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T Nishimura

Publications and source records attributed to T Nishimura.

At least 379 records · Page 21Linked to original sources
PubMed1997

cDNA cloning and expression of chicken aminopeptidase H, possessing endopeptidase as well as aminopeptidase activity.

Chicken aminopeptidase H is a cysteine protease possessing endopeptidase as well as aminopeptidase activity [Rhyu, M. R., Nishimura, T., Kato, Y., Okitani, A. & Kato, H. (1992) Eur. J. Biochem. 208, 53-59]. This enzyme exhibits molecular masses of 400 kDa on gel filtration and 52 kDa on SDS/PAGE, indicating that it consists of eight subunits with the same molecular mass. In the current study, we cloned the cDNA for the catalytic subunit of chicken aminopeptidase H. The open reading frame of the aminopeptidase H gene consists of 1362 base pairs encoding a 52-kDa protein consistent with the molecular mass determined on SDS/PAGE; the deduced amino acid sequence contains all the partial sequences determined for the purified enzyme. The sequence is similar to that of the bleomycin hydrolase of rabbit lung, which has been partially determined. The recombinant 52-kDa protein expressed in COS7 cells exhibited both aminopeptidase and endopeptidase activities, which were inhibited by monoiodoacetic acid. Furthermore, the expression of aminopeptidase H in COS7 cells was also recognized on immunoblotting. This gene is the first one for aminopeptidase H in an animal tissue whose sequence has been completely determined.

Amino Acid Sequence↗
PubMed1997

Identification and characterization of the genes for mitochondrial ribosomal proteins of Saccharomyces cerevisiae.

We have purified 13 large subunit proteins of the mitochondrial ribosome of the yeast Saccharomyces cerevisiae and determined their partial amino acid sequences. To elucidate the structure and function of these proteins, we searched for their genes by comparing our sequence data with those deduced from the genomic nucleotide sequence data of S. cerevisiae and analyzed them. In addition, we searched for the genes encoding proteins whose N-terminal amino acid sequences we have reported previously [Grohmann, L., Graack, H.-R., Kruft, V., Choli, T., Goldschmidt-Reisin, S. & Kitakawa, M. (1991) FEBS Lett. 284, 51-56]. Thus, we were able to identify and characterize 12 new genes for large subunit proteins of the yeast mitochondrial ribosome. Furthermore, we determined the N-terminal amino acid sequences of seven small subunit proteins and subsequently identified the genes for five of them, three of which were found to be new.

Amino Acid Sequence↗
PubMed1997

Reduction of telencephalin immunoreactivity in the brain of patients with Alzheimer's disease.

Telencephalin (TLN) is a cell adhesion molecule expressed in the telencephalon of the mammalian central nervous system. We have investigated immunohistochemically the expression of TLN in human brain tissue from control subjects and patients with Alzheimer's disease (AD). In control brain, neuropil of the gray matter was stained diffusely with the anti-TLN antibody. TLN immunoreactivity was markedly decreased in the brain of AD patients, particularly in the hippocampal formation.

Aged↗
PubMed1997

Glial tau-positive structures lack the sequence encoded by exon 3 of the tau protein gene.

Tau protein comprises six distinct isoforms defined by the presence or absence of sequences encoded by alternatively spliced exon 2, 3 and 10. We have investigated immunohistochemically the expression of exon 3-derived fragment (E-3) of tau protein in brains of patients with Alzheimer's disease (AD) and other neurodegenerative diseases in which the abnormal accumulation of tau protein takes place. In AD, a subset of neurofibrillary tangles, neuropil threads and dystrophic neurites in senile plaques were stained positively with an anti-E-3 antibody. In sharp contrast, glial tau-positive structures, such as astrocytic plaques and oligodendroglial coiled bodies, were negative for E-3 in all cases examined in this study. This is the first report to discriminate tau-positive inclusions in glial cells from those in neurons at the molecular level.

Aged↗
PubMed1997

Therapeutic effect of co-enzyme Q10 on idiopathic dilated cardiomyopathy: assessment by iodine-123 labelled 15-(p-iodophenyl)-3(R,S)-methylpentadecanoic acid myocardial single-photon emission tomography.

It has been reported that myocardial mitochondrial function can be improved by the administration of co-enzyme Q10 (CoQ10). Recently, iodine-123 labelled 15-(p-iodophenyl)-3-(R,S)-methylpentadecanoic acid (BMIPP) was developed for metabolic imaging using single-photon emission tomography (SPET). This study was conducted to determine whether the therapeutic effects of CoQ10 on idiopathic dilated cardiomyopathy can be evaluated by BMIPP myocardial SPET. Fifteen patients, comprising 14 men and one woman (mean age: 64+/-12 years), were examined. CoQ10 was administered at 30 mg/day for a period of 35.7+/-12.4 days. BMIPP myocardial SPET was carried out before and after CoQ10 treatment. The count ratio of the heart (H) to the upper mediastinum (M) (H/M ratio) was calculated using a region of interest method with anterior planar imaging. Representative short-axis tomograms were divided into 27 segments (three slicesxnine segments). Each segmental score was analysed semiquantitatively using a four-point scoring system (normal=0, mild low uptake=1, severe low uptake=2, defect=3). The H/M ratio showed a significant improvement, from 2.39+/-0.39 to 2.54+/-0.47, after treatment (P<0.05). The BMIPP total defect score after CoQ10 treatment was significantly decreased to 10.1+/-4.3, compared to 13. 9+/-4.5 without CoQ10 treatment (P<0.001). However, the percent fractional shortening measured using echocardiography was not significantly different before and after CoQ treatment (19.2+/-8.1 vs 19.7+/-7.1). BMIPP myocardial SPET was confirmed to be sensitive in evaluating the therapeutic effects of CoQ10 in patients with idiopathic dilated cardiomyopathy. This method is unique, since the therapeutic effects can be estimated from the perspective of metabolic SPET imaging.

Cardiomyopathy, Dilated↗
PubMed1997

Enhancement of [123I]beta-CIT binding in the striatum with clomipramine: is there a serotonin-dopamine interaction?

Many reports support the concept of serotonergic-dopaminergic interaction in the brain. However, at present, there are few methods to study this relationship in vivo. The purpose of this study was to investigate the effect of serotonin (5-HT) uptake inhibitor, clomipramine, on a dopamine (DA) transporter ligand, [123I]beta-CIT (RTI-55), in rat brain. Dose-dependent changes in [123I]beta-CIT specific binding induced by clomipramine were studied in the striatum (rich in DA transporter) and the hypothalamus (rich in 5-HT transporter). The changes in the time-activity curves of [123I]beta-CIT specific binding after clomipramine injection were also examined in these two regions. Using the cerebellum as the reference region, k3 and k4 values with and without clomipramine administration were estimated by a two-compartment kinetic analysis. Clomipramine inhibited [123I]beta-CIT specific binding in the hypothalamus, but enhanced its specific binding in the striatum in a dose-dependent manner. Kinetic analysis showed that k3 in the striatum was increased by 55%. In conclusion, enhancement of [123I]beta-CIT binding in the striatum after clomipramine administration indicated the possibility of 5-HT-DA interaction.

Animals↗
PubMed1997

Hypothermia inhibits the alveolar epithelial injury caused by hyposmotic albumin solution during preservation of the resected human lung.

This study was conducted to determine whether hypothermia inhibited alveolar epithelial injury in the resected human lung during preservation. Hyposmotic albumin solution, 248 mOsm/kg, was instilled into the alveolar spaces of resected human lungs which were inflated with an airway pressure of 7 cmH2O and stored at either 37 degrees C or 8 degrees C for 4 h. Alveolar fluid was aspirated and the influx of lactate dehydrogenase (LDH) and globulin into the alveolar spaces, as markers of alveolar epithelial injury, was measured. Ion transport and fluid clearance across the alveolar epithelium were calculated by the changes in electrolyte and albumin concentrations in the alveolar fluid, respectively. While the LDH levels and globulin concentrations increased significantly in the hyposmotic experiments at 37 degrees C, hypothermia inhibited these increases. Alveolar fluid clearance at 37 degrees C increased to 20% in the hyposmotic experiments compared with 12% in the control isosmotic experiments; however, sodium and chloride transport in the hyposmotic experiments was not significantly different from that in the isosmotic experiments. Thus, we conclude that hypothermia at 8 degrees C inhibits alveolar epithelial injury caused by the hyposmotic solution in resected human lungs. Moreover, alveolar ion and fluid clearance mechanisms were preserved across the injured alveolar epithelial cells.

Epithelium↗
PubMed1997

Evaluation of left ventricular ejection fraction from radial long-axis tomography: a new reconstruction algorithm for ECG-gated technetium-99m sestamibi SPECT.

UNLABELLED: Radial long-axis tomography can provide views similar to contrast left ventriculography (LVG) including the basal and apical areas of the left ventricle, not possible in routine short-axis tomography. We applied this method to ECG-gated Tc-99m Sestamibi (MIBI) myocardial SPECT images to estimate the left ventricular ejection fraction (LVEF). METHODS: ECG-gated Tc-99m MIBI SPECT was performed with a temporal resolution of 10 frames per R-R interval. LVEF was calculated on the basis of left ventricular volume estimates at end diastole (ED) and end systole (ES) with using an ellipsoid body model. To validate this method, LVEF's derived from ECG-gated Tc-99m MIBI SPECT were compared with those from LVG in 11 patients with coronary artery disease. RESULTS: There was a close linear correlation between LVEF values calculated from Tc-99m MIBI SPECT and those from LVG (r = 0.89, p < 0.001), although the gated SPECT underestimated LVEF compared to LVG. The technique showed excellent reproducibility (intra-observer variability, r = 0.96, p < 0.001; inter-observer variability, r = 0.71, p < 0.005). CONCLUSION: The radial long-axis tomography technique gives a good estimate of LVEF, in agreement with estimates based on LVG. ECG-gated Tc-99m MIBI SPECT can, therefore, be applicable to assess myocardial perfusion and ventricular function at the same time.

Adult↗
PubMed1997

Detection of impaired fatty acid metabolism in right ventricular hypertrophy: assessment by I-123 beta-methyl iodophenyl pentadecanoic acid (BMIPP) myocardial single-photon emission computed tomography.

Fatty acid metabolism has been reported to be impaired earlier than myocardial blood flow in left ventricular hypertrophic myocardium, e.g., in hypertrophic cardiomyopathy or hypertensive heart disease. The purpose of this study was to determine whether impaired fatty acid metabolism also occurs in right ventricular (RV) hypertrophy. The subjects consisted of 6 patients with chronic obstructive pulmonary disease, 4 with primary pulmonary hypertension, 2 each with refractory pulmonary tuberculosis, tricuspid insufficiency, pulmonary embolism, 1 each with atrial septal defect, ventricular septal defect (Eisenmenger complex), Ebstein anomaly, and endocardial defect, and 7 healthy controls. SPECT imaging with Tl-201 (Tl) and I-123 beta-methyliodophenyl pentadecanoic acid (BMIPP), and Tc-99m RBC first pass and gated blood pool scintigraphy were performed. Based on Tl planar images, the subjects were classified into 3 groups: 7 patients with no RV visualization (Group A), 11 with moderate RV visualization (Group B) and 9 with marked RV visualization (Group C). As a semi-quantitative evaluation by Tl myocardial SPECT, 3 regions in 3 representative short axial images were divided into 9 segments, each of which was graded from 0 to +3, and their sum was calculated as the RV score. The right ventricular ejection fraction (RVEF) and the left ventricular ejection fraction were obtained by Tc-99m RBC cardiac scintigraphy. The groups with marked visualization of the right ventricle had lower RVEF (p < 0.01), and there was a good correlation between the RVEF and the RV score with both Tl and BMIPP (Tl: r = -0.79, BMIPP: r = -0.70). Although a good correlation was demonstrated between the RV score with Tl and BMIPP in Groups A and B (r = 0.86, p < 0.001), in Group C, in which there was marked RV T1 visualization, the RV score with BMIPP was significantly smaller than with Tl (BMIPP vs. Tl: 11.5 +/- 3.7 vs. 16.4 +/- 3.8, p < 0.01). These findings suggest that impaired fatty acid metabolism may exist in severely hypertrophic right ventricle due to RV overload.

Aged↗
PubMed1997

Hepatotoxicity of diisopropyl ester of malonic acid and chloromalonic acids, disinfection by-products of the fungicide isoprothiolane.

The fungicide isoprothiolane (diisopropyl 1,3-dithiolane-2-ylidenemalonate) decomposes to the diisopropyl esters of malonic acid (DM), chloromalonic acid (DCM) and dichloromalonic acid (DDCM) upon aqueous chlorination. In this study, the cytotoxicity of these compounds was examined using rat hepatocytes cultured on Matrigel. DCM and DDCM caused hepatocellular death at concentrations > 0.5 mM, while DM had no effect on the cell viability even at the maximum concentration examined (4 mM). Significant lipid peroxidation, measured as 2-thiobarbituric acid reactive substances, was observed in both DCM- and DDCM-treated hepatocyte cultures, and was significantly enhanced by pretreatment with 0.1 mM bis(p-nitrophenyl)phosphate (BNPP), a carboxylesterase inhibitor. When both BNPP and SKF-525A, a cytochrome P450 inhibitor, were present in the medium, DCM-induced cytotoxicity and lipid peroxidation were significantly suppressed compared to cultures with BNPP-treatment alone. By contrast, the DDCM-induced cytotoxicity was not affected by the combined pretreatment of SKF-525A and BNPP. These results indicate that DCM is metabolically activated by cytochrome P450 in an ester form, while DDCM is activated by a mechanism other than one involving cytochrome P450. To further elucidate the cytochrome P450 isozyme involved in the metabolic activation of DCM, microsomal lipid peroxidation was studied in vitro using microsomes from rats treated with beta-naphthoflavone, musk xylene, phenobarbital, pyrazole, or dexamethasone. Among these preparations, the microsomes from dexamethasone-treated rats showed the most extensive lipid peroxidation in the presence of DCM, and the lipid peroxidation was enhanced by BNPP as observed in hepatocyte cultures. These findings suggest the possible involvement of cytochrome P450 3A in the metabolic activation of DCM.

Animals↗
PubMed1997

Changes in cytochrome P450 enzymes by 1,1-dichloroethylene in rat liver and kidney.

We examined the effect of 1,1-dichloroethylene (1,1-DCE) on microsomal cytochrome P450 (P450) enzymes in rat liver and kidney. Rats were treated intraperitoneally with 1,1-DCE daily for 4 days, at doses of 200, 400, and 800 mg/kg. Among the P450-dependent monooxygenase activities in liver microsomes, testosterone 2alpha-hydroxylase (T2AH), which is associated with CYP2C11 activity, was remarkably decreased by 800 mg/kg 1,1-DCE. The level relative to control activity was < 10%. Furthermore, immunoblotting showed that 1,1-DCE (> or = 400 mg/kg) significantly decreased CYP2C11/6 protein levels in liver microsomes. In addition, 7-methoxyresorufin O-demethylase (MROD), 7-ethoxycoumarin O-deethylase (ECOD), benzphetamine N-demethylase (BZND), chlorzoxazone 6-hydroxylase (CZ6H), and testosterone 6beta-hydroxylase (T6BH) activities were significantly decreased by the highest dose of 1,1-DCE (by 40-70%). However, the activities of other P450-dependent monooxygenases, namely 7-ethoxyresorufin O-deethylase (EROD), 7-benzyloxyresorufin O-debenzylase (BROD), aminopyrine N-demethylase (APND), erythromycin N-demethylase (EMND), lauric acid omega-hydroxylase (LAOH), and testosterone 7alpha-hydroxylase (T7AH) were not affected by 1,1-DCE at any dose. Immunoblotting showed CYP1A1/2, CYP2B1/2, CYP2E1, and CYP3A2/1 protein levels were significantly decreased by 60-66% by 1,1-DCE (800 mg/kg), whereas that of CYP4A1/2 was not affected by any dose of 1,1-DCE. By contrast, among the P450-dependent monooxygenase activities in kidney microsomes, only CZ6H activity was increased by 1,1-DCE (1.6-fold at 800 mg/kg). Also, it was observed that 1,1-DCE (800 mg/kg) significantly increased CYP2E1 protein levels by immunoblotting (approximately 1.5-fold). These results suggest that 1,1-DCE changes the constitutive P450 isoforms in the rat liver and kidney, and that these changes closely relate to the toxicity of 1,1-DCE.

7-Alkoxycoumarin O-Dealkylase↗
PubMed1997

Ocular manifestations in adult T-cell leukemia/lymphoma.

Ocular manifestations of adult T-cell leukemia/lymphoma (ATL) are rare events. However, several ocular lesions which resulted from human T-cell leukemia virus type I (HTLV-I) infection have been reported, including direct infiltration of ATL cells, cytomegalovirus retinitis, and HTLV-I-associated uveitis (HAU). The aim of this study was to characterize ocular involvement in ATL and to correlate these lesions with HTLV-I proviral DNA integration. Three patients with acute-type ATL and ocular lesions were evaluated hematologically and ophthalmologically. Analysis of HTLV-I proviral DNA was carried out with a standard Southern blot technique using DNA from abnormal lymphocytes in peripheral blood. Two patients developed intraocular lesions located within intermediate and/or posterior segments which were caused by infiltration of ATL cells. Ocular lesions in one patient, which were localized to the anterior-intermediate segment, closely resembled those of HAU. Analysis of HTLV-I proviral DNA revealed multiple integrations in all three patients. The present study indicated heterogeneity in ocular manifestations of ATL. Multiple HTLV-I proviral DNA integrations may be associated with intraocular involvement in this disease.

Adult↗
PubMed1997

A clinicopathological study of a patient with familial amyotrophic lateral sclerosis associated with a two base pair deletion in the copper/zinc superoxide dismutase (SOD1) gene.

The recognition of mutations in the copper/zinc superoxide dismutase (SOD1) gene in familial amyotrophic lateral sclerosis (FALS) has been a landmark in ALS research. We report a clinicopathological study of a female patient with FALS showing a two base pair deletion in exon 5 of the SOD1 gene. Her clinical course was rapid and she died 2 years after the onset. The SOD1 activity was down to 30% of the normal level. Western blot analysis did not reveal the mutant protein which was expected to be approximately 2.4 kDa smaller than normal SOD1 protein in molecular mass. In contrast to the neuropathological findings of the previously reported cases showing the same mutation, our case was characterized by sparing of the dorsal column and the presence of only a modest number of intracytoplasmic eosinophilic inclusions showing weak or partial immunoreaction for neurofilament and negative reaction for SOD1. Thus, the same mutation in the SOD1 gene does not necessarily induce consistent pathological changes in the central nervous system.

Adult↗
PubMed1997

Developmental expression of extracellular matrix components in intramuscular connective tissue of bovine semitendinosus muscle.

We have investigated the expression patterns of extracellular matrix components in intramuscular connective tissue during the development of bovine semitendinosus muscle by means of indirect immunofluorescence techniques. Types I, III, V, and VI collagen and fibronectin were located in the endomysium and the perimysium. Type IV collagen, laminin, and heparan sulfate proteoglycans (PGs) were exclusively located in the endomysium, and dermatan sulfate PGs existed only in the perimysium. The localization of these components in the intramuscular connective tissue of semitendinosus muscle remained unchanged throughout prenatal and postnatal growth of cattle, suggesting that they are essential for forming and maintaining structures of the endomysium and perimysium in bovine semitendinosus muscle. On the other hand, decorin was undetectable in the endomysium of neonates, although other matrix components were already expressed. It was expressed slightly in the endomysium of 2-month-old calves, and clearly detectable in the endomysium of cattle more than 6 months old. Chondroitin sulfate PGs were barely detectable in the perimysium of fetuses and neonatal calves, and progressively appeared during postnatal development of the muscle. It seems likely that these PGs are closely related to the postnatal development of the endomysium and perimysium.

Aging↗
PubMed1997

Locations of crossover breakpoints within the CMT1A-REP repeat in Japanese patients with CMT1A and HNPP.

The crossover breakpoints for Charcot-Marie-Tooth disease type 1A (CMT1A) and hereditary neuropathy with liability to pressure palsies (HNPP) are located in the CMT1A-REP repeat flanking a 1.5-Mb region of chromosome 17p11.2-12. The precise locations of the breakpoints are heterogeneous, and we analyzed the relative frequency distribution of breakpoints in 33 unrelated Japanese CMT1A and 3 unrelated HNPP families. The CMT1A-REP repeat region was divided into five regions, A, B, C, D and E, based on restriction site differences between the proximal and distal CMT1A-REP repeats. The frequency distribution of breakpoints within the CMT1A-REP repeat in the Japanese patients was 3% in region A, .78% in B/C and 19% in D, which is similar to that in Caucasian patients. This result also indicates that an 8-kb region defined by region B/C is a recombinational hotspot within the CMT1A-REP repeat in Japanese patients.

Asian People↗
PubMed1997

Contribution of hypoxia to the development of cardiomyopathy in hamsters.

OBJECTIVE: It has been hypothesized that microvascular spasms cause cardiomyopathy. To elucidate the contribution of hypoxia to the development of cardiomyopathy, the newly-developed hypoxia tracer, Tc-99m nitroimidazole, was applied to detect myocardial hypoxia in a hamster model. METHODS: Tc-99m nitroimidazole (180 MBq) and I-125 iodoantipyrine (370 kBq) were injected into cardiomyopathic Syrian hamsters or control hamsters at age 10, 25, and 40 weeks (n = 6 in each group). The myocardial uptake of Tc-99m nitroimidazole was measured and dual tracer autoradiography was performed. RESULTS: Histologic study revealed that the cardiomyopathic hamsters at age 10, 25 and 40 weeks were in the myocytolytic stage, the fibrotic and healing stage, and the hypertrophy and dilatation stage, respectively. Tc-99m nitroimidazole uptake was significantly greater in the cardiomyopathic hamsters than in the controls at age 25 weeks (cardiomyopathic hamsters, 33.3 +/- 4.7% g dose/g; control, 25.2 +/- 3.1), whereas there were no significant differences between both strains at age 10 and 40 weeks. The quantified concentration of I-125 iodoantipyrine in the cardiomyopathic hamster at age 40 weeks was significantly lower than that in the controls. When the Tc-99m nitroimidazole uptake was normalized by I-125 iodoantipyrine concentrations, the cardiomyopathic hamsters at age 25 and 40 weeks showed significantly greater uptake than the controls. CONCLUSION: The myocardium in cardiomyopathic hamsters was hypoxic at the fibrotic and healing stage and may be hypoxic at the hypertrophy and dilatation stage. This may contribute to the development of cardiomyopathy.

Animals↗