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Biomedical subjects

K Horinouchi

Publications and source records attributed to K Horinouchi.

15 recordsLinked to original sources
PubMed2000

beta(2)-adrenoceptors activate nitric oxide synthase in human platelets.

Nitric oxide (NO), generated by platelets through stimulation of nitric oxide synthase (NOS), limits platelet adhesion and aggregation after a prothrombotic stimulus. Platelet beta-adrenoceptors (betaARs) mediate inhibition of aggregation, but no direct link has been shown between these receptors and platelet adhesion or NO production. We examined NOS activity in human platelets from the conversion of L-[(3)H]-arginine to L-[(3)H]-citrulline, after betaAR stimulation or cAMP elevation. Basal NOS activity was 0.11+/-0.03 pmol L-citrulline/10(8) platelets. The betaAR agonist isoproterenol 1 micromol/L and the adenylyl cyclase activator forskolin 1 micromol/L each increased NOS activity, to 0.26+/-0.04 and 0.23+/-0.03 pmol L-citrulline/10(8) platelets, respectively (P<0.01 for each). Both responses were abolished by the adenylyl cyclase inhibitor SQ22536 50 micromol/L. NOS activation by isoproterenol or forskolin was not associated with a change in intracellular Ca(2+). In functional studies, isoproterenol inhibited U46619-induced platelet aggregation in a concentration-dependent manner, but this effect was not significantly diminished by NOS inhibition. In contrast, thrombin-stimulated platelet adhesion to cultured human umbilical vein endothelial cell monolayers was inhibited by isoproterenol, and this effect was abolished by NOS inhibition (1.3+/-0.2% versus 2.6+/-0.2% respectively; P<0.001). Effects of isoproterenol on NOS activity, platelet aggregation, and adhesion were mediated exclusively through beta(2)ARs, as determined by coincubation with betaAR subtype-selective antagonists. We conclude that beta(2)ARs activate platelet NOS by increasing cAMP, and that this activation is Ca(2+)-independent. beta(2)ARs may contribute to modulation of platelet aggregation and adhesion to endothelium, and our findings suggest that activation of the L-arginine/NO system mediates the effects of beta(2)ARs on adhesion but not aggregation.

Blood Platelets↗
PubMed2000

Reduction of peritonitis with the rectus abdominis muscle flap in a CAPD patient.

An adolescent maintained on continuous ambulatory peritoneal dialysis (CAPD) for 8 years had relapsing peritonitis involving peritoneal catheter tunnel infections. We attempted catheter removal and replacement simultaneously, with the catheter covered cylindrically by a rectus abdominis muscle flap to prevent recurrent tunnel infections. During 3 years of follow-up, there have been no episodes of peritonitis involving tunnel infection. Our modified insertion technique can eradicate tunnel infection, thus reducing peritonitis.

Adolescent↗
PubMed1997

Heterogeneity of liver disorder in type B Niemann-Pick disease.

Patients with type B Niemann-Pick disease (NPD) are known to be complicated with varying degrees of prognosis-determining liver dysfunction. To see heterogeneity of the dysfunction histologically, we performed liver biopsies on three NPD patients from three different families, who were diagnosed by enzyme assay of acid sphingomyelinase (ASM) and analysis of the ASM gene. In a severe case, of a female patient in her childhood, the liver showed definite fibrosis despite her age. In contrast, in a very mild case, of an adult male patient, the liver showed little fibrosis, though the ballooning of hepatocytes and infiltration of foamy histiocytes were observed in the tissue. Three homo-allelic mutations (S436R, A599T, and S231P) were identified in the patients. Thus, various hepatic phenotypes in type B NPD were shown to be caused by the heterogeneity of liver lesions originating from different ASM gene mutations.

Adult↗
PubMed1995

Acid sphingomyelinase deficient mice: a model of types A and B Niemann-Pick disease.

Types A and B Niemann-Pick disease (NPD) result from the deficient activity of acid sphingomyelinase (ASM). An animal model of NPD has been created by gene targeting. In affected animals, the disease followed a severe, neurodegenerative course and death occurred by eight months of age. Analysis of these animals showed their tissues had no detectable ASM activity, the blood cholesterol levels and sphingomyelin in the liver and brain were elevated, and atrophy of the cerebellum and marked deficiency of Purkinje cells was evident. Microscopic analysis revealed 'NPD cells' in reticuloendothelial organs and characteristic NPD lesions in the brain. Thus, the ASM deficient mice should be of great value for studying the pathogenesis and treatment of NPD, and for investigations into the role of ASM in signal transduction and apoptosis.

Animals↗
PubMed1991

An Epstein-Barr virus-producer line Akata: establishment of the cell line and analysis of viral DNA.

An Epstein-Barr virus (EBV)-producer line, designated Akata, was established from a Japanese patient with Burkitt's lymphoma. The Akata line possessed the Burkitt's-type chromosome translocation, t(8q- ; 14q+), and was derived from the tumor cell. Akata cells produced a large quantity of transforming virus upon treatment of cells with anti-immunoglobulin antibodies (Takada, 1984). Southern blot analysis of viral DNA indicated that the Akata EBV is nondefective and more representative of wild-type viruses. Akata cells should be useful as a source of EBV.

Antibodies, Viral↗
PubMed1980

An enzyme immunoassay for the measurement of anti-thyroglobulin autoantibody in human serum.

An enzyme-linked sandwich immunoassay using human thyroglobulin conjugated with beta-D-galactosidase and silicone rods coated with human thyroglobulin was developed for the measurement of circulating anti-thyroglobulin autoantibody. The volume of serum needed for the assay was as little as 5 microliter. The sensitivity of the assay was approximately 7 x 10(-15) mol/tube of antithyroglobulin immunoglobulin G corresponding to 220 ng/ml of serum, which was equal to or rather higher than that of radioimmunoassay. The specificity of the assay was demonstrated by (1) parallelism of the standard curve with dilution of sample sera of patients with thyroid diseases, and (2) non-detectability of anti-thyroglobulin in autoantibody in the sera of normal subjects. The precision of the assay was proven by (1) sufficient recovery of antithyroglobulin immunoglobulin G added to serum, and (2) coefficients of variance within and between assays were 6.5 to 10.3% and 4.9 to 14.1%, respectively. No effect of thyroglobulin on the present assay was observed when the ratio of the amount of thyroglobulin to that of anti-thyroglobulin immunoglobulin G was lower than 1 : 10. Furthermore, a significant correlation was observed between anti-thyroglobulin autoantibody concentrations measured by our enzyme immunoassay and those by tanned red cell hemagglutination (r = 0.78), and between those by the enzyme immunoassay and those by radioimmunoassay (r = 0.80). The application to clinical samples ensured the high sensitivity and the adequate validity of the present assay.

Autoantibodies↗