Biomedical subjects
Publications and source records attributed to E Winkler.
A case of concurrent chloroquine and Fandisar resistance is described in a traveller returning from Gabon. Mefloquine therapy resulted in clinical cure.
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This study compared the conversational repair strategies employed by language-impaired and normal children in response to a stacked series of requests for clarification. Ten linguistically normal and 10 language-impaired children were sampled from each of the following age levels, 4:10-5:10, 6:10-7:10, and 8:10-9:10, resulting in a total of 60 subjects. Each subject was asked to describe a series of action pictures for an examiner who was seated behind a screen. At regular intervals, the examiner responded to the child's description by initiating a repair sequence. Each sequence consisted of three different neutral requests for clarification ("Huh?", "What?", and "I didn't understand that.") and the subject's response to each request. Although all subjects appeared to recognize the obligatory nature of the neutral clarification requests employed, differences were observed in the repair strategies used by normal and language-impaired children. In addition, impaired and younger normal subjects had greater difficulty responding appropriately as the stacked sequence progressed.
Conversational repair sequences are an important aspect of communicative interaction. These sequences may occur in the event of communication failure if a listener requests clarification of a previous aspect of the speaker's message. The purpose of this study was to investigate the repair strategies employed in conversation by children at four age levels. Ten linguistically normal children were sampled from each of the following age levels: 2:7 to 3:10, 4:10 to 5:10, 6:10 to 7:10, and 8:10 to 9:10 (years:months), resulting in a total of 40 subjects. Each subject was asked to describe a series of action pictures for an examiner who was seated behind a screen. At regular intervals, the examiner responded to the child's description by initiating a stacked repair sequence. Results indicated that subjects at all age levels complied with the initial request for clarification the majority of the time. However, with increasing age, subjects became more adept at handling the stacked sequence of requests for clarification. Older children were more responsive to the requests, and 9-year-old subjects demonstrated a wider range of strategies in providing repairs.
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The purpose of the present study was to find out if formerly premature babies (birth weight less than or equal to 1,501 g) show differences in their neurological, psychological and linguistic development of school-age when compared to children without perinatal problems. Discrete neurological dysfunctions (clumsy child syndromes, discrete hemi-syndromes) and left-handedness were found significantly more frequently in the premature group. The test psychological investigation of the intellectual development and the development of language did not reveal significant differences between the two groups. Also with regard to the cognitive partial functions (attention, visual differentiation, serial memory performance and visuomotor coordination) the prematures were significantly behind only in serial memory performance. On the other hand the results of the psychological investigations were significantly worse in children of lower social classes independent of birth weight.
The isolated uncoupling protein (UCP) from brown fat adipose tissue mitochondria has been reconstituted into artificial phospholipid vesicles. Because of the high lability of H+ transport, several new steps have been introduced in the reconstitution; the detergent octyl-POE, the addition of phospholipids to mitochondria prior to solubilization and purification, the vesicle formation by rapid removal of detergent with polystyrene beads and of external salts by a mixed ion exchange. In the K+-loaded proteoliposomes, H+ influx can be induced by a diffusion potential on addition of valinomycin. H+ influx is inhibited to more than 90% by GTP addition, in the assay for UCP activity. By reversing delta psi with external K+, H+ efflux is measured, however, at a four times lower rate. In vesicles loaded with internal GTP, H+ influx is fully inhibited but can be activated by Dowex-OH treatment to an even higher rate than that found in the GTP-free vesicles. Binding studies with GTP show that most of the active UCP are oriented with the binding site outside as in mitochondria, and that in GTP-loaded vesicles GTP is also bound at the outside. The rate of H+ transport is linearly dependent on the membrane potential. Despite the ordered orientation, there is no 'valve' mechanism, since there is H+ efflux with a reversed potential. pH dependency is only small between pH 6.5 and 7.5, indicating that the H+-translocating site differs from the highly pH-dependent nucleotide-binding site. The turnover number of reconstituted UCP is commensurate with mitochondrial function and indicates a carrier instead of a channel-type H+ transport.(ABSTRACT TRUNCATED AT 250 WORDS)
114 patients from four clinics participated in a double blind study designed to assess the efficacy of a nifedipine-acebutolol fixed combination -10 mg + 100 mg - as compared with acebutolol -200 mg- in essential hypertension. During the ten week study the mean blood pressure readings (s.d.) 1-3 h after treatment decreased from 179.2/104.8 (10.2/6.2) to 150.3/87.7 (9.8/7.7) in the combination group and from 181.7/106.5 (14.4/7.0) to 150.4/89.0 (15.0/10.4) in the acebutolol group. The mean systolic and diastolic blood pressures were also decreased after exertion (load) and 24 hours after treatment at the end of the 6th week of the study. A doubling of the dose from week 7 to 10 did not change these figures. These results reveal the possibility of treating essential hypertension with a low dose of beta-adrenergic blocking agents in combination with 10 mg nifedipine. Both drugs were well tolerated. 3 patients (5%) in the combination group and 3 patients in the acebutolol group were withdrawn from the study because of headache and dizziness.
In 17 totally gastrectomised patients the vitamin B12-serum level was analyzed by 57Co-marked vitamin B12 according to the principle of competitive protein-bounding. Pathological low B12-serum levels in 10 patients refer to the lack of this vitamin. This, however, was only clinically manifested in one case by a megalocytic anaemia. The control of B12-serum levels by running substitution is only useful at the end of the interval between two injections. It is only at this time that it is a help in evaluating the effect of substitution. The monthly or 2-monthly vitamin B12-substitution should be preferred. No optimal substitutional effect can be achieved by injecting 1000 micrograms of vitamin B12 every three months.
In 31 pregnant women in the 32nd to 40th week of pregnancy estimations of apoprotein B in the blood serum were done. Besides this, in 15 cases the concentration of apoprotein B in the umbilical cord serum was measured. Furthermore, apoprotein B and dehydroepiandrosterone in cord serum and estriol in the serum of the mothers were measured in 10 cases. Dexamethasone was administered to 6 patients in order to prevent respiratory distress syndrome of the newborns. It has been tried to explain the changes of the parameters.
In contrast to 3 months old rats of the Wistar strain show 18 months old animals an elevation of the serum triglyceride level under the conditions of a sucrose diet (25% of the energy uptake). Clinical investigations with women show a similar age difference. These results may not be explained by the age-dependent behavior of the activity of several lipogenic enzymes of liver and adipose tissue and of their adaptation to a sucrose diet, but the age-dependent decrease of the lipoprotein lipase activity may be of special importance.
In tracer experiments which are mostly performed to determine the rate of protein turnover the treatment of protein degradation as a first-order reaction leads to a monoexponential function as a representation of the decrease of the initial labelling. In a protein mixture, however, the assumption of a single turnover constant is no more admissible. The analysis of curves by a sum of exponential functions is only a makeshift and is level less appropriate if protein degradation is only a partial process in a complex model. -- As in the cell (or, more generally, in a biological object) a multitude of proteins with very different turnover constants is present, continuous distributions of protein synthesis rates and turnover constants are proposed. The hypothesis is made that the distributions of the two quantities are independent of each other. A number of arguments lead to a gamma distribution for the turnover constants. On this basis a model for protein turnover consisting of a homogeneous pool (soluble amino acid) and an inhomogeneous one (proteins) is proposed and mathematically described by a system of integro-differential equations which is not analytically solvable in the general case. The distribution of the relative protein amount in dependence on the turnover constant as well as quantities characterizing the inhomogeneous protein pool are discussed. The analysis of a case of full dependence between synthesis and degradation rates shows the usefulness of the model also beyond its original range of validity.
In part 1 of this series a model for the protein turnover characterized by an inhomogeneous protein pool with a distribution of turnover constants was developed. This model is mathematically described, taking into account that the protein turnover is experimentally determined almost exclusively by tracer experiments, but a system of integro-differential equations. The analytical solution of this system of equations is elaborated for 3 special cases: tracer elimination from the protein pool after pulse labelling, tracer accumulation due to continuous labelling, and elimination after stopping this continuous incorporation of tracer. The applicability of the resulting modified power function is tested using an example for the literature (Garlic et al.: Biochem. J. 156, 657 (1976)) and computer generated data. On this background the existence of several classes of proteins computer generated data. On this background the existence of several classes of proteins with typical life times is discussed. Finally, the general applicability of power functions for tracer kinetic problems is treated from the point fo view of the results obtained in this paper.
In part 1 of this series [1] a model was presented fo the turnover of a protein pool consisting of proteins with different turnover constants which can be described mathematically by a set of integro-differential equations. As in the general case this system is not treatable analytically, a computer programme was developed to solve it numerically. The applicability of the programme and, more generally, of the model was tested using computer generated and real data. The analytical solutions of special cases (tracer elimination after pulse labeling and continuous labelling) which form modified power functions were given in part 2 [2]. on the basis of these functions problems of the design of experiments for a quantitative analysis of pool heterogeneities are discussed. In both cases a duration of the experiment of at least two or three times the reciprocal mean turnover constant turns out to be necessary; a combination of the two procedures is more appropriate. On the other hand, it is shown that after continuous labelling heterogeneity can largely be neglected. But with the experimental design f pulse labelling which is often used heterogeneity must always be taken into account even if it is not the direct object of the investigation since otherwise the calculated turnover constant is an error (too high by factor of about 2).
In a double blind designed treatment trial with three randomized groups of patients the effect of a fixed betablocker diuretic combination (Torrat, Boehringer Mannheim GmbH) was compared with the effect of the single components. 66 patients with essential and renal hypertension stage I and II according to the WHO definition were evaluated. 27 patients were treated with 1 tablet, 32 with 2 X 1 tablet, and 7 patients with 3 X 1 tablet daily. Besides of the blood pressure lowering effect over an observation period of 10 weeks the influence on pulse rate, potassium, blood sugar and uric acid were investigated. It could be shown that the blood pressure lowering effect was highest under the combination-drug. The treatment with the single components showed a less pronounced influence on the blood pressure, thus hinting at an additive effect of the 2 components metipranolol and butizide when given together. The combination exerts few side effects and does not influence the investigated parameters of metabolism over a longer period of time.
Formate dehydrogenase and fumarate reductase are involved in the electron transport phosphorylation system of Vibrio succinogenes. The orientation of the active sites of these enzymes in the cytoplasmic membrane of the bacterium was investigated with the aim of elucidating the mechanism of energy transduction. This was done by measuring the accessiblities of the enzymes to substrates, dyes and inhibitors both in cells and in cell-derived particles obtained with the French press. 1. After treatment of the cells with lysozyme and EDTA, followed by fractionation, both enzymes were found exclusively in the membranous fractions, while the periplasmic as well as the cytoplasmic fractions were devoid of both of the enzymic activities. 2. The sites of dye interaction of fumarate reductase were inaccessible to non-permeant dyes in cells, but were fully accessible in French-press particles. The Km for succinate as measured with the permeant methylene blue as acceptor was increased ten fold on lysis of the cells. The Km measured in the particles was similar to that of lysed cells and was not altered by lysis. 3. The rates of formate oxidation in the presence of non-permeant dyes and the Km for formate were unaffected by cell lysis. On lysis of French-press particles, formate oxidation with both permeant and non-permeant acceptors was increased about three fold. The extent of stimulation was not altered by inhibition of the enzymic activities. 4. Succinate oxidation by particles was fully inhibited by 4-chloromercuriphenyl sulfonate whereas that of cells was fully resistant. Formate dehydrogenase in cells was inhibited by 4-diazophenyl sulfonate when added together with formate. This compound also inhibited the enzyme in the particles when given in the absence of a lytic agent or after its addition. However, most of the enzyme remained active if the inhibitor was added before the lytic agent. 5. Fumarate and succinate were actively taken up by the cells from the medium, while formate did not even penetrate through the membrane of the bacteria. 6. It is concluded that the substrate and the dye-reactive sites of formate dehydrogenase face the outside, while those of fumarate reductase face the inside of the cytoplasmic membrane of cells of V. succinogenes. About 70% of the French-press particles were inverted with respect to the substrate and dye sites of the enzymes. The membrane is impermeable to formate and does not contain a specific transporter. The electrogenic liberation of protons on the outisde and the uptake of protons from the cytoplasm of the bacteria, which accompany electron transport, can be explained on the basis of the orientation of the substrate sites of the enzymes without net transport of protons across the membrane.
The post-heparin-lipolytic activity of women decreases in dependence on age. This age dependence is the result of a diminished activity of post-heparin-lipase of extrahepatic origin, whereas no age differences of the activities of hepatic lipase exist. There is a negative correlation between serum triglycerides and the post-heparin-lipolytic activity, especially between the enzyme of extrahepatic source and the triglyceride level, but not between the hepatic lipase and triglycerides. Serum-HDL-cholesterol correlated positively with the post-hepatic-lipolytic activity.