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Biomedical subjects

H Nishimura

Publications and source records attributed to H Nishimura.

At least 199 records · Page 11Linked to original sources

Angiotensin II-induced relaxation of fowl aorta.

Angiotensin II (ANG II) decreases blood pressure of fowl. To characterize the vasodilating action of ANG II and its underlying mechanisms, we examined the effect of [Asp1, Val5]ANG II (fowl ANG II) on isometric tension of fowl aortic rings. [Val5]ANG II (10(-8) to 10(-5) M) produced rapid, reversible, dose-dependent relaxation of aortas precontracted with phenylephrine. [Sar1,Ile8]ANG II blocked ANG II-induced relaxation; propranolol, atropine, methysergid, pyrilamine, and cimetidine did not. Endothelium removal abolished relaxation responses to ANG II and acetylcholine but not to isoproterenol or sodium nitroprusside. Inhibitors of phospholipase or arachidonic acid metabolism (quinacrine, indomethacin, 5,8,11,14-eicosatetraenoic acid, hydroquinone, metyrapone, SKF 525A) and a calcium channel blocker (verapamil) did not inhibit ANG II-induced relaxation, whereas indomethacin nearly completely blocked arachidonic acid-induced dilation of aortas with or without endothelia. Guanosine 3',5'-cyclic monophosphate (cGMP) levels in the aorta increased 15 s after ANG II application. Aortic relaxation was caused by 8-bromo-cGMP with or without intact endothelium. These results suggest that ANG II-induced relaxation of fowl aortas involves 1) an endothelium-dependent mechanism and 2) cGMP but not arachidonic acid metabolites.

5,8,11,14-Eicosatetraynoic Acid

Genetic polymorphisms of orosomucoid and alpha-2-HS-glycoprotein in a Philippine population.

A Philippine population was investigated for genetic polymorphism of orosomucoid 1 (ORM1), orosomucoid 2 (ORM2), and alpha-2-HS-glycoprotein (A2HS) by isoelectric focusing. The allele frequencies were: ORM1*1 = 0.7904, ORM1*2 = 0.1687, ORM1*2.1 = 0.0409, ORM2*1 = 1.0000; A2HS*1 = 0.6870, A2HS*2 = 0.3130. Compared with the Japanese population, the Philippine population has higher frequencies of ORM1*1 and A2HS*2, and lower frequencies of ORM1*2.1 and A2HS*1.

Alleles

Reliability of percutaneous test for facial nerve function. Comparison between indirect and direct stimulation method.

To evaluate the reliability of conventional tests for facial nerve denervation, comparisons of the thresholds and relationship with prognosis were made between the conventional percutaneous and direct stimulation methods in 11 cases of facial palsy decompressed and followed up for more than 6 months. Although all cases showed complete or severe nerve degeneration in the preoperative percutaneous stimulation test, the threshold for the direct intraoperative stimulation test varied from 4 V (normal) to more than 30 V. The results of the direct intraoperative stimulation test correlated well with prognosis (degree of improvement of palsy score). Our results indicate that the direct stimulation method is better than the percutaneous stimulation method as an electrodiagnostic test for nerve degeneration.

Adolescent

Defective processing of insulin-receptor precursor in cultured lymphocytes from a patient with extreme insulin resistance.

We have studied a patient with extreme insulin resistance, acanthosis nigricans, and decreased erythrocyte insulin binding. EBV-transformed lymphocytes from this patient exhibited markedly reduced binding of 125I-insulin. Radioiodination of cell surface receptors followed by immunoprecipitation with anti-receptor antibodies revealed the presence of increased amounts of a 210-kD protein but no detectable alpha or beta subunits. Continuous labeling with 2-[3H]mannose revealed the synthesis of a 190-kD precursor and a 210-kD protein. The 210-kD protein was phosphorylated in an insulin-dependent manner at high insulin concentrations. These results suggest that in this patient the biosynthesis of 190-kD receptor precursor, its terminal glycosylation, and intracellular transport to the cell surface proceed normally, while proteolytic maturation to alpha and beta subunits does not occur. We postulate that this defect either results from mutation(s) within the insulin-receptor gene, which render the precursor resistant to cleavage, or from a defect in the receptor processing enzyme.

Acanthosis Nigricans

Insulin resistance in a boy with congenital generalized lipodystrophy.

We have studied insulin resistance in a 12-year-old Japanese boy who presented with congenital generalized lipodystrophy. Oral glucose tolerance test exhibited a diabetic pattern with normal fasting plasma glucose. Results from euglycemic glucose clamp study showed decreases in both insulin sensitivity and responsiveness. Both the patient's erythrocytes and Epstein-Barr virus transformed lymphocytes showed low-normal insulin binding with a slight reduction in binding affinity in the latter. Insulin binding to the cultured fibroblasts was decreased due to a lowered affinity. In addition, they displayed a rightward shift of the insulin dose-response curve for D-14C-glucose uptake with no decrease in the maximum uptake. Insulin-stimulated autophosphorylation and kinase activity of the wheat germ agglutinin purified receptors from the Epstein-Barr virus-transformed lymphocytes appeared normal. The reason for some discrepancies in insulin binding among the cells remains unknown, and we cannot formulate a conclusion as to whether or not a primary binding defect of insulin receptors exists and contributes to insulin resistance in the patient. The decrease in insulin responsiveness demonstrated in the glucose clamp study may result from a defect at the rate-limiting step in the postbinding process of insulin action, presumably a defect in the glucose transport system in muscle tissues. The defect may be secondary to changes in in vivo circumstances.

Cell Line, Transformed

Purification of the multifunctional calmodulin-dependent protein kinases from lung and liver, and the comparison to the brain enzyme.

We purified the multifunctional calmodulin-dependent protein kinases (calmodulin-kinase) from rat lung and rabbit liver, and compared the properties of this enzyme with those of the rat brain enzyme. The lung and liver enzymes had molecular weights (Mr's) of 530,000 and 330,000 with main subunits of 52 and 51 kDa, respectively. Although the lung and liver enzymes cross-reacted with antibodies to the brain enzyme, the immunoreactivity of the lung enzyme was weaker. The substrate specificity of the three enzymes showed differences in the relative reaction rate of phosphorylation. The patterns of phosphopeptides of the lung and liver enzymes were similar to each other and only partly common to that of the 60-kDa subunit of the brain enzyme.

Animals

Regulation of glucose-transporter gene expression by insulin in cultured human fibroblasts.

To clarify the effect of insulin on glucose-transporter (GT) biosynthesis, we determined GT mRNA levels in human cultured skin fibroblasts, using HepG2 GT cDNA as a probe. Insulin specifically increased the GT mRNA level in a time- and dose-dependent manner. Time-course study demonstrated that the mRNA level peaked within 3 h of insulin (1 x 10(-7) M) addition. After remaining elevated for several hours, mRNA decreased and returned to the basal level after 24 h. In the cell strains from seven normal subjects, the mean (+/- SE) GT mRNA level determined after 3 h of treatment with 1 x 10(-7) M insulin was 164.3 +/- 8.5% of the level found in untreated control cells. The insulin dose-response curve of GT mRNA levels showed that the maximum stimulation was elicited at 1 x 10(-7) M, and the half-maximum stimulation occurred at approximately 5 x 10(-10) M. Degradation rates of GT mRNA determined in the presence of actinomycin D were not different between insulin-treated and untreated cells. These results suggest that insulin increases GT gene expression in cultured human fibroblasts.

Cells, Cultured

Occurrence of sequelae in Bell's palsy.

The occurrence of sequelae in 330 patients with Bell's palsy followed up for more than 6 months was investigated. At least one of five kinds of sequelae (synkinesis, crocodile tears syndrome, spasm, contracture, tinnitus and/or hearing loss during facial movement) was observed in 30 of the 330 cases (9.1%). Sequelae occurred at 23.9-39.0 weeks (mean) after onset of palsy and at scores of 30-34 points (mean; full score 40 points). The incidence of sequelae was correlated to the degree of facial nerve dysfunction.

Facial Muscles

Adult T-cell leukemia/lymphoma in pregnancy.

Adult T-cell leukemia/lymphoma, a lymphocytic leukemia caused by human T-cell lymphoma virus-I (HTLV-I), is prevalent in southwestern Japan. A Japanese woman with adult T-cell leukemia/lymphoma in the third trimester of pregnancy was delivered of an infant by cesarean section. She did not breast-feed the child, who has remained free from HTLV-I infection.

Adult

[Phase II study of carboplatin in ovarian cancer].

A phase II study of carboplatin was conducted in ovarian cancer by a cooperative study group consisting of 22 institutions nationwide. The overall response rate of 50 evaluable cases was 38.0%. The response rate in cases with no prior chemotherapy was 54.2% and that with prior chemotherapy was 23.1%. In addition, the response rate was 26.3% in cases that received prior CDDP-based chemotherapy. Histologically, the response rate was high in serous cystadenocarcinoma and endometrioid adenocarcinoma. Hematologic toxicities, particularly leukopenia and thrombocytopenia, were frequently observed, but well tolerated, while renal and neurologic toxicities were rare. These results suggested that carboplatin is useful in the treatment of ovarian cancer.

Adenocarcinoma

[Phase III study of carboplatin in ovarian cancer].

A phase III study of carboplatin vs cisplatin in CAP regimen for ovarian cancer was conducted by a cooperative study group consisting of 22 institutions nationwide. The response rate for 23 cases allocated to carboplatin regimen group was 34.8% and 42.1% for 19 cases allocated to cisplatin regimen group. No significant difference was observed between these two regimens in response rates, and no significant differences were noted between the two regimens in each of the clinical toxicities and abnormalities in laboratory findings. Since the carboplatin regimen group did not require hydration, or the use diuretics or antiemetics, these results suggested that carboplatin is more useful in the treatment of ovarian cancer than cisplatin.

Adult

Antitumor activity of cisplatin analogs against malignant ovarian tumor xenografts into nude mice.

The antitumor activity of new platinum analogs was studied at equitoxic doses to that of cisplatin (CDDP) in BALB/C nu-nu nude mice bearing xenografts of human ovarian malignant tumors. The following two tumor lines were used: OH-1 (serous cystadenocarcinoma) and MP-1 (mucinous cystadenoma, LPM). 1) Antitumor activity was determined for all agents from the T/C ratio for OH-1. In particular, 254-S and JM-8 were found to be much more active than the other agents. 2) Antitumor activity was determined with JM-8 from the abdominal diameter ratio for MP-1. Both JM-8 and CDDP yielded active responses which were evaluated by the CEA value. Therefore, JM-8 and CDDP were considered to be the most active agents for MP-1. 3) We evaluated the mean body weight loss of tumor bearing mice in order to study the side effects, and a great weight loss was observed with 254-S. 4) A large variety of effects were observed in the histological evaluation for the two tumor lines, and were thus difficult to discuss. Our findings suggest the necessity of individual chemotherapy for each histological type of ovarian malignant tumor.

Animals

Gastroduodenal complications in patients with adult T-cell leukemia.

Gastroduodenal endoscopic examinations were performed on 15 patients with adult T-cell leukemia (ATL). Twelve had the disease in acute form, two in chronic form and one patient was in crisis. Eight patients had gastroduodenal lesions, four esophageal candidiasis, three gastric infiltration and two duodenal ATL-cell infiltration. Four out of the five patients who had the gastroduodenal ATL-cell infiltration complained of gastroduodenal symptoms such as anorexia, upper abdominal pain, diarrhea and melena. Our observations suggested that these gastroduodenal symptoms were related to the gastroduodenal ATL-cell infiltration. Esophageal candidiasis in ATL could be related to immunodeficiency.

Adult

Association of HLA-DR2/DR4 heterozygosity with systemic lupus erythematosus in Japanese patients.

The frequency of HLA-DR2/DR4 heterozygotes was significantly higher in 85 Japanese patients with systemic lupus erythematosus (SLE), compared with healthy controls. There was no difference in frequency of the heterozygotes of HLA-DR2/non-DR4. The association with HLA-DR2/DR4 heterozygosity was highly significant in patients with SLE in whom the onset occurred under age 30 and there was no significant association in patients with SLE in whom the onset occurred at age over 30 years. The possible role of HLA-DR2/DR4 heterozygosity in the development of SLE is discussed.

Adult

[Indications for thoracotomy in pulmonary metastatic sarcoma and its prognosis].

Between 1960 and 1987, 46 patients underwent thoracotomy for pulmonary metastatic sarcoma. The histologic classification of the sarcoma was osteosarcoma in 33 patients, other malignant bone tumors in 6 and soft tissue sarcoma in 7. The cumulative five-year survival rate of the 33 patients with osteosarcoma was 23%. Ten patients survived more than 3 years and 8 of them are still alive without pulmonary metastasis. Prognosis was significantly better with intensive multidrug chemotherapy. In this series, prognosis was not significantly related to the interval from initial onset to initial treatment, that from initial treatment to pulmonary metastasis and that from pulmonary metastasis to initial thoracotomy. The five-year survival rate of the 6 patients with other malignant bone tumors was 35%, and that of the 7 patients with soft tissue sarcoma 26%. Good indications for thoracotomy in pulmonary metastatic osteosarcoma are: (1) the primary sarcoma is resected, (2) the interval from initial treatment to pulmonary metastases is more than 6 months, (3) the number of pulmonary metastases is less than 4 or 5 nodules, and (4) the number and diameter of pulmonary metastases is controlled with chemotherapy within 2 or 3 months after occurrence of metastasis.

Adolescent

Hydrolysis of phosphatidate by human placental alkaline phosphatase.

Highly purified alkaline phosphatase of human placenta catalyzed the hydrolysis of phosphatidate with quantitative formation of almost stoichiometric amounts of diglyceride and inorganic phosphate. In the presence of sodium deoxycholate, the activity was maximal at pH 8.8. The activity was strongly inhibited by L-phenylalanine but scarcely affected by NaF. These results show that alkaline phosphatase hydrolyzes phosphatidate under different conditions from those for activity of phosphatidate phosphohydrolase.

Alkaline Phosphatase