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Biomedical subjects

H Ihara

Publications and source records attributed to H Ihara.

At least 91 records · Page 5Linked to original sources
PubMed1995

The cleavage and inactivation of plasminogen activator inhibitor type 1 by neutrophil elastase: the evaluation of its physiologic relevance in fibrinolysis.

The effect of the proteolytic cleavage of plasminogen activator inhibitor type 1 (PAI-1) by human neutrophil elastase (HNE) on fibrinolysis was investigated. HNE cleaved active PAI-1 and produced low molecular weight forms of inactive PAI-1, as previously reported. Latent PAI-1 was resistant to HNE treatment. Vitronectin (VN) partially protected the cleavage. NH2-terminal sequence analysis indicated that the cleavage site was Val355-Ser356 (P4-P3). The effects of PAI-1 cleavage by HNE on clot lysis was studied in a purified system. Clot lysis time without PAI-1 was 20.0 +/- 5.0 minutes and was prolonged to 86.7 +/- 2.9 minutes by 68 nmol/L of PAI-1. It was shortened when HNE (from 0.6 nmol/L to 80 nmol/L) was added and returned to the value obtained without PAI-1 by 80 nmol/L of HNE (20.0 +/- 5.8 minutes). However, in the absence of PAI-1, elastase did not enhance clot lysis at all. Euglobulin clot lysis time was also shortened after HNE treatment. The cleavage and inactivation of PAI-1 by HNE was shown to be a novel pathway to enhance fibrinolysis.

Amino Acid Sequence↗
PubMed1995

Delayed graft function does not influence long-term outcome in cadaver kidney transplants without mismatch for HLA-DRB1.

The currently study focused on the influence of delayed graft function on the long-term graft success rate in cadaver kidneys without any mismatches for HLA-DRB1. Donor-recipient HLA-DRB1 was determined by the significant two-locus linkages of HLA-B and -DRB1. The overall 5-year graft success rate was 88% in an HLA-DRB1-compatible group, significantly higher than the 69% in an HLA-DRB1 mismatch group (P < 0.05) and the 66% in an HLA-DR mismatch (P < 0.01). Delayed graft function was observed in 182 of 223 transplants. This high incidence of 82% is due to the fact that, in Japan, kidney procurement may only occur after cardiac arrest. The incidence did not differ in each group. The 5-year success rate for grafts with delayed function was 87% in the HLA-DRB1-compatible group, again significantly superior to the 68% in the HLA-DRB1 mismatch group and the 63% in the HLA-DR mismatch cases (P < 0.05). There was, thus, no difference in graft success rate for each group, with or without delayed graft function. Consequently, we feel that delayed graft function has no impact on the long-term outcome in transplants without mismatches for HLA-DRB1.

Adult↗
PubMed1995

Effects of nicotine and electric footshock on peripheral serotonergic measures and on platelet aggregation in whole blood of rats.

The effects of nicotine and electric foot shock as well as of their combination on blood serotonergic measures and on whole blood aggregation have been analyzed. In rats subjected to electric footshock a rise (p < 0.05) in plasma but not in whole blood serotonin was observed, whereas this parameter was not influenced in nicotine-treated rats when compared to the control group. The combination of nicotine with electric footshock only slightly increased plasma serotonin and showed no effect on whole blood serotonin, but 5-hydroxyindole acetic acid (5-HIAA), the major metabolite of serotonin (5-HT), as well as the 5-HIAA/5-HT ratio were markedly increased (p < 0.01) suggesting an enhanced turnover of 5-HT under these conditions. The collagen-induced aggregation in whole blood was not influenced in nicotine-, in footshock- nor in combined-treated rats when compared to the controls. Our data indicate that stress as well as the combination of stress with nicotine may affect the serotonergic system which is in contrast to the exposure to nicotine alone.

Animals↗
PubMed1995

Changes in the central and peripheral serotonergic system in rats exposed to water-immersion restrained stress and nicotine administration.

The effects of water-immersion restraint stress (WS) on chronically nicotine-administered rats were studied in the blood and various regions of the brain. Serotonin (5-HT) levels increased in the hypothalamus, hippocampus, cortex and cerebellum following the administration of nicotine. 5-HT levels increased in all the brain regions following stress. Nicotine decreased stress-induced increased levels of 5-HT in the hippocampus and cerebellum. Nicotine administration alone increased 5-hydroxyindole acetic acid (5-HIAA) levels in the hippocampus and cerebellum. Stress alone also increased 5-HIAA levels in all the brain regions. In the cortex, 5-HT and 5-HIAA levels further increased following the administration of a combination of stress and nicotine compared to rats given stress alone. In the blood as well as in all the brain regions, except the cerebellum, stress or nicotine administration did not affect tryptophan levels. Stress given to nicotine-administered rats resulted in a decrease in tryptophan levels in the blood and plasma. Although 5-HT and 5-HIAA levels were not influenced by stress and/or nicotine administration, the 5-HIAA/5-HT ratio increased in the blood and plasma of rats administered with nicotine and exposed to stress. The effects of nicotine on the serotonergic system depend upon the kind of stress given together with the organs and brain regions involved.

Analysis of Variance↗
PubMed1995

Intra- and interindividual variation in the pharmacokinetics of tacrolimus (FK506) in kidney transplant recipients--importance of trough level as a practical indicator.

BACKGROUND: Tacrolimus (FK506) is currently used as the primary immunosuppressant in clinical kidney transplantation in some centers. The purpose of this study was to evaluate the pharmacokinetics of this drug and to see if trough level, which has been used widely in therapeutic drug monitoring, can be used as an appropriate substitute for other pharmacokinetic measurement tests. METHODS: The blood concentration-time curve was studied in 10 kidney transplant recipients on 26 occasions after oral dosage of 2 to 18 mg every 12 hours. Whole blood concentration was measured by two-step immunoabsorption assay. Methylprednisolone was used as a concomitant immunosuppressive drug. RESULTS: The blood concentration-time curves showed remarkable interindividual variation. Intraindividual variation was also found, but the degree of variation was slight compared with interindividual variation. On 17 occasions of measurement in one patient, the dose was significantly correlated with trough (r = 0.684), Cmax (r = 0.838) and AUC0-12 (r = 0.817). In nine patients on nine occasions, however, the dose was not significantly correlated with trough (r = 0.351), Cmax (r = 0.270) or AUC0-12 (r = 0.355). tmax ranged from one to four hours (mean + SD; 2.8 + 1.3) and fluctuated in both intra- and interindividual measurements. In spite of a wide variation in the blood concentration-time-curve patterns, a highly significant linear relationship between trough and Cmax or AUC0-12 was observed in both intraindividual (Cmax, r = 0.876; AUC0-12, r = 0.926) and interindividual (Cmax, r = 0.943; AUC0-12, r = 0.984) measurements. CONCLUSIONS: We conclude that trough level is a practical acceptable indicator of the blood levels of tacrolimus, and can be used to monitor blood concentration.

Adult↗
PubMed1995

[Influence of pneumoperitoneum on respiratory function during urological laparoscopic surgery].

PURPOSE: To determine the influence of pneumoperitoneum on respiratory function during urological laparoscopic surgery. MATERIALS AND METHODS: We performed laparoscopic surgery on 82 patients, 45 of these patients were examined in detail of the effect of pneumoperitoneum on the respiratory function. Of these 45 patients, 14 patients received lymphadenectomy and 31 patients received adrenalectomy. For comparative analysis, 4 patients with laparoscopic cholecystectomies were also examined. Under general anesthesia, carbon dioxide tension (PaCO2) was analyzed before, during, and after the pneumoperitoneum. The data were analysed along with 4 factors; the patient's spirographic parameters, alveolar-arterial gas difference (AaDO2), insufflation pressure for the pneumoperitoneum, and operating time. RESULT: After starting the pneumoperitoneum, PaCO2 levels rose significantly. The PaCO2 levels of patients underwent laparoscopic adrenalectomy were higher than that of patients underwent laparoscopic cholecystectomy. The preoperative vital capacity and forced expiratory volume in one second (FEV1.0) did not show a significant difference of increase in the degree of PaCO2 increase. In contrast, the important factors that were closely related to the elevation of PaCO2 were preoperative AaDO2 and intraoperative insufflation pressure. Patients with high preoperative AaDO2 (> 10 torr) showed a significant increase in PaCO2 levels after pneumoperitoneum. When insufflation pressure was high (> = 10 mmHg), there was a significant rise of PaCO2 after pneumoperitoneum. In all patients whose operating time was 300 minutes or more, high levels of PaCO2 continued on the next day after surgery. CONCLUSION: We should still carefully observe the insufflation pressure, operating time, and other ventilation conditions during laparoscopic surgery.

Aged↗
PubMed1995

[Deoxycorticosterone-producing adrenocortical carcinoma--a case report].

A 39-year-old male presented with gross hematuria and left lower abdominal discomfort. Excretory urography showed a left ureteral stone and hydronephrosis. CT scans and magnetic resonance imaging showed a solid mass at the upper pole of the left kidney. Angiography revealed a hypervascular lesion at this area. The laboratory data showed a slightly decreased serum potassium level. In the endocrinological study, the serum deoxycorticosterone (DOC) level was markedly elevated. There was, however, no evidence of hypertension. The operation was performed on November 13, 1992. The tumor was almost separated from the left kidney, but an aberrant artery which divided from the renal artery and penetrated the renal parenchyma was found. Therefore, we had to carry out en bloc removal of the tumor together with the left kidney and the ureter which contained the ureteral stone. Pathological diagnosis was adrenocortical carcinoma. After the operation, hypokalemia and the serum concentration of DOC returned to normal range. Therefore, the tumor was diagnosed as DOC producing adrenocortical carcinoma. The patient was discharged 30 days after the operation with uneventful postoperative course. He received 2.5 g of op'-DDD a day. There was no evidence of distant metastasis or local recurrence 12 months after the operation. Nineteen cases of DOC producing adrenocortical tumor have been reported in the world literature. A case and a review of the literature are herein reported.

Adrenal Cortex Neoplasms↗
PubMed1994

Correlations between platelet aggregation, fibrinolysis, peripheral and central serotonergic measures in subhuman primates.

We have studied the relationships between whole blood and plasma serotonin (5-hydroxytryptamine, 5-HT), its major metabolite 5-hydroxyindoleacetic acid (5-HIAA) and serum lipids, platelet aggregation in the whole blood and in the platelet-rich plasma (PRP), and some fibrinolytic parameters in monkeys. Plasma 5-HT was found to be positively related to 5-HT- and ADP-induced platelet aggregation, tissue plasminogen activator (tPA) activity, serum cholesterol and LDL-cholesterol, whereas 5-HT in cerebrospinal fluid correlated inversely with serum cholesterol. Plasminogen activator inhibitor (PAI) activity was positively related to LDL. Euglobulin clot lysis time was related to both tPA and PAI activities. The significance of these findings and the possible role of 5-HT in atherogenesis and hemostasis are discussed.

Animals↗
PubMed1994

Characterization of the human gene (TBXAS1) encoding thromboxane synthase.

The gene encoding human thromboxane synthase (TBXAS1) was isolated from a human EMBL3 genomic library using human platelet thromboxane synthase cDNA as a probe. Nucleotide sequencing revealed that the human thromboxane synthase gene spans more than 75 kb and consists of 13 exons and 12 introns, of which the splice donor and acceptor sites conform to the GT/AG rule. The exon-intron boundaries of the thromboxane synthase gene were similar to those of the human cytochrome P450 nifedipine oxidase gene (CYP3A4) except for introns 9 and 10, although the primary sequences of these enzymes exhibited 35.8% identity each other. The 1.2-kb of the 5'-flanking region sequence contained potential binding sites for several transcription factors (AP-1, AP-2, GATA-1, CCAAT box, xenobiotic-response element, PEA-3, LF-A1, myb, basic transcription element and cAMP-response element). Primer-extension analysis indicated the multiple transcription-start sites, and the major start site was identified as an adenine residue located 142 bases upstream of the translation-initiation site. However, neither a typical TATA box nor a typical CAAT box is found within the 100-b upstream of the translation-initiation site. Southern-blot analysis revealed the presence of one copy of the thromboxane synthase gene per haploid genome. Furthermore, a fluorescence in situ hybridization study revealed that the human gene for thromboxane synthase is localized to band q33-q34 of the long arm of chromosome 7. A tissue-distribution study demonstrated that thromboxane synthase mRNA is widely expressed in human tissues and is particularly abundant in peripheral blood leukocyte, spleen, lung and liver. The low but significant levels of mRNA were observed in kidney, placenta and thymus.

Amino Acid Sequence↗
PubMed1994

Characterization of the human gene (PTGS2) encoding prostaglandin-endoperoxide synthase 2.

The human gene (PTGS2) encoding an inducible isozyme of prostaglandin-endoperoxide synthase (prostaglandin-endoperoxide synthase 2) that is distinct from the well-characterized and constitutive isozyme (prostaglandin-endoperoxide synthase 1), was isolated using a polymerase-chain reaction-generated cDNA fragment probe for human prostaglandin-endoperoxide synthase 2. Nucleotide sequence analysis of the entire human prostaglandin-endoperoxide-synthase-2 gene demonstrated that it is more than 8.3 kb in size and consists of ten exons; this gene is very similar to the murine and chicken prostaglandin-endoperoxide-synthase-2 genes. The structures of exons in the human prostaglandin-endoperoxide-synthase-2 gene were also similar to those of the human prostaglandin-endoperoxide-synthase-1 gene (PTGS1). However, the sizes of introns in the human prostaglandin-endoperoxide-synthase-2 gene were generally smaller than those of the human prostaglandin-endoperoxide-synthase-1 gene. Primer-extension analysis indicated that the transcriptional-start site is 134 bases upstream of the translational-initiation site. The sequence of the 1.69-kb region of nucleotides preceding the transcriptional-start site and the first 0.8-kb intron contained a canonical TATA box and various transcriptional-regulatory elements (CArG box, NF-IL6, PEA-1, myb, GATA-1, xenobiotic-response element, cAMP-response element, NF-kappa B, PEA-3, Sp-1 and 12-O-tetradecanoyl-phorbol-13-acetate-response element). The nucleotide sequence of the 5'-flanking region (275 bp) of the human prostaglandin-endoperoxide-synthase-2 gene showed 63% similarity to the sequence of murine prostaglandin-endoperoxide-synthase-2/TIS10 gene, but essentially no homology to the chicken prostaglandin-endoperoxide-synthase-2 gene, and human and murine prostaglandin-endoperoxide-synthase-1 genes. A fluorescence in situ hybridization study showed that the human genes coding for prostaglandin-endoperoxide synthase 1 (PTGS1) and prostaglandin-endoperoxidase synthase 2 (PTGS2) were mapped to distinct chromosomes 9q32-q33.3 and 1q25.2-q25.3, respectively, indicating that these genes are not genetically linked.

Amino Acid Sequence↗
PubMed1994

Relationships between serum lipids, serotonin, platelet aggregation and some fibrinolytic parameters in humans.

We have studied relationships between serum lipids, plasma serotonin (5-hydroxytryptamine, 5-HT), platelet aggregation in the platelet-rich plasma (PRP), and some fibrinolytic parameters in healthy volunteers. LDL was positively related to 5-HT-induced platelet aggregation. Higher serum HDL levels were related to higher fibrinolytic activity expressed by shorter euglobulin clot lysis time (ECLT). No correlation existed between serum lipids and plasma 5-HT. Plasma 5-HT was found to be related to tissue plasminogen activator (t-PA), suggesting some link between plasma serotonin and the release of t-PA from endothelial cells. There were mutual relations among fibrinolytic parameters such as tissue plasminogen activator (t-PA) antigens, total plasminogen activator inhibitor-1 (PAI-1), t-PA-PAI-1 complex, free PAI-1, and ECLT. In conclusion higher LDL may be more thrombogenic due to enhanced 5-HT induced platelet aggregation whereas high HDL may be more protective against thrombosis due to enhancement of fibrinolysis.

Adult↗