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Biomedical subjects

S Farkas

Publications and source records attributed to S Farkas.

At least 55 records · Page 3Linked to original sources
PubMed1988

Regulation of MHC expression in vivo. Bacterial lipopolysaccharide induces class I and II MHC products in mouse tissues by a T cell-independent, cyclosporine-sensitive mechanism.

The effect of injections of bacterial LPS on the expression of class I and II products of the MHC in mouse tissues was investigated. MHC products were assessed in tissue homogenates by radiolabeled antibody binding and in tissue sections by indirect immunoperoxidase (IIP) staining. In mice given two i.p. injections of LPS from Escherichia coli or Salmonella minnesota, there were increases in class I and II MHC products in kidney, liver, heart, lung, and pancreas. Focusing on the changes in kidney, we demonstrated that the increase in MHC expression occurred in tubules and, in the case of class I, in glomeruli. LPS treatment also increased the deposition of Ig in glomeruli. Expressed on a standard curve, the total kidney class I and II expression was elevated approximately 10-fold. Time course studies indicated that increased class I expression could be induced by a single LPS injection, whereas class II induction required a second injection. The induction was influenced by the LPS sensitivity of the mice, being much greater in LPS-sensitive C3H/HeSn mice than in LPS-resistant C3H/HeJ mice. LPS induced class I and II Ag in nude mice and in mice with severe combined immunodeficiency, indicating that T cells were not required. Nevertheless, the effect of LPS was inhibitable by cyclosporine and by a mAb against IFN-gamma indicating that IFN-gamma was required for the MHC induction. We conclude that LPS induces an increase in expression and a redistribution of MHC products in kidney and in other tissues by a T cell-independent, cyclosporine-sensitive pathway. These findings are probably related to the known ability of LPS to mediate release of IFN-gamma and other cytokines.

Animals↗
PubMed1988

Effects of cyclosporine on systemic MHC expression. Evidence that non-T cells produce interferon-gamma in vivo and are inhibitable by cyclosporine.

The ability of lipopolysaccharide to induce major histocompatibility complex hyperexpression in vivo in a variety of mouse tissues--particularly kidney--and the effect of cyclosporine on this process were studied. MHC expression was measured by a radiolabeled antibody-binding assay using tissue homogenates, as well as by assessment of tissue sections by indirect immunoperoxidase staining. LPS administered to mice in two doses, 4 days apart, induced an increase in class I expression in several tissues but also induced an increase in class II expression in kidney. A similar increase in class II expression in kidney was not elicited with polyinosinic acid/polycytidylic acid, an agent that induces release of IFN-alpha/beta and increases class I MHC product expression. Thus we reasoned that LPS in vivo may release IFN-gamma, which then induces increased expression of MHC products. We validated this hypothesis by demonstrating that monoclonal antibody against IFN-gamma inhibited the induction of renal MHC products by LPS. However, the LPS effects did not require the participation of T cells, being demonstrable in nude mice and in mice with severe combined immunodeficiency. Moreover, the effect of LPS on MHC expression in normal and nude mice was inhibited by in vivo administration of monoclonal antibody against IFN-gamma just as it was in normal mice. Thus the class II hyperexpression that follows LPS is apparently mediated by non T cells and is due to the systemic release of IFN-gamma. This mechanism was inhibited by high doses of CsA in vivo, both in normal and in nude mice. The results indicate that there is a non T cell pathway for IFN-gamma release (and MHC induction) in vivo that is sensitive to CsA. This observation raises the possibility that some of the immunosuppressive effects of CsA may be due to inhibition of mediator release from non T cells.

Animals↗
PubMed1987

Problems of uridine protection.

Various routes to synthesize 5'-O-dimethoxytrityl-O4-p-nitrophenylethyl- 2'-O-p-nitrophenylethylsulfonyluridine (7) as a useful intermediate in oligoribonucleotide synthesis have been investigated. The direct sulfonylation of 5'-dimethoxytrityl-O4-p-nitrophenylethyluridine (4) gave the best results despite the fact that 7 is formed in almost equal amounts with its 3'-NPES isomer (8) and the 2',3'-di-O-NPES derivative (6).

Indicators and Reagents↗
PubMed1985

Systemic immunologic stimuli increase class I and II antigen expression in mouse kidney.

The effect of systemic immunologic stimulation on renal expression of the H-2K (class I) and Ia (class II) antigens of the mouse major histocompatibility complex was explored. We previously reported that graft-vs-host (GvH) disease in mice caused an increase in host renal Ia expression. In the present experiments, we demonstrated that Kk antigen expression also increased during GvH. Other immune stimuli (allogeneic tumor grafts or injections of allogeneic spleen cells) caused increased renal Ia (and, where studied, Kk) expression in the epithelium of some renal tubules, as demonstrated by indirect immunofluorescence (IIF) or immunoperoxidase (IIP) staining. The normal interstitial Ia staining was frequently diminished in the kidneys of mice given these stimuli. At least in the case of allogeneic tumor grafts, the changes in renal Ia and H-2K were dependent on host T cells, in that no similar change appeared in nude (nu/nu) mice bearing allogeneic tumor grafts. By histochemical techniques, most of the change was in proximal tubules. In semiquantitative absorption, the total renal Ia was usually increased (two- to 20-fold) in parallel with the IIF or IIP changes. Serial studies revealed that MHC product induction was frequently transient and was not associated with detectable histologic abnormalities. In cultured renal cells, increased Iak and Kk could be demonstrated by IIF after 4 days of culture in supernatants of lymphocytes stimulated with concanavalin A: the activity in these supernatants was probably not interleukin 2, but might have been IFN-gamma, because IFN-gamma also induced this change. We conclude that systemic immunologic stimuli alter MHC product expression in renal tubule epithelium and that this effect can be stimulated in vitro by supernatants of stimulated lymphocytes.

Acid Phosphatase↗
PubMed1983

Radial keratotomy. Effect on cornea and aqueous humor physiology in the rabbit.

Radial keratotomy may cause anatomical damage to the rabbit corneal endothelium. To determine if physiological and functional alterations occur, radial keratotomy was performed on rabbit corneas using eight incisions with sparing of a 3.5-mm central pupillary area. Cornea endothelial membrane permeabilities were determined at various times up to ten weeks following the procedure using simultaneous flux determinations of tritiated inulin and dextran labeled with radioactive carbon on isolated corneas. At all times after radial keratotomy, there was no probable physiologically important change in corneal endothelial permeability to either of the labeled compounds. Fluorophotometry performed in a second group of animals at varying intervals following radial keratotomy showed no probable physiologically important change in endothelial fluorescein permeability. Aqueous humor turnover rate was reduced 16% and 29% at one week and nine to ten weeks, respectively, following radial keratotomy.

Animals↗
PubMed1983

Radial keratotomy and corneal permeability in Owl Monkey.

Radial keratotomy was performed on Owl Monkey corneas using 8 incisions with sparing of a 3.5mm central pupillary area. Cornea endothelial membrane permeabilities were determined at 2 days, and 4 weeks, following the procedure using simultaneous flux determinations of 3H-labeled inulin and 14C-labelled dextran. Inulin permeability was increased 27% two days following the procedure, and had returned to levels comparable to the unoperated eye 4 weeks following the procedure. Dextran permeability was unaltered at both 2 days, and 4 weeks, following the procedure. This study has shown that radial keratotomy causes a transient reduction in endothelial barrier function with the production of physiologically significant 'holes' in the membrane in the immediate post-operative period. The relationship of this physiological alteration to ultimate endothelial cell function is, at the present time, unknown.

Animals↗
PubMed1981

Risk associated with the spray application of polyurethane foam.

The use of polyurethane foam in thermal insulation is increasing rapidly. In most cases, the raw products consist of toluene di-isocyanate or diphenyl methane di-isocyanate and a polyol curing agent. We studied the isocyanate exposure of workers applying the foam in confined spaces. Frequent excursions above safe limits were found with levels up to and exceeding 0.08 ppm for personal sampling and 0.148 for area sampling. Since improper devices were worn, this represented a significant risk to health.

Air Pollutants↗
PubMed1980

Pancreatic tissue pH in experimental acidosis and alkalosis.

The pH was studied in pancreatic tissue and arterial blood in 22 dogs. Respiratory acidosis was induced by CO2 inhalations in 5 dogs, respiratory alkalosis by hyperventilation in 5 dogs, metabolic acidosis by intravenous(i.v.) infusion of 0.1 N HCl in 5 dogs, metabolic alkalosis by i.v. infusion of 4.2% Na bicarbonate in 5 dogs. The differences between the shifts of blood pH and tissue pH were not significant statistically. Infusion of Ringer's solution failed to affect the pH in blood and pancreatic tissue in two control animals. It is concluded, that with an adequate tissue blood flow the pancreatic tissue pH is uninformative unless the blood pH is known.

Acidosis↗
PubMed1980

New mechanism of plasmid curing by psychotropic drugs.

Methylene blue enhanced the plasmid curing efficiency of chlorpromazine, imipramine and amitriptyline with strains of Escherichia coli K12 carrying F-prime lac or the resistance factor R-144. In contrast, methylene blue inhibited the elimination of plasmids by acridine orange and ethydium bromide at all concentrations tested. Two metabolic derivatives of chlorpromazine, chlorpromazine sulphoxide and 7.8-dioxochlorpromazine had no plasmid curing effect even in the presence of methylene blue. Amitriptyline, 7,8-dioxochlorpromazine and acridine orange were effective inhibitors of the conjugal transfer of the resistance plasmid, R-144, whilst methylene blue, chlorpromazine sulphoxide, and imipramine had only slight effects. We were therefore unable to demonstrate a simple correlation between curing ability and inhibition of plasmid transfer amongst the psychoactive drugs tested. A mechanism of plasmid curing by surface action of the drugs is suggested as an alternative to direct intercalation of the drugs into plasmid DNA.

Acridine Orange↗
PubMed1979

Elimination of F'lac plasmid by different psychotropic drugs and some related compounds.

Desipramine, trimipramine, protriptyline, noxiptyline, promazine, trimeprazine, triflupromazine and chlorprothixene methoiodide eliminated the F'lac plasmid of Escherichia coli, while thiazinanum, toluidine blue, lidocaine and procaine were ineffective in this respect. The plasmid eliminating action of the drug ceased in the presence of 0.05 M magnesium sulphate. Methylene blue did not inhibit plasmid elimination by the psychotropic drugs, and in presence of the dye even lidocaine and procaine became effective. Based on plasmid elimination in the presence of methylene blue and on the selective effects of the lon- mutant, the plasmid eliminating mechanism of psychotropic drugs seems to differ from that of acridine orange.

Animals↗
PubMed1978

Electrometric measurement of canine pancreatic tissue pH under conditions of preserved circulation and of ischaemia.

Canine pancreatic pH was measured by an electrometric method, which is described in detail. 60 measurements carried out in neuroleptanalgesia of the animals gave a mean figure of 7.29 +/- 0.10 for pancreatic pH in situ. For arterial blood pH in the same animals the mean value was 7.22 +/- 0.08. The difference between pancreatic and arterial blood pH is significant. Anaesthesia of 3 hr duration produced no significant change either in pancreatic pH or in arterial blood pH or in the serum amylase and serum lipase levels. Vascular isolation of the pancreas and adjoining duodenal segment was produced in 13 animals. In 10 of these ischaemia induced by clamping of the arterial pathways for 1 hr resulted in a fall of pH by 0.65 +/- 0.21. Restoration of blood-flow at the end of the first hour was followed by a return of pH to the original values. The 3 control animals revealed no significant changes in the pH and enzyme values.

Amylases↗