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Biomedical subjects

J Bauer

Publications and source records attributed to J Bauer.

At least 145 records · Page 8Linked to original sources
PubMed2000

TNFR1 signalling is critical for the development of demyelination and the limitation of T-cell responses during immune-mediated CNS disease.

In this review we summarize the essential findings about the function of tumour necrosis factor (TNF) and its cognate receptors TNFR1 and TNFR2, and lymphotoxin alpha (LT-alpha) ligands in immune-mediated CNS inflammation and demyelination. The advent of homologous recombination technology in rodents provides a new method which has been used during the last 5 years and has led to insights into the pathophysiology of experimental autoimmune encephalomyelitis (EAE) in an unprecedented way. Studies with knockout mice in which genes of the TNF ligand/receptor superfamily are not expressed and studies with transgenic mice overexpressing TNF and TNFR reveal the critical role of the TNFR1 signalling pathway in the control of CNS demyelination and inflammation. These studies provide novel findings and at the same time shed light on the complex pathophysiology of EAE. Together, these findings may contribute to better understanding of EAE and open new avenues in experimental therapies for multiple sclerosis.

Animals↗
PubMed2000

Inhaled nitric oxide does not enhance lipid peroxidation in patients with acute respiratory distress syndrome.

OBJECTIVE: To investigate whether inhaled nitric oxide (NO) enhances pulmonary lipid peroxidation as indicated by arterial blood levels of malondialdehyde, hexanal, and pentanal in patients with acute respiratory distress syndrome (ARDS). DESIGN: Prospective, nonrandomized, controlled trial. SETTING: Surgical intensive care unit in a university hospital. PATIENTS: Twenty-five patients with ARDS, as defined by the American-European Consensus Conference, and a PaO2/FIO2 < or = 170 mm Hg were enrolled in the study. Four healthy subjects were studied as controls. INTERVENTIONS: On enrollment of the patients in the study, a dose-response test with increasing concentrations of inhaled NO (0, 2, 10, 40, 0 ppm) was performed. Patients who showed an increase of >20% in PaO2 were designated as responders and all others as nonresponders. In responders, this dose-response test was followed by 24 hrs of continuous treatment with inhaled NO at the best NO concentration determined during the dose-response test, whereas nonresponders received standard care. For healthy volunteers, the dose-response test took the form of spontaneous breathing of the same NO concentrations. MEASUREMENTS AND MAIN RESULTS: Eighteen patients (72%) showed an increase of >20% in PaO2 during the dose-response test. This significant improvement in arterial oxygenation in responders led to a significant reduction in FIO2 (responders, 0.73 +/- 0.05 vs. nonresponders, 0.89 +/- 0.05) after 24 hrs of therapy. On enrollment, arterial blood concentrations of malondialdehyde, hexanal, and pentanal were significantly higher than those of healthy volunteers. In addition, arterial concentrations of hexanal and pentanal exceeded mixed venous levels two- to ten-fold. Inhalation of NO did not significantly alter these blood concentrations either during the dose response test or during 24 hrs of therapy. CONCLUSIONS: In patients with ARDS, malondialdehyde, hexanal, and pentanal were significantly elevated, indicating lipid peroxidation. Lipid peroxidation was not further affected by inhalation of NO.

Administration, Inhalation↗
PubMed2000

Expression of 5alpha-reductase and 3alpha-hydroxisteroid oxidoreductase in the hippocampus of patients with chronic temporal lobe epilepsy.

PURPOSE: The hippocampus is one of the principal target areas for neurosteroidal action, and the major neuroendocrine conversion of progesterone appears to be 5alpha-reduction and 3alpha-hydroxysteroid oxidoreduction, leading to the potent neurosteroid 3alpha,5alpha-tetrahydroxyprogesterone. To investigate whether the human hippocampus is equipped with the enzymes 5alpha-reductase and 3alpha-hydroxysteroid oxidoreductase (3alpha-HSOR), we studied the expression of 5alpha-reductase types 1 and 2 and 3alpha-HSOR types 1 and 2 in the resected hippocampi of patients with medically intractable chronic temporal lobe epilepsy. METHODS: We studied tissue specimens from the hippocampi of 13 women, 25 men, and four children. Quantification of different mRNAs was achieved by competitive reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: 5Alpha-reductase 1 mRNA and 3alpha-HSOR 2 mRNA were expressed in hippocampi of children and adults, whereas 5alpha-reductase 2 mRNA and 3alpha-HSOR 1 mRNA were not expressed. Neither 5alpha-reductase 1 mRNA nor 3alpha-HSOR 2 mRNA concentrations in hippocampal tissue showed any statistically significant differences between women and men or between children and adults. CONCLUSIONS: This study demonstrates for the first time mRNA expression of the type 1 isozyme of 5alpha-reductase and the type 2 isozyme of 3alpha-HSOR in the human hippocampus. The finding that both 5alpha-reductase and 3alpha-HSOR are present in the hippocampus leads us to assume the synthesis of neuroactive steroids in this human brain area.

3-Hydroxysteroid Dehydrogenases↗
PubMed2000

Mycophenolic acid in silage.

We examined 233 silage samples and found that molds were present in 206 samples with counts between 1 x 10(3) and 8.9 x 10(7) (mean, 4.7 x 10(6)) CFU/g. Mycophenolic acid, a metabolite of Penicillium roqueforti, was detected by liquid chromatography-mass spectrometry in 74 (32%) of these samples at levels ranging from 20 to 35,000 (mean, 1,400) microg/kg. This compound has well-known immunosuppressive properties, so feeding with contaminated silage may promote the development of infectious diseases in livestock.

Chromatography, Liquid↗
PubMed2000

A prospective evaluation of the clinical value of nation-wide DNA fingerprinting of tuberculosis isolates in Denmark.

SETTING: Denmark, a country with a low incidence of tuberculosis (TB). OBJECTIVE: To evaluate the value of the nation-wide DNA fingerprinting of Mycobacterium tuberculosis isolates performed in Denmark since 1992. DESIGN: Prospective study of consecutive patients with culture-verified TB from five large TB Departments in Denmark during a 7-month period in 1998. Results of IS6110 RFLP and spoligotyping were compared to those in the nation-wide Danish DNA-fingerprint database which covers approximately 95% of all culture-verified TB cases from 1992 onwards. Questionnaires asking about contact tracing and epidemiological links were sent to the patients' treating physicians. RESULTS: Of the 177 patients included in the study, 57 were Danes, one was from Iceland, 111 were immigrants, and eight were from Greenland. Responses to the questionnaires were obtained from 163 patients (92%). Four cases of unsuspected transmission were detected: one of nosocomial spread of TB, one of occupational acquisition of TB and two of transmission in an international school, leading to further contact tracing among 75 schoolchildren. These four cases were all the result of short-term contacts. In 22 cases, contact with one or more TB patient(s) was reported. In six of these, the DNA-fingerprint result revealed that the presumed contact could not be the source of infection, even though in two of the cases the known TB contact was from the household. CONCLUSION: Nation-wide DNA fingerprinting of TB isolates provides information that could not have been obtained otherwise, and contribute to the understanding of TB transmission in Danish society. In some cases the results lead to further contact tracing. Short-term contact can apparently result in transmission of TB.

Adult↗
PubMed2000

[Occurrence of zearalenone, alpha- and beta-zearalenol in bile of breeding sows in relation to reproductive performance].

Although zearalenone-induced reproductive disorders and the clinical appearance of hyperestrogenism were reproduced and documented quite often the role of zearalenone-contaminated fodder as a cause for fertility problems in sow breeding is still discussed controversial. Therefore the correlation of zearalenone and zearalenone-derivatives in bile (n = 794) and feed (n = 158) with fertility problems of unknown origin was investigated in this study. For the analysis of zearalenone and its derivatives in bile a HPLC/EIA combination was used. On the one hand, this procedure guaranteed the quantitatively reproducible detection, on the other hand, the investigation expenditure could be kept small with regard to a later effort in the routine diagnostics. The detection limits for zearalenone, alpha- and beta-zearalenol in bile were at 1.0 ng/ml, 1.0 ng/ml, and 3.0 ng/ml, respectively. Results were confirmed by GC-MS. Zearalenone and zearalenone-derivatives were detected in almost every bile analysed. The contamination rate was 96.2%. In opposition to recent investigations beta-zearalenol was perceived as a relevant metabolite in swine. The contamination rate of feeding stuffs was 25.9%. Incubation of samples with beta-glucosidase did not elevate the detected amounts of zearalenone. As the measurable concentrations in bile and fodder were only slightly correlated the analysis of bile represents a reasonable alternative for fodder investigation. However, a correlation between the occurrence of zearalenone, alpha- and beta-zearalenol in bile of sows and non-infectious reproductive disorders could not be established at the loading level found. These results are in line with those statements obtained in feeding experiments regarding the risk evaluation of zearalenone in sow reproduction.

Animal Feed↗
PubMed2000

Integrating specialized application systems into hospital information systems--obstacles and factors for success.

Hospital information systems are often huge and heterogeneous systems. To support physicians with their daily clinical work, application systems are developed which are dedicated to particular medical fields or tasks and which have to be integrated into the hospital information system. The integration process is quite complicated, because it makes the information system's infrastructure even more heterogeneous. We developed an application system for documentation and therapy planning in pediatric oncology (DOSPO) and we started to introduce it into the Department of Pediatric Oncology of Heidelberg University Hospital. The fact that DOSPO is developed as a universal system for nationwide use made the integration process more difficult. In any case, the introduction of specialized application systems has to be planned systematically in advance, regarding the prevailing information system's infrastructure, available resources and established processes. To simplify the integration process comprehensive electronic patient records for the future should be designed in a way that they can be enhanced easily by new clinical functions.

Child↗
PubMed1999

By-product formation during exposure of respiring Saccharomyces cerevisiae cultures to excess glucose is not caused by a limited capacity of pyruvate carboxylase.

Upon exposure to excess glucose, respiring cultures of Saccharomyces cerevisiae produce substantial amounts of ethanol and acetate. A possible role of a limited anaplerotic capacity in this process was investigated by overexpressing pyruvate carboxylase and by replacing it with a heterologous enzyme (Escherichia coli phosphoenolpyruvate carboxylase). Compared to the wild-type, neither the pyruvate carboxylase (Pyc)-overexpressing nor the transgenic strain exhibited reduced by-product formation after glucose pulses to aerobic glucose-limited chemostat cultures. An increased intracellular malate concentration was observed in the two engineered strains. It is concluded that by-product formation in S. cerevisiae is not caused by a limited anaplerotic capacity.

Acetates↗
PubMed1999

Expression of cytochrome P450scc mRNA in the hippocampus of patients with temporal lobe epilepsy.

The hippocampus is one of the target areas of neurosteroidal action. Expression of cytochrome P450scc (P450scc, CYP11A1), one of the key enzymes in steroid metabolism, results in de novo synthesis of the neurosteroid pregnenolone. We used a competitive RT-PCR assay to quantify the amount of P450scc mRNA in hippocampal tissue specimens obtained at neurosurgery from patients with temporal lobe epilepsy (TLE). P450scc mRNA is expressed approximately 200 times lower in the hippocampus than in adrenal tissue known for high P450scc expression. P450scc mRNA concentrations were significantly higher in the hippocampus of women (1.72 +/- 0.36 aU, arbitrary units; mean +/- s.e.m.) than of men (0.92 +/- 0.15 aU, p < 0.004). Our data show for the first time the sex-dependent expression of P450scc mRNA in the hippocampus of patients with TLE.

Adrenal Glands↗
PubMed1999

Glutamate but not interleukin-6 influences the phosphorylation of tau in primary rat hippocampal neurons.

Alzheimer's disease (AD) is characterized by amyloid plaques, neuritic degenerations, disturbed glutamatergic neurotransmission and a peculiar inflammatory response. Diffuse plaques develop into neuritic plaques when neurites undergo degeneration in the plaque area. Hyperphosphorylation of tau proteins is a major step in neuritic pathology. Interleukin-6 (IL-6) has been found in diffuse and neuritic amyloid plaques in AD. Therefore the question arises whether IL-6 is involved in the transformation of diffuse into neuritic plaques by affecting tau phosphorylation. We investigated the influence of glutamate and IL-6 on tau phosphorylation in cultured primary rat hippocampal neurons. Glutamate but not IL-6 induced a dephosphorylation of tau. Furthermore IL-6 did not influence the glutamate-induced dephoshorylation of tau. We conclude that the role of IL-6 in AD is not related to the phosphorylation of tau.

Alzheimer Disease↗
PubMed1999

Advances in cell separation: recent developments in counterflow centrifugal elutriation and continuous flow cell separation.

Cell separation by counterflow centrifugal elutriation (CCE) or free flow electrophoresis (FFE) is performed at lower frequency than cell cloning and antibody-dependent, magnetic or fluorescence-activated cell sorting. Nevertheless, numerous recent publications confirmed that these physical cell separation methods that do not include cell labeling or cell transformation steps, may be most useful for some applications. CCE and FFE have proved to be valuable tools, if homogeneous populations of normal healthy untransformed cells are required for answering scientific questions or for clinical transplantation and cells cannot be labeled by antibodies, because suitable antibodies are not available or because antibody binding to a cell surface would induce the cell reaction which should be investigated on purified cells or because antibodies bound to the surface hamper the use of the isolated cells. In addition, the methods are helpful for studying the biological reasons for, or effects of, changes in cell size and cellular negative surface charge density. Although the value of the methods was confirmed in recent years by a considerable number of important scientific results, activities to further develop and improve the instruments have, unfortunately, declined.

Animals↗
PubMed1999

Separation of plant membranes by electromigration techniques.

The review focuses on the multiple separating regimes that offers the free flow electrophoresis technique: free flow zone electrophoresis, isoelectric focusing, isotachophoresis, free flow step electrophoresis. Also, the feasibility to apply either interval or continuous flow electrophoresis is evaluated. The free flow zone electrophoresis regime is generally selected for the separation of cells, organelles and membranes while the other regimes find their largest fields of applications in the purification of proteins and peptides. The latter regimes present the highest resolution efficiency. Therefore, a large part of this review is devoted to the applicabilities of these different regimes to the purification of organelles and membrane vesicles at the preparative scale. Recent developments, both in instrumentation and procedures, are described. The major achievements in plant membrane fractionation obtained with free flow electrophoresis are outlined. The related procedures are both analytical and preparative: they separate tonoplast and plasma membrane simultaneously from the same homogenate, they discriminate for one type of membrane vesicles of opposite orientation, and process large quantities of membrane material by reason of the continuous flow mode. Recent advances using electromigration techniques that permit confirmation of the dynamic state of membranes, characterisation of complex membrane-dependent functions and discovery of new membrane-localised activities are presented.

Cell Membrane↗
PubMed1999

A tumor necrosis factor-induced model of human primary demyelinating diseases develops in immunodeficient mice.

We have reported previously that in the central nervous system (CNS) local expression of tumor necrosis factor (TNF) transgenes can trigger the development of oligodendrocyte apoptosis, primary inflammatory demyelination and neurological dysfunction, accompanied by lymphocyte and macrophage infiltration into the CNS. To distinguish between the local effects of transgene-encoded TNF and the potential encephalitogenic effects of immune infiltrates upon CNS disease pathogenesis, we have backcrossed Tg6074 TNF-transgenic mice to mice deficient in CD4, beta2-microglobulin (beta2m), immunoglobulin mu chain (Igmu) or recombination activation gene-1 (Rag-1). TNF was capable of triggering undiminished primary demyelination in all of the immunodeficient mice, in the presence of activated cells of the macrophage/microglial lineage. We conclude that TNF is sufficient to induce primary inflammatory demyelination and neurological deficits even in the absence of adaptive immunity.

Animals↗