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T Nishimura

Publications and source records attributed to T Nishimura.

At least 127 records · Page 7Linked to original sources
PubMed1995

NMR spectroscopic characterization of adinazolam mesylate: pH-dependent structure change in aqueous solution and active methylene.

The present study is to investigate structural changes of adinazolam mesylate in aqueous solution under various pH conditions by NMR spectroscopy. By plotting of the signal integration and chemical shifts of the side chain, pKa values for imine hydrolysis and the side chain amine were determined. Conformational analysis of the side chain was performed with deuterium-induced isotope effects on chemical shifts, nuclear Overhauser effects, relaxation times, and energy calculations. Hydrogen/deuterium exchange due to an active methylene at the 4-position under basic conditions was revealed.

Antidepressive Agents↗
PubMed1995

Induction of rat liver drug-metabolizing enzymes by tetrachloroethylene.

The effect of tetrachloroethylene on Phase I and II drug-metabolizing enzymes in rat liver was examined. Rats were treated orally with tetrachloroethylene daily for five days, at doses of 125, 250, 500, 1,000 and 2,000 mg/kg. The higher doses (> 500 mg/kg) of tetrachloroethylene induced the hepatic microsomal 7-pentoxyresorufin O-depentylase and 7-benzyloxyresorufin O-debenzylase activities associated with the CYP2B subfamily. 7-ethoxyresorufin O-deethylase activity was also induced about 2-fold compared with that of control rats at 500, 1,000, and 2,000 mg/kg dose levels of tetrachloroethylene. However, 7-ethoxycoumarin O-deethylase and 7-methoxyresorufin O-demethylase activities were increased significantly at only the 1,000 mg/kg dose level of tetrachloroethylene (1.4- and 1.5-fold). Although other cytochrome P450-mediated monooxygenase activities such as nitrosodimethylamine N-demethylase, aminopyrine N-demethylase and erythromycin N-demethylase were also induced by tetrachloroethylene, the relative induction to control activity was lower than those of 7-pentoxyresorufin O-depentylase and 7-benzyloxyresorufin O-debenzylase. Western immunoblotting showed that the levels of CYP2B1 and CYP2B2 proteins in liver microsomes were increased at doses of 1,000 and 2,000 mg/kg of tetrachloroethylene. In addition to cytochrome P450-mediated monooxygenases, there was significant induction of the Phase II drug-metabolizing enzymes, DT-diaphorase, glutathione S-transferase activities towards 1-chloro-2,4-dinitrobenzene and 1,2-dichloro-4-nitrobenzene, and UDP-glucuronyltransferase activities towards 4-nitrophenol and 7-hydroxycoumarin. The results indicate that tetrachloroethylene induces both Phase I (CYP2B-mediated monooxygenase) and Phase II drug-metabolizing enzymes (DT-diaphorase, glutathione S-transferase and UDP-glucuronyltransferase) in the rat liver.

Administration, Oral↗
PubMed1995

Familial amyloid polyneuropathy associated with transthyretin Gly42 mutation: a quantitative light and electron microscopic study of the peripheral nervous system.

We performed extensive quantitative analyses of the peripheral nervous system (PNS) of two siblings with familial amyloid polyneuropathy (FAP) caused by a transthyretin (TTR) Gly42 mutation. Pronounced amyloid deposition was found in the sympathetic ganglia (SyG), dorsal root ganglia (DRG) and throughout the length of the peripheral nerve fibers with some accumulation in the more proximal portion. There was severe neuronal loss in the SyG and DRG together with nerve fiber depletion in the nerve trunk, while only a small amount of amyloid deposition with mild fiber loss was seen in the spinal roots. Sprouts of regenerating axons were very scanty even in the spinal nerves or roots. A teased fiber study mainly showed demyelinating fibers, but axonal degeneration was also present throughout peripheral nerves. An electron microscopic study showed fine amyloid fibrils in direct contact with the axoplasmic membrane of demyelinated axons and destruction of axons in some areas. Amyloid deposition within the PINS in this type of FAP resembled that in type I FAP (TTR Met30). However, direct axonal damage by amyloid fibrils appeared to be more prominent in our cases than in type I FAP. Lectin histochemistry using Ulex europaeus agglutinin I demonstrated preferential depletion of small neurons in the DRG and their primary afferent fibers in the spinal dorsal horn. Primary axonal degeneration and ganglionopathy due to amyloid deposition appear to be the pathogenetic mechanisms for peripheral neuropathy in this type of FAP.

Adult↗
PubMed1995

Linkage and haplotype analysis of familial early-onset Alzheimer disease in Japanese population.

Linkage and haplotype analysis of eleven early-onset Alzheimer disease (AD) families was performed in relation to D21S210 and microsatellite DNA polymorphisms localized on chromosome 14q24.3. Linkage analysis of eight informative families out of eleven early-onset AD families disclosed the highest LOD score of 3.45 (theta = 0.00) at D14S77, while the locus of beta/A4 amyloid protein precursor gene was formally excluded within 10 cM from D21S210, given the evidence of recombinations in five families. Transmission disequilibrium study between the patients and controls without dementia indicated significant differences at D14S43 (p = 0.0001) and D14S71 (p = 0.02). Association study between genotypes linked or related to onset of AD and those of control also revealed a significant difference at D14S43 (p < 0.05), suggesting the existence of linkage disequilibrium. Moreover, the haplotypes at D14S43 linked with the onset of AD indicated a significant relationship with the mean age at onset. These results support that the major locus of early-onset familial AD is located on 14q24.3, and its close linkage to D14S43 and the existence of allelic heterogeneity were suggested.

Age of Onset↗
PubMed1995

Deletion in chromosome 17p11.2 including the peripheral myelin protein-22 (PMP-22) gene in hereditary neuropathy with liability to pressure palsies.

We report the clinical, electrophysiological, and pathological findings of two unrelated Japanese families with hereditary neuropathy with liability to pressure palsies (HNPP) and confirm the findings of a deletion of peripheral myelin protein-22 (PMP-22) gene. Electrophysiological studies revealed slowing of nerve conduction velocities of the affected nerves. Sural nerve biopsy revealed regions of myelin duplication. The copy numbers of PMP-22 gene was lower than that of normal control, suggesting deletion of 17p11.2 including PMP-22 gene. Our results indicate that HNPP in these two Japanese families is attributable to deletion of 17p11.2 including PMP-22 gene.

Aged↗
PubMed1995

Induction of hepatic drug-metabolizing enzymes by chlornitrofen (CNP) and CNP-amino in rats and mice.

The induction of hepatic drug-metabolizing enzymes by chlornitrofen (CNP) and CNP-amino was studied in the liver of male rats and mice. CNP-amino increased the activities of 7-pentoxyresorufin O-depentylase (PROD) and 7-benzyloxyresorufin O-debenzylase (BROD) as CYP2B1-dependent monooxygenase 3.6- and 4.1-fold in rats. On the contrary, these enzyme activities in mice were induced by CNP rather than by CNP-amino. Furthermore, immunoblotting showed that the protein levels of CYP2B subfamily cytochrome P450 (P450) in liver microsomes of rats and mice were increased by CNP or CNP-amino. Phase II drug-metabolizing enzymes, UDP-glucuronyltransferase (UGT) and glutathione S-transferase (GST) levels in mice were also significantly increased from 1.4 to 2.5-fold by CNP or CNP-amino. However, neither CNP nor CNP-amino affected UGT and GST in rats. These results suggest that CNP and or CNP-amino induce the P450 isoforms of CYP2B subfamily in the rat and mouse liver, and that the inducibility of drug-metabolizing enzyme by the compounds is different between rats and mice.

Animals↗
PubMed1995

Tumor-associated glycoantigen, sialyl Lewis(a) as a target for bispecific antibody-directed adoptive tumor immunotherapy.

The KM231 mAb recognizing sialyl Lewis(a) (sLe(a)) epitope of glycoprotein or glycolipid expressed on various human cancers was used to prepare bispecific antibody (BSAb) containing anti-CD3 x anti-sLe(a) mAb. The effect of anti-CD3 x anti-sLe(a) BSAb on the induction of cytotoxicity by activated T cells was investigated. The activated CD3+ T cells expressing CD8 or CD4 were induced from human peripheral blood mononuclear cells by culture with recombinant IL-2 plus immobilized anti-CD3 mAb. The activated CD8+ and CD4+ T cells showed marginal cytotoxicity against tumor cells by themselves. However, addition of anti-CD3 x anti-sLe(a) BSAb resulted in a great augmentation of their cytotoxicity against gastrointestinal tumor cells. The BSAb also triggered IL-2 production of CD4+ helper/killer T cells during lysis of tumor cells. Moreover, the BSAb was demonstrated to have a potent in vivo antitumor activity against human colon cancer implanted in nude mice by combination with CD4+ helper/killer cells. These results demonstrated that sLe(a) antigen might be a good target molecule for BSAb-directed adoptive tumor immunotherapy.

Animals↗
PubMed1995

Phenotypic and functional characteristics of in vivo-induced interleukin-12-activated killer cells.

A single i.p. administration of IL-12 (2000 U/mouse) into the mice caused the elevation of serum IFN-gamma activity and the generation of killer cells which can lyse various kinds of tumor cells including both NK-sensitive and -resistant tumor cells. Such in vivo induced killer cells were not detected in the mice treated with the same dose of IL-2. The generation of IL-12-activated killer cells (IL-12AK) peaked at day 1 and sustained their cytotoxicity until day 3 after IL-12 administration. The generation of IL-12AK was inhibited by in vivo administration of anti-asialo GM1 (ASGM1) Ab but not anti-CD4 or anti-CD8 mAbs, suggesting that the precursor cells for IL-12AK were ASGM1+CD4-CD8- NK cells. The phenotypic characterization of in vivo induced effector cells with IL-12AK activity was carried out by separating the cells with FACStar. The IL-12AK activity was highly enriched in ASGM1+CD4-8- or NK1.1+CD4-8- NK cells, but not in CD8+ T cells and CD4+ T cells. The IL-12AK cells were also generated in tumor-inoculated mice. In parallel with the in vivo generation of IL-12AK generation, the growth of i.p. inoculated MBL-2 lymphoma cells was markedly inhibited by the administration with IL-12. The in vivo antitumor activity of IL-12 was blocked by the administration of anti-ASGM1 but not anti-CD4 or anti-CD8 mAbs in concomitant with the decrease of IL-12AK generation. From these results, it was indicated that ASGM1+NK1.1+CD4-8- NK type IL-12AK cells might play an important role in IL-12-induced local therapy of tumor in vivo.

Animals↗
PubMed1995

Suppressive effect of actarit on IgA production in mice: activation of CD4+ suppressor T-cells in Peyer's patches.

We examined the effects of actarit, a new antirheumatic drug, on antibody production after LPS stimulation in mice. Actarit did not affect the proliferative response of B-cells stimulated with LPS or anti-mouse mu-chain antibody plus rIL-4. Lymphocytes in the Peyer's patches (PP) of mice with oral administration of actarit suppressed the production of IgA (not IgM and IgG) by B-cells stimulated with LPS. Actarit affected neither the serum level of IgA nor IgA secretion from the gut of mice without LPS stimulation. Actarit did not change the percentage of Thy-1+ cells in the PP lymphocyte population or that of CD4+ or CD8+ cells in the Thy-1+ fraction of PP lymphocytes. The suppressive effect of PP lymphocytes from mice treated with actarit was abrogated by the elimination of CD4+ cells (not CD8+ cells) from PP lymphocytes. These results suggest that actarit activates CD4+ suppressor T-cells in the PP, resulting in a specific suppression of IgA production after LPS stimulation.

Animals↗
PubMed1995

Effects of SDZ ENA 713, novel acetyl cholinesterase inhibitor, on learning of rats with basal forebrain lesions.

1. The effects of SDZ ENA 713, a novel acetyl cholinesterase inhibitor, on rat learning was studied using a step-down avoidance paradigm. 2. Injection of ibotenic acid into the caudolateral part of the basal forebrain (BF) innervating cholinergic neurons to the cerebral cortex, resulted in an increase in the number of trials required to obtain 300-second-latency, and also a decrease in the latency period after attaining 300-second-latency. 3. It is shown that the BF-lesioned rats are impaired in both acquisition and retention of learning. 4. Intraperitoneal injection of 0.10-0.05 mg/kg/day SDZ ENA 713 to the BF-lesioned rats showed amelioration of the learning impairment, with a decreased number of trials required to obtain 300-second-latency as well as an increase in the latency time after repeated training. 5. These results indicate that SDZ ENA 713 improves acquisition and retention impairment in BF-lesioned rats, and that this drug may be useful for demented patients with cholinergic dysfunction, such as Alzheimer's disease.

Animals↗
PubMed1995

Sequential MR signal change of the thrombus in the false lumen of thrombosed aortic dissection.

The evolution of thrombus in the false lumen was investigated in 14 patients with thrombosed aortic dissection, by reviewing the findings acquired at a total of 21 magnetic resonance imaging (MRI) examinations performed between 2 and 146 days after the onset. On electrocardiographic gated 1.5-Tesla MRI, T1-(TR/TE = 860 +/- 190 ms/17-40 ms) and T2-(TR/TE = 1620 +/- 240 ms/70-80 ms) weighted spin echo and gradient echo images were obtained, and the signal intensity of the thrombus on these images was evaluated independently by two observers. The density of the thrombus was also evaluated using computed tomography (CT) images obtained at a total of 54 examinations. On both T1- and T2-weighted images, the thrombus showed signal iso- or hypointensity compared to that of skeletal muscle during the first several days after the onset and, thereafter, showed signal intensity similar to that of fat tissue. It is suggested that the low signal intensity of the thrombus observed during the initial period after the onset was caused by the presence of deoxyhemoglobin and the high intensity observed thereafter was caused by methemoglobin. Focal discrepancy of the signal intensities within two parts of the lumen on spin echo images was observed in 7 patients, and a low-intensity layer on the surface of the thrombus inside the false lumen was observed on gradient echo images in 5 of these 7 patients. This characteristic MR signal change of the thrombus in the false lumen of thrombosed aortic dissection provides useful information concerning the age of the thrombus and in the differential diagnosis of the thrombus from a mural thrombus of aortic aneurysm.

Adult↗
PubMed1995

Expression of EGF, EGFR and PCNA in laryngeal lesions.

The expression of EGF/EGFR in 47 laryngeal surgical specimens from 44 patients was examined. PCNA analysis as an index of proliferating cells was also performed in 32 cases of laryngeal cancer, six cases of pre-cancerous lesions and nine cases of normal laryngeal mucosa. EGFR failed to show a significant correlation with tumour behaviour, but EGF expression was statistically significantly higher in malignant (SCC) than in non-malignant tissues (pre-cancerous and normal tissues) (p < 0.006), and PCNA also showed a statistically significant difference (p < 0.016) between the two. In malignant tissues when EGF/EGFR in 'double-positive' and 'double-negative' cases was compared, a statistically significant difference in PCNA was found (p < 0.029); but this was not seen in non-malignant tissues. Our results support the hypothesis that an autocrime mechanism exists in laryngeal cancer and in this mechanism EGF may play an important role in tumour progression, especially when EGFR is overexpressed.

Adult↗
PubMed1995

Enhancement of hematopoietic uptake by granulocyte colony-stimulating factor in Ga-67 scintigraphy.

The authors report on two non-Hodgkin's lymphoma cases which showed markedly enhanced Ga-67 uptake of granulopoietic area induced by recombinant human granulocyte colony-stimulating factor (rhG-CSF) administration. The rhG-CSF is a newly developed agent for reduction of infections, which stimulates the proliferation and differentiation of granulopoiesis. Use of rhG-CSF is becoming increasingly frequent because the indications are so broad that most patients with intensive chemotherapy for malignancies benefit from undergoing this treatment. In this study, the results of the two cases were: 1) G-CSF enhanced the accumulation of Ga-67 citrate in the granulopoietic area; 2) the marked uptake of red marrow looked like involvement; and 3) in contrast, the involved area became relatively "cold." These findings should be considered in the interpretation of Ga-67 scintigraphy.

Adult↗
PubMed1995

I-123 iodoamphetamine lung scanning in patients with ventilation-perfusion mismatching.

I-123 IMP is a nonparticulate agent and becomes trapped by endothelial membranes in the pulmonary capillaries. Using I-123 IMP, the authors studied six patients with ventilation-perfusion mismatch. Three of six patients had pulmonary thromboembolism, and three had pulmonary hypertension. In comparison with conventional perfusion lung scanning using Tc-99m MAA, defect sizes visualized by I-123 IMP were smaller in all patients. I-123 iodoamphetamine is a useful agent for assessing the perfusion of pulmonary arterial microvasculature which Tc-99m MAA fails to penetrate.

Amphetamines↗
PubMed1995

Inferior vena cava occlusion with pulmonary embolism because of complications due to ruptured abdominal aneurysm demonstrated by radionuclide venography.

A 66-year-old man with an abdominal aortic aneurysm confirmed by CT had bilateral swelling of the lower extremities with pain radiating to the back. Radionuclide venography and pulmonary scintigraphy demonstrated occlusion of the inferior vena cava and multiple pulmonary emboli, with a hot spot in the liver. Surgery revealed a ruptured abdominal aortic aneurysm that occluded the inferior vena cava, fistula formation, and extensive thrombosis of the inferior vena cava proximal to the occlusion site. Radionuclide venography was useful in detecting venous obstruction and the collateral formation represented by the hot spot in the liver as complications of the ruptured abdominal aortic aneurysm, and in assessing the improvement of pulmonary embolism by medical therapy.

Aged↗
PubMed1995

Myocardial metabolism of 123I-BMIPP in patients with hypertrophic cardiomyopathy: assessment by radial long-axis SPET.

To elucidate the metabolism of free fatty acid in the myocardium of hypertrophic cardiomyopathy (HCM), SPET was performed with 123I-15-(p-iodophenyl)-3-R,S-methylpentadecanoic acid (BMIPP), an analogue of free fatty acid, and with 201Tl in nine patients with HCM and eight healthy volunteers who acted as controls. For quantitative analysis of the apical area, a radial long-axis tomogram was reconstructed every 6 degrees after short-axis tomography. The relative regional uptake (RRU, %) in each segment was obtained by normalizing to the maximal value among all segments. The 3-h washout rate was calculated both for BMIPP and for 201Tl. The ratio of the RRU of BMIPP to that of 201Tl was significantly lower in the apical and antero-septal regions compared with other walls (P < 0.01) in the patients with HCM, whereas uptake of both BMIPP and 201Tl in the controls was homogeneous and there was a significant correlation between them. The coefficient of variation (CV) in all segments in the HCM patients was significantly higher (P < 0.01) than that of the controls both BMIPP and 201Tl, indicating inhomogeneous uptake of BMIPP in the HCM patients. The washout rate of BMIPP over 3 h was significantly higher in the patients with HCM (mean +/- S.D. 26.3 +/- 7.3%) than the controls (18.3 +/- 7.5%, P < 0.05). The ratio of segmental washout rate of BMIPP to that of 201Tl in the HCM patients was increased, especially in the septum and apex.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗