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Biomedical subjects

T Nishimura

Publications and source records attributed to T Nishimura.

At least 307 records · Page 17Linked to original sources
PubMed1998

Changes in hepatic cytochrome P450 enzymes by cis- and trans-1,2-dichloroethylenes in rat.

1. We examined the effect of cis- and trans-1,2-dichloroethylenes (DCEs) on hepatic microsomal cytochrome P450 (P450) enzymes in the male and female rat. Rats were treated intraperitoneally with 7.5 mmol/kg cis- or trans-1,2-DCE daily for 4 days. 2. Among the hepatic microsomal P450-dependent monooxygenase activities tested, testosterone 2 alpha-hydroxylase (T2AH) activity in the male rat, which is associated with CYP2C11, was decreased by both cis- and trans-1,2-DCE isomers. The levels to control activities were 53 and 63% respectively. Furthermore, immunoblotting showed that both isomers significantly reduced the CYP2C11/6 protein level in liver microsomes from the male. The levels of testosterone 6 beta-hydroxylase (T6BH) activity and CYP3A2/1 protein in the male rat were reduced by cis-1,2-DCE but not trans-1,2-DCE. 3. cis-1,2-DCE decreased ethoxycoumarin O-deethylase (ECOD), benzyloxyresorufin O-debenzylase (BROD), chlorzoxazone 6-hydroxylase (CZ6H) and testosterone 7 alpha-hydroxylase (T7AH) activities in the male rat by 29, 28, 34 and 27% respectively. On the other hand, trans-1,2-DCE significantly increased 7-ethoxyresorufin O-deethylase (EROD) and 7-methoxyresorufin O-demethylase (MROD) activities in the male rat 1.4- and 1.9-fold respectively. Immunoblotting showed that cis-1,2-DCE reduced CYP1A1/2 and CYP2B1/2 protein levels, whereas trans-1,2-DCE increased CYP1A1/2 and CYP2B1/2 protein levels in the male rat. 4. The activities of other P450-dependent monooxygenases, namely benzphetamine N-demethylase (BZND), aminopyrine N-demethylase (APND), erythromycin N-demethylase (EMND) and lauric acid omega-hydroxylase (LAOH), in the male rat were hardly affected by either 1,2-DCE isomer. In the female rat there were no apparent changes in P450-dependent monooxygenase activities upon treatment with the 1,2-DCE isomers. 5. These results suggest that 1,2-DCEs mainly affect male-specific P450 isoforms in the rat liver and that these changes may relate to the toxicity of 1,2-DCEs.

Animals↗
PubMed1998

Ex vivo evidence for asymmetric tyrosine phosphorylation of ZAP-70 on double-positive thymocytes in the positive selection process.

Antigen stimulation via TCR in mature T cells provides rapid induction of tyrosine phosphorylation of intracellular substrates including ZAP-70. To study the potential involvement of tyrosine phosphorylation in CD4+CD8+ [double-positive (DP)] thymocytes in the positive selection process in vivo, we isolated and analyzed them in the presence of phosphatase inhibitor. DP thymocytes were obtained from TCR transgenic mice (TCR-Tg) expressing MHC class I- or class II-restricted TCR in selecting and non-selecting MHC backgrounds respectively. The phosphorylation of ZAP-70 in DP thymocytes of class I-restricted TCR-Tg was significantly higher in the positively selecting background than in the non-selecting one. However, such a phosphorylation difference between selecting and non-selecting TCR-Tg was found to be considerably less in class II-restricted TCR-Tg. A similar bias for ZAP-70 phosphorylation was also observed on selecting DP thymocytes when I-A(beta) deficient- and beta2-microglobulin-deficient mice were compared. These ex vivo studies suggest that TCR-mediated signaling on DP thymocytes induces ZAP-70 phosphorylation under a different manner of engagement of TCR to class I and class II molecules in the positive selection process.

Animals↗
PubMed1998

Patterns of care study of radiation therapy for cervix cancer in Japan: the influence of the stratification of institution on the process.

BACKGROUND: To improve the quality of radiation oncology in Japan, Patterns of Care Study (PCS), a widely known quality assurance (QA) program in the USA, was introduced. The feasibility was tested by collecting nationwide data by extramural audit for cervix cancer. METHODS: From July 1996 through February 1997, PCS audits were performed for 29 institutions nationwide. On the basis of the facility survey by Tsunemoto, 13 institutions were classified as A1 (university hospital/cancer center), 10 as B1 (other institutions treating >120 patients/year) and six as B2 (other institutions treating <120 patients/year). Medical charts for the patients treated for cervix cancer between 1992 and 1994 were reviewed based on the data format of the US PCS. The total number of patients surveyed was 432. RESULTS: Simulation was used for >90% of the patients in both A1 and B1-2 institutions. However, in B1-2, planning for 5% of the patients was performed with only a clinical set-up (p = 0.0287). A daily fraction with a size of 200 cGy was given to >65% of patients in A1 and to <47% in B1-2. On the other hand, >50% of those in B1-2 were treated with daily fractions of 180 cGy and less compared with 25% in A1 institutions (p < 0.0001). Brachytherapy was utilized more frequently for patients in Stages II (p = 0.0365), III (p = 0.0015) and IV (p = 0.0483) in A1 than in B1-2. As for external beam equipment, linear accelerators with 10 MV or more were used for 83% of the patients in A1. However, in B1-2 institutions, machines with lower energy were used for 38% of the patients (p < 0.0001). The median number of full-time-equivalent (FTE) radiation oncologists was 2.7 in A1, 0.65 in B1 and 0.2 in B2. CONCLUSIONS: Institutional stratification, including equipment and personnel, was found to affect significantly the patterns of care for cervix cancer. Therefore, to improve the quality of radiation therapy nationwide, improvements in equipment and in supply of FTE personnel are extremely important. PCS was found to have great potential for a practical evaluation of how much improvement will be required in Japan.

Adult↗
PubMed1998

Reversible ischemia in hippocampal areas by retrograde cerebral circulation surgery for thoracic aortic aneurysm with Tc-99m ECD brain SPECT.

Because hippocampal neurons are quite vulnerable to the anoxic brain injury that sometimes occurs in aortic arch surgery in humans, hippocampal ischemia should be a sensitive indicator of global cerebral ischemia. It was concluded that the hypothermic retrograde cerebral circulation technique for aortic arch surgery could not only be performed safely with respect to the brain, but could also increase blood flow to the hippocampal areas, probably as a result of restoration of blood flow in the thoracic aorta.

Adult↗
PubMed1998

Decreased hippocampal blood flow related to memory impairment after cardiovascular surgery: assessment by reconstructed SPECT parallel to the longitudinal axis of the hippocampal formations.

Hippocampal damage has been linked to memory impairment. To clarify the relationship between decreased hippocampal blood flow and memory impairment in patients after cardiovascular surgery, the authors compared Tc-99m HMPAO SPECT findings and Mini Mental State Examination (MMSE) scores. Eight patients who had valve replacement, two who underwent aorto-coronary bypass, two who had aortic aneurysm replacement and one who had a ventricular septal defect closure were included in this study. Cerebral perfusion was estimated using reconstructed tomographic images, which were parallel to the longitudinal axis of the hippocampal formations. The hippocampal uptake ratios of Tc-99m HMPAO were calculated and normalized to that of the cerebellum. In three patients whose MMSE score decreased after surgery, the hippocampal uptake ratio was significantly reduced (0.69 +/- 0.09) compared with the remaining 10 patients whose MMSE scores did not decrease after surgery (0.91 +/- 0.02). These data suggest that SPECT imaging parallel to the longitudinal axis of the hippocampus is sensitive to decreased hippocampal blood flow, and decreased hippocampal blood flow is related to memory impairment in some patients after cardiovascular surgery.

Adolescent↗
PubMed1998

Comparison of dual-isotope acquisition of 201Tl and 99Tcm-tetrofosmin for the detection of ischaemic heart disease and determination of the optimal imaging time of 99Tcm-tetrofosmin.

Comparative studies of thallium-201 (201Tl) and 99Tcm-tetrofosmin for the detection of ischaemic heart disease (IHD) have previously been reported. These 201Tl and 99Tcm-tetrofosmin studies were usually performed separately with different exercise loads at an interval of several days. Here, we used a dual-isotope technique with exercise myocardial SPET (single photon emission tomography) in 17 patients with IHD and 10 patients with normal coronary arteries. The triple-energy window (TEW) method was applied for cross-talk correction. SPET imaging was performed at 10 and 70 min (S1 and S2) after the injection of 99Tcm-tetrofosmin (222 MBq) and 201Tl (74 MBq) at peak exercise to determine the optimal imaging time of 99Tcm-tetrofosmin. The S2 value was obtained 35 min after the subject drank a glass of milk to accelerate hepatobiliary clearance. Twenty-five minutes after S2, 37 MBq of 201Tl were reinjected at rest and SPET imaging (S3) was performed. Immediately after S3, 666 MBq of 99Tcm-tetrofosmin were reinjected and SPET imaging (S4) was performed 50 min later. Representative short and vertical long axis tomograms were divided into 17 segments. Each segment was assessed using a 4-point scoring system. The defect score was defined as the sum of each segmental score. The defect scores for imaging at exercise were 14.3 +/- 11.4 for 201Tl at S1, 11.4 +/- 8 for 99Tcm-tetrofosmin at S1 and 9.7 +/-9.8 for 99Tcm-tetrofosmin at S2 (P < 0.01), respectively. The washout rate of 99Tcm-tetrofosmin for the first hour was 15.5 +/- 7.3% and 11.8 +/- 7.7% (P < 0.01), respectively, for the normal and ischaemic segments. The image quality of 201Tl at S1 was almost equivalent to that of 99Tcm-tetrofosmin at S1/S2. The overall sensitivity and specificity for the detection of ischaemia was 94% and 82% for 201Tl at S1, 89% and 86% for 99Tcm-tetrofosmin at S1, and 88% and 95% for 99Tcm-tetrofosmin at S2, respectively. The overall accuracy was 86%, 88% and 92%, respectively. The myocardial viability score was 7.4 +/- 7.1 for 201Tl at S3 and 5.8 +/- 7.0 for 99Tcm-tetrofosmin at S4 (P < 0.01). The results indicate that the diagnostic accuracy of 99Tcm-tetrofosmin for myocardial ischaemia is almost equivalent to that of 201Tl as assessed by dual SPET imaging, and that the optimal imaging time for 99Tcm-tetrofosmin is within 10-35 min (S1) after exercise.

Coronary Disease↗
PubMed1998

Increased use of inhaled corticosteroids and reduced hospitalizations in adult asthmatics: 11 years' experience in a Japanese hospital.

Until recently, inhaled corticosteroids have not been recognized as a first-line drug mainly because of the traditional polypharmaceutical approach to asthma in Japan. To examine the trend more precisely following the introduction of inhaled corticosteroids, we retrospectively analysed the relation between the number of prescriptions for anti-asthma drugs including inhaled corticosteroids and the number of hospitalizations due to asthma exacerbation, near fatal episodes and deaths from asthma for a period of 11 years from 1986 to 1996 at Kobe City General Hospital (KCGH). A marked decline in these actual indices in patients attending KCGH, which shows the improvement in asthma control, started coincidentally with the increased use of inhaled corticosteroid, which was followed by both a discontinuation of the trend for increased use of inhaled beta-agonists and the decreased use of oral anti-asthma agents. There was no significant difference in the mean duration of hospital stays between 1988 and 1996. Although the intensification of patient education is likely to play an important role in enhancing the protective effect of inhaled corticosteroids, we highly suspect that the major contributory factor in the great decline in hospitalizations is the increased use of inhaled corticosteroids.

Administration, Inhalation↗
PubMed1998

IL-1ra versus IL-1 levels in prostatic fluid from prostatitis patients.

Recent papers reported that the balance between the production of IL-1ra and IL-1 probably influences the regulation of host responses, the severity and prolongation of the inflammatory reaction in some diseases. Therefore, in our continuing investigation to clarify the significance of leukocytosis and its prolongation in prostatic fluid from prostatitis patients, we investigated whether low levels of IL-1ra versus IL-1 beta secreted in prostatic fluid were the cause of prolonged prostatitis, especially nonbacterial prostatitis (NBP). As a result of the present study, we concluded that a low level of IL-1ra in relation to that of IL-1 secreted in prostatic fluid is unlikely to cause prolongation of NBP for the following reasons: (1) IL-1 beta was detected in 5 of 10 cases (50.0%), but was slightly elevated in only 2 cases (20.0%) at 14 and 17 pg/ml; (2) the average IL-1ra level was not statistically low compared with that in prostatic fluid from acute bacterial prostatitis (ABP) patients who were cured promptly with antibiotics, and (3) in 5 cases of NBP in which IL-1 beta was detected, the average IL-1ra/IL-1 beta ratio was 118 which was comparable to or even higher than that in 3 ABP and 14 acute bacterial cystitis cases in which IL-1 beta was detected and the ratios were 40 and 88, respectively.

Adult↗
PubMed1998

Detection of activated platelets in urine by double immunofluorescence in children with IgA nephropathy.

The relationship between the activation of platelets (PLT) in urine and renal histological findings in children with IgA nephropathy (IgAN), thin basement membrane disease (TBMD), and minimal-change nephrotic syndrome (MCNS) was examined. The ratio of activated PLT to total PLT (activated and nonactivated PLT) was examined by double immunofluorescence using rhodamine-conjugated P selectin antibody (activated PLT) and fluorescein isothiocyanate conjugated PLT membrane glycoprotein antibody (GPIIb/IIIa, total PLT); the effect of urine on activation on PLT was also investigated. The number of activated PLT and the ratio of activated PLT to total PLT in urinary sediments were significantly higher in children with IgAN with diffuse mesangial proliferation than in those with TBMD or MCNS. PLT were activated by addition of urine in 13 out of 27 children with IgAN, and the activity was higher in the urine of those with active glomerular or interstitial lesions, while the urine of children with TBMD or MCNS had no effect. The presence of activated PLT and the effect of urine on PLT activation may be associated with the active glomerular or interstitial lesions in IgAN.

Adolescent↗
PubMed1998

Power spectral analysis of heart rate variability in a horse with atrial fibrillation.

This study has demonstrated the power spectral analysis of heart rate variability in a horse with atrial fibrillation. A large peak in the high frequency (HF) area of the power spectrum appeared in the horse. Hourly heart rate, the low frequency (LF) power, the HF power, and LF/HF ratio were almost constant during the recording period. The values of HF and LF power in the horse with atrial fibrillation were much larger than those in normal horses. The normalized unit of HF (HF n.u.) was much larger than that of LF (LF n.u.). Furthermore, the LF/HF ratio was very small in the horse. These results suggest that the ventricular rhythm has a respiratory related periodicity in the horse with atrial fibrillation and the predominant parasympathetic activity may modulate the intrinsic behavior of the atrioventricular node during atrial fibrillation.

Animals↗
PubMed1998

[Reproductive and developmental toxicity study of sodium N-[2-[4-(2,2-dimethylpropionyloxy) phenylsulfonylamino] benzoyl] aminoacetate tetrahydrate (ONO-5046.Na (1). Fertility study in rats].

Fertility study of sodium N-[2-[4-(2,2-dimethylpropionyloxy) phenylsulfonylamino] benzoyl] aminoacetate tetrahydrate (ONO-5046.Na), a novel neutrophil elastase inhibitor, was conducted in Sprague-Dawley (SD) rats. ONO-5046.Na was administered intravenously at doses of 18.75, 37.5 and 75 mg/kg/day to male rats from 64 prior to mating, through the mating period and until necropsy, and to female rats from 15 days prior to mating until Day 7 of gestation, in order to examine its effects on fertility and reproductive performance of males and females and the development of their fetuses. There were no changes attributable to ONO-5046.Na in general signs, body weight, food consumption or autopsy findings in males and females. No drug-related changes were observed in estrous cycles, copulation and fertility indices in males and females. Pituitary weight of dams was decreased in each of the ONO-5046.Na treated groups, but no histopathological changes were observed in the pituitary. In the cesarean section findings in dams, ONO-5046.Na had no effects on the number of corpola lutea, the number of live fetuses, the implantation ratio, the resorbed and dead fetus ratio, fetal or placental weight, or the incidences of external, skeletal or visceral anomalies of the fetuses. From these results, it is considered that the NOAEL of ONO-5046.Na is 75 mg/kg/day for general and reproductive toxicity in males and females and for developmental toxicity in their fetuses.

Animals↗
PubMed1998

[Reproductive and developmental toxicity study of sodium N-[2-[4-(2,2-dimethylpropionyloxy) phenylsulfonylamino] benzoyl] aminoacetate tetrahydrate (ONO-5046.Na) (2). Study for effects on pre- and postnatal development in rats, including maternal function].

Prenatal and postnatal toxicity of sodium N-[2-[4-(2,2-dimethylpropionyloxy) phenylsulfonylamino] benzoyl] aminoacetate tetrahydrate (ONO-5046.Na), a novel inhibitor of human neutrophil elastase, was studied in Sprague-Dawley (SD) rats. ONO-5046.Na was injected intravenously at doses of 0, 18.75, 37.5 and 75 mg/kg/day to pregnant rats from day 7 of pregnancy to day 20 after delivery. All pregnant rats were allowed to deliver naturally for postnatal examination of their offspring. No adverse effects on dams were observed in clinical signs, body weight change, food consumption, pregnant, delivery or lactating performances. ONO-5046.Na did not affect the postnatal development of offspring, including birth index, survival index, physical and functional development, motor activity, emotionality, learning ability and reproductive performance. From these results, it is considered that the NOAEL of ONO-5046.Na is 75 mg/kg/day for dams and their offspring.

Animals↗
PubMed1998

[Reproductive and developmental toxicity study of sodium N-[2-[4-(2,2-dimethylpropionyloxy) phenylsulfonylamino] benzoyl] aminoacetate tetrahydrate (ONO-5046.Na) (3). Teratogenicity study in rabbits].

Teratogenicity of sodium N[2-[4-(2,2-dimethylpropionyloxy) phenylsulfonylamino]benzoyl] aminoacetate tetrahydrate (ONO-5046.Na), a novel inhibitor of human neutrophil elastase, was studied. ONO-5046.Na was injected intravenously at doses of 0, 7.5, 15 and 30 mg/kg/day to pregnant Kbl: NZW rabbits from day 6 to day 18 of pregnancy. All female rabbits were sacrificed on day 29 of pregnancy and their fetuses were examined. There were no clinical signs or death attributable to ONO-5046.Na. One dam in the control group and 3 dams in the 30 mg/kg/day group aborted. Body weight gain in the 15 and 20 mg/kg/day groups and food intake in the 30 mg/kg/day group were decreased during the administration period. These changes had recovered by the end of the study. Kidney weight was increased in the 30 mg/kg/day group. There were no effects of ONO-5046.Na in necropsy findings at cesarean section in dams at any dose levels. Developmental toxicity of ONO-5046.Na was not found at any dose levels. From these results, it is considered that the NOAEL of ONO-5046.Na is 7.5 mg/kg/day for pregnant animals and 30 mg/kg/day for fetuses.

Animals↗
PubMed1998

Efficacy and limitation of F-18-fluorodeoxyglucose positron emission tomography during fasting to assess myocardial viability in the acute phase of myocardial infarction.

OBJECTIVE: The present study was designed to determine the ability of positron emission tomography (PET) to assess myocardial viability and ischemia in acute myocardial infarction (MI) after reperfusion therapy (thrombolysis and/or coronary angioplasty). METHODS: PET with fluorine-18-labeled fluorodeoxyglucose (FDG) under fasting conditions and thallium-201 single-photon emission computed tomography (TL) were analyzed in 21 patients one week following MI. Myocardial viability was also assessed by regional wall motion using serial analysis of 2-D echocardiography or left ventriculography. RESULTS: Marked uptake of FDG together with a residual perfusion defect were observed in the infarct region in all patients one week post MI. However, in 9 of the 21 patients, the infarct-related coronary artery had no significant stenosis after reperfusion therapy and remained patent in one month post MI suggesting no myocardial ischemia. In contrast, in 4 of the 21 patients the regional wall motion was akinetic and there was a complete defect observed with TL imaging at one month post MI, indicating no viability in the infarct region. CONCLUSIONS: PET using fasting FDG at one week post MI had a limitation to predict myocardial viability or ischemia.

Acute Disease↗
PubMed1998

Mechanism of impaired left ventricular wall motion in the diabetic heart without coronary artery disease.

OBJECTIVE: To elucidate whether impairment of the myocardial free fatty acid (FFA) metabolism and small vessel abnormalities in the myocardium are etiologic or contributory factors of myocardial dysfunction in patients with NIDDM without any significant coronary artery disease. RESEARCH DESIGN AND METHODS: We performed myocardial imaging with 123I-labeled beta-methyl-p-iodophenyl pentadecanoic acid (BMIPP), a branched analog of FFA, and dipyridamole-infusion 201thallium scintigraphy (Dip) in nine patients who demonstrated left ventricular wall motion abnormalities without any significant coronary artery disease and in fifteen control cases. As an index of myocardial FFA metabolism, the heart-to-mediastinum count ratio (H/M) of BMIPP was calculated from the mean count in the regions of interest at the heart and the upper mediastinum. RESULTS: Nine patients with reduced wall motion documented by left ventriculography (LVG), (hypokinetic group) demonstrated significantly lower BMIPP uptake (2.1 +/- 0.2, mean +/- SD) than fifteen patients with normal wall motion (normokinetic group) (2.3 +/- 0.2, P < 0.05). Regional ventricular wall motion observed by LVG, regional BMIPP uptake, and regional redistribution phenomenon (RD) were evaluated for five regions of the left ventricle: anterior, septal, apical, lateral, and inferoposterior regions. Wall motion was abnormal in 24 out of 120 regions. Regional BMIPP uptake was reduced in 47 regions. RD in Dip was observed in 23 regions. In regional analysis, the existence of defect in the BMIPP image showed significant correlation with wall motion abnormality (P < 0.01), but there was no significant relationship between the RD in Dip and regional wall motion abnormality (P = 0.16). Myocardial biopsy specimens obtained from the right ventricle of 20 patients showed no pathologic changes, with the exception of two patients. CONCLUSIONS: Our findings suggest that impairment of myocardial FFA metabolism rather than small vessel abnormalities in the myocardium is responsible for modest left ventricular dysfunction in patients with diabetes.

Adult↗
PubMed1998

Changes in mechanical strength of intramuscular connective tissue during postmortem aging of beef.

We studied changes in mechanical strength during postmortem aging of bovine semitendinosus muscle using intramuscular connective tissue (IMCT) preparations from muscle stored at 4 degrees C. In the preparation, muscle fiber elements were removed, leaving a virtually intact structure of the endomysium and perimysium. The shear-force value of the IMCT preparation remained unchanged up to 10 d postmortem and decreased linearly thereafter. The yield of the perimysial fraction, which was measured as an indicator of mechanical properties of the perimysium, remained almost unchanged up to 14 d postmortem, and decreased gradually thereafter. These results suggest that the mechanical strength of the intramuscular connective tissue changes slowly during postmortem aging of beef; it remains almost unchanged for up to 10 d postmortem and progressively decreases thereafter. Thus, intramuscular connective tissue seems to affect beef tenderization in extended aging.

Animals↗
PubMed1998

Basic and clinical studies on ApoE gene typing by line probe assay (LiPA) as a biological marker for Alzheimer's disease and related disorders: multicenter study in Japan.

The fundamental reagent capability and clinical significance of ApoE gene typing has been investigated. The result of each test shows that the reagent capability satisfied the expected standard. Four-hundred thirty-nine samples classified into three groups (Alzheimer's disease (AD), other types of dementia and nondementia) were measured to examine the clinical significance. The rate of epsilon 4 genotype of each group was 31.5%, 14.6%, 10.4%, respectively. The AD group had a higher rate than the other groups (p < 0.001). The measurement of ApoE genotype is suggested to be useful as one of the guidelines in the diagnosis of AD.

Age Factors↗