Extended, monolayer flat islands and exciton dynamics in Ga0.47In0.53As/InP quantum-well structures.
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Biomedical subjects
Publications and source records attributed to W Seifert.
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Induction of the jun-B and/or c-jun transcription factors is part of the immediate early response to diverse stimuli that induce alterations in cellular programs. While c-jun is a protooncogene whose expression is required for induction of cell proliferation, jun-B has recently been found to be induced by stimuli inducing differentiation in various cell lines. Furthermore, its expression is largely restricted to differentiating cells during embryogenesis. To determine the functional significance of these findings, we used antisense phosphorothioate oligodeoxynucleotides to inhibit expression of the two genes in proliferating and neuronally differentiating cells. While selective inhibition of c-jun expression reduced proliferation rates, inhibition of jun-B protein synthesis markedly increased proliferation in 3T3 fibroblasts, human mammary carcinoma cells and PC-12 pheochromocytoma cells, suggesting jun-B involvement in negative growth control. Neuronal differentiation of PC-12 cells induced by nerve growth factor (NGF) was prevented by inhibition of jun-B protein synthesis. PC-12 cells not only failed to grow neurites but also remained in the proliferative state. Furthermore, in cultured primary neurons from rat hippocampus, inhibition of jun-B expression, again, markedly reduced morphological differentiation. Conversely, inhibition of c-jun protein synthesis enhanced morphological differentiation of both primary neurons and PC-12 tumor cells. Thus, jun-B expression is required for neuronal differentiation and its balance with c-jun activity is involved in regulating key steps in proliferation and differentiation processes.
Findings from a study based on the longitudinal data of the German Socio-Economic panel (annual data, 1984-1988, N = 5516 individuals, 18-64 years) confirmed differences in health between unemployed and employed persons. The health satisfaction of unemployed persons is on a lower level as well as health impairments. This was only partially due to socio-demographic characteristics. The differences by employment status were stable in all years between 1984 and 1988. However, there were no indications for a causal influence of unemployment on health impairments. A constant health-satisfaction of persons loosing their job and of the re-employed, compared to their initial ratings, supported the selection hypotheses. This means that during the study period persons in poorer health are more likely to loose their job and persons in better health are more likely to be re-employed.
Ischemic venous thrombosis that led to necrosis of four toes developed in an 81-year-old man. Despite the extensive thrombosis, results of blood clotting tests showed an extremely low prothrombin time (20%). Plasma mixing studies demonstrated an inhibitor that may have features in common with the lupus anticoagulant. Lupus anticoagulant also simulates hemorrhagic diathesis in vitro, whereas in vivo it is associated with thrombosis and thromboembolism. In contrast to the lupus anticoagulant, the inhibitor found in this patient was active within the extrinsic clotting system. Systemic steroids led to rapid clinical resolution paralleled by normalization of the prothrombin time and disappearance of the inhibitor.
Basic fibroblast growth factor (bFGF) is a multifunctional protein that stimulates proliferation, migration and differentiation of various cell types of the mammalian brain. In rat astrocyte cell cultures bFGF stimulates DNA synthesis after exogenous addition. This article will focus on the endogenous pathway of bFGF in rat astrocytes in cell cultures. After a single administration of bFGF antisense phosphorothioate oligodeoxynucleotide (PTO) a significant inhibition of DNA synthesis was observed. A control oligodeoxynucleotide does not inhibit DNA synthesis, while specific antisense c-myc PTO did inhibit DNA synthesis. Addition of anti bFGF PTO suppresses the expression of bFGF protein in Western blot analysis. These results suggest that bFGF may be an endogenous growth signal in developing astrocytes.
Hydrogen peroxide (H2O2) is a type of active oxygen species produced mainly in blood by inflammation, ischemia or anoxia. Treatment of rat neonatal cortical astrocytes in culture with 0.2-1.0 mM H2O2 which is lethal for hippocampal neurons, increases nerve growth factor (NGF) and basic fibroblast growth factor (bFGF) mRNA content in a time dependent manner. H2O2 also increases c-fos mRNA expression, which is probably involved in the gene regulation of both NGF and bFGF. Maximal induction was reached after 6 h of incubation (5.7-fold increase in NGF and 2.4-fold induction of bFGF mRNA). Hydrogen peroxide induced bFGF and NGF gene expression suggests that neurotrophic factors in astrocytes could be induced by lesion, consistent with their protective function in the CNS.
Basic FGF mRNA induction by bFGF was investigated in cell cultures from rat brain, i.e. postnatal day 2 cortex and embryonic day 18 hippocampus. In situ hybridization shows that after bFGF treatment (10(-10) M) for 14 h neurones and glial cells show a remarkable increase in bFGF mRNA production. Incubation of astrocytes with antisense bFGF phosphorothioate oligodeoxynucleotides (bFGF-PTOs) resulted in an inhibition of both bFGF induced and serum induced proliferation. The results indicate that bFGF is capable of inducing its own mRNA production. This induction, i.e. new synthesis of bFGF mRNA, seems to be essential for the mitogenic effect of both bFGF and serum components.
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The dependence of 3[H]-L-glutamate uptake on the presence of sodium, chloride, or calcium ions or on a combination of the three was investigated in astrocyte primary cultures. A stimulating effect on glutamate uptake by each of the ions tested was found. In addition to the comparably small effect by calcium alone, calcium exhibits a synergistic effect on the sodium- and chloride-dependent uptake. The sodium-dependent transport accumulates the glutamate analogue D-aspartate as well as L-glutamate. L-aspartate is taken up by about 50% of the values observed for L-glutamate transport. Sodium-dependent glutamate uptake is strongly inhibited by aspartate-beta-hydroxamate (A beta H) and threo-beta-hydroxyaspartate (T beta H). Quisqualate is less potent in inhibiting this uptake. In contrast, the chloride- and the calcium-dependent uptake systems do not handle D- and L-aspartate as substrates. A beta H and T beta H are only poor inhibitors of these transporters while quisqualate reduces glutamate uptake almost completely. Kinetic data of all uptake systems were estimated. High and low affinity components of each individual system are demonstrated by Eadie-Hofstee analysis. Hill plots indicate that high and low affinity uptake may be due either to two respective uptake sites for Na(+)-, Cl(-)-, and Ca(++)-dependent glutamate transport, or to two glutamate binding sites for each single transport system with negative cooperativity.
Blood and plasma levels and excretion of labeled compounds and of the unchanged drug were measured after i.v. injection of 54 micrograms and p.o. administration of 540 micrograms of the ergoline derivative, terguride (CAS 37686-84-3), labeled with tritium, in 6 elderly male volunteers. Following i.v. injection plasma levels of terguride declined with a half-life of 0.5 h and those of radiolabeled compounds with half-lives of 0.5 h, 7 h and 19 h. The total clearance was 17 ml/min/kg and the volume of distribution was 0.7 l/kg. After p.o. administration terguride was rapidly and completely absorbed. The bioavailability was around 20%. Elimination of labeled compounds was complete within 7 days and proceeded mainly via the urine. Computer simulation of plasma levels after 4-times-a-day multiple administrations indicated slight accumulation of metabolites (factor 3) and no accumulation of terguride (factor 1).
Changes in ganglioside composition, biosynthesis and individual distribution were studied in hippocampal regions after unilateral destruction of the entorhinal cortex. After 1 and 3 days postlesion (dpl), a decrease in ganglioside content was detected in area dentata (AD) and pyramidal cell regions CA1-CA3 (CA), both ipsilateral and contralateral to the lesion. By 5 dpl all the values had returned to control values, except in AD which showed a dramatic increase in total ganglioside content reaching a maximum at 12 dpl. By 30 dpl this area also showed control content. A significant increase in biosynthesis of gangliosides was observed at 5 and 8 dpl in the hippocampus ipsilateral to the lesion without changes in the contralateral counterpart. Individual ganglioside distribution showed a pronounced change in GM1 and GQ1b with small changes in the other major gangliosides. Significant differences were observed in the distribution of gangliosides between the two hippocampal regions studied in unoperated control animals. GD1a was more concentrated in AD, whereas GQ1b, GT1b and GD1b predominated in CA. The data presented here indicate that important modifications in ganglioside content as well as pattern occur in the deafferented hippocampus a phenomenon that could be related with the known effect of gangliosides on neuritogenesis observed in cell culture studies.
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Results from two clinical pharmacokinetic studies are given. The first study was an observational study in oral contraceptive users who took either a combination of gestodene and ethinyl estradiol (pill A, Femovan) or desogestrel and ethinyl estradiol (pill B, Marvelon). A total of 69 women (39 receiving pill A and 30 receiving pill B) were evaluated to determine serum ethinyl estradiol, sex hormone-binding globulin, corticosteroid-binding globulin, and cortisol levels. Samples were obtained on 1 day during the tenth to twenty-first days of pill intake. All women received the respective oral contraceptive for at least 3 months. The test power was such that an 80% difference of 1 standard deviation of each target variable would have been detected (alpha = 0.05; beta = 0.1). No statistically significant differences were found in sex hormone-binding globulin, corticosteroid-binding globulin, or cortisol serum levels between both groups. Time and height of maximum ethinyl estradiol levels were identical as was the area under the curves. Ex vivo protein-binding analysis of the progestins revealed a free portion of 0.6% for gestodene and 2.5% for 3-ketodesogestrel as the active metabolite of desogestrel. Sex hormone-binding globulin-bound portions were much higher for gestodene (75.3% +/- 9.1%) than for 3-ketodesogestrel (31.6% +/- 12%). The remaining fractions were bound to albumin. In a second study, ethinyl estradiol-bioequivalence from pills A and B was investigated in 18 women in a controlled, single-dose, randomized, crossover design. The area under the ethinyl estradiol serum levels were identical up to 4 hours after pill intake between both treatments. According to the relatively low variation in data in this group of women, a 10% difference in ethinyl estradiol-availability could have been detected. Both studies indicate that the pharmacokinetics of ethinyl estradiol were independent of the concomitantly administered progestin, that is, desogestel and gestodene.
A new monosaccharide microparticle based echocardiographic contrast agent (SH U 508) was injected intravenously into five healthy male volunteers following which the heart was imaged in an apical four-chamber view. Volumes of 2, 4, 8, and 16 mL of SH U 508 were incrementally injected into each volunteer. Concentrations of 50, 100, 200, 300, and 400 mg microparticles per mL of suspension were used in five successive examinations. Left heart opacification of diagnostic value was obtained during the whole cardiac cycle with concentrations of 300 and 400 mg/mL. There was no interference in imaging of the left ventricular walls due to increased attenuation. SH U 508 showed a good tolerance. No side effect was observed and no clinical relevant changes were observed in the heart rate, blood pressure, ECG, blood chemistry, hematology or urinalysis findings. This new agent may greatly extend the role of cardiac ultrasound and may also permit the examination of the arterial circulation in other organs.
The genes coding for the class-II Serratia marcescens restriction-modification system have been cloned and expressed in E. coli. Recombinant clones, restricted incoming phage only poorly; the recombinant plasmids, however, became fully modified in vivo, i.e. completely resistant against digestion with R.SmaI. The determined nucleotide sequence of the cloned system revealed three open reading frames with lengths of 252 bp, 741 bp, and 876 bp. Through various deletion experiments and an insertion-mutation experiment the 876 bp open reading frame could be assigned to the SmaI DNA modification enzyme and the 741 bp open reading frame to the SmaI restriction endonuclease. Mapping of the transcription start sites of the genes revealed that the SmaI endonuclease is transcribed as polycistronic mRNA together with a 252 bp long preceding open reading frame of unknown function. No homology was found when comparing the amino acid sequence of M.SmaI with the published sequences of m5C-specific DNA modification methyltransferases. On the other hand, a stretch of 14 amino acids in the C-proximal region of M.SmaI shows a significant homology to the C-proximal amino acid sequences of the N6A-methyltransferases M.HinfI and M.DpnIIA and the N4C-methyltransferase M.PvuII.
Two monoclonal antibodies (mabs) which recognized the 68 kDa subunit of the rat neurofilament triplet were isolated. In immunoblots with SDS-solubilized and reduced proteins, these mabs recognized their epitopes equally well in embryonic and in adult tissue. However, these epitopes were developmentally regulated in paraformaldehyde-fixed rat brain sections. They were abundant in all compartments of differentiating neurons, whereas in mature neurons their presence was markedly attenuated, with a moderate abundance in perikarya and larger dendrites and low concentrations in axons. Thus, a differential developmental modification, possibly involving the masking of an epitope, is demonstrated for the small neurofilament polypeptide in rat and monkey brain tissue.
Rat hippocampal slices were perfused with epidermal growth factor (EGF) at a concentration of 10(-8) M. EGF is a well known mitogen which exhibits neurotrophic action on neurons of the CNS. During extra- and intracellular recordings in the pyramidal cell body layer of the CA1-region no influence of EGF on evoked potentials was seen if single-pulse or paired-pulse stimulation was used. Furthermore EGF has no influence on the resting membrane potential of the cells investigated. However after tetanic stimulation a significant increase in the magnitude of long-term potentiation was observed. Therefore it is concluded, that EGF might be involved in modulation of neuronal plasticity.
Ganglioside GM1 3H-labelled at the terminal galactose was added to astrocyte cell cultures. GM1 incorporation was studied in the two typical forms of astrocytes in cell culture of flat and stellate morphology. There was a strong time- and concentration-dependent increase in GM1 incorporation for both cell types of astrocytes. The incorporation of GM1 into the stellate form increased continuously up to 48 h (maximum time studied), while the incorporation into the flat form reached a plateau at the same time. After 2 h of GM1 incubation additional gangliosides appeared; the latter resulted from the metabolism of the GM1 incorporated, indicating that astrocytes in cell culture can biosynthesize more complex gangliosides. To confirm that GM1 was indeed incorporated into astrocytes, two other different approaches were used. Astrocyte cells treated with 3H-GM1 were visualized using autoradiography. The specific marker for GM1, rhodamine-labelled choleratoxin, was used to detect the incorporated GM1 using fluorescence microsocpy. In both cases GM1 treated cells were intensely labelled. These observations indicate that exogenous GM1 ganglioside can also be integrated into the astrocyte membranes as occurs in other types of cells and membranes.