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H Nishimura

Publications and source records attributed to H Nishimura.

At least 307 records · Page 17Linked to original sources
PubMed1996

Angiotensin-converting enzyme-independent pathways of angiotensin II formation in human tissues and cardiovascular diseases.

The tissue renin-angiotensin system plays an integral role in the homeostasis of blood pressure and in the pathogenesis of cardiovascular remodeling. These effects are primarily mediated through the paracrine and autocrine actions of locally produced angiotensin II (A II). It is generally accepted that the conversion of angiotension I to A II is mainly due to angiotensin-converting enzyme (ACE). However, there are several in vitro and in vivo reports of ACE-independent synthesis of A II in hypoxic and ischemic heart and blood vessels, which may also contribute to cardiovascular pathology. The differential cellular and regional expression of ACE and chymase in the human heart and blood vessels suggests distinct pathophysiologic roles for these two A II-forming enzymes. The study of different pathways involved in tissue A II formation, including that of ACE- and chymase-independent enzymes, will clarify their respective contribution to the pathophysiologic changes in cardiovascular diseases, and help in planning a more comprehensive clinical strategy. This report reviews the properties of human heart chymase, an A II-forming serine proteinase, and compares it with those of ACE.

Angiotensin II↗
PubMed1996

[A case-control study of ovarian cancer to identify its risk factors].

To analyze the association between the potential risk factors and ovarian cancer, we conducted a case-control study from October, 1994 to January, 1996 in northern Kyushu. We interviewed 78 patients whose ovarian cancer was histologically confirmed, and 346 controls, selected from women at mass screening, who had not ever suffered from a cancer or an ovarian disorder. An odds ratio (OR) and its 95% confidence interval (95% CI) were estimated by the conditional logistic regression method. As a result, it was found that the risk was significantly increased for a family history of ovarian cancer in a mother or a sister (OR = 2.85, 95% CI 1.01-8.08), for heavier maximum body weight in the past (trend, OR = 1.31, 95% CI 1.06-1.63), and for larger maximum body mass index (trend, OR = 1.30, 95% CI 1.06-1.60). Conversely, the risk was significantly decreased with the number of parities (trend, OR = 0.57, 95% CI 0.39-0.83), and with experience in having ever taken oral contraceptive pills (OR could not be calculated, p < 0.05). The positive relationship of maximum body weight or maximum body mass index to the ovarian cancer risk may in part explain the recent increase in the incidence of ovarian cancer in Japan.

Alcohol Drinking↗
PubMed1996

Mechanism of elevated local oxidant stress in early anti-glomerular basement membrane nephritis: an evaluation of oxidant production and superoxide dismutase expression.

The present study was designed to identify the mechanism of increased oxidant stress in the rat model of anti-glomerular basement membrane nephritis. Sixty-three Sprague-Dawley rats were injected with nephrotoxic serum and evaluated 1 to 24 hours later. In these rats, CeCl3 deposition, an index of hydrogen peroxide production, was observed on the surfaces of glomerular endothelial cells and polymorphonuclear leukocytes, whereas no such depositions were observed in controls. Renal cortical level of lipid peroxidation products (phosphatidylcholine hydroperoxide) was significantly (p < 0.05) elevated at one hour after the injection and remained elevated at least for 24 hours. Protein levels of glomerular Mn-superoxide dismutase (SOD) decreased from 1.55 +/- 0.38 microgram/mg protein to 0.67 +/- 0.18 microgram/mg protein at one hour and normalized by 12 hours after the injection. The activity of the enzyme showed a similar trend. In contrast, Mn-SOD mRNA increased 3.4-fold at 3 hours after the injection. In situ hybridization showed increased Mn-SOD mRNA expression in glomeruli. Cu/Zn-SOD mRNA expression was transiently suppressed. These results indicated that both increase in local production of reactive oxygen species (ROS) and reduction in antioxidant enzyme activities are responsible for the enhanced oxidant stress in the heterologous phase of anti-glomerular basement membrane nephritis. The paradoxical increase in Mn-SOD mRNA expression indicates that the posttranscriptional down regulation of Mn-SOD (i.e., reduction in protein and activity) and the increased ROS may activate transcription of the gene.

Animals↗
PubMed1995

Endogenous interleukin 10 prevents apoptosis in macrophages during Salmonella infection.

To elucidate the biological roles of endogenous interleukin 10 (IL-10) in macrophage responses during bacterial infection, we examined in vitro effects of neutralizing IL-10 by anti-IL-10 monoclonal antibodies (mAb) on apoptosis of the peritoneal macrophages following Salmonella choleraesuis infection. Marked increments of TNF-alpha production were observed in the culture supernatant later than 6 h after in vitro culture with anti-IL-10 mAb. These macrophages succumbed to apoptosis at this stage accompanied by marked increment of IL-1 release, despite the expression of higher amount of endogenous heat shock protein 70, an inhibitor of TNF-alpha-mediated apoptosis. These results suggest that endogenous IL-10 plays an essential role in protection of Salmonella-infected macrophages from autocrine suicide caused by excessive production of TNF-alpha after killing of Salmonella.

Animals↗
PubMed1995

Chemical modification and inactivation of phospholipases A2 by a manoalide analogue.

Chemical modification and inactivation of bovine pancreatic, porcine pancreatic, Naja naja atra and Pseudechis australis phospholipases A2 (PLA2s), belonging to Group I, and of Trimeresurus flavoviridis, Vipera russelli russelli and Agkistrodon halys blomhoffii PLA2s, belonging to Group II, were investigated by the use of a manoalide (MLD)-analogue, 1-(2,5-dihydro-hydroxy-5-oxo-3-furanyl)-8,12-dimethyl-4-formyl-3,7, 11-tridecatrienol. At appropriate time intervals, residual PLA2 activities towards monodispersed, anionic mixed micellar and non-ionic mixed micellar substrates were measured. We tested the protective effect of micellar n-dodecylphosphocholine (n-C12PC) on enzyme inactivation. Inactivation of pancreatic PLA2s (Group I) was only observed towards anionic mixed micellar substrates. This inactivation was completely prevented by the presence of micellar n-C12PC. From a fragmentation study of modified bovine pancreatic PLA2 using lysyl endopeptidase, we speculated that Lys-56 of this enzyme was modified by MLD-analogue and that this modification was responsible for enzyme inactivation. Inactivation of non-pancreatic PLA2s was observed towards all types of substrate, except that no significant inactivation of N. naja atra PLA2 (Group I) towards monodispersed substrate was noted. Micellar n-C12PC protected N. naja atra PLA2 (Group I) completely from inactivation by MLD-analogue, but had lesser protective effects on P. australis PLA2 (Group I), T. flavoviridis and V. russelli russelli PLA2s (Group II). However, no significant protection of A. halys blomhoffii PLA2s (Group II) activity was observed. These results indicate that the inactivation of pancreatic and N. naja atra PLA2s originates from the modification of Lys residues at the interfacial recognition site, and that inactivation of P. australis, T. flavoviridis and V. russelli PLA2s arises from the modification of Lys residues at the catalytic site, interfacial recognition site and regions outside both sites. The inactivation of A. halys blomhoffii PLA2 was assumed to be due to the modification of Lys residues outside the two sites described above.

Amino Acid Sequence↗
PubMed1995

Synthesis, absolute configuration, and enantioselectivity of antiretroviral effect of (R)-(-)- and (S)-(+)-cytallene. Lipase-catalyzed enantioselective acylations of (+/-)-N4-acylcytallenes.

Enantioselectivity of acylations of (+/-)-cytallene (1b), (+/-)-N4-acetylcytallene (11a), (+/-)-N4-benzoylcytallene (11b), and (+/-)-N4-(9-fluorenylmethoxycarbonyl)cytallene (11c) using vinyl butyrate or acetate catalyzed by lipases in organic solvents was investigated. Reactions with 1b, 11a, and adenallene (1a) did not display a high enantioselectivity but all resulted in a predominant acylation of the (-)-enantiomers. Application of the Lowe-Brewster rule led to a tentative assignment of the R-configuration to all acylated products. Studies of the time course of acylation of (+/-)-N4-benzoylcytallene (11b) in chloroform, tetrahydrofuran (THF), tetrahydropyran (THP), tetrahydrothiophene (THT), and dioxane with lipase PS30 and/or AK showed that the reaction in THF catalyzed by lipase AK was the most promising for resolution of 11b. Indeed, a large-scale acylation afforded, after separation and deprotection of intermediates 3e and 10d, (+)- and (-)-cytallene (3c and 2b) in high yield and enantioselectivity. Acylation of 11c in THF led also to formation of 3c and 2b in high enantioselectivity. Single crystal X-ray diffraction established the S-configuration of (+)-cytallene (3c), thus confirming the assignment made on the basis of Lowe-Brewster rule. An improved large-scale synthesis of (+/-)-cytallene (1b) is also described. The R-enantiomer 2b inhibited the replication of a primary human immunodeficiency virus (HIV-1) isolate in phytohemagglutinin-activated peripheral blood mononuclear cells (PHA-PBM) with IC50 0.4 and IC90 1.7 microM. (+/-)-Cytallene (1b) exhibited IC50 0.8 and IC90 3.4 microM. Both compounds completely suppressed replication of HIV-1 at 10 microM with no detectable cytotoxicity. The S-enantiomer (3c) was inactive.

Acylation↗
PubMed1995

Adenosine kinase-deficient mutant of Saccharomyces cerevisiae.

A cordycepin-resistant mutant strain of Saccharomyces cerevisiae (CD-R2) was found to be deficient in adenosine kinase. This mutant accumulated S-adenosylhomocysteine during growth in the presence of exogenous adenosine and it grew in a pseudohyphal manner in the presence of this nucleotide.

Adenosine↗
PubMed1995

Diversity of V gamma gene segments rearranged to the J gamma 4 gene in mice.

Because there are limited numbers of V gamma gene segments and most V gamma rearrangements occur within clusters of the J gamma-C gamma genes in mice, gamma-chains display limited diversity compared with other TCR chains. In this study, we examined the nucleotide sequences of the V gamma-J gamma genes expressed in the gamma delta T cells appearing at the inflamed sites after Salmonella infection in DBA/2 mice. Most of the productive gamma gene rearrangements were V gamma 1-J gamma 4, whereas V gamma 2 and a unique V gamma, the 5' region of which was identical with sequences of the V gamma 2 gene, and the 3' region of which was identical with that of the V gamma 1 gene, were found to be rearranged to J gamma 4 gene, albeit at low frequency. Analysis of the ontogenic appearance of the rearrangements in the J gamma 4-C gamma 4 locus revealed that V gamma 2-J gamma 4 gene rearrangement was frequent in fetal thymocytes at the early stage of gestation. Most of the early fetal V gamma 2-J gamma 4 rearrangements exhibited the identical junction, a nonfunctional canonical sequence. The sequence analysis of the coding joint and the reciprocal recombination signal joint suggests that short homology-mediated direct recombination and chromosomal inversion mechanism are involved in fetal V gamma 2-J gamma 4 gene rearrangement. Taken together, our data suggest that the recombination of multiple V gamma segments with J gamma 4 can diversify the V gamma repertoire.

Amino Acid Sequence↗
PubMed1995

cDNA and deduced amino acid sequence of human PK-120, a plasma kallikrein-sensitive glycoprotein.

PK-120 is a substrate for plasma kallikrein (PK), recently purified from human plasma. Here we have established the cDNA sequence for human PK-120 mRNA. The deduced amino sequence of PK-120 revealed that it consists of 902 amino acid residues with a calculated mass of 116,423 Da. The putative cleavage sites by PK have been proposed, suggesting that PK-120 may be a precursor of a bioactive peptide. Most interestingly, PK-120 showed significant sequence identities to heavy chains (HCs) of the inter-alpha-trypsin inhibitor (ITI) superfamily.

Amino Acid Sequence↗
PubMed1995

The role of gamma delta T cells in priming macrophages to produce tumor necrosis factor-alpha.

The secretion of tumor necrosis factor (TNF)-alpha from macrophages is regulated by both priming and triggering signals. We found that macrophages from mice lacking gamma delta T cells [T cell receptor (TCR) delta-/- mice], which lack the gene encoding the delta chain, produced only small amounts of TNF-alpha in response to lipopolysaccharide (LPS) and showed a reduced level of expression of CD14. Pre-incubation of macrophages from TCR delta-/- mice with gamma delta T cells from their TCR delta +/- littermates restored their capacity to produce TNF-alpha in response to LPS. The priming activity of gamma delta T cells was in part inhibited by neutralizing anti-interferon (IFN)-gamma monoclonal antibodies. Collectively, these results suggest that gamma delta T cells play a role in priming macrophages to a steady state of activation via IFN-gamma secretion, which allows them to produce TNF-alpha when exposed to LPS.

Animals↗
PubMed1995

Abnormal T cell activation and skewed T cell receptor V beta repertoire usage in Japanese patients with idiopathic portal hypertension.

Idiopathic portal hypertension (IPH), a disorder of unknown etiology, is characterized by a noncirrhotic portal hypertension associated with splenomegaly, hypersplenism, and anemia. We examined the surface phenotypes of T cells and the T cell receptor V beta repertoire in patients with IPH. The T cells in peripheral blood samples and from spleens showed a marked increase in frequencies of HLA-DP(+)- and HLA-DR(+)-activated T cells and the observed high frequencies in the blood were to a considerable extent reduced after splenectomy. Thus, the continuous activation of T cells may occur initially in the spleen. Investigation of T cell receptor V beta repertoire revealed a significant skewing of V beta 9 and V beta 11 in both peripheral blood and splenic T cells and V beta 12 in splenic T cells. The IPH may be a disease mediated by a continuous stimulation with either a certain antigen or more likely a superantigen.

Adult↗
PubMed1995

High thoracic neurinoma mimicking femoral neuralgia.

We report a case of spinal neurinoma at a high thoracic level, whose main presentation was intractable pain in a body part innervated by the right femoral nerve. Sensations of pain and temperature were impaired in the right thigh, but usual symptoms of myelopathy were undetectable. In conjunction with the other reports, this case suggests that spinal tumors at high thoracic levels can produce remote symptoms mimicking peripheral neuropathy such as femoral or sciatic neuralgia.

Femoral Nerve↗
PubMed1995

Biomedical and biotechnological applications of PEG- and PM-modified proteins.

Chemical modification of proteins and other bioactive molecules with polyethylene glycol (PEG) or its derivatives (PM) can be used to tailor molecular properties to particular applications, eliminating disadvantageous properties or conferring new molecular functions. Complexes of therapeutic proteins and PEG or PM show reduced immunoreactivity, prolonged clearance times and improved biostability. Modification with PEG can also increase the solubility and activity of enzymes in organic solvents, thus extending their potential for application in organic syntheses and biotransformation processes.

Amino Acid Sequence↗
PubMed1995

Mechanisms of angiotensin II formation in humans.

Various organs, including the heart and blood vessels, apparently contain tissue renin-angiotensin systems. Through autocrine and paracrine activity, locally produced angiotensin II (Ang II) may well play an important role in cardiovascular homeostasis; in pathological conditions. Ang II may also contribute to the remodelling of the heart and vasculature. In addition to angiotensin converting enzyme (ACE), a cardiac Ang II forming serine proteinase (human heart chymase) has been identified in the left ventricle of the human heart. The different cellular and regional distributions of ACE and chymase in the heart as well as in the blood vessels suggest distinct pathophysiological roles for these two Ang II forming enzymes. Several reports indicate that both ACE-dependent and ACE-independent Ang II formation appear to occur in hypoxic or ischaemic hearts or blood vessels in vivo and seem to be involved in the pathological changes seen in these organs. However, chymase-dependent Ang II formation--which is chymostatin sensitive but aprotinin insensitive--does not explain all ACE-independent Ang II formation. Therefore, it is important to elucidate the mechanisms of tissue Ang II formation in humans and their contribution to the pathophysiological changes in cardiovascular disease.

Angiotensin II↗