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Biomedical subjects

M Nishikawa

Publications and source records attributed to M Nishikawa.

At least 649 records · Page 36Linked to original sources
PubMed1987

The role of atrial pressure in secreting atrial natriuretic polypeptides.

The role of atrial pressure and catecholamines in secreting human atrial natriuretic polypeptides (hANP) were investigated in patients with acute or old myocardial infarction (AMI or OMI). No differences were observed in hANP levels obtained from brachial vein, right atrium, pulmonary artery and femoral artery, suggesting that hANP degradation in the pulmonary circulation has little clinical significance in hANP measurement. Plasma hANP levels in 10 patients with AMI were higher than those in controls and significantly correlated to both mean right atrial pressure (mRA) and pulmonary wedge pressure (PCW) (r = 0.76, p less than 0.05; r = 0.95; p less than 0.01, respectively). In 12 patients with OMI, plasma hANP levels were normal at rest and were significantly increased (p less than 0.01) with bicycle ergometer exercise associated with significant elevations of plasma catecholamine levels, mRA, and PCW. However, the increments of hANP correlated only to those of PCW. These results suggest that the elevation of atrial (principally left atrial) pressure rather than catecholamine stimulates hANP secretion.

Aged↗
PubMed1987

Selective reduction of hepatic cytochrome P450 content in patients with intrahepatic cholestasis. A mechanism for impairment of microsomal drug oxidation.

Alteration of the components of the mixed-function oxidase system, including cytochrome P450, cytochrome b5, cytochrome P450 reductase, and cytochrome b5 reductase, was examined in liver microsomes prepared from needle biopsy samples of 12 patients with intrahepatic cholestasis. The rate of p-nitroanisole O-demethylation in the microsomes was also measured as the activity of cytochrome P450-dependent drug oxidation. The cytochrome P450 content (0.29 +/- 0.05 nmol/mg microsomal protein) in the patients was significantly lower than that in the 11 control subjects (0.41 +/- 0.09). The rate of p-nitroanisole O-demethylation was also significantly lower in the patients. However, the cytochrome b5 content and the activities of the reduced forms of nicotinamide adenine dinucleotide phosphate- and nicotinamide adenine dinucleotide-cytochrome c reductases did not differ between the two groups. Thus, selective reduction of cytochrome P450 seems to play a major role in the impairment of microsomal drug oxidation during intrahepatic cholestasis. Moreover, the reduction of cytochrome P450 was correlated with the serum concentrations of total bilirubin and bile acid but not with the serum glutamic oxaloacetic transaminase value. These observations suggest that the reduction of cytochrome P450 might be related to the severity of cholestasis.

Adult↗
PubMed1987

Studies on WF-3681, a novel aldose reductase inhibitor. I. Taxonomy, fermentation, isolation and characterization.

WF-3681 was isolated from a cultured filtrate of Chaetomella raphigera as a novel inhibitor of aldose reductase. It was extracted with ethyl acetate and then purified with silica gel chromatography. Its molecular formula was determined to be C13H12O5 by elemental analysis and high resolution electron impact mass spectrometry. IC50 of WF-3681 was 2.5 X 10(-7) M for partially purified aldose reductase of rabbit lens.

Aldehyde Reductase↗
PubMed1987

WF-10129, a novel angiotensin converting enzyme inhibitor produced by a fungus, Doratomyces putredinis.

WF-10129 is an angiotensin converting enzyme (ACE) inhibitor produced by Doratomyces putredinis. IC50 of the compound is 1.4 X 10(-8) M for the ACE activity. WF-10129 was purified from cultured filtrate by successive ion exchange chromatography and HPLC. The chemical structure 1 was elucidated on the basis of spectroscopic and chemical evidence. The compound is a dipeptide composed of L-tyrosine and a novel amino acid. WF-10129 inhibits the pressor response of angiotensin I when administered intravenously at 0.3 mg/kg in rats.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1987

[A case of hepatocellular carcinoma with extrahepatic portal vein obstruction due to tumor invasion, responsive to oral administration of UFT].

A 38-year-old male was admitted to Ikeda Municipal Hospital because of thrombocytopenic purpura and abnormal liver function. Computed tomography and ultrasonography of the liver showed a 5 by 5 cm mass in the right lobe of the liver. Hepatic angiography revealed a hypervascular tumor in the right lobe of the liver and extrahepatic portal venous obstruction. A diagnosis of hepatocellular carcinoma with extrahepatic portal venous obstruction due to tumor invasion was made. Endoscopic examination showed marked esophageal varices with red color sign. Oral administration of UFT at a daily dose of 400 mg was started. Though ascites and frequent hemorrhage from esophageal varices were observed, these symptoms disappeared completely after 8 months administration of UFT. Endoscopic examination revealed disappearance of the esophageal varices, and recanalization of the extrahepatic portal vein was confirmed by the second hepatic angiography. Computed tomography showed no growth of the liver tumor. These data suggest that UFT was effective in this case.

Administration, Oral↗
PubMed1987

[Clinical trial of SM-108 in myeloproliferative disorders].

SM-108 (4-carbamoylimidazolium-5-olate) is a new purine antagonist which blocks IMP dehydrogenase, the key enzyme of de novo GMP biosynthesis. Eleven patients were entered into a clinical study of SM-108 for the treatment of myeloproliferative disorders. These included 10 cases of chronic myelogenous leukemia (CML) and one case of essential thrombocythemia (ET). Two cases of CML had received prior chemotherapy. SM-108 was given orally at a dose of 400-600mg/m2 daily. Of nine evaluable cases, four cases of CML achieved complete responses and two cases of CML achieved partial responses (response rate = 66.7%). The duration of drug action was short, and the daily dosage required adjustment at frequent intervals. Long-term response without therapy has not been seen with SM-108 in CML. There was no response in the case of ET. The side effects included constipation (1/11), diarrhea (1/11) and mild hepatic toxicity (1/11). No cardiac or renal toxicity was observed.

Adult↗
PubMed1987

Morphological study of lipoprotein particles in the livers of ventromedial hypothalamus lesioned rats.

Ultrastructure of the liver in ventromedial hypothalamus (VMH) lesioned rats was studied in parallel with biochemical examination. Ten weeks after the operation, VMH lesioned rats became markedly obese. Electron microscopic examination of the liver revealed lipid droplets in the cytoplasm and a high load of lipoprotein particles in the Golgi elements. Lipoprotein particles, 40-50 nm in diameter, in the Golgi elements, were scattered throughout the cytoplasm. Concentrations of triglyceride and esterified cholesterol markedly increased in the liver, while those of free cholesterol and phospholipids did not increase. Serum concentrations of triglyceride, total cholesterol and HDL-cholesterol in VMH lesioned rats were higher than control ones. These data suggest that lipoprotein synthesis was markedly increased in the livers of VMH lesioned rats.

Animals↗
PubMed1987

Effect on IgE production of transplanted cultured thymic fragments.

The effect of cultured thymic fragment (CTF) transplantation on the IgE response of nude mice was studied. Nude mice (BALB/c nu/nu) were immunized with a mixture of tetanus toxoid and aluminium gel intraperitoneally. Non-CTF transplanted nude mice could not regulate IgE production nor synthesize specific IgE antibody, and all died at 16 weeks of age. Nude mice that were transplanted with CTF from allogeneic low responder strains (C57BL/6, SJL), allogeneic high responder strain (ASW) and syngeneic high responder strain (BALB/c) could regulate IgE production, and these lived a normal life span. Additionally, the tetanus toxoid-specific IgE antibody response, which was estimated by PCA, paralleled that seen in the strain of the thymus donor, i.e. BALB/c and ASW thymus reconstitution produced the highest response, whereas SJL and C57BL/6 recipients' levels were significantly less (P less than 0.05). We postulate that the lesser responses were due to the determination of the phenotype response by the thymic microenvironment. The low responses were shown to be due to regulator T-cell imbalance. These data show that BALB/c T-cell precursors developing in non-BALB/c thymuses interact with BALB/c B cells to produce levels of IgE antibody that are more characteristic of the non-BALB/c differentiating microenvironment than of their own genetic background.

Aluminum Hydroxide↗
PubMed1986

1-(5-Isoquinolinesulfonyl)-2-methylpiperazine(H-7), a potent inhibitor of protein kinases, inhibits the differentiation of HL-60 cells induced by phorbol diester.

Treatment of the human promyelocytic leukemia cell line HL-60, with 12-o-tetradecanoylphorbol acetate (TPA) results in the differentiation into macrophage-like cell. A potent inhibitor of protein kinase C, 1-(5-isoquinolinesulfonyl)-2-methylpiperazine(H-7), suppressed the proliferation of HL-60 cells and also inhibited TPA-induced cell differentiation of these cells. N-(2-guanidinoethyl)-5-isoquinolinesulfonamide(HA-1004), a weaker analog of H-7, failed to inhibit this TPA-induced cell differentiation. H-7 also inhibited TPA-induced protein phosphorylation in these cells. Thus, protein kinase C-mediated phosphorylation may be involved in the process of TPA-induced HL-60 cell differentiation.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1986

Platelet activating factor (PAF) involvement in endotoxin-induced thrombocytopenia in rabbits: studies with FR-900452, a specific inhibitor of PAF.

PAF (1 ug/kg) injected intravenously (i.v.) into anesthetized rabbits resulted in marked loss of circulating platelets and leukocytes. Administration of FR-900452 1-methyl-3-(1-(5-methylthiomethyl-6-oxo-3-(2-oxo-3-cyclopenten-1-y lidene)- 2-piperazinyl) ethyl)-2-indolinone, a specific PAF inhibitor, at a dose of 10 mg/kg i.v. with 10 min prior to the PAF injection significantly prevented both changes. On the other hand, PAF has been considered as a mediator of endotoxin shock. Therefore, in order to determine whether endogenous PAF contributes to the occurrence of thrombocytopenia or leukopenia in endotoxin shock, we assessed the effect of FR-900452 on the thrombocytopenia and the leukopenia following bolus i.v. injection of E.coli endotoxin (0.03 mg/kg) in rabbits. As a result, pretreatment with the compound (10 mg/kg, i.v.) significantly reduced the thrombocytopenia at 60 and 180 min after the endotoxin injection. In contrast, FR-900452 did not reduced the leukopenia at any time of after endotoxin. These results indicate that PAF might be involved in the occurrence of thrombocytopenia in rabbit endotoxemia and the contribution of PAF to the leukopenia is much less extent than that to the thrombocytopenia.

Animals↗
PubMed1986

Effect of pretreatment with cadmium/cysteine or metallothionein on accumulation of cadmium challenged with either complexes.

The effect of pretreatment with cadmium (Cd) complexes on the distribution and accumulation of Cd in the liver and kidneys was examined for the Cd complexes that are reabsorbed site-selectively at the renal proximal tubules of rats. Cd was administered simultaneously with excess cysteine or as metallothionein (MT) and then challenged by either complex, the former complex being reabsorbed preferentially at the S3 segment of proximal tubules of the outer stripe of the outer medullary zone, while the latter complex was reabsorbed at the S1 + S2 segments of proximal tubules. Cd in the kidneys was increased by pretreatment with either complex. On the other hand, pretreatment reduced the distribution of Cd to the liver. However, no site-selective effects were observed with either complexes. Calcium concentration, which was elevated significantly in the kidneys by a single injection of both complexes, was reduced by pretreatment.

Animals↗
PubMed1986

Nystagmus during attack in Menière's disease.

Nystagmus in Ménière's disease before the vertiginous attack to its end was recorded using a newly devised long recording portable electronystagmograph. The nystagmus to the affected side was recorded before the patient complained of vertigo, while the non-affected side was recorded at the onset of the attack. And the nystagmus to the affected side was recorded in the middle and at the end of the attack.

Dominance, Cerebral↗