Biomedical subjects

T Hata

Publications and source records attributed to T Hata.

At least 235 records · Page 13Linked to original sources

PubMed1996

Interleukin-6, interleukin-8, and granulocyte elastase in newborns with fetal distress.

OBJECTIVE: Our purpose was to investigate the participation of cytokines and neutrophils in fetal distress. STUDY DESIGN: Umbilical cord serum interleukin-6 (IL-6), interleukin-8 (IL-8), and plasma granulocyte elastase (GEL) were measured in 30 normally grown newborns without fetal distress (Group A), 10 growth-retarded newborns without acute fetal distress (Group B), 5 normally grown newborns with fetal distress (Group C), and 5 growth-retarded newborns with fetal distress (Group D). Umbilical arterial blood pH and PO2 were also measured. RESULTS: Umbilical arterial blood pH and PO2 in either Group C or Group D were significantly lower than those in either Group A or Group B. The concentration of IL-6 in Group D was significantly higher than that in either Group A, B, or C. The level of IL-8 in either Group C or Group D was significantly higher than that in either Group A or Group B. The concentrations of GEL in Group D was significantly higher than that in either Group A or Group B. CONCLUSION: This study suggests that fetal distress in utero causes an elevation of immune factors such as IL-6, IL-8 and GEL.

Acidosis↗

PubMed1996

Fetal ophthalmic artery blood flow velocity waveforms.

OBJECTIVE: To evaluate alterations in vascular impedance of the fetal ophthalmic artery (OA) with advancing gestation. STUDY DESIGN: Color Doppler flow imaging and pulsed Doppler ultrasonographic assessment were performed on 28 normal fetuses, at gestational ages ranging from 21 to 40 weeks. The pulsatility index (PI) was calculated for the OA and the middle cerebral artery (MCA). Optimal models for these PI values were determined by regression analysis. A normal range of PI values for both arteries was generated. RESULTS: In the OA, the model showed a parabolic pattern during pregnancy, as was the case for MCA. The predicted PI values for the OA were always lower than those for the MCA. CONCLUSION: Our study is the first to demonstrate alterations in regional vascular impedance of the fetal OA with advancing gestation. These data provide a foundation for the evaluation of fetal ocular circulation in normal and abnormal pregnancies.

Blood Flow Velocity↗

PubMed1996

Synthesis of endothelin-1 in rat uterus during pregnancy.

Endothelin is a potent vasoconstrictive peptide first isolated from the supernatant of cultured porcine aortic endothelial cells. The purpose of this study was to determine the source of endothelin-1 (ET-1) production in rat uterus during pregnancy and to clarify its role in normal pregnancy. ET-1, as recognized by immunohistochemistry, was weakly expressed only in endometrial glandular cells in nonpregnant rats but was intensely expressed in both glandular and myometrial cells in the early postpartum period. In situ hybridization confirmed the localization of prepro-ET-1 mRNA in the cytoplasm of endometrial glandular and myometrial cells but not in stromal cells or in smooth muscle cells of blood vessels. Northern blot analysis detected prepro-ET-1 mRNA in myometrial tissue from pregnant but not nonpregnant rats. In particular, the expression of prepro-ET-1 mRNA was strongest in the early postpartum period compared with the various stages of pregnancy. These results indicate that, in addition to endothelial cells and endometrial glandular cells, myometrial cells also produce ET-1 and its production significantly increases in the early postpartum period. Therefore, ET-1 may play a pivotal role in controlling bleeding from the placental bed through myometrial contraction.

Animals↗

PubMed1996

Diabetes with the 3243 mitochondrial tRNALeu(UUR) mutation. Characteristic neuroimaging findings.

OBJECTIVE: To investigate the basis of central nervous system dysfunction in diabetes associated with the 3243 mitochondrial tRNA mutation, we studied neuroimaging findings in patients with this disease. RESEARCH DESIGN AND METHODS: We screened 205 diabetic patients. Those patients who had the 3243 mutation in leukocytes or muscle were enrolled. All the subjects underwent computed tomography (CT), magnetic resonance imaging (MRI), magnetic resonance angiography (MRA), and N-isopropyl-p-[123I]iodoamphetamine ([123I]IMP) single-photon emission computed tomography (SPECT) of the brain. RESULTS: None of the nine subjects with the 3243 mutation had the typical clinical picture of mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes, and none had neurological focal signs. CT or MRI revealed diffuse brain atrophy in three patients (33%) and cerebellar atrophy in one (11%). Abnormal high intensity areas were observed on MRI in five patients (56%). The overall prevalence of brain abnormalities was 56% (5 of 9) on CT and 78% (7 of 9) on MRI scans. MRA revealed no stenotic lesions. SPECT showed reduced accumulation of [123I]IMP in the right or left parieto-occipital region in eight patients (89%). CONCLUSIONS: Reduced accumulation of [123I]IMP in the parieto-occipital cortex was found in a high proportion of our subjects on SPECT. This imaging finding might be characteristic of diabetes associated with the 3243 mitochondrial tRNA mutation and may be a sign of latent central nervous system dysfunction.

Adult↗

PubMed1996

Effect of dehydroepiandrosterone sulfate on fetal middle cerebral artery flow velocity waveforms in term pregnancy.

OBJECTIVE: To investigate whether bolus injection of dehydroepiandrosterone sulfate (DHAS) is associated with changes in fetal middle cerebral artery flow velocity waveforms in term pregnancy. METHODS: Ten normal full-term pregnant women received the administration of a 200-mg intravenous dose of DHAS in 20 ml of 5% dextrose. Ten normal full term pregnant women received 20 ml 5% dextrose as controls. Color Doppler flow imaging and pulsed Doppler ultrasonographic assessments were made on fetuses in each group before and 10 min, 30 min, 60 min, 90 min. and 120 min after DHAS or dextrose administration. The pulsatility index (PI) values for the middle cerebral artery, and umbilical artery, and fetal heart rate were recorded. RESULTS: In the DHAS group, middle cerebral artery PI decreased from baseline by 24% (p<.05) after 10 min, and the mean reduction was 22% (p<.05) after 30 min. The PI returned to the baseline value 60 min later. In the control group, there was no change in middle cerebral artery PI. No change was found in umbilical artery PI or fetal heart rate in the control or DHAS group. CONCLUSION: DHAS induces a significant decrease in the fetal middle cerebral artery PI, which suggests a possible decrease in fetal cerebral vascular impedance in term pregnancy.

Adult↗

PubMed1996

Plasma M-CSF as an indicator of response to chemotherapy in adult T cell leukemia patients.

The plasma concentration of macrophage colony-stimulating factor (M-CSF) was measured in 10 patients with acute type adult T cell leukemia (ATL) during the clinical course before and after chemotherapy. M-CSF concentration decreased significantly when the patients achieved complete remission (CR) or partial remission (PR) (t-test: p = 0.0001). Five of the patients showed disease progression after several months of PR, and plasma M-CSF increased at that time (t-test: p = 0.0456). Thus, plasma M-CSF concentration appeared to accurately reflect the disease activity in ATL. In support of these results, all three ATL cell lines established from these patients secreted M-CSF in vitro after stimulation with phorbol myristate acetate (PMA) or concanavalin A (Con A). Plasma M-CSF concentration, however, increased transiently when the patients were febrile (t-test: p = 0.0001), even though their ATL condition was unchanged. Taken together, these results indicate that there are two sources of increased plasma M-CSF concentration in ATL; ATL cells themselves and normal parenchymal cells that cause this increase as the result of elevated body temperature due to inflammation.

Adult↗

PubMed1996

Features of the cytokines secreted by adult T cell leukemia (ATL) cells.

Adult T cell leukemia (ATL) cells show a mature helper-inducer T cell phenotype and are thought to secrete many kinds of cytokines in vivo, complicating the clinical features in these patients. In an attempt to specify the cytokines produced by ATL cells, we measured the cytokine concentration in the culture supernatants of three ATL cell lines, all of which were confirmed to be true peripheral blood ATL cell in origin. All these cell lines showed the same cytokine production profile, secreting IL1-alpha, IL1-beta, LD78(MIP-l alpha), TNF-alpha, IFN-gamma, and GM-CSF, but not secreting IL-1 alpha, IL-1 beta, IL-1 receptor antagonist (IL-1 Ra), IL-4, IFN-alpha, and G-CSF irrespective of the stimulatory agents used. Such limited cytokine production may indicate the specific origin of ATL cells within the helper-inducer T cell subtypes. Moreover, these results explain some of the unusual clinical features of ATL patients.

Adult↗

PubMed1996

Osteotropic drug delivery system (ODDS) based on bisphosphonic prodrug. III: Pharmacokinetics and targeting characteristics of osteotropic carboxyfluorescein.

An osteotropic drug delivery system (ODDS) based on a bisphosphonic prodrug has been developed as a novel method for site-specific and controlled delivery of drugs to the bone. The pharmacokinetics and the targeting efficiency of a bisphosphonic prodrug of carboxyfluorescein (CF), disodium (fluorescein-6-carbonyloxy) acetoaminomethylene bisphosphonate (CF-BP), was investigated in rats. After intravenous injection, CF-BP was rapidly taken up into the skeleton, and subsequently cleared from the bone by hydrolysis of its ester linkage at a half-life of 3.2 days. On the other hand, the bone concentration of regenerated CF gradually increased to reach the maximum at 14 days and slowly decreased up to 56 days. Kinetical analysis revealed that bone tissue acts as a reservoir of regenerated CF to supply the parent compound into the systemic circulation. In contrast with CF-BP, CF injected intravenously showed rapid clearance from the plasma and extremely low bone distribution. Therapeutic availability (TA) and drug targeting index (DTI), which were calculated on the basis of the AUCs for CF in the bone and plasma after injection of CF-BP and CF, were 1551 and 6689, respectively. These results suggest that ODDS has a potential to improve not only apparent potency but also therapeutic index of the drugs which exhibit their pharmacological effects in the bone.

Animals↗

PubMed1996

Intratumoral blood flow analysis in ovarian cancer: what does it mean?

The objective of this study is to evaluate the significance of intratumoral blood flow in ovarian cancer. Forty-seven patients with histologically proved ovarian cancer underwent transvaginal gray scale sonography, and color and Doppler sonography before surgery. Intratumoral blood flow velocity waveforms obtained from architecture within the tumor were recorded, and resistive index and peak systolic velocity were calculated. Neither resistive index values nor peak systolic velocity values differed significantly among the histological diagnoses, regardless of stage (including metastatic tumor) or morphologic classification of tumor. These results suggest that intratumoral blood flow analysis in ovarian cancer cannot provide information on individual tumor characteristics.

Adolescent↗

PubMed1996

[Surgical treatment of infective endocarditis : an analysis of the risk factor for operative mortality].

From January 1980, through December 1995, 60 patients underwent surgical treatment of infective endocarditis (IE) at Sakakibara Hospital. Of 60 patients, 40 showed active endocarditis and 20 healed endocarditis at the time of operation. The over-all hospital mortality was 10% (6/60). The complication of cerebral accident (embolism and bleeding) was related to a higher incidence of operative mortality. The reconstructions of destruction and disruption of ventricular-aortic or mitral-aortic continity in the presence of acute infection of the annular tissue were in need of radical and complex surgical techniques. It is recommended to follow up these patients thoughtfully and to perform reoperation or re-reoperation before a patient develops severe heart failure or multiple organ failure.

Adult↗

PubMed1996

A species comparison of 14C-labeled 7-ethoxycoumarin metabolism in precision-cut liver slices from guinea pig and dog using a phosphor imaging system.

The metabolism of 14C-labeled 7-ethoxycoumarin (7EC) has been investigated in precision-cut liver slices from guinea pigs and dogs. 7EC was incubated with slices in 12-well plates (4 slices/well; n = 3) for up to 8 hr. In addition, a new simple method was established for analyzing 7EC and its metabolites simultaneously by using thin-layer chromatography-radioluminography (TLC-RLG). In both species, 7EC was taken up rapidly into the slices and metabolized extensively under the conditions used (no serum fraction supplemented), showing both phase I and phase II metabolism. In guinea pig medium samples, 4-ethoxy-2-hydroxyphenylacetic acid (EHPA) and 7-hydroxycoumarin (7HC) glucuronide were major metabolites. In dogs, conjugated 7HCs (with D-glucuronic acid and sulfate) were major products but EHPA was formed only to a small extent. These results suggest that deethylation in dogs occurs to a much greater extent than in guinea pigs. These results demonstrate the advantages of precision-cut liver slices as a powerful tool to investigate the species specific metabolism of xenobiotics, since the conditions employed enabled both phase I and phase II reactions in vitro.

Animals↗

PubMed1996

Interactions of FK506 (tacrolimus) with clinically important drugs.

The effect of eight drugs on the metabolism of FK506 (tacrolimus) by human liver microsomes was studied at a substrate concentration of 10 microM. NADPH-dependent oxidative metabolism of FK506 was inhibited 20, 15, and 10% by quinidine, omeprazole, and sulindac, respectively, at 100 microM. Theophylline, diclofenac, indomethacin, phenylbutazone, and cimetidine (at ten times molar excess of FK506) and all eight drugs (at equal molar concentration) had slight effects on metabolism. The effects of these drugs were much weaker than that of cyclosporin A. The effect of FK506 on NADPH-dependent oxidation of prednisolone and theophylline by human liver microsomes were also studied. FK506 inhibited prednisolone metabolism in a concentration-dependent manner but exhibited a negligible effect on theophylline metabolism. The results suggest potential for interactions between FK506 and drugs metabolized by the cytochrome P450 3A subfamily.

Drug Interactions↗

PubMed1996

Metabolic fate of iodine-123-BMIPP in canine myocardium after administration of etomoxir.

UNLABELLED: To clarify the metabolic fate of 123I-(-p-iodophenyl)-3-R,S-methylpentadecanoic acid (BMIPP) in dysfunctional myocardium, a comparison between normal dogs and those with etomoxir administration was studied using an open-chest canine model. METHODS: Using open-chested dogs under anesthesia, we created a system to release all the blood in the great cardiac vein outside without recirculation, if necessary. Iodine-123-BMIPP was directly injected into the left anterior descending artery, its extraction, retention and washout rate in the early phase were calculated, and the metabolites in the myocardium were evaluated using a high-performance liquid chromatography. Moreover, these factors were compared between normal dogs and those pretreated with etomoxir, that creates a condition similar to ischemia. RESULTS: Although rapid extraction of BMIPP from the plasma into the myocardium and the subsequent retention were unchanged, early washout (8 min) of radioactivity significantly increased (49.6% +/- 13.3%-->70.5% +/- 10.7%, p < 0.05) with etomoxir. The levels of the full metabolite formed by complete oxidation of BMIPP decreased significantly with etomoxir (21.4% +/- 10.9%-->5.5% +/- 3.5%, p < 0.01). In addition, back diffusion of BMIPP increased (25.1% +/- 8.0%-->41.9% +/- 12.0%, p < 0.05) in the etomoxir-treated animals without affecting the levels of alpha-oxidation metabolite and the intermediate metabolites. CONCLUSION: BMIPP is very sensitive to etomoxir and is suitable for assessing mitochondrial dysfunction. Iodine-123-BMIPP might be a promising radiopharmaceutical for the evaluation of ischemic heart disease, cardiomyopathy and mitochondrial encephalomyopathy.

Animals↗

PubMed1996

Binding of tacrolimus (FK506) with human plasma proteins re-evaluation and effect of mycophenolic acid.

Protein binding of tacrolimus (FK506) in human plasma was re-evaluated by equilibration dialysis and compared with that of FK506 previously reported by two different methods (about 99 and 77% by an ultrafiltration and ultracentrifugation method, respectively). The binding determined in this study was about 99% irrespective of FK506 concentrations added (0.5-10 ng/ml) and this value was very close to that estimated by the ultrafiltration method. The effect of mycophenolic acid (MPA, an active form of the immunosuppressant mycophenolate mofetil) and its glucuronide (MPAG, a major metabolite of mycophenolate mofetil in human plasma) on the binding was studied at concentration levels of 1 and 10 ng/ml of FK506. The binding was not affected significantly by the addition of MPA (25-100 micrograms/ml) and/or MPAG (100-1500 micrograms/ml). FK506 has already been reported not to cause significant changes of plasma protein binding of MPA. The results indicate that the unbound fraction of FK506 is about 1% in human plasma and that concomitant administration of FK506 and mycophenolic mofetil does not cause the drastic change of the binding of FK506 and MPA with human plasma proteins.

Antibiotics, Antineoplastic↗

PubMed1996