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Biomedical subjects

R A Roth

Publications and source records attributed to R A Roth.

At least 325 records · Page 18Linked to original sources
PubMed1983

Effects of monocrotaline and monocrotaline pyrrole on 5-hydroxytryptamine and paraquat uptake by lung slices.

Treatment of rats with monocrotaline (MCT) or its reactive pyrrole metabolite, dehydromonocrotaline (MCTP), injures pulmonary capillary endothelium and other lung cell types. The mechanism by which pulmonary damage occurs is unknown. To investigate the possibility that the metabolites of MCT can injure lung cells directly, slices of lung from male Sprague-Dawley rats were incubated with chemically synthesized MCTP (0.1-1.0 mM). The ability of the slices to accumulate 5-hydroxytryptamine (5HT) was then examined. After 5 hours exposure to MCTP in vitro, there was no change in either 5HT or PQ uptake at any of the MCTP concentrations tested. Similar results were obtained when lung slices were incubated with liver slices and MCT to generate MCT metabolites in vitro. In contrast, treatment in vivo with MCTP resulted in a 35% decrease in the uptake of 5HT and a 15% decrease in the uptake of PQ by lung slices 14 days after treatment. These results suggest that damage does not occur by direct interaction of MCTP with the lung tissue or that functional injury is slow to develop. Alternatively, the damage in vivo may be mediated by factors not present in the sliced tissue.

Animals↗
PubMed1982

The effects of carbon monoxide and hypoxic hypoxia on amine-containing cells in the tracheal epithelium of young rabbits.

Endogenously fluorescent, singly occurring amine-containing cells in tracheal epithelium were examined in 3-, 10-, and 28-day-old rabbits. These cells are pyramidal in shape with the apex projected toward the tracheal lumen. The cytoplasm exhibits a yellow fluorescence which is predominantly supranuclear. Occasional, infranuclear, fluorescent cytoplasmic processes project from the cells. The numbers of fluorescent cells per unit length of trachea increase with age. Acute exposure of 10-day-old rabbits to 13% O2 decreases the number of detectable fluorescent cells in the tracheal compared to controls exposed to room air. Similarly, exposure to 750 ppm carbon monoxide decreases the number of fluorescent epithelial cells appearing in tracheas of 10- and 28-day-old rabbits. These results suggest that the amine-containing epithelial cells of the trachea respond to tissue hypoxia and that decreased airway pO2 is not necessary to elicit a response.

Aging↗
PubMed1982

Monoclonal antibodies to the human insulin receptor block insulin binding and inhibit insulin action.

Antibodies to the insulin receptor were prepared in BALB/c mice by immunization with IM-9 human lymphocytes, a cell type that has a large number of plasma membrane insulin receptors. The spleens of these mice were then removed, and their lymphocytes were fused to a mouse myeloma cell line, FO cells. After screening over 1,200 resulting hybrids, one stable hybrid was obtained that produced IgG1 antibodies directed towards the insulin receptor. This antibody blocked 125I-labeled insulin binding to its receptor by more than 90% in three human tissues: IM-9 cultured lymphocytes, freshly isolated adipocytes, and placenta membranes. In contrast, the antibody did not inhibit insulin binding to rat adipocytes and rat liver plasma membranes, suggesting that the antibody was species specific. In IM-9 cells, which had their proteins prelabeled with [35S]methionine, the antibody precipitated two polypeptides with molecular weights of 135,000 and 95,000; these molecular weights are identical to those previously identified as the alpha and beta subunits of the insulin receptor. The monoclonal antibody inhibited the actions of insulin on both human adipocytes and fibroblasts, suggesting that the antibody was an antagonist of insulin action. The present studies suggest, therefore, that monoclonal antibodies to the insulin receptor may provide new insights into the structure of the insulin receptor and its interaction with insulin.

Adipose Tissue↗
PubMed1982

Nonrespiratory metabolic function and morphology of lung following exposure to polybrominated biphenyls in rats.

Exposure to polybrominated biphenyls (PBBs) resulted in increased activity of microsomal arylhydrocarbon hydroxylase and ethoxyresorufin-O-deethylase in rat lung. Clearance of 5-hydroxytryptamine (5-HT) and angiotensin 1 by perfused lungs was decreased by PBBs. However, PBBs had no effect on the activity of epoxide hydrolase, monoamine oxidase, or angiotensin-converting enzyme in lung. The only histopathologic change detected in lungs from PBB-treated rats was an increase in alveolar type II cell lamellar bodies. Selective accumulation of certain PBB congeners by lung was not observed in this investigation.

Animals↗
PubMed1982

Pneumotoxicity and thrombocytopenia after single injection of monocrotaline.

Adult Sprague-Dawley rats were treated once with 105 mg/kg monocrotaline (MCT) subcutaneously or an equivalent volume of isotonic saline and examined 2, 5, 10, and 14 days later. The earliest changes observed were in the platelet count, which was decreased in the MCT animals at 2, 5, and 10 days postinjection. Clearance of perfused 5-hydroxytryptamine, a function of pulmonary vascular endothelium, was unaltered in isolated lungs of treated rats until 5 days after dosing but decreased progressively thereafter in the MCT animals and was 24% less than controls by 14 days. The magnitude of this effect was dose related. Inflow perfusion pressure was elevated in perfused lungs of MCT-treated animals at day 14. Right heart hypertrophy, measured as an increase in the ratio of right ventricle to left ventricle plus septum weights, was not evident until 14 days after treatment. A larger dose of MCT (130 mg/kg) resulted in significant mortality, whereas a lower dose (60 mg/kg) did not result in right ventricular hypertrophy 2 wk after treatment. The treatment regimen described has advantages over administration of MCT by ingestion and may prove suitable for investigations of the mechanism by which MCT results in pulmonary hypertension.

Alanine Transaminase↗
PubMed1982

Flow dependence of norepinephrine extraction by isolated perfused rat lungs.

Disposition of perfused norepinephrine (NE) was studied in isolated rat lungs at several perfusate flows, including that occurring in vivo. Lungs were ventilated with 95% O2-5% CO2 and perfused at 37 degrees C with recirculating medium initially containing 90 nM [14C]NE. In agreement with previous studies the fraction of NE removed in a single pass through the pulmonary vasculature was 0.30 +/- 0.03 by lungs perfused at low flow (10 ml/min; 7.2 ml.min-1.g lung-1). This extraction ratio decreased with increasing flow, so that in lungs perfused at 45 ml/min (31.8 ml.min-1.g lung-1) the extraction ratio was 0.09 +/- 0.01. The concentration of NE metabolites in the perfusate reservoir increased with time of perfusion. The rate of appearance of deaminated and O-methylated metabolites in the recirculating perfusion medium was not markedly influenced by flow. NE that accumulated in lung was metabolized before reentry into the perfusion medium. These results indicate that extraction of NE by rat lung is markedly dependent on flow and suggest that removal of NE by lung is not highly efficient at normal organ perfusion rates.

Animals↗
PubMed1981

Role of disulfide interchange enzyme in immunoglobulin synthesis.

The role of disulfide interchange enzyme in protein biosynthesis was evaluated by studying the enzyme from mouse lymphoid tissue. The enzyme isolated from lymphoid cells was shown to have no tissue-specific characteristics. It was identical with the enzyme synthesized by mouse liver in its biochemical and immunological properties and its capacity to promote both disulfide bond formation and insulin degradation. In contrast to liver, the levels of enzyme in lymphoid tissues were found to vary with immunoglobulin secretory activity, Assays of lymphoid cells and their transformed counterparts showed that the enzyme contents of cells actively secreting immunoglobulin were 1-2 orders of magnitude higher than that of unstimulated B cells or non-immunoglobulin-producing T cells. The increase in enzyme levels paralleled the increase in immunoglobulin synthesis after antigen or mitogen stimulation and was independent of the class of immunoglobulin produced. This correlation indicated that the enzyme plays a critical role in the formation of intramonomer bonds common to all immunoglobulin molecules. Supporting data were obtained by assaying the ability of the enzyme to promote the polymerization of mouse pentamer IgM in vitro. The enzyme was found to catalyze the formation of the interchain bonds required for monomer IgM assembly but not the formation of the intermonomer bonds required for pentamer assembly. The sum of these results provides strong evidence that disulfide interchange enzyme functions in the in vivo synthesis protein disulfide bonds.

Amino Acids↗
PubMed1981

Insulin-ricin B chain conjugate. A hybrid molecule with ricin-binding activity and insulin biological activity.

The polypeptide hormone insulin and the binding portion of ricin toxin, the B chain, were linked via a disulfide bond. This insulin-ricin B chain conjugate bound to insulin receptors with a potency one-twentieth that of native insulin. Rat HTC hepatoma cells, a cultured cell line that has relatively few insulin receptors, bound the conjugate to a much greater degree than insulin. Binding occurred predominantly via the ricin B chain portion of the conjugate since binding was not inhibited by insulin but was inhibited by galactose, a known inhibitor of the interaction of ricin B chain to its receptor. In HTC cells, the insulin-ricin B chain conjugate at 330 nM stimulated amino acid uptake to 225% of controls, a value higher than that for insulin which stimulated uptake to only 167% of controls. The conjugate also stimulated tyrosine aminotransferase activity in HTC cells with a potency value approximately one-half that of insulin. Both of these activities of the insulin-ricin B chain conjugate in HTC cells were inhibited by 100 mM galactose (90% and 80%, respectively), whereas the ability of insulin to stimulate these activities was not inhibited significantly by this sugar. The results suggest, therefore, that one can construct hybrid molecules consisting of binding proteins and polypeptide hormones and that these hybrid molecules can have binding and biological activities which are different from the parent hormone molecule.

Animals↗
PubMed1981

Identification of a lymphocyte enzyme that catalyzes pentamer immunoglobulin M assembly.

A protein with immunoglobulin M-polymerizing activity was isolated from the membrane fraction of mouse plasmacytoma cells secreting pentamer IgM. The isolation was achieved by taking advantage of the solubility of the protein in 50% ammonium sulfate, its relatively high net negative charge, and its sedimentation at 4.2 S. Analyses of the purified preparations showed that the polymerizing protein catalyzes the assembly of pentamer IgM in vitro; less than 1 mol of enzyme/10 mol of monomer IgM and 2 ml of J chain were found to promote 50% polymerization. Evidence that the enzyme also plays an essential role in the in vivo assembly process was obtained from the reaction rates of the polymerization catalyzed in vitro, the similarity between the pentamer IgM molecules synthesized in vitro and in vivo, and the finding that polymerizing enzyme is a specific product of B lymphocytes. Analyses of the mechanism of polymerization suggested that polymerizing enzyme is a sulfhydryl oxidase; it was found to be inactivated by chelating agents and to resemble Cu2+ in catalyzing the formation of IgM intersubunit disulfide bonds. These results raise the possibility that the assembly of pentamer IgM does not involve disulfide interchange is previously thought, but proceeds by the direct oxidation of monomer IgM and J chain sulfhydryls.

Animals↗
PubMed1980

Crohn disease of penile and scrotal skin.

Genital cutaneous involvement with Crohn disease is an uncommon complication which has been described only recently. A case is presented of a young man with Crohn disease involving the penile and scrotal skin four years after total colectomy for Crohn disease. The histopathology and management are discussed. While the complications of Crohn disease vary in the literature, we believe involvement of the skin of the genitalia is uncommon.

Adult↗
PubMed1980

Varicosities of renal venous system.

A forty-four-year-old woman was evaluated for filling defects in the renal pelvis by intravenous pyelography and was found to have varicosities of the renal vein by renal vein angiography.

Adult↗