine calcitonin by rat kidney microsome.
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Biological activity of porcine calcitonin was most actively inactivated by the rat kidney homogenate than by other tissue homogenates. Among the various subcellular fractions of the rat kidney homogenate examined, microsome fraction was most active in the in vitro inactivation of porcine calcitonin. Inactivation of porcine calcitonin by the rat kidney microsome was dependent on pH and temperature. Inactivating activity of the rat kidney microsome was inhibited by 1 X 10(-3) M monoiodoacetate and 1 X10(-5) M p-chloromercuribenzoate. These results suggest that porcine calcitonin is probably inactivated by a SH-enzyme in the rat kidney microsomes. However, the participation of other enzymes cannot be ruled out, since the inactivating activity of the rat kidney microsome fraction is also inhibited by 1 X 10(-4) M diisopropylfuorophosphate.
| 8,306
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[Studies of various factors in thyrotropoin releasing hromone TRH) radioimmunoassay for serum (author's transl)].
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To study the significance of TRH in the hypothalamo-pituitary-thyroid axis measurement of TRH in body fluid are needed. We previously reported TRH radioimmunoassay for urine. TRH radioimmunoassay for serum has not established yet, because TRH immunoreactivity is inactivated with serum. We investigated effects of various factors on this inactivation and method for prevention of this inactivation. Synthetic TRH was added to normal human serum at 4 degrees C and incubated at 60 degrees C, 37 degrees C, 20 degrees C, 4 degrees C or -20 degrees C for various intervals. After incubation, recovery of TRH was measured. After one hour incubation, recovery of TRH was 9.2% at 37 degrees C, 34.5% at 20 degrees C, 100% at 4 degrees C or -20 degrees C. Incubation of TRH serum mixtures at 65 degrees C after incubation at 37 degrees C resulted in some recovery of TRH. After one hour incubation at 37 degrees C, recovery of TRH was 9.2% at serum pH 7.0, 100% at serum pH 3.0 to 5.0 or 11.0. Recovery of TRH was increased in accordance with stepwisely increase of serum dilution. Concentrations of serum thyroid hormone did not affect recovery of TRH. Smaller quantities of TRH were more rapidly inactivated. Inactivation of TRH immunoreactivity could be prevented addition of BAL (over 0.25 mg/ml) or mixture of 8-Hydroxyquinoline (HQ) and Tween 20(T) (over 0.1 mg/ml of HQ and 1 lmg/ml of T). Duration of effectiveness of BAL was short. Effectiveness of HQT continued for 12 weeks, if HQT treated serum was stored at -20 degrees C. From above data it was suggested that TRH immunoreactivity might be inactivated with enzyme system and other factors and TRH levels in the serum might be able to measure with addition of HQT to serum.
| 8,343
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[Cutaneous side effects of systemic drugs. Part 4 of a synopsis. 6/7. Drugs affecting the central nervous system. C. Drug-induced photosensitivity. D. Drug-induced changes of skin color].
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This, the fourth part of a synopisis of cutaneous side effects of drugs, covers the drugs affecting the central nervous system: antiepileptics, hypnotics, narcotics and psychopharmaceutics; the myorelaxants and antiallergics follow, and lastly there is a section on drug addiction and placebo. The various cutaneous side effects are listed in chart form referring to more than 500 sources. A drug index is attached for handy reference. The reviews of certain drug induced skin disorders are continued with tables covering photosensitivity and changes in skin colour. Phototoxicity, photoallergy and light sensitivity by porphyria are differentiated. The various pigmentation disorders, colour changes due to metal deposits as well as different localisations are included.
| 8,344
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