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Biomedical subjects

W J Smith

Publications and source records attributed to W J Smith.

155 records · Page 9Linked to original sources
PubMedDate not supplied

Inhibition of sulfur mustard-increased protease activity by niacinamide, N-acetyl-L-cysteine or dexamethasone.

The pathologic mechanisms underlying sulfur mustard-induced skin vesication remain undefined. Papirmeister et al. (1985) have postulated a biochemical mechanism for sulfur mustard-induced cutaneous injury involving DNA alkylation, metabolic disruption, and enhanced proteolytic activity. We have previously utilized a chromogenic peptide substrate assay to establish that human peripheral blood lymphocytes exposed to sulfur mustard exhibited enhanced proteolytic activity. In this study, compounds known to alter the biochemical events associated with sulfur mustard exposure or to reduce protease activity were tested for their ability to block the sulfur mustard-increased proteolysis. Treatment of cells with niacinamide, N-acetyl-L-cysteine, or dexamethasone resulted in a decrease of sulfur mustard-increased protease activity. Complete inhibition of sulfur mustard-increased proteolysis was achieved by using protease inhibitors (antipain, leupeptin, and 4-(2-aminoethyl)-benzenesulfonylfluoride). These data suggest that therapeutic intervention in the biochemical pathways that culminate in protease activation or direct inhibition of proteolysis might serve as an approach to the treatment of sulfur mustard-induced pathology.

Acetylcysteine↗
PubMedDate not supplied

Biochemical manipulation of intracellular glutathione levels influences cytotoxicity to isolated human lymphocytes by sulfur mustard.

Glutathione (GSH) is the major nonprotein thiol that can protect cells from damage due to electrophilic alkylating agents by forming conjugates with the agent. Sulfur mustard (HD) is an electrophilic alkylating agent that has potent mutagenic, carcinogenic, cytotoxic, and vesicant properties. Compounds that elevate or reduce intracellular levels of GSH may produce changes in cytotoxicity induced by sulfur mustard. Pretreatment of human peripheral blood lymphocytes (PBL) for 72 hr with 1 mM buthionine sulfoximine (BSO), which reduces intracellular GSH content to approximately 26% of control, appears to sensitize these in vitro cells to the cytotoxic effects of 10 microM HD but not to higher HD concentrations. Pretreatment of PBL for 48 hr with 10 mM N-acetyl cysteine (NAC), which elevates intracellular glutathione levels to 122% of control, appears to partially protect these in vitro cells from the cytotoxic effects of 10 microM HD but not to higher HD concentrations. Augmentation of intracellular levels of glutathione may provide partial protection against cytotoxicity of sulfur mustard.

Acetylcysteine↗
PubMedDate not supplied

Sulfur mustard-increased proteolysis following in vitro and in vivo exposures.

The pathologic mechanisms underlying sulfur mustard (HD)-induced skin vesication are as yet undefined. Papirmeister et al. (1985) postulate enhanced proteolytic activity as a proximate cause of HD-induced cutaneous injury. Using a chromogenic peptide substrate assay, we previously reported that in vitro exposure of cell cultures to HD enhances proteolytic activity. We have continued our investigation of HD-increased proteolytic activity in vitro and have expanded our studies to include an in vivo animal model for HD exposure. In vitro exposure of human peripheral blood lymphocytes (PBL) to HD demonstrated that the increase in proteolytic activity is both time- and temperature-dependent. Using a panel of 10 protease substrates, we established that the HD-increased proteolysis was markedly different from that generated by plasminogen activator. The hairless guinea pig is an animal model used for the study of HD-induced dermal pathology. When control and HD-exposed PBL and hairless guinea pig skin where examined, similarities in their protease substrate reactivities were observed. HD-exposed hairless guinea pig skin biopsies demonstrated increased proteolytic activity that was time-dependent. The HD-increased proteolytic response was similar in both in vitro and in vivo studies and may be useful for elucidating both the mechanism of HD-induced vesication and potential treatment compounds.

Animals↗
PubMedDate not supplied

Effect of extracts of Angelica polymorpha on reaginic antibody production.

An aqueous extract of Angelica polymorpha was examined for its immunoregulating properties. Its effect on the production of antibodies was tested in (C57BL/6 X DBA/2)F1 mice. When the animals were treated daily with the extract, the serum titers of reaginic antibodies normally observed after a single injection dinitrophenylovalbumin (DNP3-OA) were significantly lower, and the higher and more sustained reaginic titers induced by booster injections of DNP3-OA were also inhibited. The immunosuppressive activity was observed both by oral and intraperitoneal administration of the extract, and it was not removed by dialysis. In contrast, the serum titers of IgG were not significantly altered by the administration of the extract. The extract had little or no effect on the passive cutaneous anaphylaxis reaction or the release of histamine from sensitized rat lung fragments.

Administration, Oral↗
PubMedDate not supplied

Complexity of human T-cell antigen receptor beta-chain constant- and variable-region genes.

Immune systems of vertebrates function via two types of effector cells, B and T cells, which are capable of antigen-specific recognition. The immunoglobulins, which serve as antigen receptors on B cells, have been well characterized with respect to gene structure, unlike the T-cell receptors. Recently, cDNA clones thought to correspond to the beta-chain locus of the human and mouse T-cell receptor have been described. The presumptive beta-chain clones detect gene rearrangement specifically in T-cell DNA and show homology with immunoglobulin light chains. The similarity of the T-cell beta-chain gene system to the immunoglobulin genes has been further demonstrated by the recent observation of variable- and constant-region gene segments as well as joining segments and putative diversity segments. We report here the characterization of cDNA and genomic clones encoding human T-cell receptor beta-chain genes. There are two constant-region genes (C beta 1 and C beta 2), each capable of rearrangement and expression as RNA. The gene arrangement, analogous to that of mouse beta-chain genes, shows strong evolutionary conservation of the dual C beta gene system in these two species.

Base Sequence↗
PubMedDate not supplied

Racial differences in pressure, volume and renin interrelationships in essential hypertension.

The interrelationships of arterial pressure, plasma volume (PV), and plasma renin activity were studied in 152 consecutive male patients with uncomplicated essential hypertension. Of these, 22 (17 white and 5 black) subjects had normal plasma volumes and because of the small number were not included in the analysis of results. The remaining 130 (35 black and 95 white) patients were classified as having either expanded or contracted plasma volume. A higher percentage of black (43%) than white (21%) subjects were volume expanded (PV > 19 ml/cm) and a lower percentage of blacks (57%) than whites (79%) were volume contracted (PV < 17 ml/cm). There was not significant difference in mean arterial pressure and plasma renin activity between the volume expanded and contracted black patients. In contrast, the white patients with contracted plasma volume had significantly higher arterial pressures (p < 0.05) and plasma renin activity (p < 0.001) than those with expanded plasma volume. More blacks than whites had low plasma renin activity and did not manifest the inverse relationship of plasma renin activity to plasma volume as did the whites. These data confirm and extend previous observations that the relationship between plasma volume and plasma renin activity (PRA) in the male patient with essential hypertension seems to differ between the black and white race. Efforts to explain the low PRA in black patients might be best directed toward those patients with suppressed PRA and with contracted intravascular volume.

Black People↗
PubMedDate not supplied

Investigations on N-nitrosopyrrolidine in dry-cured bacon.

Dry-cured or "country-style" bacon is a low volume specialty product typically made by small producers whose production practices vary widely. These practices include the direct application of dry-cure formulations containing varying concentrations of salt, sugar, flavoring agents, sodium nitrite, and sometimes sodium nitrate, and the use of lengthy curing and processing times. Because of the possibility of generating higher levels of N-nitrosopyrrolidine (NPYR) after frying in this product type compared with pump-cured bacon, an investigation was carried out on dry-cured bacon obtained from cooperating state or federally inspected establishments. Three different samples from each of the 16 plants were analyzed. Only one sample from each of 2 different producers exceeded the Food Safety and Inspection Service (FSIS) action level of 17 ppb NPYR, indicating that the majority of samples tested were in compliance. A significant correlation (P less than 0.01) was found between residual NaNO2 prior to frying and NPYR after frying. The elimination of added nitrate in the dry-cure formulations is recommended.

Animals↗
PubMedDate not supplied

Comparison of three methods for determination of N-nitrosopyrrolidine in fried dry-cured and pump-cured bacon.

Three methods, the mineral oil distillation (MOD), the dry column (DC), and a low temperature vacuum distillation (LTVD), for the determination of N-nitrosopyrrolidine in dry-cured and pump-cured bacon were compared. Each method uses the thermal energy analyzer for the determinative step. The coefficients of variation for repeatability were 10.3% (MOD), 7.2% (DC), and 9.1% (LTVD) for the dry-cured bacon study and 8.7% (MOD), 8.5% (DC), and 7.1% (LTVD) for the pump-cured bacon study. The pooled coefficients of variation for between-method reproducibility were 11.8% for the dry-cured bacon and 10.8% for the pump-cured bacon. The pooled coefficients of variation for repeatability were 9.0% for the dry-cured bacon and 8.2% for the pump-cured bacon. These values compare favorably with the values from previous collaborative or validation studies of the individual methods, and the methods can be considered to be equivalent.

Animals↗