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| 1.
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Nakanishi, Chiaki ; Nagaya, Noritoshi ; Ohnishi, Shunsuke ; Yamahara, Kenichi ; Takabatake, Shu ; Konno, Tetsuo ; Hayashi, Kenshi ; Kawashiri, Masa-aki ; Tsubokawa, Toshinari ; Yamagishi, Masakazu ; 中西, 千明 ; 今野, 哲雄 ; 林, 研至 ; 川尻, 剛照 ; 山岸, 正和
概要:
金沢大学医薬保健研究域医学系<br />Background: Mesenchymal stem cells (MSC) are multipotent and reside in bone marrow (BM), adipose tis
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sue and many other tissues. However, the molecular foundations underlying the differences in proliferation, differentiation potential and paracrine effects between adipose tissue-derived MSC (ASC) and BM-derived MSC (BM-MSC) are not well-known. Therefore, we investigated differences in the gene and secretory protein expressions of the 2 types of MSC. Methods and Results: ASC and BM-MSC were obtained from subcutaneous adipose tissue and BM of adult Lewis rats. ASC proliferated as rapidly as BM-MSC, and had expanded 200-fold in approximately 2 weeks. On microarray analysis of 31,099 genes, 571 (1.8%) were more highly (>3-fold) expressed in ASC, and a number of these genes were associated with mitosis and immune response. On the other hand, 571 genes (1.8%) were more highly expressed in BM-MSC, and some of these genes were associated with organ development and morphogenesis. In secretory protein analysis, ASC secreted significantly larger amounts of growth factor and inflammatory cytokines, such as vascular endothelial growth factor, hepatocyte growth factor and interleukin 6, whereas BM-MSC secreted significantly larger amounts of stromal-derived factor-1α. Conclusions: There are significant differences between ASC and BM-MSC in the cytokine secretome, which may provide clues to the molecule mechanisms associated with tissue regeneration and alternative cell sources.<br />出版者照会後に全文公開
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| 2.
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Funada, Akira ; Konno, Tetsuo ; Fujino, Noboru ; Muramoto, Akihiko ; Hayashi, Kenshi ; Tsubokawa, Toshinari ; Sakata, Kenji ; Kawashiri, Masa-aki ; Takeda, Yoshiyu ; Ino, Hidekazu ; Yamagishi, Masakazu ; 舟田, 晃 ; 今野, 哲雄 ; 藤野, 陽 ; 林, 研至 ; 坂田, 憲治 ; 川尻, 剛照 ; 武田, 仁勇 ; 井野, 秀一 ; 山岸, 正和
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金沢大学医薬保健研究域医学系<br />Background: Although the renin - angiotensin system (RAS) can affect the development of left ventric
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ular (LV) hypertrophy, few data exist regarding the relationships between RAS polymorphisms and alteration of LV function. The effect of RAS polymorphisms on LV function in genotyped hypertrophic cardiomyopathy (HCM) was examined in the present study. Methods and Results: The study group comprised 126 carriers with sarcomere gene mutations from 49 HCM families (64 males, mean age 51±21 years). LV morphology and function were evaluated by echocardiography. In angiotensin-converting enzyme (ACE) insertion/deletion (I/D), the D allele (n=81) exhibited significantly larger LV end-systolic dimension (LVDs) (32±11 mm) and lower ejection fraction (56±15%) than those with the II genotype (28±7 mm and 62±12%, respectively, P<0.05; n=45). Although angiotensin II type 1 receptor (AT1-R) A/C1166 polymorphism did not affect echocardiographic parameters, the presence of the ACE D allele with the AT1-R C1166 allele (n=9) was associated with larger LVDs (37±17 mm) and lower ejection fraction (48±20%) compared with other genotypes (30±9 mm and 58±14%, respectively, P<0.05; n=117). Under these conditions, severe LV hypertrophy was frequently associated with LV wall thinning. Conclusions: The presence of both the ACE D and AT1-R C1166 allele is associated with LV dilation with systolic dysfunction in genotyped HCM. In addition to the severity of LV hypertrophy, screening for these RAS polymorphisms could contribute to further risk stratification of patients with HCM, although other genetic polymorphisms should be further examined.<br />出版者照会後に全文公開
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| 3.
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Demura, Masashi ; Wang, Fen ; Yoneda, Takashi ; Karashima, Shigehiro ; Mori, Shunsuke ; Oe, Masashi ; Kometani, Mitsuhiro ; Sawamura, Toshitaka ; Cheng, Yuan ; Maeda, Yuji ; Namiki, Mikio ; Ino, Hidekazu ; Fujino, Noboru ; Uchiyama, Katsuharu ; Tsubokawa, Toshinari ; Yamagishi, Masakazu ; Nakamura, Yasuhiro ; Ono, Katsuhiko ; Sasano, Hironobu ; Demura, Yoshiki ; Takeda, Yoshiyu
概要:
金沢大学医薬保健研究域医学系<br />Objective: Nuclear receptors are involved in a wide variety of functions, including aldosteronogenes
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is. Nuclear receptor families NR4A [nerve growth factor-induced clone B (NGFIB), Nur-related factor 1 (NURR1) and neuron-derived orphan receptor 1 (NOR1)] and NR2F [chicken ovalbumin upstream promoter-transcription factor 1 (COUP-TFI), COUP-TFII and NR2F6) activate, whereas NR5A1 [steroidogenic factor 1 (SF1)] represses CYP11B2 (aldosterone synthase) gene transcription. The present study was undertaken to elucidate the mechanism of differential regulation of nuclear receptors between cardiovascular and adrenal tissues. Methods: We collected tissues of artery (n = 9), cardiomyopathy muscle (n = 9), heart muscle (noncardiomyopathy) (n = 6), adrenal gland (n = 9) and aldosterone-producing adenoma (APA) (n = 9). 5′-rapid amplification of cDNA ends (RACE) identified transcription start sites. Multiplex reverse-transcription PCR (RT-PCR) determined use of alternative noncoding exons 1 (ANEs). Results: In adrenocortical H295R cells, angiotensin II, KCl or cAMP, all stimulated CYP11B2 transcription and NR4A was upregulated, whereas NR2F and NR5A1 were downregulated. 5′-RACE and RT-PCR revealed four ANEs of NGFIB (NR4A1), three of NURR1 (NR4A2), two of NOR1 (NR4A3) and two of SF1 (NR5A1) in cardiovascular and adrenal tissues. Quantitative multiplex RT-PCR showed NR4A and NR5A1 differentially employed multiple ANEs in a tissue-specific manner. The use of ANEs of NGFIB and NURR1 was significantly different between APA and artery. Changes in use of ANEs of NGFIB and NOR1 were observed between cardiomyopathy and noncardiomyopathy. The NR4A mRNA levels in artery were high compared with cardiac and adrenal tissues, whereas the NR5A1 mRNA level in adrenal tissues was extremely high compared with cardiovascular tissues. Conclusion: NR4A and NR5A1 genes are complex in terms of alternative promoter use. The use of ANEs may be associated with the pathophysiology of the heart and adrenal gland. © 2011 Wolters Kluwer Health | Lippincott Williams & Wilkins.
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Yamamoto, Ryusuke ; Tada, Hayato ; Tsubokawa, Toshinari ; Konno, Tetsuo ; Hayashi, Kenshi ; Saito, Takekatsu ; Kawashiri, Masa-aki ; Ohta, Kunio ; Yachie, Akihiro ; Yamagishi, Masakazu
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Tada, Hayato ; Tsubokawa, Toshinari ; Konno, Tetsuo ; Hayashi, Kenshi ; Uchiyama, Katsuharu ; Kawashiri, Masa-aki ; Tomita, Shigeyuki ; Ino, Hidekazu ; Watanabe, Go ; Yamagishi, Masakazu
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| 6.
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Tada, Hayato ; Tsubokawa, Toshinari ; Konno, Tetsuo ; Hayashi, Kenshi ; Uchiyama, Katsuharu ; Kawashiri, Masa-aki ; Tomita, Shigeyuki ; Ino, Hidekazu ; Watanabe, Go ; Yamagishi, Masakazu
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| 7.
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Tada, Hayato ; Konno, Tetsuo ; Aizu, Motohiko ; Yokawa, Junichiro ; Tsubokawa, Toshinari ; Fujii, Hiroshi ; Hayashi, Kenshi ; Uchiyama, Katsuharu ; Matsumura, Masami ; Kawano, Mitsuhiro ; Kawashiri, Masa-aki ; Yamagishi, Masakazu
概要:
We report a case with pulmonary veno-occlusive disease (PVOD) associated with systemic sclerosis which exhibits strong r
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esistance to pulmonary vasodilator. A 55-year-old female with severe pulmonary hypertension was admitted to our hospital to be introduced to epoprostenol infusion therapy. She was diagnosed as having pulmonary arterial hypertension (PAH) associated with systemic sclerosis at the age of 51. Several aggressive treatments with pulmonary vasodilators, including oral prostaglandin, endothelin receptor antagonists, and phosphodiesterase 5 inhibitors, failed to improve her symptoms. We introduced continuous intravenous epoprostenol therapy from 2 μg/kg/min for her. However, pulmonary edema appeared and worsened in a dose-dependent manner. We made a diagnosis of PVOD clinically at that time. Thereafter, pulmonary edema gradually disappeared consistent with the reduction of the dose of epoprostenol infusion. She died of renal failure and infection 4 months after the introduction of epoprostenol infusion therapy. A histological examination revealed severe stenosis and occlusions of pulmonary veins as well as pulmonary arteries over a wide area. We suggest that prevalence of veno-occlusive type of disease could be one of the major mechanisms of less responsive or even refractory to pulmonary vasodilator therapies in patients with PAH associated with connective tissue disease. © 2011 Japanese College of Cardiology.
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| 8.
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論文
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Tada, Hayato ; Konno, Tetsuo ; Aizu, Motohiko ; Yokawa, Junichiro ; Tsubokawa, Toshinari ; Fujii, Hiroshi ; Hayashi, Kenshi ; Uchiyama, Katsuharu ; Matsumura, Masami ; Kawano, Mitsuhiro ; Kawashiri, Masa-aki ; Yamagishi, Masakazu
概要:
We report a case with pulmonary veno-occlusive disease (PVOD) associated with systemic sclerosis which exhibits strong r
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esistance to pulmonary vasodilator.A 55-year-old female with severe pulmonary hypertension was admitted to our hospital to be introduced to epoprostenol infusion therapy. She was diagnosed as having pulmonary arterial hypertension (PAH) associated with systemic sclerosis at the age of 51. Several aggressive treatments with pulmonary vasodilators, including oral prostaglandin, endothelin receptor antagonists, and phosphodiesterase 5 inhibitors, failed to improve her symptoms. We introduced continuous intravenous epoprostenol therapy from 2. μg/kg/min for her. However, pulmonary edema appeared and worsened in a dose-dependent manner. We made a diagnosis of PVOD clinically at that time. Thereafter, pulmonary edema gradually disappeared consistent with the reduction of the dose of epoprostenol infusion. She died of renal failure and infection 4. months after the introduction of epoprostenol infusion therapy. A histological examination revealed severe stenosis and occlusions of pulmonary veins as well as pulmonary arteries over a wide area. We suggest that prevalence of veno-occlusive type of disease could be one of the major mechanisms of less responsive or even refractory to pulmonary vasodilator therapies in patients with PAH associated with connective tissue disease. © 2011 Japanese College of Cardiology.
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| 9.
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Furuta, Takuya ; Tsubokawa, Toshinari ; Takabatake, Shu ; Ohtake, Hiroshi ; Watanabe, Go ; Yamagishi, Masakazu
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金沢大学附属病院循環器内科<br />Early and accurate diagnosis of infective aortic aneurysms (IAA) is critical for adequate treatment t
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o optimize patient outcome. We report the case of an 84-year-old man who complained of severe back pain with high fever and was finally diagnosed as Escherichia coli-related IAA. Computed tomography showed a periaortic soft tissue density and irregular fringe adjacent to the non-dilated abdominal aorta suggesting the presence of pseudoaneurysm. In addition to intravenous antibiotic injection, an aneurysmectomy with extensive debridement and an in situ graft, were successfully performed. The case emphasizes the potential for rapid IAA change and the need for frequent radiologic follow-up. © 2011 The Japanese Society of Internal Medicine.
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