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91.
92.
Hori M Kitabatake A Tsutsui H Okamoto H Shirato K Nagai R Izumi T Yokoyama H Yasumura Y Ishida Y Matsuzaki M Oki T Sekiya M;J-DHF Program Committee 《Journal of cardiac failure》2005,11(7):542-547
BACKGROUND: Heart failure consists of two phenotypes: systolic heart failure and diastolic heart failure (DHF). A growing body of evidence demonstrated benefits of beta-blocker, angiotensin-converting enzyme inhibitor, and angiotensin II receptor blocker in systolic heart failure; however, evidence leading to therapeutic strategy of DHF is lacking. METHODS AND RESULTS: The Japanese Diastolic Heart Failure Study (J-DHF) is a multicenter, prospective, randomized trial designed to assess effects of beta-blocker in patients with DHF. A total of 800 patients (400 patients in each group) will be enrolled. The primary outcome is a composite of cardiovascular death and unplanned admission to hospital for congestive heart failure. Other outcomes include all-cause mortality, worsening of the symptoms of heart failure, or a need for modification of the treatment for heart failure. Serial assessment of echocardiographic and neurohumoral parameters and cost analysis of the treatment regimen will be conducted. The follow-up period is a minimum of 2 years. CONCLUSION: This study will provide important evidences for the treatment of DHF. 相似文献
93.
Matsumoto K Morishita R Tomita N Moriguchi A Komai N Aoki M Matsumoto K Nakamura T Higaki J Ogihara T 《Heart and vessels》2003,18(1):18-25
Hepatocyte growth factor (HGF) is a unique growth factor with many protective functions. Previously, we demonstrated that
HGF stimulated growth of endothelial cells without replication of vascular smooth muscle cells (VSMC) and that angiotensin
(Ang) II significantly decreased local HGF production in VSMC. Moreover, we also reported that high glucose significantly
decreased local vascular HGF production. Therefore, we examined effects of Ang II blockade on vascular HGF expression and
endothelial injury in diabetic hypertensive rats. An angiotensin-converting enzyme inhibitor (quinapril) and an Ang II type
1 receptor antagonist (GA-0113) or vehicle was administrated to diabetic spontaneously hypertensive rats (SHR-DM), in whom
diabetes was induced by streptozotocin. Endothelial function was evaluated by the vasodilator response to acetylcholine, and
the expression of vascular HGF and its receptor, c-met, was examined by immunohistochemistry. Both quinapril and GA-0113 significantly
improved the vasodilator response to acetylcholine (P < 0.01), while vehicle did not as compared to untreated normotensive Wistar-Kyoto rats (WKY). We next examined the effects
of Ang II blockade on vascular HGF expression in SHR-DM. Importantly, the vascular HGF level was markedly decreased in SHR-DM
as compared to WKY, while Ang II blockade by quinapril or GA-0113 significantly increased positive staining for HGF in SHR-DM.
Similarly, staining of its specific receptor, c-met, was less in the blood vessels of SHR-DM as compared to WKY. In contrast,
Ang II blockade also significantly increased c-met production in SHR-DM. The present data demonstrated the improvement of
endothelial dysfunction by Ang II blockade in SHR-SM, accompanied by an increase in vascular HGF and c-met.
Received: June 7, 2002 / Accepted: September 21, 2002
Acknowledgments We wish to thank Rie Kosai and Keiko Yamaguchi for their excellent technical assistance. This work was partially supported
by grants from the Japan Health Sciences Foundation, a Grant-in-Aid from The Ministry of Public Health and Welfare, a Grant-in-Aid
for the Development of Innovative Technology, a Grant-in-Aid from Japan Promotion of Science, and through Special Coordination
Funds of the Ministry of Education, Culture, Sports, Science and Technology, the Japanese Government.
Correspondence to N. Tomita 相似文献
94.
Fumichika Nishimura Masanao Shibasaki Kunio Ichikawa Tadao Arinami Emiko Noguchi 《Allergology international》2006,55(1):55-58
BACKGROUND: CD14 is an essential component of the receptor for lipopolysaccharide (LPS). LPS stimulates T-helper type 1 (Th1) cytokine expression, potentially suppressing Th2 immune responses involved in IgE-mediated allergic diseases. Previous studies have reported that -159C/T, a promoter polymorphism of CD14, is associated with total serum IgE levels and atopy, but other studies have shown conflicting results. METHODS: To examine possible associations of CD14 polymorphisms with asthma susceptibility, we performed transmission disequilibrium tests (TDTs) of 137 Japanese families identified through children with atopic asthma. RESULTS: We found no association between -159C/T polymorphism and asthma (p= 0.37). Quantitative TDT and ANOVA showed no association between the -159C/T genotype and total serum IgE levels. We also performed a meta-analysis of data from all available studies. Neither a fixed-effects model nor a random-effect model showed a significant odds ratio for the -159C/T polymorphism (p > 0.1). CONCLUSIONS: Our data indicate that CD14 does not contribute substantially to susceptibility to asthma. Further studies examining both genotypes and environmental factors will be necessary to elucidate the role of CD14 in the development of allergic diseases. 相似文献
95.
Katsutoshi Murata Shozo Kusachi Takashi Murakami Kunio Nogami Masahiro Murakami Satoshi Hirohata Youkou Tominaga Issei Komatsubara Takao Tsuji 《Clinical cardiology》1997,20(1):61-66
Background: Iodine-123 metaiodobenzylguanidine (123I-MIBG) concentrates in adrenergic neurons and has been developed for evaluation of the sympathetic nervous system. Recent studies have demonstrated that the normal heart is clearly visualized by 123I-MIBG cardiac scintigraphy, whereas abnormal 123I-MIBG myocardial uptake and washout have been demonstrated in patients after myocardial infarction and in patients with congestive cardiomyopathy, long QT syndrome, and ventricular tachycardia. Hypothesis: Based on evidence from recent studies, it can be hypothesized that 123I-MIBG uptake is related to histopathologic changes in the myocardium. Methods: The relation of 123I-MIBG uptake to the histologic findings for the heart was studied in 24 patients with dilated cardiomyopathy (DCM). The study group did not include patients with complicating disorders that primarily affect the adrenergic nervous system. The 123I-MIBG uptake was visually assigned one of four grades using the two criteria of the mean score for six regional uptake grades (mean score) and the global score obtained by visual evaluation of the entire image (global score). The 123I-MIBG uptake score was also determined for the region at which the biopsy specimen was obtained (biopsy region score). The histologic findings were evaluated by assigning one of four grades for each of the following five factors: myocyte hypertrophy, myocardial fibrotic change, myocyte degeneration and necrosis, mononuclear cell infiltration, and myocyte disarray. The sum for all grades was defined as the total score, and the global score was also assigned to the overall histologic findings. Results: All of the global, mean, and biopsy region scores for 123I-MIBG uptake correlated significantly with the global and total scores for the histologic findings. Among the histologic factors, myocyte degeneration showed score correlated with all global, mean, and biopsy region scores for the uptake. Myocyte hypertrophy was associated weakly with the 123I-MIBG uptake scores. Conclusion: These results indicate that 123I-MIBG uptake imaging is associated with histopathologic abnormalities in patients with DCM. 相似文献
96.
Clinical and Portal Hemodynamic Features in Cirrhotic Patients Having a Large Spontaneous Splenorenal and/or Gastrorenal Shunt 总被引:1,自引:0,他引:1
Kunihiko Ohnishi Shinichi Sato Masayuki Saito Hidetaka Terabayashi Takatsune Nakayama Masaaki Saito Nobuyoshi Chin Shinji Iida Fumio Nomura Kunio Okuda 《The American journal of gastroenterology》1986,81(6):450-455
Clinical and portal hemodynamic features in 28 cirrhotic subjects with a large spontaneous spleno- and/or gastrorenal shunt were studied in comparison with 30 control cirrhotic cases without such collaterals. Forty-six percent of the former had chronic hepatic encephalopathy, but none of the latter was encephalopathic. These patients with large renal shunts were divided into those with and those without encephalopathy. Large esophageal varices were significantly less common in patients with a large shunt and encephalopathy compared with those who had a large shunt but no encephalopathy, and the control. But there was no significant difference of past variceal bleeding among these three groups. In all those with encephalopathy, part of superior mesenteric venous blood was shunting through these collaterals into the left renal vein or inferior vena cava, but the same was not demonstrable in patients with a large shunt and no encephalopathy and control cirrhotics. In the chronic encephalopathic, portal venous flow was estimated to be less than one-half of that in control cirrhotics, and the portion of superior mesenteric venous blood that was flowing hepatofugally through a large shunt into the left renal vein seemed about the same or greater than the portal venous flow. Thus, a large spontaneous spleno- and/or gastrorenal shunt might prevent development of large esophageal varices but not variceal hemorrhage and it increased a risk of chronic hepatic encephalopathy. 相似文献
97.
Nobuhiko Kobayashi Takanori Yasu Satoshi Yamada Nobuki Kudo Masatoshi Kuroki Kunio Miyatake Masanobu Kawakami Muneyasu Saito 《Circulation journal》2003,67(7):630-636
Microbubbles have been reported to enhance ultrasound (US)-related side effects in animal systems. The present study investigated the influence of contrast ultrasonography (US) with perflutren lipid microspheres, a recently developed second-generation contrast agent, on microvessels. Rat mesentery was exposed to 1.8-MHz pulsed US with intravenous injection of perflutren (0.1 or 1.0 ml/kg) or Levovist (300 mg/kg), and the microvessel bleeding and endothelial cell injury was examined. Impaired endothelial cells were identified by the fluorescence of propidium iodide. Microvessel bleeding was examined also in the rat myocardium. The interaction between 0.1 ml/kg of perflutren and US exposure did not cause microvessel bleeding, and did not increase endothelial cell injury compared with the sham operation, unless frequent, strong US exposure occurred. When the dose was increased to 1.0 ml/kg, the combination of perflutren and US exposure resulted in capillary bleeding and increased endothelial cell injury in capillaries and venules (p<0.01). However, the incidence of microvessel bleeding and endothelial cell injury did not exceed that with Levovist microbubbles. In the myocardium, microvessel bleeding was not observed under any conditions. In conclusion, perflutren lipid microspheres enhanced US-related microvessel injury as with other contrast agents at the dose of 1.0 ml/kg, but not with 0.1 ml/kg and the appropriate US setting. 相似文献
98.
Masaki Takasugi Koji Hayakawa Daisuke Arai Kunio Shiota 《Mechanisms of ageing and development》2013,134(7-8):331-337
In mammals, differences in liver function and aging have been observed between sexes; however, the epigenetic mechanisms underlying such differences remain largely unexplored. In this study, we investigated sex- and age-dependent DNA methylation status in the mouse liver. We analyzed 90 known sex-differentially expressed genes, and identified sex-dependent methylation in Zfp809, Hsd3b5, Treh, Cxcl11, Cyp17a1, and Nnmt genes. After 4 weeks of age, we noted the gradual establishment of sex-dependent hypomethylation in each of these genes in either males or females. The exposure of male mice to female-like growth hormone (GH) profile repressed male-predominant hypomethylation and promoted female-predominant hypomethylation. The occurrence of age-dependent hypomethylation, including at loci for which we also observed sex-dependent changes in DNA methylation, was accompanied by the downregulation of DNMT3A/B. In addition, we found that age-dependent hypomethylation was promoted through liver regeneration induced by partial hepatectomy, suggesting that DNMT activities were not enough to retain methylation levels. In conclusion, our results demonstrate that sex-dependent GH profiles influence the age-progressive hypomethylation under decreased DNMT3A/B levels in certain regions of the genome. 相似文献
99.
100.
Yukari Okita Ling Zheng Kunio Kawanishi Hirotoshi Miyoshi Kazuyoshi Yanagihara Mitsuyasu Kato 《Genes to cells : devoted to molecular & cellular mechanisms》2021,26(5):336-343
Three-dimensional (3D) culturing mimics the heterogeneous cellular conditions of the in vivo tumor microenvironment compared to 2D monolayer-cultured cells and 3D cultures of established cancer cell lines (sphere culture) or patient-derived cancer cells (organoid culture) are frequently used for cancer research or drug screening and evaluation. To establish more cost and time-efficient 3D culture methods for cancer cell lines, we supplemented sphere culture medium with polyvinyl alcohol (PVA) and found that 3D sphere cultures of breast and pancreatic cancer cell lines were significantly increased. Mechanistically, we found that PVA prevented cell death and promoted cellular proliferation while maintaining levels of stemness-related gene expression. Furthermore, we showed that polyvinyl formal resin (PVF) 3D scaffolds made by cross-linked PVA can function in serum-free, long-term 3D cultures to support maintenance of sphere- or tumor-like cell masses for diverse cancer cell types. Taken together, we demonstrate the effectiveness of PVA and PVF in human cancer cell line culture protocols. 相似文献