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Biomedical subjects

T Ohata

Publications and source records attributed to T Ohata.

At least 37 records · Page 2Linked to original sources
PubMed1998

Early detection of cardiac damage with heart fatty acid-binding protein after cardiac operations.

BACKGROUND: It is still difficult to evaluate myocardial damage in the acute phase of reperfusion in cardiac operations. We investigated the clinical significance of human heart fatty acid-binding protein (HH-FABP) for detecting myocardial damage after cardiac operations earlier than creatine kinase MB isoform or troponin-T. METHODS: Blood samples from 20 patients who underwent coronary artery bypass grafting were collected serially after reperfusion to measure serum levels of creatine kinase-MB, troponin-T, and HH-FABP. RESULTS: Serum HH-FABP levels peaked earliest after reperfusion. In addition, the maximum serum HH-FABP level was predictable immediately after reperfusion. The maximum serum HH-FABP level correlated with the maximum serum creatine kinase-MB or troponin-T level, as well as with the aortic cross-clamp time or the maximum dose of catecholamines administered after reperfusion. CONCLUSIONS: Measurements of HH-FABP allow for earlier evaluation of myocardial damage in the acute phase of reperfusion. Human heart fatty acid-binding protein may be a useful indicator of myocardial damage after cardiac operations.

Adult↗
PubMed1998

Interleukin-6 derived from hypoxic myocytes promotes neutrophil-mediated reperfusion injury in myocardium.

BACKGROUND: Reperfusion injury in the myocardium has recently been considered to be a type of inflammation, and close attention has been paid to the possible involvement of neutrophils, complement, and cytokines in the onset of this injury. Recently, it has been reported that serum levels of interleukin-6 are elevated significantly after myocardial infarction. The major site of interleukin-6 production and its exact roles are still unknown. In this study, we hypothesized that myocytes may produce interleukin-6 during hypoxia and this may play a role in neutrophil-mediated reperfusion injury. METHODS AND RESULTS: In the clinical study, 20 patients who underwent coronary artery bypass grafting were divided into 2 groups: group F, in which patients were treated with a serine protease inhibitor (FUT-175, 2 mg/kg per hour) during cardiopulmonary bypass, and group C (untreated patients). In group C, myocardial interleukin-6 production, as determined by the difference between the interleukin-6 level in the cardiopulmonary bypass circuit and its level in coronary venous blood, increased significantly after reperfusion (12+/-4 pg/mL) as compared with that before aortic crossclamping (2+/-2 pg/mL). In group F, the increase in the interleukin-6 level was suppressed significantly (before aortic crossclamping, 3+/-2 pg/mL; after reperfusion, 4+/-3 pg/mL). The interleukin-6 production differed significantly between group C and group F. In the in vitro experimental study, the supernatant from myocytes exposed to 2 hours of hypoxia (group 2H) showed significantly higher levels of interleukin-6 (455+/-260 pg/mL) than that from normoxic myocytes (group N) (47+/-15 pg/mL). This interleukin-6 production was suppressed by the addition of FUT-175 (123+/-24 pg/mL). The interleukin-6 production by endothelial cells of coronary vessels did not differ between group 2H (283+/-151 pg/mL) and group N (151+/-86 pg/mL). In a coincubation system with a monolayer of endothelial cells on collagen membrane and myocytes under collagen membrane in a modified Boyden chamber, 2 hours of coincubation showed a significantly higher percent of neutrophil transendothelial migration (group 2H vs N, 78%+/-13% vs 26%+/-11%), value of chemiluminescence (22+/-8 vs 5+/-2 x 10(3) counts/3 minutes), and percent of irreversibly damaged myocytes (48%+/-17% vs 12%+/-8%) than normoxic coincubation. In contrast, anti-interleukin-6 monoclonal antibody significantly attenuated neutrophil transendothelial migration (42%+/-19%) and irreversible damage of myocytes (26%+/-15%) in 2 hours of coincubation. CONCLUSIONS: Interleukin-6 is produced from myocardium during ischemia and reperfusion in patients undergoing coronary bypass grafting. This interleukin-6 may be derived from hypoxic myocytes and play a role in neutrophil-mediated reperfusion injury in myocardium.

Animals↗
PubMed1998

Evidence for linkage of human primary systemic carnitine deficiency with D5S436: a novel gene locus on chromosome 5q.

Primary systemic carnitine deficiency (SCD) is a rare hereditary disorder transmitted by an autosomal recessive mode of inheritance. The disorder includes cardiomyopathy, muscle weakness, hypoketotic coma with hypoglycemia, and hyperammonemia. In this study, we conducted a linkage analysis of a Japanese SCD family with a proband-a 9-year-old girl-and 26 members. The serum and urinary carnitine levels were determined for all members. The entire genome was searched for linkage to the gene locus for SCD, by use of a total of approximately 300 polymorphic markers located approximately 15-20 cM apart. In the family, there were two significantly different phenotypes, in terms of serum free-carnitine levels: low serum free-carnitine level (29.5+/-5.0 microM; n=14) and normal serum free-carnitine level (46.8+/-6.2 microM; n=12). There was no correlation of urinary free-carnitine levels with the low serum-level phenotype (putative heterozygote), but in normal phenotypes (wild type) urinary levels decreased as the serum levels decreased; renal resorption of free carnitine appeared to be complete in wild-type individuals, when the serum free-carnitine level was <36 microM. Linkage analysis using an autosomal dominant mode of inheritance of heterozygosity revealed a tight linkage between the disease allele and D5S436 on chromosome 5q, with a two-point LOD score of 4.98 and a multipoint LOD score of 5.52. The haplotype analysis revealed that the responsible genetic locus lies between D5S658 and D5S434, which we named the "SCD" locus. This region was syntenic with the jvs locus, which is responsible for murine SCD. Phylogenic conversion of the SCD locus strongly suggests involvement of a single gene, in human SCD.

Carnitine↗
PubMed1998

Inhibition by 1'-acetoxychavicol acetate of lipopolysaccharide- and interferon-gamma-induced nitric oxide production through suppression of inducible nitric oxide synthase gene expression in RAW264 cells.

Although nitric oxide (NO) is an important biological mediator, excessive production in inflammation is thought to be a causative factor of cellular injury and cancer in the long term. In the present study the effects of 1'-acetoxychavicol acetate (ACA), which has anticarcinogenic properties, on NO production in murine macrophage cell line RAW264 cells stimulated with lipopolysaccharide or interferon-gamma were examined. ACA suppressed NO production dose dependently with an IC50 of 160 ng/ml (680 nM). The decrease in NO production was shown to parallel reduced expression of iNOS mRNA and protein. The influence of ACA on transcription factors, such as NF-kappaB, AP-1 and Stat1, which are involved in expression of the iNOS gene was assessed. ACA was found to suppress degradation of IkappaB, an NF-kappaB inhibitory factor, and consequently inhibit NF-kappaB activation. Activation of AP-1 and Stat1 was also blocked by ACA treatment. Thus we demonstrate that ACA exerts potent inhibitory effects on NO production, apparently mediated by modulation of activation of several transcription factors. This could contribute to the anticarcinogenic properties of ACA.

Animals↗
PubMed1998

Case report: Steatonecrosis in the upper abdomen following transcatheter arterial embolization for hepatocellular carcinoma.

A 66-year-old female with liver cirrhosis was treated by transcatheter arterial embolization (TAE) for a small hepatocellular carcinoma. She developed steatonecrosis with tenderness which occurred in the upper abdomen after TAE. The hepatic falciform artery from the middle hepatic artery was detected by arteriography. Necrosis in the upper abdomen was considered to be due to ischaemic changes caused by micromaterials for embolization of this artery, injuries of hepatic arterial endothelia slowly caused by carcinostatics, and chemotoxicity. It was considered that such complication as observed in this patient should be taken into consideration when performing TAE.

Aged↗
PubMed1998

[Antifungal susceptibility of clinically isolated Candida albicans by broth microdilution method].

In this study we investigated the antifungal susceptibility of 285 strains of Candida albicans isolates at Kinki University Hospital from March 1995 to December 1996. The antifungal agents tested were fluconazole, miconazole, intraconazole, amphotericin B and flucytosine. The susceptibility testing were performed according to the broth microdilution method standardized by National Committee for Clinical Laboratory Standards (M27-T). Most isolates of C. albicans showed relatively a low MIC value and the MIC90S were calculated at 1 microgram/ml; fluconazole, 0.125 microgram/mg; miconazole, 0.06 microgram/ml; itraconazole, 1 microgram/ml; amphotericin B, 0.25 microgram/ml; flucytosine. There was only one strain that showed high resistance against fluconazole and it showed cross-resistance against miconazole and itraconazole. There were two flucytosine resistant strains. The MICs of amphotericin B were tightly clustered and resistant strain were not observed.

Amphotericin B↗
PubMed1997

Diamond beam-position monitor for undulator radiation and tests at the Tristan Super Light Facility.

A photon beam-position monitor using a diamond foil as a position-sensitive device has been developed for use on insertion-device beamlines of third-generation synchrotron radiation facilities such as SPring-8, and was tested on the undulator beamline of the Tristan Super Light Facility at KEK. The beam test results show that the diamond monitor can be operated in a photoconductive mode like a semiconductor detector. It has a linear working range of about +/-1 mm and a position sensitivity of less than 3 mum. The stability of the monitor was confirmed by continuous operation under low photon beam intensity conditions.

Journal Article↗
PubMed1997

Increased expression of inducible and endothelial constitutive nitric oxide synthases in rat colon tumors induced by azoxymethane.

Nitric oxide (NO) is an important bioregulatory mediator involved in a variety of biological processes under both physiological and pathological conditions. To assess whether NO production is altered in colon carcinogenesis, the expression levels and localization of two isoforms of NO synthase, inducible NO synthase (iNOS) and endothelial constitutive NO synthase (eNOS), were examined by immunoblot and immunohistochemical methods in normal colonic mucosa and colon carcinomas induced by azoxymethane in male F344 rats. All colon carcinoma tissues examined were found to have an increased expression of iNOS and eNOS proteins as compared to normal colonic mucosa. In particular, the pronounced staining of iNOS protein localized to the luminal surface of carcinoma epithelial cells was not detectable in normal colon epithelium. The neovasculature in tumor tissues also demonstrated intense eNOS immunoreactivity in endothelial cells. These findings indicate that NO production is markedly elevated in azoxymethane-induced rat colon carcinomas, suggesting that regulatory pathways involving this mediator have some biological relevance to colon carcinogenesis in this model.

Adenocarcinoma↗
PubMed1997

Effect of cardiopulmonary bypass under tepid temperature on inflammatory reactions.

BACKGROUND: Cardiopulmonary bypass (CPB) causes inflammatory reactions and abnormal responses of vascular resistance. Theoretically, the difference in the blood temperature during CPB may influence the degree of CPB-induced inflammatory reactions. METHODS: To elucidate the effect of the perfusate temperature during CPB, serum levels of inflammatory cytokines, neutrophil elastase, complements, and vasoactive substances were measured in 18 patients undergoing elective coronary artery bypass grafting under tepid temperature (34 degrees C) and moderate hypothermia (28 degrees C). Respiratory index and systemic vascular resistance index during and after CPB and intubation time after postoperative course were also analyzed. RESULTS: The patterns of the change in interleukin-8 and neutrophil elastase were significantly different between the two groups. The tepid group showed an earlier decrease in interleukin-8 and neutrophil elastase levels as compared with the hypothermic group. The prostaglandin E2 level just after CPB was significantly higher in the tepid group than in the hypothermic group. Systemic vascular resistance index and respiratory index and intubation time were significantly lower in the tepid group than in the hypothermic group. CONCLUSIONS: These results demonstrated that tepid CPB affected the inflammatory cytokine release and neutrophil activation compared with hypothermic CPB, resulting in the attenuation of respiratory dysfunction. This may suggest a beneficial effect of tepid temperature in CPB with possible attenuation of the postperfusion syndrome.

Bradykinin↗
PubMed1997

A chick wingless mutation causes abnormality in maintenance of Fgf8 expression in the wing apical ridge, resulting in loss of the dorsoventral boundary.

We analyzed a Japanese chick wingless mutant (Jwg) to know a molecular mechanism underlying wing development. We observed expression patterns of eleven marker genes to characterize the mutant. Expressions of dorsoventral (DV) and mesenchymal marker genes were intact in nascent Jwg limb buds. However, expression of Fgf8, a marker gene for the apical ectodermal ridge (AER), was delayed and shortly disappeared in the wing regressing AER. Later on, ventral expression of dorsal marker genes of Wnt7a and Lmx1 indicated that the wing bud without the AER became bi-dorsal. In addition, the posterior mesoderm became defective, as deduced from the impaired expression patterns of Sonic hedgehog (Shh), Msx1, and Prx1. We attempted to rescue a wing by implanting Fgf8-expressing cells into the Jwg wing bud. We found that FGF8 can rescue outgrowth of the wing bud by maintaining Shh expression. Thus, the Jwg gene seems to be involved in maintenance of the Fgf8 expression in the wing bud. Further, it is suggested that the AER is required for maintenance of the DV boundary and the polarizing activity of the established wing bud.

Animals↗
PubMed1997

Suppression of nitric oxide production in lipopolysaccharide-stimulated macrophage cells by omega 3 polyunsaturated fatty acids.

Although nitric oxide (NO) is an important biological mediator, its excessive production in inflammation is thought to be a causative factor for cellular injury and, over the long term, cancer. In the present study, the effects of several fatty acids on NO production in murine macrophage cell line RAW264 cells stimulated with lipopolysaccharide were examined. Suppression of NO production was observed with the omega 3 polyunsaturated fatty acids (PUFAs), docosahexaenoic acid, eicosapentaenoic acid and alpha-linolenic acid, in a dose-dependent fashion. In contrast, no inhibition was observed with omega 6 PUFA (linoleic acid), omega 9 PUFA (oleic acid) or a saturated fatty acid (stearic acid). Western and northern blot analyses suggested that suppression of the induction of inducible NO synthase gene expression is responsible for the inhibition of NO production by omega 3 PUFAs. The inhibitory effect of omega 3 PUFA on NO production in activated macrophages could contribute to their cancer chemopreventive influence.

Animals↗
PubMed1997

Biocompatibility of heparin-coated circuits in pediatric cardiopulmonary bypass.

In this study, we evaluated the biocompatibility of heparin-coated circuits in pediatric cardiopulmonary bypass (CPB). Eight patients were divided into 2 groups: the control group (Group C) and heparin-coated group (Group H). In Group H, CPB circuits, including the arterial pump, oxygenator, and cannulas were heparin-coated. Before, during, and after CPB, blood samples were obtained to assess the platelet counts (Plat), alpha 2-plasmin plasminogen inhibitor complex (PIC), thrombin-antithrombin III complex (TAT), C3 activation products (C3a), interleukin (IL)-6, IL-8, and polymorphonuclear neutrophil leukocyte (PMN) elastase. There was no significant difference in Plat, PIC, or TAT between groups. Group H showed significantly low levels of C3a (during and after CPB), PMN elastase (during CPB), and IL-6 (after CPB). These data demonstrated that in pediatric CPB, heparin-coated CPB circuits reduced the activation of complements and the production of PMN elastase and IL-6, suggesting the superior biocompatibility of the heparin-coated circuits.

Anticoagulants↗
PubMed1997

The mesenchymal factor, FGF10, initiates and maintains the outgrowth of the chick limb bud through interaction with FGF8, an apical ectodermal factor.

Vertebrate limb formation has been known to be initiated by a factor(s) secreted from the lateral plate mesoderm. In this report, we provide evidence that a member of the fibroblast growth factor (FGF) family, FGF10, emanates from the prospective limb mesoderm to serve as an endogenous initiator for limb bud formation. Fgf10 expression in the prospective limb mesenchyme precedes Fgf8 expression in the nascent apical ectoderm. Ectopic application of FGF10 to the chick embryonic flank can induce Fgf8 expression in the adjacent ectoderm, resulting in the formation of an additional complete limb. Expression of Fgf10 persists in the mesenchyme of the established limb bud and appears to interact with Fgf8 in the apical ectoderm and Sonic hedgehog in the zone of polarizing activity. These results suggest that FGF10 is a key mesenchymal factor involved in the initial budding as well as the continuous outgrowth of vertebrate limbs.

Amino Acid Sequence↗
PubMed1997

Single and repeated intravenous toxicity studies of pamiteplase (genetical recombination) in rats and monkeys.

Single and repeated intravenous toxicity studies of Pamiteplase (genetical recombination) YM866, a novel recombinant human tissue-type plasminogen activator, were conducted. No animal died from toxic effects of YM866 after single administration to F344 rats, squirrel monkeys and cynomolgus monkeys. Male and female F344 rats were given YM866 intravenously for 4 weeks at doses of 0 (vehicle), 0.1, 0.3 and 1 mg/kg/day. An increase in platelet count, slight decreases in hemoglobin and hematocrit, increases in plasma phospholipids, total cholesterol and total protein, and liver weight were observed at 1.0 mg/kg. Histopathology revealed no changes in any organ except for hemorrhage at the injection sites. These changes recovered after 4 weeks of withdrawal. Male and female squirrel monkeys were given YM866 intravenously for 4 weeks at doses of 0 (saline), 0 (vehicle), 0.1, 0.3 and 1 mg/kg/day. Prolongation of coagulation time at the injection site was observed at 0.3 mg/kg or more. Subcutaneous hemorrhage and a transient decrease in locomotor activity were observed at 1 mg/kg. Prolongation of coagulation time at the injection site was considered to be related to the pharmacological action of YM866. The results show that the approximate single lethal dose of YM866 is more than 60 mg/kg in rats, and more than 10 mg/kg in squirrel monkeys and cynomolgus monkeys. The no-toxic-effect level of YM866 after repeated administration for 4 weeks in rats and squirrel monkeys is considered to be 0.3 mg/kg.

Animals↗
PubMed1997

Reproductive toxicity, mutagenicity and antigenicity of pamiteplase (genetical recombination).

Pamiteplase (genetical recombination), YM866, is a novel recombinant modified human tissue-type plasminogen activator developed by Yamanouchi Pharmaceutical Co. Ltd., Tokyo, Japan. An intended route of administration in the clinical use of this drug is intravenous administration. We conducted an intravenous fertility and general reproduction studies of this drug in male and female rats and teratology study of this drug in rabbits at the dose levels of 0 (vehicle control), 0.1, 0.3 or 1 mg/kg/day. In the rat, no treatment-related abnormalities were observed up to the maximum dose in parental animals and their offspring. In the teratology study in rabbits, prolonged coagulation time at the injection site was observed at 0.3 mg/kg or more. One death and one abortion occurred at 1 mg/kg on days 22 and 23 of pregnancy, respectively. No toxic effects on the litters were observed up to the maximum dose. Results of evaluation of the mutagenicity of YM866 and its ability to induce chromosome aberrations using the L5178Y TK+/- mouse lymphoma assay, human lymphocyte chromosome aberration assay and the micronucleus assay in mice were negative. Evaluation of the immunogenicity of YM866 by repeated intravenous injection in chimpanzees elicited no confirmed antibody titers.

Abnormalities, Drug-Induced↗
PubMed1996

Attenuation of cardiopulmonary bypass-derived inflammatory reactions reduces myocardial reperfusion injury in cardiac operations.

In cardiac operations endopeptidase (protease) inhibitor may be beneficial in reducing myocardial injury when administered in the cardiopulmonary bypass prime. Nafamostat mesilate was evaluated in 20 patients who underwent coronary artery bypass grafting. The patients were divided into a control group (n = 10) and a nafamostat group (n = 10). Nafamostat (2 mg/kg per hour) was continuously given during cardiopulmonary bypass in the nafamostat group. The age, number of grafts, cardiopulmonary bypass time, and aortic crossclamp time were similar between groups. In the control group, neither tumor necrosis factor-alpha nor interleukin-1 levels showed any significant change during cardiopulmonary bypass, whereas interleukin-6 and interleukin-8 levels, percent expression of adhesion molecule (CD18) on neutrophils, and CH50 assay results increased significantly during cardiopulmonary bypass. As compared with the control group, the nafamostat group showed significantly lower levels of interleukin-6 (123 +/- 57 versus 40 +/- 22 pg/ml, respectively) and interleukin-8 (96 +/- 13 versus 66 +/- 14 pg/ml, respectively). The nafamostat group showed a significantly lower difference of CH50 assay results and malondialdehyde levels between coronary sinus blood and arterial blood and peak values of creatine kinase MB (43 +/- 12 IU/L versus 19 +/- 6 IU/L) during the postoperative course compared with findings in the control group. These results demonstrated that inflammatory reactions induced by cardiopulmonary bypass had adverse effects on myocardial recovery after aortic crossclamping and that nafamostat mesilate given during cardiopulmonary bypass appeared to reduce myocardial reperfusion injury by attenuating such inflammatory reactions. Attenuation of inflammatory reactions of cardiopulmonary bypass should be considered in the strategy of myocardial protection.

Benzamidines↗
PubMed1996

An infant case of Ebstein's anomaly of the tricuspid valve with abnormal diastolic filling pattern of the left ventricle.

We report herein an infant case of Ebstein's anomaly with abnormal diastolic filling pattern of the left ventricle. We also compare the case with a comparable case without such abnormal filling pattern. The patient, who had pulmonary valve stenosis, patent ductus arteriosus and mild mitral regurgitation, underwent transventricular valvotomy at 30 days of age. Postoperative course was uneventful. Serial Doppler echocardiographic studies were performed at 2 hr, 40 days, and 52 days of age. Peak velocity and flow velocity-time integral of early diastole, and ratios of the peak velocities and velocity time integrals of the early diastole and atrial contraction were below the 95% confidence limits of the normal controls. Our case suggests that left ventricular diastolic dysfunction may exist in the Ebstein's anomaly when it is associated with mitral valve abnormality such as mitral regurgitation.

Diastole↗