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Biomedical subjects

E Tsutsumi

Publications and source records attributed to E Tsutsumi.

12 recordsLinked to original sources

Roles of renal cytochrome P450-dependent arachidonic acid metabolites in hypertension.

Cytochrome P450 represents the third metabolic pathway of arachidonic acid giving rise to several biologically active compounds, such as 19-HETE, 20-HETE and EETs and their corresponding DHETs. The kidney is the rich source of these metabolites which have some important biologic actions within the kidney. These metabolites have a wide and contrasting spectrum of biological and renal effects, from vasodilation to vasoconstriction and from inhibition to stimulation of Na-K-ATPase, their relative production rates may influence not only renal hemodynamics but also pro- and anti-hypertensive mechanisms of hypertension. There is increasing evidence that the abnormality of these metabolites in animal models of hypertension. However, sufficient evidence of the physiological and pathophysiological roles of hypertension in man is still lacking.

Animals

Effect of furosemide on serum clearance and renal excretion of digoxin.

Serum turnover and urinary excretion of digoxin with or without oral furosemide were studied in six healthy subjects who received 0.006 mg/kg body weight digoxin intravenously. During furosemide treatment, the total amount of urinary digoxin did not change but the digoxin clearance during the diuretic phase and the digoxin excretion after the diuresis decreased significantly. The average serum half-life was prolonged from 37 hours in the control period to 86 hours in the furosemide period. Decreased glomerular filtration rate by volume depletion might have been responsible for the decreased excretion of digoxin, but there was no significant difference in urine volume after diuresis between the two periods, suggesting the possibility of inhibition of tubular secretion of digoxin by furosemide. It is also possible that serum digoxin concentration may be elevated if furosemide were given more frequently.

Adult

Reactive lymphocyte blastogenesis in canine renal transplantation.

Reactive lymphocyte blastogenesis was investigated by 3H-thymidine uptake of peripheral lymphocytes. Canine renal allotransplantations were performed in 19 dogs, which were divided into three groups by different immunosuppressive therapies. The first group, not treated with any immunosuppressants, showed the highest 3H-thymidine uptake, but the third group, treated with prednisolone (1.5 mg/kg/day) and azathioprine (4 mg/kg/day), did not show remarkable 3H-thymidine uptake except for 2 dogs which died of severe acute rejection. Single use of prednisolone (second group) was less effective in suppression of blastogenesis compared with the combined use of azathioprine and prednisolone. In addition to these experiments, the effects of surgical operation, blood transfusion, and infection on lymphocyte blastogenesis were investigated. Renal autotransplantation did not produce remarkable blastogenesis, but blood transfusion and infection caused strong lymphocyte blastogenesis. Periodical increases of 3H-thymidine uptake were observed in the infected animal.

Animals

Some properties of rabbit anti-human thymus serum.

A highly specific anti-human T lymphocyte serum (AHTS) was obtained by sequentially absorbing rabbit anti-human thymocyte serum (ATS) with human red cells, neutrophils, Burkitt's lymphoma cells (Daudi cells), liver, kidney and glutaraldehyde insolubilized human serum. The immunofluorescent staining revealed that the basement membrane of human renal glomeruli reacts with AHTS before being absorbed with kidney. Specificities of AHTS were studied by the cytotoxicity test, inhibition of PHA responses, inhibition of E-resulting and immunofluorescent staining.

Animals

Quantitative studies o the activities of anti-human tonsil sera and anti-human spleen sera against B lymphocyte.

Anti-human B lymphocyte serum (AHBS) was obtained by absorbing rabbit anti-human tonsil serum (ATOS) or rabbit anti-human spleen serum (ASPS) with human red cells, liver, neutrophils, thymocytes and glutaraldehyde insolubilized human serum. Specificities of AHBS were checked by the cytotoxicity test, inhibition test of EAC-rosetting and inhibition of PWM responses. Raji cells of Burkitt's lymphoma originating from B-cells and acknowledged as non-immunoglobulin bearing on the cell surface were stained with AHBS according to the immunofluorescent technique. ATOS showed a higher cytotoxic titer against peripheral B-cells and inhibited EAC-rosetting stronger than ASPS did. On the other hand, macrophages in peripheral blood, Kupffer cells in the liver and certain cells of the thymus-medulla were stained with ASPA, but not with ATOS, even after intensively absorbing ASPS with thymocytes.

Antilymphocyte Serum

Biliary elimination of diazepam in man.

The metabolism of 14C-5-diazepam has been studied in 5 patients with T tube biliary drainage. A single bolus of 40 to 50 muCi was given intravenously and blood, urine, and bile were analyzed from 5 to 14 days. The mean half-life of elimination from blood was 93.2 hr; the major metabolite noted in blood was N-desmethyl-diazepam. In urine the average recovery of radioactivity was 48.9% and consisted of 3 OH-diazepam, 4'OH-diazepam, and oxazepam. In bile the average recovery of radioactivity was 5.35% (corrected to a bile flow of 700 ml was 15.0%) and consisted of the same metabolites as in the urine. Essentially no diazepam or N-desmethyl-diazepam was found, and therefore an enterohepatic circulation cannot be held to account for the prolonged half-life of these substances in man.

Adult

The effect of oxisuran on differential inhibition of cell-mediated immunity.

Oxisuran, 2-[(methylsulfinyl) acetyl] pyridine suppressed allogeneic skin graft rejection in rats. In PHA responses and one way mixed lymphocyte culture, suppression of cell-mediated immunity was indicated. However, little inhibition of PFCs was observed with Oxisuran, and unlike Azathioprine or Neocarzinostatin, Oxisuran did not concomitantly suppress antibody-producing system in rats. These data suggest that selective suppression of cell-mediated immunological responses by Oxisuran is possible in rats, and Oxisuran may be a better immunosuppressant for clinical organ transplantation.

Animals