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Biomedical subjects

G Wolf

Publications and source records attributed to G Wolf.

At least 469 records · Page 26Linked to original sources

Subcutaneously applied magnesium protects reliably against quinolinate-induced N-methyl-D-aspartate (NMDA)-mediated neurodegeneration and convulsions in rats: are there therapeutical implications.

Quinolinate (QUIN), an agonist of the N-methyl-D-aspartate (NMDA) subtype of the glutamate receptor, was used to model glutamate-induced primary or secondary brain damage. Rats intracerebroventricularly injected with QUIN (1 mumol in 2 microliters) showed convulsive reactions and heavy neurodegeneration in the hippocampal formation. MgSO4 (1 M solution injected subcutaneously; 0.6 or 0.3 g/kg) was found to protect completely against QUIN neurotoxicity if administered simultaneously or 1 h after exposure to QUIN. Preliminarily, LD50 for MgSO4 was estimated approximately at 1.2 g/kg. The application of magnesium is discussed to be a potentially powerful therapeutic principle in case of brain injury and convulsive disorders.

Animals↗

[Health hazards associated with flying and diving. ENT aspects].

The popularity of scuba diving among the general public and the great increase in air travel are increasingly associated with health problems. In the ENT sector, such problems mainly take the form of barotrauma that can arise from changes in the volume of gases enclosed within body cavities, due to fluctuations in pressure during diving and air travel. More rarely, decompression illness can occur when the required time for decompression is ignored by a diver coming up to the surface, or when a sudden loss of pressure occurs in the cabin of a plane, leading to the liberation of nitrogen dissolved in body fluids. Pathomechanisms, symptoms and treatment of barotrauma affecting the middle and inner ear and the sinuses, together with the effects of decompression errors on the organs of hearing and balance, are described, and suggestions for their prevention given. Fitness for diving and air travel, together with diseases that render these inadvisable, are discussed.

Aerospace Medicine↗

The kinetics of fibronectin synthesis and release in normal and tumor promoter-treated human lung fibroblasts.

The present study is a detailed kinetic analysis of the synthesis, release and multimerization of fibronectin (FN) in normal and tumor promoter-treated human lung fibroblasts. Pulse/chase and surface labeling experiments were performed to follow the fate of both newly synthesized and preexisting cell-surface FN over time. The majority of FN (80%) left the intracellular compartment within one hour of synthesis. However, the rate of direct secretion was very low and after one hour, 70% of newly synthesized FN was still at the cell surface. This material was primarily dimeric. Dimeric and multimeric (very high molecular weight) FN was detectable at the cell surface and in the medium 4 hours after synthesis. Pulse-labeled FN multimer levels peaked at 12 hours and declined thereafter. After 24 hours, 85% of pulse-labeled FN had been shed into the medium and the labeled FN remaining at the cell surface was primarily multimeric. Surface labeling experiments confirmed that the majority of FN resides at the cell surface prior to release into the medium. One hour treatment with the phorbol ester tumor promoter, 12-0-tetradecanoyl phorbol-13-acetate (TPA), stimulated a nine-fold increase in release of preexisting, dimeric cell-surface FN (125I-labeled). The major effect of longer term TPA treatment up to nine hours was continued depletion of dimeric cell-surface FN. Increased release of cell-surface multimeric FN was also stimulated by TPA, but to a much lesser extent. Release of newly synthesized (pulse-labeled) dimeric FN was also stimulated by TPA though much less than pre-existing FN, and TPA treatment produced a small decrease in the steady-state level of multimeric FN. Thus, preexisting cell-surface FN and newly synthesized FN differ dramatically in their susceptibility to TPA treatment.

Cells, Cultured↗

Changes in glutamate-related enzyme activities in the striatum of the rat following lesion of corticostriatal fibres.

The behaviour of enzymes putatively involved in glutamate/aspartate transmitter metabolism (glutamate dehydrogenase, aspartate amino-transferase, alanine aminotransferase, gamma-glutamyl-transpeptidase) was studied in the striatum 3, 7, 14 days and 7 weeks after mechanical destruction of corticostriatal fibres. For a period of up to seven days after unilateral lesion, enzyme activities were significantly diminished (by up to 13% based on protein) in the ipsilateral striatum as compared to the striatum of the intact side. Later, the enzyme activities in the ipsilateral striatum recovered. After seven weeks, an increase was observed for glutamate dehydrogenase activity, whereas the activity of alanine aminotransferase showed a transient rise enzyme levels is interpreted as being attributable to the destruction of nerve endings which are considered to be glutamatergic, interfering with various compensating processes (e.g. glial cell proliferation) which occur with advancing times after lesion.

Alanine Transaminase↗

Hepatic encephalopathy influences high-affinity uptake of transmitter glutamate and aspartate into the hippocampal formation.

The present work was carried out to study the influence of ammonia and factors from sera and cerebrospinal fluid (CSF) from patients with different degrees of chronic liver diseases on [3H]D-aspartate (Asp) and [3H]L-glutamate (Glu) high-affinity uptake into the rat hippocampal formation. For comparison, high-affinity uptake of Glu and Asp was determined in human hippocampal brain tissue obtained at autopsy from cirrhotic patients dying in hepatic coma and from control brains free from neurological, psychiatric, or hepatic diseases. Sera and CSF from patients with chronic liver failure and hepatic encephalopathy (HE) were seen to reduce dramatically Glu and Asp uptake into rat hippocampal dendritic layers. A close inverse relationship was found to exist between the level of ammonia in the sera and the inhibition of uptake, both phenomena correlating highly with the extent of liver failure. The present findings, obtained after dilution of sera from patients with HE while maintaining initial ammonium levels, elucidate, however, that ammonia alone cannot account for the reduction in Glu/Asp uptake capacity. The inhibition of Asp uptake into human hippocampal formation of patients dying in hepatic coma was even more pronounced when compared to that found in rat hippocampus incubated in sera and CSF from patients. Glu/Asp uptake into brain tissue is supposed to be an important factor in the pathogenesis of HE accompanying liver dysfunctions.

Adult↗

Proximal percutaneous balloon angioplasty and distal bypass for multilevel arterial occlusion. Veterans Administration Cooperative Study No. 199.

Multiple sites of atherosclerotic occlusion in high risk patients may be treated by angioplasty of the iliac obstruction and distal reconstruction. We report 18 male patients with symptomatic peripheral vascular disease in whom proximal iliac percutaneous transluminal angioplasty was combined with femoropopliteal bypass (11), femorotibial bypass (2), or femorofemoral bypass (5). There were no operative deaths. The pretreatment ankle brachial index of 0.40 +/- 0.04 was increased to 0.64 +/- 0.04 by discharge (p = 0.0001), and remained significantly increased through 27 months (0.65 +/- 0.07) (p = 0.0001). During the follow-up period of 2-57 (mean 27 months) one dilated iliac artery required repeated percutaneous transluminal angioplasty and revision of the femoropopliteal bypass at three months. Two late amputations of study limbs occurred at two years and three years due to progression of distal disease in the infrapopliteal segment. Four patients died during the follow-up period of ischemic heart disease (3) and lung carcinoma (1). Life table analysis shows a 76% success rate for the combined procedures at two years. In selected, high risk patients, proximal iliac dilatation and distal bypass is an acceptable alternative reconstruction for multilevel occlusion.

Aged↗

Immunohistochemical demonstration of glutamate dehydrogenase in the postnatally developing rat hippocampal formation and cerebellar cortex: comparison to activity staining.

Distribution patterns of activity and immunohistochemical staining for glutamate dehydrogenase were compared during the postnatal development of rat hippocampal formation and cerebellar cortex. On postnatal day 5, dendritic layers of the hippocampal formation showed only a very weak enzyme activity. Similarly, when studied at the same age, the external granule cell layer and Purkinje cells of the cerebellar cortex exhibited a very faint and moderate staining, respectively. With advancing age, in both brain regions a marked postnatal increase in glutamate dehydrogenase activity occurred in neuropil area as glutamatergic structures matured. However, compared to activity staining, both brain regions of early postnatal stages showed a relatively high level of glutamate dehydrogenase-like immunoreactivity. In this case, the immunohistochemical staining of hippocampal dendritic layers and of the molecular layer of the cerebellar cortex was rather diffuse, being not very similar to parameters of the maturation of the respective glutamatergic structures. In contrast to the activity staining for the enzyme, the immunohistochemical labelling in adult rats revealed a selective predominance of immunoreactivity in astroglial cells from postnatal day 5 onwards. The Bergmann glia in the cerebellar cortex exhibited the strongest intensity of immunoreactivity. Generally, the patterns of immunoreactivity were found to depend on the fixation procedure adopted. Concluding from our results, glutamate dehydrogenase is demonstrable in glial and in neuronal cell elements as well. Therefore, it is recommended that activity staining and the immunohistochemical procedure be combined to study qualitative and quantitative aspects of glutamate dehydrogenase in nervous tissues.

Aging↗

High-affinity glutamine uptake of the rat hippocampus during postnatal development: a quantitative autoradiographic study.

Glutamine uptake into hippocampal slices of the rat was investigated autoradiographically. The characteristics of registered [14C]glutamine uptake such as the incubation with the radiolabelled amino acid at a concentration of 3.5 mumol/l, sodium dependency, the distribution pattern of radioactive material, and the postnatal development of uptake capacity are comparable with those of high-affinity uptake of glutamate. Densitometric evaluation of grain density over hippocampal layers exhibited a marked enhancement of uptake capacity in the neuropil areas during the first postnatal weeks. In the strata oriens and radiatum (CA1) radiolabelling increased from day 2 to 25 by about 390 and 410%, in the strata oriens and lacunosum-moleculare of CA3 by about 350 and 375%, respectively. In contrast, the rise in the accumulation rate in cell body layers was negligible. The temporal and topographical profiles of glutamine uptake in the hippocampal neuropil correlated with those of the activity of phosphate-activated glutaminase and parameters of maturation of the glutamatergic transmission system which have fairly similar time characteristics, suggesting a mutually causative relationship of all these factors.

Aging↗

Quinolinate neurotoxicity and glutamatergic structures.

Neurotoxic properties of quinolinic acid following intracerebroventricular application were investigated in the hippocampal formation of 12- and 30-day-old rats. Quinolinic acid neurodegenerative potency was found to depend on the survival time, the dose applied and the developmental stage of the animal. Pretreatment with kynurenic acid and ketamine as well as the transection of the perforant path were noted to protect major parts of the hippocampal cell layers from quinolinic acid-induced degenerative effects. The results are interpreted in view of a putative dependence of quinolinic acid neurotoxicity on the presence of established synaptic, in particular glutamatergic, processes which play a major role in the hippocampal formation and mature during the first postnatal weeks. For comparison, we studied local effects of quinolinic acid on superior cervical and dorsal root ganglia in which glutamate inputs obviously do not occur; no signs of neuronal vulnerability were seen.

Age Factors↗

Glomerular angiotensinase A in the rat: increase of enzyme activity following renal ablation.

Angiotensinase A (aminopeptidase A; ATA) is an angiotensin II splitting exopeptidase, which is localized in endothelial and epithelial cells of the glomerular tuft. In order to investigate the influence of a reduction in renal mass on enzyme activity, ATA activity was measured in isolated rat glomeruli five and 14 weeks after 1-1/3 nephrectomy. Glomerular ATA activity in remnant kidneys increased significantly after five weeks following ablation compared with glomeruli of two kidney control rats (5.34 +/- 4.02 vs. 1.71 +/- 1.96 mU/mg protein, P less than 0.05). After 14 weeks, however, this difference was no longer present. Treatment of rats with enalapril or saralasin inhibited the increase of ATA seen five weeks after renal ablation, whereas indomethacin had no effect on enzyme activity. Furthermore, normal two kidney rats, treated with furosemide, revealed a higher glomerular ATA than two kidney controls (5.5 +/- 2.64 vs. 2.1 +/- 1.7 mU/mg protein, P less than 0.05). In vitro superfusion of isolated glomeruli with enalaprilate or furosemide from rats after renal ablation did not influence enzyme activity, however, superfusion with 0.05 mM angiotensin II or 0.05 mM saralasin significantly reduced ATA. Our results suggest that glomerular ATA might be involved in the early regulation of the intrarenal renin-angiotensin system and could modify glomerular adaptation to reduce renal mass by affecting angiotensin II degradation.

Adaptation, Physiological↗

[Comparison of the diagnostic value of the individual examination steps (triple diagnosis) in breast cysts].

Basic examination (palpation and mammography) as well as triple diagnosis (sonography, aspiration cytology, pneumocystography) are employed in the diagnosis and therapy of mamma cysts. Among 133 aspirated cysts we found by sonography 6 complicated cysts; 4 of these were cyst wall carcinomas. We found one further complicated cyst by aspiration cytology with a PAP IV; therefore, this sonographically uncomplicated cyst was extirpated as well resulting in cystic mastopathy without any signs of malignancy. Sonography and pneumocystography agreed perfectly in the diagnosis of cysts. Additionally mammography revealed 3 occult carcinomas located beside uncomplicated cysts. Hence, in no case should mammography be omitted. Sonography is a reliable instrument in judging cysts; therefore, aspiration cytology or pneumocystography may be left out in special cases.

Adult↗

Phagocytosis of opsonized fluorescent microspheres by equine polymorphonuclear leukocytes.

Equine blood polymorphonuclear leukocytes (PMN) were isolated by buffy coat and hypotonic lysis of residual erythrocytes. A highly reproducible method is described for measuring the uptake of opsonized latex microspheres by equine PMN using flowcytometry. The use of cytochalasin D allowed for differentiation of ingested from attached particles. The kinetics of phagocytosis in vitro is shown for different experimental conditions. We developed an assay for evaluation of phagocytic capacity of PMN which allows the assessment of drugs for their influence on phagocytosis in vivo as well as in vitro.

Animals↗

Angiotensin II induces cellular hypertrophy in cultured murine proximal tubular cells.

In the present study we demonstrate that a murine proximal tubular cell line (MCT cells), expressing angiotensin II (ANG II) receptors [dissociation constant (Kd) = 0.89 nM; receptor density (R0) = 46,900 receptors/cell] in culture, can be induced to hypertrophy after the daily addition of exogenous ANG II (10(-8) M). This hypertrophic response was characterized by an increase in total cellular protein content, by an enhancement of [3H]leucine incorporation into precipitable proteins, and by an augmentation in cell size by cytofluorography. This ANG II effect producing MCT cell enlargement was demonstrable in the absence of cellular proliferation. Proliferation of MCT cells, however, could be induced by epidermal growth factor (EGF) or platelet-derived growth factor (PDGF), and pretreatment of rested MCT cells with ANG II further enhanced EGF-induced cell division. ANG II-induced hypertrophy in MCT cells was factor specific, in that it could be blocked with saralasin, and not induced by angiotensin I (ANG I). This hypertrophic response was also independent of prostaglandin E2 synthesis but was transducible by pertussis toxin-sensitive G proteins and involved, to some extent, the activation of Na(+)-H+ exchange. ANG II, as well as EGF and/or PDGF, moreover, could induce the cellular oncogenes c-fos, c-myc, c-N-ras, but not c-cis, which suggests that early gene activation is probably not a specific prerequisite for hypertrophy. Our findings demonstrate that ANG II, in culture, can be a single-factor event capable of inducing hypertrophy in proximal tubular cells.

Amiloride↗

Cyclosporin A stimulates transcription and procollagen secretion in tubulointerstitial fibroblasts and proximal tubular cells.

The brief study described in this report was undertaken to determine whether cyclosporin A had any direct effect on the expression of tubulointerstitial procollagens in cultured renal cells. Our findings indicate that murine tubulointerstitial fibroblasts secreted significantly more procollagen type I after the addition of cyclosporin A, whereas syngeneic proximal tubular cells expressed significantly more types I and IV procollagen after cyclosporin stimulation. These increases in procollagen gene product correlated concordantly with changes in the levels of cytoplasmic mRNA with procollagen-specific cDNA probes. Transfection of these fibroblasts and proximal tubular cells with chimeric gene constructs containing enhancer/promoter elements for alpha2(I) and alpha 1(IV) procollagen linked to a chloramphenicol acetyltransferase reporter gene indicates that the stimulatory effect of cyclosporin on procollagen expression depends, at least to some extent, on an increase in transcriptional activity.

Animals↗