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Biomedical subjects

H Okuda

Publications and source records attributed to H Okuda.

At least 145 records · Page 8Linked to original sources
PubMed1997

Platelet aggregation is impaired during anaesthesia with sevoflurane but not with isoflurane.

PURPOSE: Halothane suppresses platelet aggregation in vitro and ex vivo, and prolongs bleeding time. In a previous in vitro study we demonstrated that sevoflurane had a more suppressive effect on platelet aggregation than did halothane. The present study investigated whether the clinical use of sevoflurane affected platelet aggregation ex vivo. METHODS: Thirty-eight patients undergoing minor elective surgery were divided randomly into sevoflurane and isoflurane groups. Anaesthesia was induced with thiopentone i.v., and was maintained with sevoflurane or isoflurane with nitrous oxide. Blood was collected to measure platelet aggregation induced by adenosine diphosphate (ADP) and epinephrine. The first (control) blood collection was performed in the operating room before induction of anaesthesia, and the second 5-10 min after tracheal intubation but before the start of surgery, when the end-expiratory sevoflurane or isoflurane concentrations had stabilised at 1-1.5 times the minimum alveolar concentration (MAC) and mean arterial pressures were between 80-120% of preanaesthetic values. RESULTS: In all samples obtained during sevoflurane anaesthesia (n = 15), ADP and epinephrine could not induce secondary aggregation, although they did induce primary aggregation. In contrast, in the isoflurane group, both primary and secondary aggregation were observed in 14 out of 15 patients, and secondary aggregation was abolished in only one of the samples obtained during anaesthesia. CONCLUSIONS: Sevoflurane, but not isoflurane, alters platelet aggregation in the clinical situation, possibly by suppression of thromboxane A2 formation.

Adult↗
PubMed1997

Dinucleotide repeat in the 3' flanking region provides a clue to the molecular evolution of the Duffy gene.

The Duffy blood group system consists of three alleles, FYA, FYB, and FY. To study the molecular evolution of the three alleles, we established the polymorphism of a dinucleotide (GT) repeat sequence (designated FyGT/C) in the 3' flanking region of the Duffy gene, and studied the relationship between FyGT/C and Duffy polymorphism in Japanese, people of African origin, and chimpanzee. By single-strand conformation polymorphism and sequence analysis, five and two alleles were identified in Japanese and Africans, respectively. In 110 random Japanese, the FyGT/C genotypes observed were in agreement with Hardy-Weinberg law. From the sequence of the chimpanzee Duffy gene, including both flanking regions, FYB was identified as the ancestral gene of the human alleles. The FyGT/C sequences associated with the FY allele of Africans were distinct from those of Duffy positives, whereas the FYB and FYA alleles shared common FyGT/C sequences. Thus, it is suggested that the first split took place between the FYB and FY alleles, and the second between the FYB and FYA alleles.

Alleles↗
PubMed1997

Effects of baicalein isolated from Scutellaria baicalensis on interleukin 1 beta- and tumor necrosis factor alpha-induced adhesion molecule expression in cultured human umbilical vein endothelial cells.

We examined the effects of nine flavonoids isolated from Scutellariae radix on interleukin-1 beta (IL-1 beta)- and tumor necrosis factor-alpha (TNF-alpha)-induced adhesion molecule expression in cultured human umbilical vein endothelial cells (HUVECs). Among them, we found that baicalein (5,6,7-trihydroxy flavone) dose-dependently inhibited IL-1 beta and TNF-alpha-induced endothelial leukocyte adhesion molecule-1 (ELAM-1) and intercellular adhesion molecule-1 (ICAM-1) expressions. Its 50% inhibitory concentrations (IC50) for the IL-1 beta-induced ELAM-1 and ICAM-1 expressions were 2.3 x 10(-5) M and 4.0 x 10(-5) M, respectively. The IC50 for the TNF-alpha-induced ELAM-1 and ICAM-1 expressions were 1.5 x 10(-5) M and 3.1 x 10(-5) M, respectively. In addition, protein C-kinase (PKC) inhibitor H7 also inhibited the ELAM-1 and ICAM-1 expressions induced by IL-1 beta and TNF-alpha.

Cell Adhesion Molecules↗
PubMed1997

Histamine-release effectors from Angelica dahurica var. dahurica root.

Six compounds isolated from the EtOAc fraction of the dried roots of Angelica dahurica var. dahurica inhibited compound 48/80-induced histamine levels in mouse peritoneal cavity (in vivo). Bergapten, oxypeucedanin hydrate, and byakangelicin inhibited compound 48/80-induced histamine elevation at a dose of 25 mg/kg. Conversely, sec-O-acetylbyakangelicin [8-(2-acetoxy-3-hydroxy-3-methylbutoxy)-5-methoxypsoralenI enhanced compound 48/80-induced histamine elevation at a dose of 25 mg/kg, while phellopterin and oxypeucedanin had no effect.

Animals↗
PubMed1997

Effects of flavonoids isolated from scutellariae radix on fibrinolytic system induced by trypsin in human umbilical vein endothelial cells.

Studies on the effects of flavonoids isolated from the roots of Scutellaria baicalensis on the fibrinolytic system induced by trypsin in cultured human umbilical vein endothelial cells (HUVECs) showed that baicalein (1) strongly inhibited the reduction of t-PA production and the elevation of PAI-1 production induced by trypsin. The IC50 for PAI-1 production was 3.7 microM. In addition, wogonin (3), oroxylin A (5), skullcapflavone II (6), and 2',5,5',7-tetrahydroxy-6',8-dimethoxyflavone (7) inhibited the elevation of PAI-1 induced by trypsin, though less strongly; their IC50 were 105, 61, 110, and 88 microM, respectively. These findings suggest that baicalein prevents the thrombotic tendency induced by trypsin.

Cell Line↗
PubMed1997

The expression of vascular endothelial growth factor and transforming growth factor-beta associates with angiogenesis in epithelial ovarian cancer.

The object of this study was to clarify the association between microvessel density and clinicopathologic factors, as well as the association of angiogenic factors (vascular endothelial growth factor [VEGF] and transforming growth factor-beta [TGF-beta]) with tumor angiogenesis and patient survival in epithelial ovarian cancer. The expression of VEGF and TGF-beta was evaluated by immunohistochemical staining in 60 patients with epithelial ovarian cancer. The microvessel density, assessed by immunostaining for factor VIII-related antigen in the most neovascularized areas, varied depending on histological types but not on International Federation of Gynecology and Obstetrics stage. Patients with stage III carcinomas and positive TGF-beta had more extensive peritoneal dissemination and a worse outcome. The microvessel density of VEGF-rich and TGF-beta positive tumors was significantly higher than that of VEGF-poor and TGF-beta negative tumors. Angiogenesis appears to be an early event in epithelial ovarian cancer and may be induced differently in tumors of different histological types. The expression of VEGF and TGF-beta associates with the promotion of angiogenesis, and the expression of TGF-beta is a prognostic indicator in epithelial ovarian cancers.

Carcinoma↗
PubMed1997

Effects of flavonoids isolated from scutellariae radix on the production of tissue-type plasminogen activator and plasminogen activator inhibitor-1 induced by thrombin and thrombin receptor agonist peptide in cultured human umbilical vein endothelial cells.

The effects of different flavonoids isolated from the roots of Scutellaria baicalensis Georgi on the production of tissue-type plasminogen activator (t-PA) and plasminogen activator inhibitor-1 (PAI-1) induced by thrombin and thrombin receptor agonist peptide, Ser-Phe-Leu-Leu-Arg-Asn-Pro-Asn-Asp-Lys-Tyr-Glu-Pro-Phe, have been examined in cultured human umbilical vein endothelial cells (HUVECs). Thrombin and thrombin receptor agonist peptide induced production of both t-PA and PAI-1 and the elevation of intracellular free calcium concentration ([Ca2+]i). Baicalein isolated from Scutellariae Radix dose-dependently inhibited PAI-1 production induced by thrombin and thrombin receptor agonist peptide; its concentrations for 50% inhibition (IC50) were 6.8 and 3.5 microM, respectively. Other flavonoids had no effect. In contrast, flavonoids isolated from Scutellariae Radix had no effect on production of t-PA induced by thrombin and thrombin receptor agonist peptide. Baicalein inhibited the elevation of [Ca2+]i induced by thrombin and thrombin receptor agonist peptide and, at a concentration of 1000 microM, slightly increased t-PA production. These findings suggest that the mechanism by which baicalein inhibits PAI-1 production induced by thrombin and thrombin receptor agonist peptide might be by reduction of [Ca2+]i elevation. The results suggest that baicalein in Scutellariae Radix might be active as a drug in the treatment of arteriosclerosis and thrombosis.

Calcium↗
PubMed1997

Fruiting-inducing activity and antifungal properties of lipid components in members of Annelida.

Fruiting-inducing activity and antifungal properties of lipid components in the phylum Annelida were examined. Some amphoteric cerebrosides carrying a phosphocholine group showed fruiting-inducing activity on Schizophyllum commune, and one of them possessed activity comparable to that of Sch II, the most potent substance known. Furthermore, alkyl lysophosphatidylcholines were found to have an inhibitory effect on the growth of phytopathogenic fungi, Alternaria kikuchiana and Phomopsis mali. The relationship between structure and biological activities is discussed.

Alternaria↗
PubMed1997

[Lethal drug interactions of the new antiviral, sorivudine, with anticancer prodrugs of 5-fluorouracil].

In 1993 eighteen Japanese patients with cancer and herpes zoster, a viral disease, died from interactions of the new oral antiviral drug, sorivudine (SRV: 1-beta-D-arabinofuranosyl-(E)-5-(2-bromovinyl)uracil), with oral anticancer prodrugs of 5-fluorouracil (5-FU) within 40 d after SRV was approved by the Japanese government and began to be used clinically. Before the death, most of these patients had severe symptoms of toxicity, including diarrhea with bloody flux and marked decreases in white blood cell and platelet counts. All of these patients received SRV daily for several days while being administered long-term anticancer chemotherapy with one of the oral 5-FU prodrugs. There was no acute toxic symptom in patients who received SRV alone or SRV and the other types of anticancer drugs. A toxicokinetic study was carried out using rats to investigate the mechanism of the acute death in the patients caused by drug interactions between SRV and 5-FU prodrugs. Rats were orally coadministered SRV with tegafur (FT: 1-(2-tetrahydrofuryl)-5-fluorouracil), a 5-FU prodrug that most of the patients were considered to receive before the death. All the rats receiving SRV and FT once daily showed extremely elevated levels of 5-FU in the plasma and tissues, including bone marrow and small intestines, and died within 10 d, while the animals given the same repeated dose of SRV or FT alone were still alive over 20 d without any appreciable toxic symptom. Before their death, there were a marked damage of bone marrow, a marked atrophy of intestinal membrane mucosa, marked decreases in white blood cells and platelets, diarrhea with bloody flux, and severe anorexia as reported for the patients. Data obtained by in vivo and in vitro studies indicated that (E)-5-(2-bromovinyl)uracil (BVU), generated from SRV by the gut flora and absorbed through the intestinal membrane, was reduced in the presence of NADPH to a reactive form by hepatic dihydropyrimidine dehydrogenase (DPD), a key enzyme regulating the tissue 5-FU levels from FT, bound covalently to DPD as a suicide inhibitor, and markedly retarded the catabolism of 5-FU. An irreversible inactivation by BVU of rat and human DPDs, expressed in E. coli for the latter, was observed in the presence of NADPH with their purified preparations in a manner reciprocal to radiolabelling of the enzyme proteins with [14C]BVU. SRV showed no inhibitory effect on the rat and human DPDs in the presence of NADPH.

Administration, Oral↗
PubMed1997

Lethal drug interactions of sorivudine, a new antiviral drug, with oral 5-fluorouracil prodrugs.

Rats were orally co-administered sorivudine (SRV: 1-beta-D-arabinofuranosyl-(E)-5-(2-bromovinyl)uracil), a new oral antiviral drug for herpes zoster, with the oral anticancer drug tegafur (FT: 1-(2-tetrahydrofuryl)-5-fluorouracil) as a prodrug of 5-flourouracil (5-FU) once daily to investigate a toxicokinetic mechanism of 15 Japanese patients' deaths recently caused within a brief period by the drug interaction of these drugs. All the rats showed extremely elevated levels of 5-FU in plasma and tissues, including bone marrow and small intestine, and died within 10 days, whereas the animals given the same dose of SRV or FT alone were still alive over 20 days without any appreciable toxic symptom. Before their death, there was marked damage of bone marrow, marked atrophy of intestinal membrane mucosa, marked decreases in white blood cells and platelets, diarrhea with bloody flux, and severe anorexia as reported with the Japanese patients. Data obtained by in vivo and in vitro studies strongly suggested that (E)-5-(2-bromovinyl)uracil generated from SRV by gut flora was reduced in the presense of NADPH to a reactive form by hepatic dihydropyrimidine dehydrogenase (DPD), a key enzyme determining the tissue 5-FU levels, bound covalently to DPD as a suicide inhibitor, and markedly retarded the catabolism of 5-FU.

Administration, Oral↗
PubMed1997

Norepinephrine-induced lipolysis in rat fat cells from visceral and subcutaneous sites: role of hormone-sensitive lipase and lipid droplets.

Norepinephrine-induced lipolysis was examined in visceral (epididymal and omental) and subcutaneous (abdominal and femoral) fat cells in rats. Hormone-induced lipolysis was considerably higher in the visceral fat cells than in the subcutaneous cells. A higher hormone-sensitive lipase (HSL) activity was present in the visceral than in the subcutaneous fat cells. Endogenous lipid droplets were prepared from rat visceral (epididymal and omental) and subcutaneous (abdominal and femoral) fat cells and norepinephrine-induced lipolysis was examined in a cell-free system consisting of the lipid droplets prepared from fat cells from each site and a fixed amount of HSL from rat epididymal adipose tissue. In this cell-free system, norepinephrine induced a higher rate of lipolysis with lipid droplets from the visceral than from the subcutaneous fat cells. These findings suggest that the difference in norepinephrine-induced lipolysis between visceral and subcutaneous fat cells may be due to the differences in HSL activity and lipid droplet character at each site.

Abdomen↗
PubMed1997

Genotyping for RhC/c and RhE/e by PCR using allele-specific oligonucleotide primers.

The Rh blood group system has five major antigens D, C/c, and E/e. These antigens are encoded in RHD and RHCE genes. In this report, we describe a systemic method for RhC/c and RhE/e genotyping by PCR using allele-specific oligonucleotide primers (ASO-PCR). The ASO-PCR was carried out to determine the RhC/c and RhE/e genotypes in DNA samples from 513 Japanese donors. Genotypes of RhC, RhE, and Rhe were in full concordance with serological phenotypes in 511 donors. However, in two cases with the phenotype of ccdee, the C-specific ASO-PCR product was also detected in addition to the c-specific one. This method is simple and quite useful for the RhC/c and RhE/c genotyping, although further investigation on the 2 exceptional ccdee cases is needed.

Base Sequence↗
PubMed1997

[Bladder carcinoma presenting with hypercalcemia: a case report].

A 47-year old woman was referred to our hospital with nausea, vomiting and the loss of body weight. Pelvic computed tomography and magnetic resonance imaging revealed an invasive bladder tumor on the left lateral wall, accompanied with calcification. Laboratory examination revealed marked hypercalcemia (20.6 mg/dl) and elevated serum parathyroid hormone-related protein-intact (29.9 pmol/l), which was apparently produced by the tumor. Treatment with pamidronate and colloid infusion resulted in normocalcemia. Anterior pelvic exenteration was performed. Histopathological diagnosis was transitional cell carcinoma > adenocarcinoma, G3, pT4pN2M0, stage IV. She died of cancer 7 months postoperatively.

Carcinoma, Transitional Cell↗
PubMed1997

Lethal drug interactions of sorivudine, a new antiviral drug, with oral 5-fluorouracil prodrugs.

Rats were orally co-administered sorivudine (SRV: 1-beta-D-arabinofuranosyl-(E)-5-(2-bromovinyl)uracil), a new oral antiviral drug for herpes zoster, with the oral anticancer drug tegafur (FT: 1-(2-tetrahydrofuryl)-5-fluorouracil as a prodrug of 5-fluorouracil (5-FU) once daily to investigate a toxicokinetic mechanism of 15 Japanese patients' deaths recently caused within a brief period by the drug interaction of these drugs. All the rats showed extremely elevated levels of 5-FU in plasma and tissues, including bone marrow and small intestine, and died within 10 days, whereas the animals given the same dose of SRV or FT alone were still alive over 20 days without any appreciable toxic symptom. Before their death, there was marked damage of bone marrow, marked atrophy of intestinal membrane mucosa, marked decreases in white blood cells and platelets, diarrhea with bloody flux, and severe anorexia as reported with the Japanese patients. Data obtained by in vivo and in vitro studies strongly suggested that (E)-5-(2-bromovinyl)uracil generated from SRV by gut flora was reduced in the presense of NADPH to a reactive form by hepatic dihydropyrimidine dehydrogenase (DPD), a key enzyme determining the tissue 5-FU levels, bound covalently to DPD as a suicide inhibitor, and markedly retarded the catabolism of 5-FU.

Animals↗
PubMed1997

[Mitrofanoff procedure with bladder-sparing urethrectomy in female urethral carcinoma: report of a case].

A 60-year-old woman with urethral carcinoma treated by bladder sparing surgery is reported. A tumor of Grabstald's clinical stage C2 arose from the anterior urethra infiltrated into the distal wall of vagina with invasion of vaginal mucosa. Pathological findings revealed poorly differentiated squamous cell carcinoma. She underwent a wide local excision of the urethra and the anterior vaginal wall with preserving the bladder. An appendicovesicostomy (Mitrofanoff procedure was selected for the urinary diversion. This technique provided a small stoma, appropriate continence, normal bladder sensation and preseving renal function. Bladder-sparing urethrectomy could be an alternative treatment for female urethral tumors.

Appendix↗