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H Nishimura

Publications and source records attributed to H Nishimura.

At least 271 records · Page 15Linked to original sources
PubMed1997

Genetic analysis in Japanese kindreds of congenital type I antithrombin deficiency causing thrombosis.

We have identified two novel minor deletions (case 1; -TA or -AT at nucleotide 9831-3 in exon 5 and case 2; -A at nucleotide 7640-1 in exon 4), one novel nonsense mutation (case 3; TAT to TAA at nucleotide 7491 in exon 4), and one recurrent nonsense mutation (case 4; CGA to TGA at nucleotide 5381 in exon 3A) in Japanese kindreds with congenital type I antithrombin deficiency. The deletion detected in case 1 represented a symmetric element (CTCTGTCTC) and possessed a direct repeat (CTCTATGTCTC). The deletion in case 2 was recognized in a consensus sequence (TGAAT) and possessed a direct repeat (GATGAA). The nonsense mutation in case 3 formed a palindrome (CCGTTAACGG) and that in case 4 was caused by a CpG dinucleotide mutation. These results confirm that the mutations of congenital type I antithrombin deficiency are not random events but are influenced strongly by DNA sequences.

Adult↗
PubMed1997

[Ethanol injection therapy to the lung cancer].

Ethanol injection was tried in patients who underwent exploratory thoracotomy. There were 4 males and 1 female, adenocarcinoma in 3 cases, large cell carcinoma in 1 case, and metastatic lung cancer in 1 case. We grasped the lung included the tumor, and injected ethanol directly into the tumor. Maximum dose of injected ethanol was within 10 ml. There were no any complications postoperatively in all patients. Postoperative course was followed by means of chest CT. Three patients whose preoperative cancer stage was early stage gained good results in local control, two patients whose preoperative cancer stage was stage III B in one patient and metastatic cancer rapidly growing in other patient had no effects. Ethanol injection into the lung tumor was easy to perform and safety, and has direct effect in local control of the tumor in especially small sized.

Adenocarcinoma↗
PubMed1997

Chemical modification of L-asparaginase with comb-shaped copolymer of poly(ethylene glycol) derivative and maleic anhydride.

L-asparaginase from Escherichia coli, an antitumor enzyme, was chemically modified with a comb-shaped copolymer of poly(ethylene glycol) derivative and maleic anhydride (activated PM). The PM-modified asparaginase lost the immunoreactivity with retaining high enzymic activity and also prolonged the clearance time in blood. Intraperitoneal administration of PM-asparaginase markedly increased the mean survival-time of lymphoma L5178Y-bearing mice in comparison with that of unmodified asparaginase. Pretreatment of mice with PM-asparaginase before immunizing with unmodified asparaginase extremely suppressed the anti-asparaginase antibody production.

Animals↗
PubMed1997

Angiotensin II increases plasminogen activator inhibitor-1 and tissue factor mRNA expression without changing that of tissue type plasminogen activator or tissue factor pathway inhibitor in cultured rat aortic endothelial cells.

Angiotensin converting enzyme inhibitors (ACE-I) have been reported to prevent the recurrence of cardiovascular events. The mechanism of this decrease, however, can not be completely explained by anti-hypertensive and anti-hypertrophic effects of ACE-I. To investigate the mechanism of this decrease, we studied the regulation of plasminogen activator inhibitor-1 (PAI-1), tissue type plasminogen activator (TPA), tissue factor (TF), and tissue factor pathway inhibitor (TFPI) by angiotensin II (Ang II) in cultured rat aortic endothelial cells. Ang II increased PAI-1 and TF mRNA expression without affecting that of TPA or TFPI. These inductions were accompanied by increases in PAI-1 and TF activities and were inhibited by a type I Ang II receptor antagonist. The results suggest that Ang II decreases the antithrombotic properties of endothelial cells which increases the chance of thrombosis. Thus, inhibition of the renin-angiotensin system may be beneficial to prevent thrombus formation in treatment of ischemic heart disease.

Angiotensin II↗
PubMed1997

Pharmacological profile of a novel synthetic inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme A reductase.

Pharmacological properties of NK-104 ((+)-monocalcium bis¿(3R,5S,6E)-7-[2-cyclopropyl-4-(4-fluorophenyl)-3-quinolyl++ +]-3,5-dihydroxy-6- heptenoate¿, CAS 147526-32-7), a novel synthetic inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, were investigated. The kinetic study, using rat liver microsomal HMG-CoA reductase, revealed that NK-104 is a competitive inhibitor of HMG-CoA reductase with a Ki of 1.7 nmol/l. To examine the inhibitory effect on sterol synthesis in vivo, de novo synthesis of sterols from [14C]acetate 3 h after oral administration of NK-104 was measured in rats. NK-104 showed marked inhibition in liver (ED50 0.13 mg/kg) and in ileum (ED50 0.20 mg/kg), but much weaker in the other tissues. The inhibitory effect of NK-104 on liver sterol synthesis lasted over 6 h, while that of pravastatin and simvastatin disappeared 6 h after administration of the drugs twice the ED50s. Due to induction of HMG-CoA reductase, initial suppression of hepatic sterol synthesis by pravastatin and simvastatin was compensated, and the cumulative change in hepatic sterol synthesis during 12 h after drug administration was remarkably negative only with long-acting NK-104. Hypolipidemic effects of NK-104 (0.03, 0.1, 0.3 and 1 mg/kg p.o. for 2 weeks) were examined in beagle dogs. NK-104 reduced plasma total cholesterol dose-dependently (13.1, 18.5 and 20.2% at doses of 0.1, 0.3 and 1 mg/kg, respectively), and also plasma triglycerides by 0.1 mg/kg or more. Pravastatin (1 and 3 mg/kg) and simvastatin (3 mg/kg) lowered plasma total cholesterol (14.0, 15.4 and 17.4%, respectively), but did not significantly affect plasma triglyceride levels. These results indicate that NK-104 is a potent, liver-selective, long-acting HMG-CoA reductase inhibitor with a high cholesterol- and triglyceride-lowering potency.

Animals↗
PubMed1997

Evaluation of magnetic resonance angiography on portosystemic collaterals in cirrhotic patients.

OBJECTIVE: We examined the usefulness of imaging portosystemic collaterals accompanying liver cirrhosis by magnetic resonance angiography (MRA), which facilitates imaging of the vascular system without contrast medium. METHODS: MRA was performed in 30 patients with liver cirrhosis. Of the 30 patients, percutaneous transhepatic portography (PTP) was performed in 10 patients, and conventional arterial portography (CAP) was performed in 20 patients. The three-dimensional (3D) phase contrast method was used for MRA. Study 1: The ability to image portosystemic collaterals was compared between PTP or CAP and MRA. Study 2: The usefulness of MRA for evaluating the effect of treatment on gastric and esophageal varices was examined. RESULTS: Study 1: In comparing PTP and MRA (n = 10), the left gastric vein (n = 10), splenorenal (gastrorenal) shunt (n = 5), and paraumbilical vein (n = 2) were imaged similarly. However, MRA did not reveal any esophageal varices (n = 10). In comparing CAP and MRA (n = 20), the left gastric vein (n = 17), splenorenal (gastrorenal) shunt (n = 10), and paraumbilical vein (n = 4) were imaged similarly. Whereas CAP revealed esophageal varices (n = 4) in four patients, MRA revealed esophageal varices in only one patient. Study 2: When the effect of treatment for varices was evaluated, MRA 3 wk after embolization therapy for gastric varices (n = 4) confirmed the disappearance of gastrorenal shunt. However, it was impossible to evaluate esophageal varices by MRA. CONCLUSIONS: It was possible to image portosystemic collaterals accompanying liver cirrhosis by MRA. MRA was useful as a routine examination. Furthermore, it was useful for evaluating the effect of embolization therapy on gastric varices.

Adult↗
PubMed1997

[Antigenic drift of type A and B influenza viruses].

Epidemics of influenza of the past 10 years were reviewed by integrating records from Morbidity and Mortality Weekly Reports of the United States and Infectious Agents Surveillance Reports in Japan, as well as data of antigenic drift of epidemic strains. Nucleotide-sequencing analyses of field isolates have shown characteristic amino acid substitutions in their hemagglutinin molecules, and phylogenetic analyses have indicated evolutionary relationships among the viruses. Integration of information obtained from both epidemics and molecular analyses would help our understanding of antigenic drift and evolution of influenza viruses.

Antigenic Variation↗
PubMed1997

Potential for involvement of Fas antigen/Fas ligand interaction in apoptosis of epithelial cells by intraepithelial lymphocytes in murine small intestine.

Intestinal epithelial cells (i-EC), which move to the villus tips from the crypts, rapidly die by apoptosis at the villus tips and are perpetually renewed at the crypts. To determine whether the Fas antigen (Fas)/Fas ligand (FasL) system is involved in the mechanism leading to apoptosis of i-EC, we examined the expression of Fas and FasL on the i-EC and intestinal intraepithelial lymphocytes (i-IEL) in normal mice. A high level of Fas was expressed on both the i-EC and i-IEL, whereas FasL was expressed in the i-IEL, especially in high-density fraction upon separation (high-density i-IEL), but not in the i-EC. The high-density i-IEL exhibited cytotoxicity against not only Fas transfectant but also the i-EC, and the cytotoxicity was inhibited by addition of Fas-Fragment c chimeric fusion protein. Thus, a significant fraction of i-IEL, such as high-density i-IEL, may partly contribute to induction of apoptosis in the effete i-EC via Fas/FasL interaction.

Animals↗
PubMed1997

[Four cases of adrenal tumor discovered through examination before surgery for lung cancer].

Preoperative CT and Ultrasonography (US) showed adrenal tumors in four patients with lung cancer. Although metastasis of the cancer to the adrenal gland was suspected, a definitive diagnosis could not be made by CT and US alone. MRI is as ineffective as CT and US. Needle biopsy is useful if tumor cells are detected, but not unless they are discovered. Surgery, therefore, is necessary to establish the final diagnosis. (Adrenalectomy was performed on all cases, one of which had metastasis). No particular complications occurred after adrenalectomy. Adrenalectomy was considered unavoidable to determine stage and treatment policies in patients suspected of metastasis in imaging diagnosis.

Adenocarcinoma↗
PubMed1996

Myocardial sympathetic denervation prevents chamber-specific alteration of beta-adrenergic transmembrane signaling in rabbits with heart failure.

OBJECTIVES: The purpose of this study was to assess the effect of myocardial sympathetic denervation on the chamber-specific alteration of beta-adrenergic signaling in left ventricular failure in rabbits. BACKGROUND: Local abnormalities in sympathetic nerve terminals, including the neuronal reuptake of norepinephrine, are thought to be responsible for the chamber-specific regulation of beta-adrenergic signaling in heart failure. METHODS: Sixteen rabbits were given 6-hydroxydopamine, 25 mg/kg body weight intravenously on days 1 and 2 and 50 mg/kg intravenously on days 7 and 8. Another 16 rabbits received vehicle. Aortic regurgitation was induced in eight of the 6-hydroxydopamine-treated and eight of the vehicle-treated rabbits on day 14. Another eight of the 6-hydroxydopamine-treated and eight of the vehicle-treated rabbits underwent a sham operation. The hearts were excised for biochemical analysis on day 21. RESULTS: Hemodynamic characteristics on day 21 showed left ventricular failure in both the aortic regurgitation groups. The plasma norepinephrine concentration on day 21 was higher in both the aortic regurgitation groups than in the sham groups. The beta-adrenoceptor densities and isoproterenol plus 5'-guanylylimidodiphosphate-, 5'-guanylylimidodiphosphate- and sodium fluoride-stimulated adenylyl cyclase activities were decreased only in the failing left ventricle of the vehicle-pretreated aortic regurgitation group, but in both ventricles of the 6-hydroxydopamine-pretreated aortic regurgitation group. The basal and forskolin-stimulated adenylyl cyclase activities were similar in both the aortic regurgitation groups and in the sham groups. CONCLUSIONS: Sympathetic denervation prevented chamber-specific alterations in beta-adrenergic signaling in acute left ventricular failure. Local loss of sympathetic nerve endings, and especially the defective neuronal norepinephrine reuptake, are likely to be responsible for the chamber-specific alteration of the beta-adrenoceptor-G protein-adenylyl cyclase system in heart failure in rabbits.

Adenylyl Cyclases↗
PubMed1996

Chimeric mice carrying 'regional' targeted deletion of the angiotensin type 1A receptor gene. Evidence against the role for local angiotensin in the in vivo feedback regulation of renin synthesis in juxtaglomerular cells.

We have developed chimeric mice carrying 'regional' null mutation of the angiotensin type 1A (AT1A) receptor, the AT1 receptor subtype exclusively present in mouse juxtaglomerular (JG) cells. The chimeric mouse (Agtr1a -/- <--> +/+) is made up of wild-type (Agtr1a +/+) cells or cells homozygous for Agtr1a deletion (Agtr1a -/-). In the latter, the AT1A coding exon was replaced with a reporter gene, lacZ. In Agtr1a -/- <--> +/+ mice, these two clones of cells are found to be clustered and display patchy distributions in the kidney and heart. Tracking of lacZ activities in hetero- (Agtr1a +/-) and homozygous (Agtr1a -/-) deletion mutant offspring from Agtr1a -/- <--> +/+ mice revealed that the promoter activity of Agtr1a is localized in JG cells, afferent arteriolar walls, glomerular mesangial region and endothelial cells, and apical and basolateral proximal tubule membranes. The JG apparatuses of Agtr1a -/- mice are markedly enlarged with intense expression of renin mRNA and protein. In Agtr1a -/- <--> +/+ mice, these changes were proportional to the degree of chimerism. Within a given Agtr1a -/- <--> +/+ mouse, however, the degree of JG hypertrophy/hyperplasia and the expression of renin mRNA and protein were identical between Agtr1a +/+ and Agtr1a -/- cells. Thus, in the in vivo condition tested, the local interaction between angiotensin and the AT1 receptor on the JG cells has little functional contribution to the feedback regulation of JG renin synthesis.

Angiotensins↗
PubMed1996

Functional localization of sensorimotor cortex by somatosensory evoked potentials produced by femoral nerve stimulation.

Cortical somatosensory evoked potentials (SSEPs) can be used to localize the central sulcus during a craniotomy. In particular, contralateral median nerve stimulation producing SSEPs can disclose the location of the central sulcus around the sensorimotor hand representation area. However, the median nerve cannot be stimulated in patients who undergo craniotomy at locations other than the hand representation area. The present study attempts to localize the central sulcus in the lateral surface of the brain near the interhemispheric fissure by stimulating the contralateral femoral nerve to produce SSEPs. Somatosensory evoked potentials were recorded between the superior lip of the interhemispheric fissure and 1.5 to 2 cm laterally in the cortex. Only seven of the 12 patients studied showed a phase reversal of the initial component across the central sulcus. The polarity was negative in the postcentral gyrus and positive in the precentral gyrus. The other five patients did not show a phase reversal of the initial component across the central sulcus. The amplitude was highest in the postcentral gyrus and the polarity was positive. Based on these results, the authors hypothesize that stimulating the contralateral femoral nerve to produce SSEPs and then analyzing the distribution of the SSEPs may provide a method for functional localization of the sensorimotor cortex around the interhemispheric fissure during craniotomy.

Journal Article↗
PubMed1996

Synthesis and pharmacological activity of triazole derivatives inhibiting eosinophilia.

In order to develop novel antiasthmatic agents based on a new mechanism of action, a series of 3-substituted 5-amino-1-[(methylamino)(thiocarbonyl)]-1H-1,2,4-triazole derivatives were synthesized and evaluated in a model in which eosinophilia was induced in the airway through intravenous (iv) injection of Sephadex particles on days 0, 2, and 5. After screening of several hundred derivatives, we finally identified the highly potent eosinophilia inhibitor 5-amino-3-(4-chlorophenyl)-1-[(methylamino)(thiocarbonyl)]-1H-tria zole (23c, GCC-AP0341), which had ID50 values of 0.3 and 0.07 mg/kg when administered orally (os) and intraperitoneally (ip), respectively. This compound showed complete inhibition of the hypersensitivity induced by ascaris inhalation at an ip dose of 1 mg/kg as well as low toxicity, with an LD50 value of > 2.0 g/kg in mice. Extensive study of its mechanism of action revealed that 23c inhibited eosinophil survival induced by interleukin-5 (IL-5), but had little or no effect on leukotriene D4 (LTD4) or platelet-activating factor (PAF)-induced responses. Taken together, these results suggest 23c as a novel candidate for the treatment of chronic asthma. Further studies are now underway.

Animals↗
PubMed1996

Inhibition of mucosal lipid hyperoxidation by green tea extract in 1,2-dimethylhydrazine-induced rat colonic carcinogenesis.

Phosphatidylcholine hydroperoxide (PCOOH) measured using a chemiluminescence detector to examine colonic mucosal lipid hyperoxidation increased after injection of 1,2-dimethylhydrazine and green tea extract (GTE), which we previously showed inhibited carcinogenesis and oxidative DNA damage in the gastrointestinal tract. Therefore, the hyperoxidation of membrane phospholipids reflected well the degree of DNA damage and carcinogenic alteration, and may be a useful intermediate biomarker for initiation of carcinogenesis.

1,2-Dimethylhydrazine↗
PubMed1996

Effects of a nonapeptide thymic hormone on intestinal intraepithelial lymphocytes in mice following administration of 5-fluorouracil.

A significant fraction of murine small intestinal intraepithelial lymphocytes (i-IELs) mature in local sites outside the thymus. However, there is evidence suggesting that extrathymic differentiation of i-IELs is still influenced by the thymus or thymus-derived factors. Facteur thymique serique (FTS), a nonapeptide thymic hormone, is involved in several aspects of intra- and extrathymic T cell differentiation in vivo. In this study, we investigated the effects of FTS on the kinetics of i-IELs in mice following a single administration of 5-fluorouracil (5-FU). FTS treatment significantly accelerated the recovery in cell number of i-IELs after administration of 5-FU. Flow cytometric analysis revealed that this accelerated recovery was mainly due to a rapid increase in CD8 alpha alpha+ i-IELs. Similar findings were also evident in adult thymectomized (ATX) mice, indicating that FTS treatment caused a rapid recovery of CD8 alpha alpha+ i-IELs following 5-FU administration in the absence of a functional thymus. Furthermore, expression levels of the mRNAs for interleukin-2, interferon-gamma, and transforming growth factor beta 1 in the i-IELs were augmented by FTS treatment. Notably, FTS treatment protected mice from 5-FU-induced lethal toxicity, accompanied with an inhibition of the translocation of Enterobacteriaceae. These results suggest that FTS has an important function in the extrathymic maturation and activation of i-IELs in the small intestine following 5-FU administration, which may contribute at least partly to the protection against 5-FU-induced lethal toxicity.

Animals↗