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Biomedical subjects

W Schmidt

Publications and source records attributed to W Schmidt.

At least 343 records · Page 19Linked to original sources
PubMed1993

Adenosine influences the high-affinity uptake of transmitter glutamate and aspartate under conditions of hepatic encephalopathy.

The high-affinity uptake of transmitter glutamate and aspartate in hippocampal slices incubated in sera from patients with hepatic encephalopathy was dramatically reduced in neuropil areas by more than 50% compared with the control level. Adenosine compensates for these reduction in reuptake capacity in a concentration-dependent fashion reaching normal values at 500 microM adenosine. The renormalization of glutamate and aspartate uptake caused by adenosine might reasonably be expected to have potential therapeutic implications for the treatment of hepatic encephalopathy.

Adenosine↗
PubMed1993

Characterization of human brain kynurenine aminotransferases using [3H]kynurenine as a substrate.

The brain metabolite kynurenic acid is an established broad-spectrum antagonist at ionotropic excitatory amino acid receptors. In the human brain, two distinct enzymes are capable of synthesizing kynurenic acid from its bioprecursor L-kynurenine. Using [3H]kynurenine as the substrate, the two kynurenine aminotransferases (kynurenine aminotransferase I and kynurenine aminotransferase II) are now characterized using partially purified enzyme preparations. When assayed at its pH optimum of 10.0, kynurenine aminotransferase I showed pronounced oxo acid specificity (pyruvate >> 2-oxoglutarate). This co-substrate selectivity was lost when assays were performed at pH 7.4. Kynurenine aminotransferase I activity was potently inhibited by 2 mM glutamine, tryptophan or phenylalanine, but not by 2 mM alpha-aminoadipate or glutamate. In contrast to kynurenine aminotransferase I, kynurenine aminotransferase II showed a shallow pH curve with an optimum of about 7.4, displayed virtually equal activity with all of the nine 2-oxo acids tested and was not susceptible to inhibition by any of 10 amino acids (2 mM) which are known to serve as substrates for enzymatic transamination. Kinetic analyses, performed at pH 7.4 (kynurenine aminotransferases I and II) and 10.0 (kynurenine aminotransferase I), and using various concentrations of kynurenine, pyruvate or 2-oxoglutarate, respectively, substantiated the differences between the two enzymes and further elucidated the pH dependence of kynurenine aminotransferase I activity [apparent Km values for kynurenine with 1 mM 2-oxoglutarate: 515 microM (pH 7.4) and 22 microM (pH 10.0)]. Taken together, these data suggest that under physiological conditions, human brain kynurenic acid may derive preferentially from kynurenine aminotransferase II.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acids↗
PubMed1993

Functional properties of isolated stroma and epithelium from rat ventral prostate during androgen deprivation and estrogen treatment.

To identify the functional activities of prostatic stroma under different hormonal conditions, isolated stroma and epithelium from rat ventral prostate (RVP, intact or one week castrated or estrogen-treated), were studied in metabolic labeling experiments. Using a semiquantitative stereological procedure, the relative proportion of the epithelial and stromal compartment was determined in situ. In addition, the distribution of the androgen receptor was visualized by in situ hybridization and by immunocytochemistry. In castrated animals protein biosynthesis of the stroma and epithelium exceeded the control value by a factor 7 and 5, respectively. In estrogen-treated animals protein biosynthesis was reduced, reaching only between one tenth and one fifth of the control value. The amount of stroma obtained from these animals was very low. These results were confirmed by stereological findings and indicate a differential regulation of prostatic stroma and epithelium after estrogen challenge and androgen deprivation. Estrogen receptor was induced in epithelium and stroma in estrogenized animals whereas the androgen receptor was reduced in experimental specimens. During estrogenization the biosynthetic activity of both stroma and epithelium is depressed, while estrogen responsivity of the epithelium in terms of estrogen receptor expression is increased. Androgen withdrawal results in active transformation of the gland through increased stromal biosynthetic activity and epithelial regression.

Androgens↗
PubMed1993

[Evaluation of the antepartum CTG course in cases of highly pathologic Doppler flow findings].

In a group of 79 pregnancies with highly abnormal Doppler-flow findings in foetal vessels the value of antepartal CTG criteria was evaluated in detail. In cases with absent enddiastolic flow (AEDF) the prognostical value was not further increased by antepartal pathological CTG findings. In cases with permanently normal antepartal CTG's, however, foetal outcome was fairly good (median duration of pregnancy 38 + 6 weeks, median foetal birth weight 2,545 grams, arterial pH < 7.20 in 9%). This was true also in the presence of pathological Doppler-flow findings except AEDF. In cases with pathological antepartal CTG findings in the antepartal course of pregnancy the loss of acceleration was most frequent (82%), followed by decreased frequency (53%) or narrowed amplitude (38%) of the foetal heart rate variation. Combination of both methods (Doppler sonography and CTG) is recommended clinically because the rate of uncertain findings can be reduced. Especially in cases with AEDF an active management would be justified before CTG's become pathological.

Aorta↗
PubMed1993

Effects of chronic hypoxia and exercise on plasma erythropoietin in high-altitude residents.

The present study was performed to evaluate the effects of chronic inspiratory hypoxia and its combination with physical exercise on plasma erythropoietin concentration ([EPO]). Eight natives from the Bolivian Plateau were investigated at 3,600 m above sea level at rest as well as during and up to 48 h after exhaustive exercise (EE) and 60 min of submaximal (60%) cycle ergometer exercise (SE). Ten sea-level subjects were used as a control group for resting values. The mean resting plasma [EPO] of the high-altitude group (19.5 +/- 0.7 mU/ml) did not differ from that of the sea-level group (18.1 +/- 0.4 mU/ml) but was higher than would be expected from the relationship between [EPO] and hematocrit at sea level. Five hours after both types of exercise, [EPO] decreased by 2.1 +/- 0.8 (EE, P < 0.01) and 1.6 +/- 0.8 mU/ml (SE, P < 0.05); 48 h after SE, [EPO] increased by 2.6 +/- 0.9 mU/ml (P < 0.05). It is concluded that 1) high-altitude natives need relatively high [EPO] to maintain their high hematocrit and 2) exercise at low basal arterial PO2 does not directly increase plasma [EPO] in high-altitude residents but seems to exert suppressive effects.

Acclimatization↗
PubMed1992

Age-related changes in kynurenic acid production in rat brain.

Two separate in vitro assays were used to examine the biosynthesis of the broad spectrum excitatory amino acid receptor antagonist kynurenic acid (KYNA) during the life span of the adult rat. Assessment of KYNA's anabolic enzyme kynurenine aminotransferase revealed steady increases between 3 and 24 months of age in all five brain regions examined. No changes were observed in the liver. The changes were particularly pronounced in the cortex and in the striatum where enzyme activity increased three-fold during the period studied. KYNA production from its bioprecursor L-kynurenine was also investigated in tissue slices and was found to be significantly enhanced in the cortex and hippocampus of old animals. The effect of depolarizing agents or sodium replacement was virtually identical in tissues from young and old rats. These data, which are in excellent agreement with reports on an age-dependent increase of KYNA concentration in brain tissue, suggest an enhanced KYNA tone in the aged brain. Together with the reported decline in cerebral excitatory amino acid receptor densities with age, increased production of KYNA may play a role in cognitive and memory dysfunction in old animals.

Aging↗
PubMed1992

Localization of kynurenine aminotransferase immunoreactivity in the rat hippocampus.

The localization and distribution of kynurenine aminotransferase (KAT), the biosynthetic enzyme of the excitatory amino acid receptor antagonist, kynurenic acid, was studied in the rat hippocampal formation with immunohistochemical methods. The enzyme was found mainly in glial cells that could be distinguished as 3 types on the basis of their shapes and locations. Typically, these cells shared the morphological features of astrocytes and exhibited glial fibrillary acidic protein immunoreactivity as demonstrated by a double-labeling technique. The distribution of KAT-containing glial cells was heterogeneous throughout the hippocampal formation. In the hippocampus, the stratum lacunosum-moleculare of Ammon's horn and the hilus contained a higher density of KAT-positive glial cells than other regions, whereas the lowest density of KAT glial cells was observed in the granule cell layer of the dentate gyrus and in the stratum radiatum of CA subfields. In the subicular complex, the density of KAT-containing glial cells was generally higher in the superficial than in the deep layer. Hippocampal neurons exhibiting KAT immunoreactivity, distinguished as nonpyramidal cells, were very few in number and mainly distributed in strata oriens and pyramidale of Ammon's horn. Substantially more KAT-positive neurons were observed in layers II and III of the subicular complex. The organization of cellular elements containing KAT may be of relevance for the function and possible dysfunction of kynurenic acid in the rat hippocampal formation.

Animals↗
PubMed1992

Analysis of infectious complications occurring after solid-organ transplantation.

To improve our understanding of posttransplant infections, we analyzed bacterial, viral, fungal, parasitic, and other infections in 604 consecutive recipients of kidney (n = 518), kidney-pancreas (n = 82), kidney-liver (n = 3), or kidney-islet (n = 1) allografts (355 cadaveric, 14 living-unrelated, 235 living-related donors) who also received cyclosporine, azathioprine, and prednisone immunosuppression. Recipients of cadaveric grafts received additional induction immunosuppression (antilymphocyte globulin or murine monoclonal antibody OKT3). Rejection episodes were treated with high-dose steroids, and either antilymphocyte globulin or OKT3 was administered when clinically indicated. Perioperative antibiotics and posttransplant prophylactic acyclovir sodium or ganciclovir sodium, trimethoprim-sulfamethoxazole, and clotrimazole or nystatin (Mycostatin) were administered to all recipients. Two hundred thirteen patients (35.3%) were found to have had no identifiable infections, while 391 (64.7%) had either isolated bacterial (97 [16.1%]), viral (53 [8.8%]), or fungal (34 [5.6%]) infections or combination (concurrent or sequential) infections with bacterial plus viral (46 [7.6%]), bacterial plus fungal (66 [10.9%]), viral plus fungal (20 [3.3%]), bacterial plus viral plus fungal (64 [10.6%]), or bacterial plus viral plus fungal plus parasitic (11 [1.8%]) pathogens in the posttransplantation period. Renal allograft survival (percentage, actuarial method) was diminished in patients with infections at both 1 year (91% vs 83%) and 3 years (81% vs 76%) after transplantation, as was actuarial patient survival (1 year, 97% vs 92%; 3 years, 93% vs 88%). We conclude that infection remains a major cause of both patient demise and allograft loss following successful solid-organ transplantation.

Adolescent↗
PubMed1992

The amniotic fluid compartment: the fetal habitat.

This study begins with a phylogenetic overview of the fetal membranes in terrestrial vertebrates. It is, of course, well known that the human amnion differs very little from that of other recent members of the phylum, although during evolution the development of the placenta has brought about extensive changes in the chorion. Much of the structure and many of the functions of both the amnion and chorion laeve can be interpreted from a comparative point of view (e.g., production of lipids). The next section deals with the ontogeny of the human amniotic sac, and the histogenesis and functional structure of the fetal membranes. It concludes with a structural analysis of the single layers of the fetal membranes at the end of pregnancy. Light and electron microscopy and histochemical examination are combined with experimental investigations; the striking differences and departure from any possible "norm", however, made the interpretation of morphological findings particularly difficult. Explanations for these differences are put forward: the texture of the connective tissue elements is only approximately determined and therefore gives rise to many irregularities; differences in the structure of cells depend upon their functional state; and the cells exist in groups which reciprocally exchange functional activity with each other. It is emphasized that the amniotic epithelium produces lipids which then appear in the same composition in the amniotic fluid. The fibroblasts in the amniotic connective tissue may, when necessary, be transformed into phagocytes (the so-called Hofbauer cells). Within the fetal membranes one can also observe glucose metabolism which, apart from the supply of local energy and the storage of glycogen, is concerned with production of phospholipids, triglycerides, glycoproteins, proteoglycans, and collagen (types I, III, and IV). A similar process of glucose metabolism is found in the trophoblast, especially the building-up of an extracellular matrix (the so-called fibrinoid), which seems to play a part in the formation of an immune barrier. An attempt is made to correlate the various differentiated cells of the trophoblast with particular functions. The vacuolated cells obviously store glucose. Others, as lectin-binding investigations have shown, are concerned with production of the extracellular matrix. They produce a three-dimensional latticework between the cells, and reach out as far as the borders of the chorionic connective tissue. In this regard, the microtexture of the amniotic and chorionic connective tissue provides a basis for a more precise understanding of their mechanical stability.(ABSTRACT TRUNCATED AT 400 WORDS)

Amniotic Fluid↗
PubMed1992

Scotopic versus photopic pattern onset-offset electroretinograms.

We investigated the contribution of rods and cones to the human pattern electroretinogram to onset and offset checkerboards of different spatial frequency and wavelength in a 39 degrees x 39 degrees field. Under strictly scotopic conditions, there was a negative potential at onset and a positive potential at offset, whereas under photopic conditions, there was a positive potential at onset and a negative/positive potential at offset. Thus, the waveform to pattern onset (offset) was that of the luminance electroretinogram to decreasing (increasing) luminances. For pattern onset, the sensitivity difference 486-601 nm under scotopic and photopic conditions closely followed the luminosity function of rods and cones. The amplitude of the scotopic onset response increased with check size up to 3 degrees 30' and that of the photopic onset response, up to 30'. With larger checks, the scotopic and photopic onset response markedly decreased. This indicates antagonistic center-surround organization of the receptive fields under both scotopic and photopic conditions. By contrast, the offset response monotonically increased with check size under scotopic and photopic conditions, which suggests a luminance component in the pattern electroretinogram. Consequently, the pattern electroretinogram to reversing checkerboards has to be regarded as a mixture of both pattern- (contrast) and luminance-specific components.

Adolescent↗
PubMed1992

Time-resolving luminescence techniques for possible detection of forest decline. I. Long term delayed luminescence.

Needles from spruces at different environmental and physiological conditions were analyzed by long term delayed luminescence in the seconds-range (LDL) using a novel set-up with on-line computer and a specially written computer program. Upon red light induction, the LDL-kinetics showed a super-position of three exponentially decaying components ("fast", "medium" and "slow") with reaction constants of kf = 5-15 s-1, km = 0.8-1.8 s-1 and ks = 0.13-0.23 s-1, ks-values are fairly independent of the individual tree and quite stable throughout the whole year. They are also independent of the status and localization, i.e. the physiological situation of the individual tree. However, km- and kf-values as well as the related amplitudes Am and Af exhibit a general, significant seasonal variation and obviously are correlated with the damage class or the environmental situation of the individual tree. Therefore, the measurement of long term delayed luminescence might offer a valuable piece of information in search of an early detection of forest decline.

Ecology↗
PubMed1992

Time-resolving luminescence techniques for possible detection of forest decline. II. Picosecond chlorophyll fluorescence.

Needles from spruces at different environmental and physiological conditions were analyzed by picosecond fluorescence spectroscopy using a novel laser diode and single photon counting detection. The decay curves of chlorophyll fluorescence showed a superposition of three exponentially decaying components with time constants of T1 = 100-200 ps, T2 = 300-500 ps and T3 = 2.0-3.5 ns. A high relative intensity of the long-lived component was found in damaged spruces as well as in trees showing first symptoms of yellowing, needle loss or parasite infection, although all measurements were carried out with green needles which appeared visually intact. Therefore, fluorescence spectroscopy with subnanosecond time resolution seems to be a valuable attempt for an early detection of forest decline.

Chlorophyll↗
PubMed1992

Pentylenetetrazol kindling and factors of glutamate transmitter metabolism in rat hippocampus.

Male Wistar rats administered repetitively with pentylenetetrazol developed a dose-dependent enhancement of seizure behaviour referred to as pentylenetetrazol kindling. After a daily dose of 40 mg pentylenetetrazol/kg or physiological saline (control rats) injected intraperitoneally for a period of two weeks, hippocampal tissue was studied autoradiographically for high-affinity uptake of [3H]glutamate and, by activity staining, for aspartate aminotransferase and glutamate dehydrogenase. Most prominent changes were found in neuropil areas known to be endowed with glutamatergic structures. The uptake capacity of glutamate decreased by 48% (maximum rate), whilst activities of aspartate aminotransferase and glutamate dehydrogenase elevated to 140 and 130%, respectively. Cytochrome c oxidase activity was found to be unaffected. The findings indicate an important role of factors of the glutamate metabolism in the kindling process with respect to the production, utilization, and availability of transmitter glutamate.

Animals↗
PubMed1992

Radioiodination of S-type lipopolysaccharide. Possibilities and limitations of labelling of the carbohydrate chain by periodate oxidation.

S-type Lipopolysaccharide (LPS) from E. coli O 139:K 82 (B) was radiolabelled by coupling 125I-tyramine to the carbohydrate chain of LPS after oxidation of sugar residues carrying vicinal hydroxy groups, with sodium metaperiodate. The specific activity amounted to 1.3 kBq/microgram LPS. As LPS is a mixture of molecules with different carbohydrate chain lengths that are associated to large micelles of high kinetic stability, the preparation and the properties of the tracer exhibit some peculiarities. Most important, partial cleavage of the carbohydrate chains of LPS is caused on radioiodination by the procedure described. As a consequence, the tracer differs markedly from the starting LPS with respect to carbohydrate chain length distribution. Another feature of special interest is the variation of the specific activity (radioactivity/unit mass) for LPS molecules of different carbohydrate chain lengths. Because of the kinetic stability of LPS micelles, the equilibration of radioiodinated and non-radioactive LPS aggregates requires their solubilization by a detergent and its subsequent removal by dialysis. It could be demonstrated that short-chain LPS molecules predominantly associate to larger micelles than long-chain molecules. Regardless of these restrictions, the 125I-LPS proved to be useful for certain analytical purposes.

Carbohydrate Metabolism↗