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B Ruhland

Publications and source records attributed to B Ruhland.

7 recordsLinked to original sources
PubMed2000

Tumor necrosis factor induces tumor necrosis via tumor necrosis factor receptor type 1-expressing endothelial cells of the tumor vasculature.

Activation of endothelial cells, fibrin deposition, and coagulation within the tumor vasculature has been shown in vivo to correlate with the occurrence of tumor necrosis factor (TNF)-induced tumor necrosis in mice. In the present study we investigated which target cells mediate the TNF-induced necrosis in fibrosarcomas grown in wild type (wt), TNF receptor type 1-deficient (TNFRp55-/-), and TNF receptor type 2-deficient (TNFRp75-/-) mice. TNF administration resulted in tumor necrosis exclusively in wt and TNFRp75-/-, but not in TNFRp55-/- mice, indicating a dependence of TNF-mediated tumor necrosis on the expression of TNF receptor type 1. However, using wt and TNFRp55-/- fibrosarcomas in wt mice, we found that TNF-mediated tumor necrosis was completely independent of TNF receptor type 1 expression in tumor cells. Thus we could exclude any direct tumoricidal effect of TNF in this model. Soluble TNF induced leukostasis in wt and TNFRp75-/- mice but not in TNFRp55-/- mice. TNF-induced leukostasis in TNFRp55-/- mice was restored by adoptive bone marrow transplantation of wt hematopoietic cells, but TNF failed to induce tumor necrosis in these chimeric mice. Because TNF administration resulted in both activation and focal damage of tumor endothelium, TNF receptor type 1-expressing cells of the tumor vasculature, likely to be endothelial cells, appear to be target cells for mediating TNF-induced tumor necrosis.

Animals↗
PubMed2000

Human cardiac beta1- or beta2-adrenergic receptor stimulation and the negative chronotropic effect of low-dose pirenzepine.

OBJECTIVES: The M1-muscarinic receptor antagonist pirenzepine in low doses (<1 mg intravenously) decreases heart rate. We investigated whether these effects of pirenzepine differ in volunteers with activated cardiac beta1-adrenergic receptors versus activated cardiac beta2-adrenergic receptors. METHODS: In 17 male volunteers (25 +/- 1 years) we studied effects of pirenzepine infusion (0.5 mg intravenous bolus followed by continuous infusion of 0.15 microg/kg/min) on heart rate and heart rate-corrected duration of electromechanical systole (QS2c, as a measure of inotropism) that had been stimulated by activation of cardiac beta1-adrenergic receptors (bicycle exercise in the supine position for 60 minutes at 25 W) or cardiac beta2-adrenergic receptors (continuous intravenous infusion of 100 ng/kg/min terbutaline). RESULTS: Bicycle exercise and terbutaline infusion significantly increased heart rate and shortened QS2c. When pirenzepine was infused 20 minutes after the beginning of the exercise or terbutaline infusion, heart rate decreased in both settings by approximately the same extent (approximately -10 to -14 beats/min), although exercise and terbutaline infusion continued; however, QS2c was not affected. Pirenzepine (0.05 to 1 mg intravenous bolus)-induced decrease in heart rate was abolished after 6 days of transdermal scopolamine treatment of volunteers. CONCLUSIONS: Low-dose pirenzepine decreased heart rate by muscarinic receptor stimulation, because this was blocked by scopolamine. Moreover, low-dose pirenzepine did not differentiate between cardiac beta1- or beta2-adrenergic receptor stimulation; however, low-dose pirenzepine did not affect cardiac contractility as measured by QS2c. Low-dose pirenzepine therefore exerted a unique pattern of action in the human heart: it decreased heart rate (basal and beta1- and/or beta2-adrenergic receptor-stimulated) without affecting contractility.

Adrenergic beta-Agonists↗
PubMed1996

Versatile approach to encoding combinatorial organic syntheses using chemically robust secondary amine tags.

Encoded combinatorial organic synthesis has recently emerged as a powerful tool for the discovery of biologically active compounds from complex chemical libraries. This report describes a new encoding methodology that uses chemically robust secondary amines as tags. These amines are incorporated into an N-[(dialkylcarbamoyl)methyl]glycine-coding oligomer through simple chemistry that is compatible with a wide range of polymer-supported transformations useful in combinatorial synthesis. In the decoding process acidic hydrolysis of the tagging polymer regenerates the secondary amines, which after dansylation are resolved and detected at sub-picomole levels by reversed-phase HPLC. The versatility of this strategy is demonstrated here by encoded syntheses of members of several representative heterocyclic compound classes, including beta-lactams, 4-thiazolidinones, and pyrrolidines.

Anti-Bacterial Agents↗
PubMed1991

Ethanol influences class I and class II MHC antigen expression on human fetal islet-like cell clusters.

Several autoimmune diseases have been linked to an aberrant expression of major histocompatibility complex (MHC) products Ethanol enhances Class I and Class II products on a variety of cell types, and there is evidence for an autoimmune etiology in numerous pathologies associated with alcoholism. We examined whether ethanol alters the expression of Class I and Class II MHC products on human fetal islet-like cell clusters. Incubation of islet-like clusters for 48 hr in ethanol at a starting concentration of 1.5% increased the percentage of single cells expressing Class I. The percentage of cells expressing Class II did not change, but their relative mean fluorescence increased significantly. These findings suggest that alcohol ingestion could alter MHC expression on pancreatic islet cells in vivo perhaps affecting the development of diabetes in genetically predisposed individuals. These findings also support the hypothesis that the rising incidence of type 1 diabetes seen in areas of the world where the per capita consumption of alcohol is also increasing may be a consequence of the immunological effects of alcohol intake.

Ethanol↗
PubMedDate not supplied

Lipid A antibody determinations using ELISA on patients at a children's hospital: a preliminary report.

Using the enzyme-linked immunosorbent assay (ELISA), we studied the IgG and IgM antibody titers in various groups of pediatric patients (n = 81) infected with gram-negative organisms. Unlike the control group (n = 12), IgG antibodies were detected in only five (all under four months of age) of 19 children with sepsis. We assume that either the IgG antibodies are used up during the infection, or the lack of IgG antibodies results in a disposition to sepsis; the latter is more probable. Seventeen of 18 patients with urinary tract infections and proven renal involvement were IgM-positive. This indicates a permanent antigen stimulus, possibly in the form of a fixed antigen complex. Because of the heterogeneity of the groups studied, no overall statements can be made for the 93 children studied, some of whom were studied repeatedly. These children included 17 with tracheal colonization, 17 with recurrent urinary tract infections without proven renal changes and six with wound infections.

Adolescent↗
PubMedDate not supplied

Human fetal islet response to interferon gamma.

Investigation was made of the ability of human fetal islets to express major histocompatibility complex class I and class II gene products after in vitro exposure to 1,000 U/ml Interferon Gamma (IFN) for 48 hours as well as the effect of such exposure on insulin secretion and autologous mixed islet lymphocyte response. Flow cytometry analysis revealed that the mean fluorescence activity of both HLA-ABC (class I) and HLA-DR (class II) was significantly (p < 0.01) increased vs the control after IFN incubation. (class I: Control = 125 +/- 35 SD, IFN = 995 +/- 418 S.D.; class II: Control = 70 +/- 30 SD, IFN = 300 +/- 74 S.D.). Cells containing surface expression of DR and intracellular insulin by flow cytometry following depletion of phagocytic cells were also quantified and increased from 0 to 0.67 percent following exposure to IFN. Autologous splenocytes responded to cells previously incubated with IFN with a three fold increase in 3H-thymidine uptake. Interferon gamma exposed, DR positive insulin containing cells contained one third the insulin of DR negative insulin containing cells (2.1 +/- 1.5 vs 6.6 +/- 3.4 microU/cell) but were nevertheless capable of stimulated insulin secretion. Thus, pharmacologic events leading to increased fetal pancreatic interferon concentrations initiate both immune and nonimmune processes that may predispose susceptible individuals to diabetes.

Cell Division↗