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T Nishimura

Publications and source records attributed to T Nishimura.

At least 163 records · Page 9Linked to original sources
PubMed2000

Effect of 4-tert-octylphenol on cytochrome P450 enzymes in rat liver.

The effects were studied of 4-tert-octylphenol (OP) on hepatic cytochrome P450 enzymes in rats. Rats were treated intraperitoneally with OP twice, at doses of 5, 10, and 20 mg/kg. Among the cytochrome P450-dependent monooxygenase activities, testosterone 2alpha-hydroxylase activity, which is associated with CYP2C11, was significantly decreased by OP at all doses. The level relative to control activity was 67-22%. CYP3A2-dependent monooxygenase, testosterone 6beta-hydroxylase activity was also decreased by 51% by OP at 20 mg/kg. Furthermore, immunoblotting showed that OP (10 or 20 mg/kg) significantly decreased CYP2C11/6 and CYP3A2/1 protein levels. However, the reduction ratio of CYP2C11/6 and CYP3A2/1 protein levels by OP treatment was lower than that of testosterone 2alpha-hydroxylase and testosterone 6beta-hydroxylase activities. The Cl(int) (Vmax/Km) value for testosterone 2alpha-hydroxylase was significantly decreased by OP at all doses, whereas the Cl(int) value for testosterone 6beta-hydroxylase was only decreased by OP at 20 mg/kg. In addition, 7-ethoxycoumarin O-deethylase activity was significantly decreased by 32% by the highest dose of OP. By contrast, CYP1A1-, CYP1A2-, CYP2A1-, CYP2B1/2-, CYP2D1-, CYP2E1- and CYP4A1/2/3-dependent monooxygenase activities were not affected by OP at any dose. These results suggest that OP changes the male-specific cytochrome P450 isoforms in rat liver, and that these changes closely relate to the toxicity of OP.

Animals↗
PubMed2000

Detection of viable cortical neurons using benzodiazepine receptor imaging after reversible focal ischaemia in rats: comparison with regional cerebral blood flow.

To elucidate the utility of benzodiazepine receptor imaging for the detection of viable cortical neurons, dual-tracer autoradiography using iodine-125 iomazenil (IMZ) and iodine-123 N-isopropyl-4-iodoamphetamine (IMP) was performed in a model of reversible focal ischaemia during the acute and subacute phases. The right middle cerebral artery of anaesthetized rats was occluded for 60 min using an intraluminal filament and reperfused. In the acute phase study, 125I-IMZ (370 kBq) was injected via the femoral vein at 2 h after reperfusion, and 123I-IMP (37 MBq) was injected at 50 min post-injection. Rats were sacrificed 10 min after the injection of 123I-IMP. In the subacute phase study, the same procedure was performed at 5 days after reperfusion. In the acute phase, the IMP uptake was significantly decreased in almost all areas of the lesioned hemisphere, an exception being the cerebellum; however, the IMZ uptake was significantly decreased only in ischaemic cores. The discrepancy between IMZ and IMP uptake was observed in the lateral neocortex and the lateral caudate putamen (CPu), which were most frequently damaged in this ischaemic model. In the subacute phase, the IMZ uptake in lesioned rats was significantly decreased only in the parietal lobe and hippocampus, though the IMP uptake was decreased in many regions of lesioned hemispheres (the frontal, parietal cortex, CPu, hippocampus and thalamus). Histopathological findings indicated that both the IMP and the IMZ uptake was markedly decreased in necrotic areas. Although the IMP uptake was significantly decreased in the ischaemic areas, the IMZ uptake was maintained in these areas. These results suggest that benzodiazepine receptor imaging is superior to regional cerebral blood flow imaging for the detection of viable cortical neurons in both the acute and subacute phases of ischaemia.

Animals↗
PubMed2000

Bilateral Jejuno-mesenteric flap for reconstruction of complicated pharyngoesophageal defect.

The surgical management of an infectious and fistulous wound with a pharyngoesophageal tumor is one of the greatest challenges for head and neck and plastic surgeons. The free jejunal transfer has been the standard technique for pharyngoesophageal reconstruction, and the free omental flap has been one of the most reliable methods for reconstructing contaminated wounds. A jejuno-mesenteric flap is suitable for such complicated wounds. Pharyngoesophageal defects are reconstructed by the jejunum, and contaminated and heavily irradiated neck wounds are covered with the mesenteric flaps connected with a revascularized jejunum. The technique described here possesses the advantages of both a free jejunal flap and an omentum flap. Therefore, it is a reliable method for reconstructing the pharyngoesophageal defects of complicated wounds.

Esophageal Neoplasms↗
PubMed2000

The neural basis of perceptual and conceptual word priming--a PET study.

Positron emission tomography scans were obtained in 13 normal subjects during perceptual and conceptual word priming tasks with the aim to investigate the neural system specific to the two priming conditions. In the prescan phase, subjects were primed perceptually or conceptually with two separate procedures, while in the scan phase, they performed the same stem completion task. Therefore we could compare the results of the two priming tasks in a direct manner. A fixation control task and a baseline task (completion of stems that did not correspond to previously seen words) were also given. A specific blood flow decrease was found in the left inferior temporal cortex in the perceptual word priming condition and in the left superior temporal / inferior parietal cortex in the conceptual word priming condition. Each blood flow change may reflect transient changes in the cortical areas subserving the processing of the perceptual and conceptual components of word priming.

Adult↗
PubMed2000

Interaction of bisphenol A with rat hepatic cytochrome P450 enzymes.

The effect of bisphenol A (BPA) on the kinetics of cytochrome P450 (P450)-dependent monooxygenases in rat liver microsomes was studied. Testosterone 16beta-hydroxylase (TS16BH) and testosterone 2alpha-hydroxylase (TS2AH) activities were extensively inhibited by BPA at 100 microM (69% and 74%, respectively). The inhibition type was mixed for both P450-dependent monooxyganases. The Ki of TS16BH and TS2AH from Lineweaver-Burk plots were 25.9 and 24.9 microM, respectively. The activities of acetanilide 4-hydroxylase (AA4H), 7-ethoxycoumarin O-deethylase (ECOD), bufuralol 1'-hydroxylase (BF1'H), chlorzoxazone 6-hydroxylase (CZ6H) and testosterone 6beta-hydroxylase (TS6BH) were also effectively inhibited by BPA at 100 microM (43-52%). The inhibition type of these P450-dependent monooxygenases was mixed or uncompetitive, and the K(i)s (50.5-88.5 microM) were higher than those of TS16BH and TS2AH. By contrast, the values of IC50 and Ki of testosterone 7alpha-hydroxylase (TS7AH) and lauric acid omega-hydroxylase (LAOH) for BPA were >1000 microM. These results suggest that BPA interacts with rat hepatic CYP1A2, CYP2A2, CYP2B2, CYP2C11, CYP2D1, CYP2E1 and CYP3A2 in vitro.

Air Pollutants, Occupational↗
PubMed2000

Uveal effusion syndrome: clinical features, surgical treatment, histologic examination of the sclera, and pathophysiology.

PURPOSE: To clarify clinical features and pathophysiology and to evaluate surgical outcome of subscleral sclerectomy for primary uveal effusion syndrome. DESIGN: Prospective, consecutive noncomparative case series. PARTICIPANTS: Nineteen eyes of 16 patients diagnosed with uveal effusion syndrome treated in our clinic between 1989 and 1998. METHODS: Patients were examined by routine ophthalmologic examinations, fluorescein and indocyanine green angiography; measurement of the axial length of the eyeball; magnetic resonance imaging; and echography. Subscleral sclerectomy (sclerectomy under the scleral flap) was performed at the equator on all patients. Histologic examination of excised sclera was carried out on all samples. Patients were followed for outcome over time. MAIN OUTCOME MEASURES: Reattachment of the choroid and retina with resolution of the serous fluid. RESULTS: Three subgroups were identified: In type 1, nanophthalmic eye; the eyeball is small (average axial length 16 mm) and high hypermetropic (average +16 diopters); in type 2, the eyeball size is normal (average axial length 21 mm) with small refractive error; and in type 3, the eyeball size is normal. Histologically, types 1 and 2 demonstrated abnormal sclera with disorganization of collagen fiber bundles and deposits of proteoglycans in the matrix, whereas type 3 showed normal sclera. Subscleral sclerectomy was effective for types 1 and 2, inducing postoperative resolution of the subretinal fluid. However, type 3 eyes were not helped by this technique. CONCLUSIONS: Primary uveal effusion syndrome is caused by abnormalities of the sclera and increased resistance to transscleral fluid outflow as subscleral sclerectomy is an effective treatment in types 1 and 2 only, correct preoperative classification is essential for early surgical management.

Adult↗
PubMed2000

Biodistribution of 3,4-dihydro-5-[11C]methoxy-1(2H)-isoquinolinone, a potential PET tracer for poly(ADP-ribose) synthetase.

Poly(adenosine diphosphate-ribose) synthetase (PARS) is a nuclear enzyme that is activated by deoxyribonucleic acid (DNA) strand breaks and participates in DNA repair. Excessive PARS activation, however, leads to cell death due to depletion of adenosine triphosphate (ATP). To evaluate whether it is possible to detect excessive activation of PARS with positron emission tomography (PET), we examined the pharmacokinetics of 3,4-dihydro-5-[(11)C]methoxy-1(2H)-isoquinolinone ([(11)C]MIQO), a potent poly(ADP-ribose) synthetase inhibitor, in the brain of rats and monkeys. Although the uptake of [(11)C]MIQO in the brain of normal rats was low, [(11)C]MIQO was rapidly incorporated into and then quickly washed out from the brain. The uptake of the radiotracer in the brain of normal monkeys was also low; however, [(11)C]MIQO gave a distribution image that differed from that of cerebral blood flow obtained by [(15)O]water-PET. No localization of [(11)C]MIQO in the brain of normal monkeys was observed. Low accumulation of some radioactivity was also observed in muscles surrounding the brain of monkeys, but did not seem to interfere with measurement of [(11)C]MIQO uptake in the brain with PET. Thus, detection of [(11)C]MIQO uptake with PET may be useful for detecting PARS activity in ischemic injury.

Animals↗
PubMed2000

Potentiation of antitumor effect of NKT cell ligand, alpha-galactosylceramide by combination with IL-12 on lung metastasis of malignant melanoma cells.

The combined therapeutic effect of natural killer T (NKT) cell ligand alpha-galactosylceramide (alpha-GalCer) and IL-12 against highly metastatic B16-BL6-HM melanoma cells was investigated. In comparison with a single administration of alpha-GalCer or IL-12, the combined treatment of tumor-bearing mice with alpha-GalCer plus IL-12 caused a super-induction of serum IFN-gamma levels, though alpha-GalCer-induced IL-4 production was rather inhibited. In parallel with the augmented IFN-gamma production, the natural killing activity against YAC-1 cells and syngeneic B16-BL6-HM melanoma was greatly augmented by the combined therapy. The major effector cells responsible for natural killing activity induced by alpha-GalCer plus IL-12 were enriched in both NK1.1+ TCRalphabeta+ NKT cells and NK1.1+ TCRalphabeta- NK cells. The preventing effect of alpha-GalCer or IL-12 alone against lung metastasis of B16-BL6-HM was also enhanced by the combination therapy. The antitumor activity of alpha-GalCer was totally abolished in NKT-deficient mice. However, IL-12-induced antitumor activity was not eliminated in NKT-deficient mice though it was inhibited by anti-asialo GM1 Ab treatment. These findings suggested that alpha-GalCer synergistically act with IL-12 to activate both NKT cells and NK cells, which may play a critical role in the strong prevention of distant tumor metastasis at early stages of tumor-bearing. These data will provide a novel tool for the prevention of tumor metastasis using NKT-specific ligands alpha-GalCer and IL-12.

Animals↗
PubMed2000

A new method for assaying adhesion of cancer cells to the greater omentum and its application for evaluating anti-adhesion activities of chemically synthesized oligosaccharides.

A new ex vivo method for assaying adhesion of cancer cells to the greater omentum has been developed using mouse greater omentum and [3H]labelled human gastric and mouse colorectal cancer cells. Since the adhesion rates were found to increase up to 18 h and labelled cells seemed to be stable during the period, the present method could be useful for investigating adhesion of cancer cells to the greater omentum, which must occur at the first step of the peritoneal dissemination. The adhesion of cancer cells to the greater omentum was inhibited by a series of chemically synthesized oligosaccharides and Gal beta1,3[3OMeGal beta1,4GlcNAc beta1,6]alphaBn was found to be the best inhibitor. The anti-tumor effect of this novel tetrasaccharide in vivo was shown in preliminary experiments using Balb/c mice and colon26 cells.

Animals↗
PubMed2000

A clinical study on suicide among schizophrenics.

We conducted a clinical investigation of 80 suicides who met the DSM-III-R criteria for schizophrenia. The results using this approach showed no significant difference with those of preceding studies, and general features regarding the phenomenology of suicide among schizophrenics worldwide were recognized. The present study, however, served to underscore the following points: (i) suicide of schizophrenics must be considered a concern at all stages of the disease; (ii) the subjective strength of the will to die may be more important for the committing suicides than the lethality of the methods employed; and (iii) a change in the environment, for example, a hospital admission or discharge, may trigger suicide. A control group of 80 living schizophrenics with no past attempted suicide was then matched to the suicide group with respect to sex and illness duration, in order to identify the predictors of suicide. In a logistic regression analysis, the presence of suicidal ideation, degree of anxiety estimated by positive and negative syndrome scale, and birth order were revealed as predictors of suicide. As to the birth order, the risk is higher in middle children.

Adult↗
PubMed2000

Rotavirus infection in children in Japan.

Currently, a high morbidity of rotavirus diarrhea has been seen in children in developed and developing countries. Improvement of the vaccines is necessary in order to reduce the burden of diarrhea caused by rotavirus. A survey of rotavirus infection from diarrheal stool specimens in children of seven regions in Japan was conducted from 1984 to 1999. The present study discusses the survey results and reviews the national and international data of more than 23 papers and congress proceedings about rotavirus infection in Japan. We analyze the prevalence of rotavirus infection in acute diarrheal in- and outpatients, the distribution of rotavirus G-serotypes and surveillance data for seasonality and age groups in Japan. The data indicated that rotavirus is the most important cause of diarrhea in Japan among young children, with the prevalence ranging from approximately 9.7 to 88%. The most common rotavirus strains belonged to serotype G1, specifically since 1993. Serotypes G2, G3 and G4 had also been documented to be predominantly based in the area and year before 1992. However, untypeable rotavirus strains had been found each year, with a prevalence up to 56.7% which suggests that rare serotypes (except G1-4) or new serotypes might exist. Unexpectedly, in Tokyo and Sapporo from 1998 to 1999, G9 was found to be the first most prevailing serotype with a high prevalence of 52.9 and 71.4%, respectively. Despite these data from different geographic areas, the year under investigation was relatively clear in respect to seasonality, with a peak of rotavirus activity in late winter (February) through early spring (March). Age distribution had also characterized that the infection was predominant among children aged 1-2 years of age, although it was also common in children of 2-3 years. In addition, mixed infection with bacteria was documented.

Adolescent↗
PubMed2000

Post-voiding repeated renal ultrasonography for slight hydronephrosis detected during screening for asymptomatic microhematuria.

BACKGROUND: There is not a well established method for further screening of asymptomatic microhematuria found through annual health examinations. However, it is apparent that a large number of examiners are using ultrasonography for screening. When slight hydronephrosis is found through screening, it is difficult to determine whether further examinations, such as intravenous pyelography (IVP), should be performed. In this paper, we discuss the usefulness of post-voiding repeated renal ultrasonography, which was applied to 57 patients with slight hydronephrosis found in a screening. METHODS: Ultrasonography in the kidney and the urinary bladder at the ultrasound laboratory of Toma Hospital was carried out on a total of 1906 patients with asymptomatic microhematuria, which was found by routine annual health examination, from January 1996 to December 1998. Slight hydronephrosis was found in 57 (14 males and 43 females) of 1906 patients and post-voiding repeated renal ultrasonography was carried out on all patients. RESULTS: Slight hydronephrosis had disappeared and IVP was avoided in 22 (38.6%) of 57 patients. Of 35 cases in which slight hydronephrosis persisted after urination, there were no abnormalities on IVP in 32 patients, while abnormalities were found in three patients. Two of these had ureteropelvic junction stenosis and the remaining one had a ureteral stone. CONCLUSION: The results of this study indicate that post-voiding repeated renal ultrasonography is useful for avoiding unnecessary further examination to determine whether upper urinary tract obstruction exists, when slight hydronephrosis is observed upon screening by simultaneous renal and urinary bladder ultrasonography for asymptomatic microhematuria.

Female↗
PubMed2000

Renal masses detected by general health checkup.

BACKGROUND: A total of 60,604 persons underwent a general health checkup at Toma Hospital, Saitama, Japan, between January 1993 and June 1997, and transabdominal ultrasonography (US) was performed on all persons. We investigated the usefulness of transabdominal US in detecting renal tumors during general health checkups. METHODS: A definite diagnosis was made in cases where the re-examination by US revealed calculus with acoustic shadow or a simple cyst. Computed tomography (CT) was conducted in patients suspected of having a renal tumor, and a diagnosis of renal angiomyolipoma (AML) was made if plain CT gave evidence of a fatty component. Patients diagnosed as having a renal cell carcinoma (RCC) with non-uniform enhancement underwent nephrectomy. If a definite diagnosis could not be made even by contrast CT, the monitoring by US and contrast CT once a year was continued. RESULTS: Of 97 (0.16%) patients whose transabdominal US findings indicated a diagnosis of suspected renal tumor, 58 underwent the re-examination by US; of these, CT was conducted in 47. Detailed US revealed a hyperechoic pattern in 44 patients, a mixed pattern in nine and an isohypoechoic pattern with internal echo in five. By plain CT, 24 patients were diagnosed as having AML, and two as having renal calcification. Contrast CT enabled a diagnosis of renal cyst to be made in two patients and renal tumor in 14. All 14 patients with RCC except one underwent nephrectomy, which provided pathologic evidence supporting the diagnosis. Five patients had a tumor unidentifiable by CT, with continuing periodic follow-up by US and CT. Eleven patients underwent no CT. CONCLUSION: Of the 60,604 persons who underwent a general health checkup, we found 14 cases of RCC and 24 cases of AML. As a small RCC has a favorable prognosis, patients greatly benefit from early detection; therefore, we should recognize the importance of identifying renal masses by US screening during general health checkups.

Adolescent↗
PubMed2000

Preprimed artificial lung for emergency use.

We investigated the possibility of preprimed storage of an artificial lung (AL), aiming at facilitating its emergency use. Test ALs, consisting of a special microporous hollow fiber membrane made of polyolefin in which direct blood-gas contact was completely eliminated, were preprimed with saline solution, sterilized by gamma-ray irradiation, and evaluated after 1-3 months of storage at room temperature. A small amount of bubble was noted in the priming solution after storage in some ALs, which most likely originated from the air dissolved in the priming solution or persisted in the liquid compartment at priming. Although the preprimed solution contained several polyolefin-breakdown products due to irradiation, including ethyl alcohol, n- and t-butyl alcohol, acetone, and carbon dioxide, the levels of these substances were at concentrations known to be not toxic. Endotoxin concentration was negligible. In SEM observation, no perceptible microstructural change was observed in the hollow fibers after preprimed storage. Maximum tensile stress and ultimate elongation of the hollow fiber in the test ALs were reduced by approximately 20% and 3%, respectively, from those of the control AL. The influence of preprimed storage on gas-exchange function was examined in a venoarterial bypass animal study using a goat. Oxygen transfer function was well preserved whereas carbon dioxide removal function was slightly lowered according to the storage term in the stored ALs compared with those of a nonpreprimed control AL. On the basis of these results, we conclude that preprimed storage of the AL with gamma-ray sterilization is basically feasible and realistic.

1-Butanol↗
PubMed2000

Effects of reduced pulse pressure to the cerebral metabolism during prolonged nonpulsatile left heart bypass.

We investigated changes in the cerebral metabolism with long-term reduced pulse pressure. Nine goats underwent pulsatile left heart bypass (LHB) for 2 weeks while awake, and nonpulsatile LHB was subsequently conducted for 4 weeks. The average pulse pressure during nonpulsatile LHB (13, 10, 11, and 11 mm Hg at the 1st, 2nd, 3rd, and 4th nonpulsatile LHB week, respectively) was significantly lower than that during pulsatile LHB (36 mm Hg). There were no significant differences in either arterio-jugular venous oxygen differences (AJDO2) and cerebral oxygen extraction ratio between the 2nd pulsatile LHB week and the 1st, 2nd, 3rd, and 4th nonpulsatile LHB weeks. The arterio-jugular venous glucose differences, jugular venous-arterial lactate differences (JAD Lactate), and lactate oxygen indexes (JAD Lactate/AJDO2) also remained unchanged during the entire course of the experiments. In conclusion, the cerebral metabolism during nonpulsatile LHB did not change compared to that during pulsatile LHB.

Analysis of Variance↗
PubMed2000

Functional heterogeneity among bone marrow-derived dendritic cells conditioned by T(h)1- and T(h)2-biasing cytokines for the generation of allogeneic cytotoxic T lymphocytes.

Three distinct bone marrow (BM)-derived dendritic cells (BMDC) were expanded from BALB/c BM cells by culture with (i) granulocyte macrophage colony stimulating factor (GM-CSF) plus IL-3, (ii) GM-CSF, IL-3 plus T(h)1-biasing cytokines (IL-12 and IFN-gamma) or (iii) GM-CSF, IL-3 plus T(h)2-biasing cytokines (IL-4). All of these cells expressed the DC-specific marker CD11c, and were designated as BMDC0, BMDC1 and BMDC2 cells respectively. BMDC1 cells exhibited superior T cell-stimulating activity in allogeneic mixed lymphocyte culture (MLC), while BMDC2 showed inferior stimulating activity. Specifically, BMDC1, as compared with BMDC2, induced a higher frequency of IFN-gamma-producing CD8(+) T cells in MLC. Moreover, BMDC1, but not BMDC2, were strong inducers of H-2(d)-specific cytotoxic T lymphocytes (CTL) in MLC. BMDC0 always showed intermediate stimulatory activity; however, when BMDC0 were cultured with IFN-gamma, they differentiated into BMDC1-like stimulator cells concomitant with the up-regulation of both MHC antigens and co-stimulatory molecules. In contrast, BMDC2 were refractory to differentiation into superior stimulator cells by treatment with IFN-gamma, although this treatment enhanced MHC expression. These findings indicate that T(h)1- and T(h)2-biasing cytokines, in addition to their effect on T(h) cell differentiation, may play a critical role in the functional skewing of DC. These findings have important implications for the development of DC-based immunotherapies.

Animals↗
PubMed2000

The interface between innate and acquired immunity: glycolipid antigen presentation by CD1d-expressing dendritic cells to NKT cells induces the differentiation of antigen-specific cytotoxic T lymphocytes.

In vivo administration of NKT cell ligand, alpha-galactosylceramide (alpha-GalCer), caused the activation of NKT cells to induce a strong NK activity and cytokine production by CD1d-restricted mechanisms. Surprisingly, we also found that alpha-GalCer induced the activation of immunoregulatory cells involved in acquired immunity. Specifically, in vivo administration of alpha-GalCer resulted in the induction of the early activation marker CD69 on CD4(+) T cells, CD8(+) T cells and B cells in addition to macrophages and NKT cells. However, no significant induction of CD69 was observed on cells from CD1d- or V(alpha)14 NKT-deficient mice, indicating an essential role for the interaction between NKT cells and CD1d-expressing dendritic cells (DC) in the activation of acquired immunity in response to alpha-GalCer. Indeed, in vivo injection of alpha-GalCer resulted not only in the activation of NKT cells but also in the generation of CD69(+)CD8(+) T cells possessing both cytotoxic T lymphocyte (CTL) activity and IFN-gamma-producing ability. Tumor-specific CTL generation was also accelerated by alpha-GalCer. The critical role of CD40-CD40 ligand (CD40L)-mediated NKT-DC interaction during the development of CD69(+)CD8(+) CTL by alpha-GalCer was demonstrated by blocking experiments using anti-CD40L mAb. These findings provide direct evidence for a critical role of CD1d-restricted NKT cells and DC in bridging innate and acquired immunity.

Adjuvants, Immunologic↗