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Biomedical subjects

H Nishimura

Publications and source records attributed to H Nishimura.

At least 325 records · Page 18Linked to original sources

[Evaluation of the retrosternal space and the retrocardiac space on normal left lateral radiographs of the chest].

Left lateral chest radiographs with normal studies were evaluated in 100 Japanese (50 females and 50 males) to compare the radiolucency of the retrosternal space (RSS) with that of the retrocardiac space (RCS) and to measure the RSS. In 56 (56%) cases, the RSS was equally radiolucent to the RCS. In 40 (40%) cases, the RSS was less radiolucent than the RCS (33 of 50 females and 7 of 50 males). The difference between the sexes was statistically significant (p = 0.0001). The RSS was more radiolucent than the RCS in only 4 (4%) males. Frontal chest radiographs of 50 females were classified into one of three groups (Small, Medium, or Large) depending on the size of soft tissue opacity of the breast. The differences between the radiolucency of the RSS and RCS were statistically significant between the Small and Medium and the Small and Large groups (both p < 0.0001). The strength of the relationship between the radiolucency and body-to-fat ratio was statistically significant (p = 0.0028). Results of data comparison between females and males remained significant when adjusted for differences in body-to-fat ratio (p < 0.0001). The distance on the chest radiograph from the sternum to the most anterior aortic border (the distance of RSS) could be measured on only 37 (37%) lateral chest radiographs, and the averages and standard deviations were as follows: 2.2 +/- 0.5 in all cases, 2.0 +/- 0.5 in females, and 2.4 +/- 0.5 in males. The difference between the sexes was statistically significant (p < 0.05). In conclusion, an RSS that is more opaque (less radiolucent) than the RCS is a frequent normal finding because of the opacity of the breast and fat tissue, especially in females, and the length of the RSS is shorter in females than in males.

Adult↗

[Dynamic study of the liver with helical scanning: determination of hepatic contrast enhancement in routine studies].

Helical CT makes possible imaging of the entire liver in as few as 20 seconds during a single breath hold. This method is thus superior to conventional dynamic CT. In this study, optimal late scanning time and optimal volume of contrast medium in the liver were determined with helical CT in routine studies. (1) Optimal late scanning time In 50 cases, CT images of the liver were obtained at various times following the administrations of contrast medium (1.4 ml/kg). Scanning was started at 60,90,120,150 and 180 seconds after injection. Enhancement of the liver and detection of hepatic and portal veins were best at 60 seconds, followed at 90 seconds. However, a scanning delay of 60 seconds still had an effect on the arterial phase. The optimal late scanning time was thus concluded to be at 90 seconds. (2) Optimal volume of contrast medium In 40 cases, CT images of the liver were obtained following the administration of various amounts of contrast medium (1.0 ml, 1.2 ml, 1.4 ml, 1.6 ml/kg) to determine the optimal volume. No significant difference was found between 1.6 ml/kg compared and 1.4 ml/kg of administered contrast medium. It is evident from the present data that a scanning delay of 90 seconds appears to be optimal and a contrast medium volume of 1.4 ml/kg (body weight) is best for conducting helical dynamic CT on the liver.

Female↗

Angiotensin I converting enzyme and chymase in cardiovascular tissues.

Recent studies have provided evidence that the human cardiovascular tissues contain components of the renin-angiotensin system: angiotensinogen, renin, angiotensin I converting enzyme (ACE), chymase and angiotensin II (Ang II) receptors. In addition to ACE, a cardiac Ang II forming serine proteinase, human heart chymase, has been identified in the human left ventricle. Unlike rat heart, only a minor (approximately 11%) component of Ang II forming activity in the human left ventricle was due to ACE, since the majority (approximately 80%) of activity was due to chymase. Human heart chymase has been purified to homogeneity and characterized. Recently, the cDNA and gene for this enzyme have been cloned. Biochemical characterization revealed that heart chymase is the most efficient and specific Ang II forming enzyme described thus far. The different cellular and regional distribution of ACE and heart chymase in the heart as well as in blood vessels implies distinct pathophysiological roles for these two Ang II forming enzymes. Several reports indicate that ACE-independent Ang II formation appears to take place in hypoxic or ischemic heart or blood vessel in vivo and to be involved in vascular remodeling after balloon injury. Therefore, it is very important to clarify the detailed mechanisms of the tissue Ang II formation in humans and its contribution to the pathophysiological changes in cardiovascular disease. In this review, we review the pathophysiological roles of the two main Ang II forming enzymes, ACE and chymase, in cardiovascular homeostasis.

Animals↗

[Chemotherapy for recurrent ovarian cancer].

The standard treatment for ovarian cancer is cytoreductive surgery followed by platinum-based combination chemotherapy. Although high response rates of this treatment are reported, 40-60% of patients achieving a complete response may relapse. Therefore, second-line chemotherapy is required. Second-line chemotherapy of patients with recurrent ovarian cancer should be based on their sensitivity to first-line chemotherapy and the platina-free interval. Patients who respond to the platina-based chemotherapy still may be sensitive to further platina-based chemotherapy. Patients who do not respond to the platina-based chemotherapy or who have relapses shortly after first-line chemotherapy should be considered clinically resistant to further platina-based chemotherapy. For such patients the chemotherapy regimen should be changed. These regimens include paclitaxel and hexamethylmelamine. The effect of intraperitoneal chemotherapy may depend on the size of the largest residual tumor nodule and the patient's sensitivity to previous chemotherapy.

Adenocarcinoma, Clear Cell↗

[Report of nationwide questionnaire: intraperitoneal chemotherapy for advanced ovarian cancer based on clinical results--reports of 5th "Gynecologic Intraperitoneal Chemotherapy Study Group" meeting].

We established the "Gynecologic Intraperitoneal Chemotherapy Study Group" in October, 1990. To date 5 annual meetings have been held during the Japanese Cancer Therapy Meeting. The members decided to establish a standard protocol of intraperitoneal chemotherapy (IP-CTX) for advanced ovarian cancer based on the clinical results obtained at each institution. Thus we first collected the clinical data from the affiliated institutes. Questionnaires concerning the indication of IP-CTX and the resulting data were sent to physicians working at 267 facilities in January, 1994. As a result, the reply rate was 28.8% (77/267). According to the results from 40 institutions, the consensus was that patients with residuum less than 0.5 cm in diameter after primary debulking surgery were suitable for IP-CTX. However, the remaining 37 institutions reported that patients with a macroscopic residuum less than 2 cm in diameter or those with bulky residuum greater than 2 cm in diameter demonstrated good responses to IP-CTX. Thus, further analyses are required to elucidate the appropriate indication and establish the standard protocol of IP-CTX for ovarian cancer in a clinical setting.

Antineoplastic Agents↗

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↗

[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↗

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↗

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↗

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↗

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↗

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↗