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Biomedical subjects

R Bauer

Publications and source records attributed to R Bauer.

At least 253 records · Page 14Linked to original sources
PubMed1995

Biological and pharmacological activities and further constituents of Hyptis verticillata.

Several extracts of Hyptis verticillata and isolated compounds were evaluated for their anti-inflammatory, antibacterial, antisecretory, and cytotoxic properties. The aerial parts yielded (R)-5-hydroxypyrrolidin-2-one and essential oil with the main components alpha-pinene, beta-pinene, and thymol. Spectroscopic methods (UV, IR, 1H-NMR, 13C-NMR, mass, CD) fully characterized (R)-5-hydroxypyrrolidin-2-one, as it was isolated by a bioassay guided fractionation. The essential oil, (R)-5-hydroxypyrrolidin-2-one, as well as the previously isolated rosmarinic acid and dehydropodophyllotoxine contributed to the antibacterial effects of H. verticillata. Furthermore, rosmarinic acid showed significant capillary stabilizing effects. Sideritoflavone inhibited prostaglandin synthase to a significant extent and had antisecretory effects comparable to those of NPPB. The cytotoxicity of the aqueous extract, as demonstrated using KB and HT 29 cell lines, may be of toxicological relevance in cases of internal application.

Animals↗
PubMed1995

Inhibition of endotoxin-induced cytokine release and neutrophil activation in humans by use of recombinant bactericidal/permeability-increasing protein.

To investigate the effects of a recombinant endotoxin-binding protein, bactericidal/permeability-increasing protein (rBPI23), on cytokine release and neutrophil activation in endotoxemia in humans, 8 volunteers were challenged twice with endotoxin and concurrently received either rBPI23 or placebo in a randomized, placebo controlled, double-blind crossover study, rBPI23 treatment significantly lowered circulating endotoxin levels (P = .02) and resulted in a significant reduction in the release of tumor necrosis factor (TNF), soluble TNF receptors p55 and p75, interleukin (IL)-6, IL-8 (P < .01 for each), and IL-10 levels (P = .02) but did not prevent the endotoxin-induced rise in body temperature. The early endotoxin-induced leukopenia was blunted (P = .08), and neutrophil degranulation, as measured by circulating levels of elastase/alpha 1-antitrypsin complexes (P = .03) and lactoferrin (P < .01), was largely prevented by rBPI23. The results of this study indicate that rBPI23 is capable of neutralizing many of the biologic effects of endotoxin in humans.

Antimicrobial Cationic Peptides↗
PubMed1995

Cloning and characterization of a second AP-2 transcription factor: AP-2 beta.

AP-2 has been characterized previously as a unique 52 x 10(3) M(r) transcription activator encoded by a single gene that is expressed in a restricted pattern during embryonic morphogenesis of the peripheral nervous system, face, skin and nephric tissues. Here we report the isolation of genomic and cDNA clones encoding for a second AP-2 related transcription factor, designated AP-2 beta. AP-2 beta binds specifically to a series of well-characterized AP-2 binding sites, consensus to the sequence G/CCCN3GGC, and transactivates transcription from a reporter plasmid under the control of an AP-2-dependent promoter. A C-terminal domain known to mediate homodimerization of the previously cloned AP-2 alpha transcription activator is highly conserved and sufficient to mediate interaction between the two proteins. Northern blot and in situ hybridizations revealed that the two genes are expressed in murine embryos between days 9.5 and 19.5 p.c. Coexpression of both mRNAs was detected in many tissues at day 13.5 and 15.5 of embryogenesis but some regions of the developing brain and face including the primordium of midbrain and the facial mesenchyme differed in their expression pattern of AP-2 genes. AP-2 alpha and AP-2 beta signals in the central and peripheral nervous system overlapped with regions of developing sensory neurons. In adult tissues AP-2 alpha expression was found mainly in the skin, eye and prostate and AP-2 beta expression in the kidney. In summary, our analyses of embryonic and adult mice demonstrate that two different AP-2 transcription factors are specifically expressed during differentiation of many neural, epidermal and urogenital tissues.

Amino Acid Sequence↗
PubMed1994

Stimulus-specific fast oscillations at zero phase between visual areas V1 and V2 of awake monkey.

Synchronization of fast cortical oscillations (35-90 Hz) has been proposed as a basis of sensory integration. This hypothesis requires stimulus specific oscillations that occur synchronously in different cortical areas of awake animals. Here, we demonstrate the presence of, and phase-locking between, high amplitude stimulus specific oscillations (50-90 Hz) in striate (V1) and extra striate (V2) visual cortex of an awake monkey. Oscillations of multiple unit spikes and local field potentials occurred with an average V1-V2 phase difference near zero. This finding was unexpected because V1 and V2 are thought to be serially arranged in the primate's visual processing stream. However, near zero-phase synchronization among cortical areas might enable fast and effective communication via the many reciprocal cortico-cortical connections for processes such as sensory integration.

Animals↗
PubMed1994

The genomic structure of the human AP-2 transcription factor.

The transcription factor AP-2 is encoded by a gene located on chromosome 6 near the HLA locus. Here we describe the genomic organization of the AP-2 gene including an initial characterization of the promoter. We have mapped two mRNA initiation sites, the entire exon-intron structure and located two polyadenylation sites. The mature AP-2 mRNA is spliced from 7 exons distributed over a region of 18 kb genomic DNA. A recently cloned inhibitory AP-2 protein is generated by alternative usage of a C-terminal exon. The proline-rich transactivation motif is encoded by a single exon within the N-terminal region in contrast to the complex DNA binding and dimerization motif which involves amino acid residues located on four different exons. The sites of mRNA initiation are located 220 and 271 bases upstream from the ATG translation start site. Although the promoter contains no canonical sequence motifs for basal transcription factors, such as TATA-, CCAAT- or SP-1 boxes, it mediates cell-type-specific expression of a CAT reporter gene in PA-1 human teratocarcinoma cells and is inactive in murine F9 teratocarcinoma cells. We demonstrate that the promoter of the AP-2 gene is subject to positive autoregulation by its own gene product. A consensus AP-2 binding site is located at position -622 with respect to the ATG. This site binds specifically to bacterially expressed AP-2 as well as to multiple proteins, including AP-2, present in PA-1 and HeLa cell nuclear extracts. A partial AP-2 promoter fragment including the AP-2 consensus binding site is approximately 5-fold transactivated by cotransfection of an AP-2 expression plasmid.

Animals↗
PubMed1994

The aggregation behavior of zinc-free insulin studied by small-angle neutron scattering.

The aggregation behavior of zinc-free insulin has been studied by small-angle neutron scattering as a function of pH and ionic strength of the solution. The pair distance distribution functions for the 12 samples have been obtained by indirect Fourier transformation. The results show that the diameter of the aggregates is 40 A at pH 11 and 10 mM NaCl, independent of the protein concentration. The largest diameter of about 120 A is found for pH 8, 100 mM NaCl, and a protein concentration of 10 mg/ml. Estimates of the pair distance distribution functions, free of inter-particle correlation effects, were obtained by an indirect Fourier transformation, omitting the data at small scattering vectors, which are influenced by these effects. By this procedure the weight-averaged molecular mass and the average radius of gyration were determined. These parameters vary from 1.3 times the monomer mass and 14 A, to 6.8 times the monomer mass and 31 A, respectively. The mass distribution between the oligomers was determined by a model based on the crystal structure of zinc-free insulin. The results from this model and the Fourier transformations have been compared to an equilibrium model recently introduced by Kadima et al. (1993). The neutron scattering results agree well with the predictions of this model except that broader mass distributions are suggested by neutron scattering.

Crystallization↗
PubMed1994

Fibrin structures during tissue-type plasminogen activator-mediated fibrinolysis studied by laser light scattering: relation to fibrin enhancement of plasminogen activation.

The aim was to relate fibrin structure and the stimulatory effect of fibrin on plasminogen activation during t-PA-mediated fibrinolysis using Lys78-plasminogen as activator substrate. Structural studies were undertaken by static and dynamic laser light scattering, cryo transmission electron microscopy and by the measurement of conversion of fibrin to X-, Y- and D-fragments. The kinetics of plasmin formation were monitored by measurement of the rate of pNA-release from Val-Leu-Lys-pNA. The process of fibrin formation and degradation comprised three phases. In the first phase, protofibrils with an average length of about 10 times that of fibrinogen were formed. The duration of this phase decreased with increasing t-PA concentration. The second phase was characterized by a sudden elongation and lateral aggregation of fibrin fibers, most pronounced at low levels of t-PA, and by formation of fragment X-polymer. The third phase was dominated by fragmentation of fibers and by formation of Y- and D-fragments. Plasmin degraded the fibers from within, resulting in the formation of long loose bundles, which subsequently disintegrated into thin filaments with a length of less than 10 and a mass per length close to one relative to fibrinogen. Plasmin generation at high t-PA concentrations sets in just prior to (and at low t-PA concentrations shortly after) the onset of the rapid second phase of elongation and lateral aggregation of fibrin fibers. The maximal rate of plasmin formation per mol t-PA was the same at all concentrations of activator and was achieved close to the time of the peak level of fragment X-polymer. Plasmin formation ceased after formation of substantial amounts of Y- and D-fragments. At this stage the length was between 300 and 3 and the mass per length close to 1, both relative to fibrinogen. In conclusion our results indicate that (1) formation of short fibrin protofibrils is the minimal requirement for the onset of the stimulatory effect of fibrin on plasminogen activation by t-PA, (2) formation of fragment X protofibrils is sufficient to induce optimal stimulation of plasminogen activation, and (3) plasmin degrades laterally aggregated fibrin fibers from within, resulting in the conversion of the fibers into long loose bundles, which later disintegrate into thin filaments.

Amino Acid Sequence↗
PubMed1994

[Total i.v. anesthesia with S-(+)-ketamine in orthopedic geriatric surgery. Endocrine stress reaction, hemodynamics and recovery].

UNLABELLED: Clinically-used ketamine is a racemic mixture of two isomers, S-(+)- and R-(-)-ketamine. Previous investigations showed the anaesthetic potency of S(+)-ketamine to be three times higher than that of R-(-)-ketamine. It was the aim of this study to compare the effects of S-(+)-ketamine and racemic ketamine on endocrine and cardiovascular parameters, recovery, and side effects in geriatric patients during total intravenous anaesthesia (TIVA) for orthopaedic surgery. METHODS: Forty patients over 60 years of age scheduled for elective hip or knee replacement were investigated in a double-blind, randomised design. For induction of TIVA, patients received 0.1 mg midazolam, 0.5 mg atropine, 1 mg/kg S(+)-ketamine or 2 mg/kg racemic ketamine, respectively, 2 mg vecuronium, and 1.5 mg/kg suxamethonium. After intubation and relaxation with a total dose of 0.1 mg/kg vecuronium, a continuous infusion of 2 mg/kg per hour S-(+)- or 4 mg/kg per hour racemic ketamine was administered throughout surgery. Blood samples were taken through a central venous catheter at seven time-points, before induction as well during and after surgery, until the 1st postoperative morning for analysis of adrenaline, noradrenaline (by high-pressure liquid chromatography with electrochemical detection), anti-diuretic hormone (ADH), adrenocorticotropic hormone (ACTH), cortisol (by radioimmunoassay), glucose, and lactate. In addition, systolic arterial pressure (SAP), heart rate (HR), and arterial oxygen saturation were measured, and the time intervals between the end of ketamine infusion and the return of consciousness and orientation were protocolled. The incidence and assessment of dreams and other side effects were reported by the patients. RESULTS: Biometric data of the groups were comparable, the mean age of both groups being 68 years. Plasma adrenaline, noradrenaline, ADH, ACTH, cortisol, and glucose as well as SAP and HR increased significantly (P < 0.05) during the course of anaesthesia. The influence on lactate levels was not significant. There were no differences between S(+)- and racemic ketamine with respect to these parameters. Three patients in the ketamine-racemate group showed severe arterial hypertension and were withdrawn from the study. Recovery clearly improved after administration of S(+)-ketamine compared to the racemate. Simple orders were followed after 2.0 +/- 3.4 versus 4.9 +/- 6.8 min (P = 0.07), orientation with respect to person returned after 5.7 +/- 4.0 versus 14.6 +/- 10.0 min (P < 0.001) and spatial orientation after 8.2 +/- 5.4 versus 17.4 +/- 9.7 min (P < 0.001). After racemic ketamine, 1 patient remembered a negative dream and 1 patient a positive dream. In the S(+)-group, 1 positive dream was reported. No intraoperative awareness was reported, and all patients would accept the same anaesthesia again. CONCLUSIONS: Increases in cardiovascular parameters and insufficient reduction of the stress response with respect to ADH, ACTH, and cortisol seem to require a more potent hypnotic element during TIVA with ketamine. With regard to endocrine and cardiovascular parameters, the pharmacodynamic effects of racemic and S-(+)-ketamine were comparable. Because of the significant improvement in recovery and the reduced quantitative drug load, S-(+)-ketamine offers a clinical advantage compared with currently used racemic ketamine.

Aged↗
PubMed1994

[Pemphigus chronicus benignus familiaris (Hailey-Hailey disease) and bipolar affective disease in 3 members of a family].

We report on three family members suffering from both autosomal dominant Hailey-Hailey disease and bipolar affective disorder. As molecular biology techniques have made the localization of genes causing simple Mendelian traits possible as a routine task, the gene for Hailey-Hailey disease will presumably be localized in the foreseeable future. The Hailey-Hailey gene and its chromosomal surrounding will then be a region of interest for linkage studies in bipolar affective disorder.

Biopsy↗
PubMed1994

[Successful treatment of panarteritis nodosa with low-dose methotrexate therapy].

We report on a 45-year-old male patient who presented a classic polyarteritis nodosa (PAN). The clinical course extended over 7 years. In spite of 2 years immunosuppressive therapy with azathioprine and methylprednisolone the course was progressive. Low-dose methotrexate therapy was the only treatment that controlled the disease, leading to rapid clinical and histopathological remission. In low concentrations methotrexate acts as an IL-1 inhibitor, and it obviously suppresses the pathogenetic mechanism of PAN.

Arteries↗
PubMed1994

Antibodies against CD4+ lymphocytes in plasma of HIV-infected patients are related to CD4 cell depletion in vivo.

The role of autoimmune phenomena in the pathogenesis of AIDS is not well understood. Antibodies against CD4+ lymphocytes are frequently detectable in HIV-infected patients. However, the relevance of these antibodies is unknown. In this study anti-CD4 cell antibodies in plasma of HIV-infected patients were compared to patients' CD4 cell count. Lymphocytes of a healthy donor were incubated with plasma of patients and controls. Antibodies against CD4+ lymphocytes were detected using anti-human Ig antibodies and monoclonal anti-CD4 antibodies simultaneously. The degree of staining was visualized by flow cytometry. The experiments revealed that 60% of HIV-infected patients harbored anti-CD4 cell antibodies in their plasma. Anti-CD4 cell antibodies were not detectable in plasma of healthy controls. Patients with anti-CD4 cell antibodies in their plasma presented with significantly lower numbers of circulating CD4+ lymphocytes (P = 0.025). The degree of antibody reactivity was negatively correlated to patients' CD4 cell counts (P = 0.02). In conclusion there is evidence for an association between plasma anti-CD4 cell antibodies and CD4 cell depletion. Whether this association represents an epiphenomenon or a pathogenetic relevant pathway needs to be investigated in further studies.

Antilymphocyte Serum↗
PubMed1994

Enzyme activity patterns of myosin ATPase, alpha-glycerophosphate dehydrogenase and succinate dehydrogenase within different muscle fibre types.

Muscle fibre compositions of five different rabbit muscles were determined by combining two enzyme-histochemical reactions (NADH tetracolium oxidoreductase and myosin ATPase after alkaline preincubation). The differentiation into the fibre types, fast twitch glycolytic (FTG), fast twitch oxidative (FTO), and slow twitch oxidative (STO) was possible by a reliable staining classification. Aim of the study was the estimation of enzyme activity patterns within the three different fibre types. For this purpose, four serial cross-sections with several enzyme histochemical reactions were performed: alkaline combination method for fibre type determination, the reactions of myosin ATPase, alpha-glycerophosphate dehydrogenase (GPDH), and succinate dehydrogenase (SDH). The measurement procedure for the estimation of enzyme activities was based on the proportionality between the intensity of the enzyme histochemical staining reaction and the degree of enzyme activity. The activities of GPDH (indicator for glycolytic metabolism) and SDH (oxidative metabolism) were inverse. The calcium-activated myosin ATPase showed only little activity in slow twitch fibres after alkaline preincubation. In contrast to slow twitch fibres, ATPase activity in fast twitch fibres was relatively high. The results showed that the classification of muscle fibre types due to their myosin ATPase activities and their main metabolisms (oxidative and glycolytic respectively) is justified.

Animals↗
PubMed1994

Peroxidative status and glutathione content of the brain in normal weight and intra-uterine growth-retarded newborn piglets.

The peroxidative and glutathione status as well as the production of reactive oxygen species were studied in the brain of normal weight (NW) and intra-uterine growth-retarded (IUGR) newborn piglets. In NW as well as IUGR newborn piglets reduced (GSH) and oxidized (GSSG) glutathione, lipid peroxides, iron stimulated lipid peroxidation, H2O2 production and lucigenin and luminol amplified chemiluminescence are very similar in the different brain regions, with one exception. In the cerebellum, higher GSH concentration, higher superoxide anion generation, lower levels of lipid peroxides and a tendency toward a lower capacity of H2O2 production were seen. But the intra-uterine growth retardation to body weights of half the average body weights of the respective litter did not influence the peroxidative status and the GSH/GSSG equilibrium in the brain of newborn piglets.

Animals↗
PubMed1994

In vitro inhibition of cyclooxygenase and 5-lipoxygenase by alkamides from Echinacea and Achillea species.

Polyunsaturated alkamides isolated from Achillea species, Echinacea angustifolia DC., Anacyclus pyrethrum (L.) Link, and Aaronsohnia pubescens (Desf.) Bremer & Humphries, (Compositae) were shown to possess inhibitory activity in in vitro cyclooxygenase (sheep seminal microsomes) and 5-lipoxygenase (porcine leukocytes) assays. Activity appeared to depend on the particular structure of the alkamides.

Amides↗
PubMed1994

Anti-inflammatory active polyacetylenes from Bidens campylotheca.

The n-hexane extract of Bidens campylotheca Schultz Bip. ssp campylotheca (Compositae) showed significant in vitro inhibition of cyclooxygenase (CO) and 5-lipoxygenase (5-LO). Five polyacetylenes, heptadeca-2E,8E,10E,16-tetraene-4,6-diyne (1), heptadeca-2E,8Z,10E,16-tetraene-4,6-diyne (2), heptadeca-2E,8E,16-triene-4,6-diyne-10-ol (3), safynol (5) and, as a new compound, safynol-2-O-isobutyrate (4) could be isolated and their structures elucidated mainly by UV, MS, NMR, and COSY-NMR. The isolated compounds exhibited a significant inhibitory effect on cyclooxygenase and 5-lipoxygenase.

Acetylene↗
PubMed1994

Anti-lymphocyte antibodies in plasma of HIV-1-infected patients preferentially react with MHC class II-negative T cells and are linked to antibodies against gp41.

It has previously been shown that HIV-infected patients develop anti-lymphocyte antibodies. The relationship between anti-lymphocyte antibodies and antibodies against different viral antigens is unknown, and it remains controversial whether some lymphocyte subpopulations are targeted preferentially. We have set out using three-colour flow cytometry to measure antibodies against different lymphocyte subsets. Staining with anti-human immunoglobulin and two MoAbs was performed to characterize the immunoglobulin load of different lymphocyte subsets. Comparison was done between patients' antibody reactivity against HIV-1 antigens and anti-lymphocyte antibodies. We were able to demonstrate the presence of anti-lymphocyte antibodies in approximately 75% of the HIV-infected patients (n = 78) (healthy controls were all negative). MHC class II-negative T cells showed a stronger reaction with anti-lymphocyte antibodies than B cells or MHC class II-positive T cells. Patients with antibodies against CD4 lymphocytes showed a significantly higher antibody reaction with the retroviral antigen gp41 than patients without these antibodies. An association between anti-lymphocyte antibodies and antibody reactivity against other HIV-1 antigens was not noticed. In conclusion, anti-lymphocyte antibodies in HIV-1-infected patients show a preferential reactivity with T cells which lack expression of MHC class II molecules. There is an increased antibody reactivity against gp41 in patients with anti-CD4+ T cell antibodies. The association hints at a specific origin of anti-lymphocyte antibodies in HIV-1-infected patients due to cross-reactivity with viral epitopes or network phenomena. These anti-CD4 cell antibodies could be of interest in the clinical course of HIV infection.

Antigen-Antibody Reactions↗