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論文
Wada, Taizo ; Maeba, Hideaki ; Ikawa, Yasuhiro ; Hashida, Yoko ; Okumura, Akiko ; Shibata, Fumie ; Tone, Yumi ; Inoue, Masayuki ; Koizumi, Shoichi ; Takatori, Hajime ; Sakai, Yoshio ; Kaneko, Shuichi ; Yachie, Akihiro
出版情報: International Journal of Hematology.  85  pp.191-194,  2007-04-01.  日本血液学会 = Japanese Society of Hematology
URL: http://hdl.handle.net/2297/16857
概要: 金沢大学附属病院小児科<br />Reactive plasmacytosis is a transient expansion of plasma cell progenitors and precursors. This r are condition has been reported to occur mainly in infections and tumors. We describe a case of acute hepatitis A presenting with marked peripheral blood plasmacytosis. Plasma cells made up 27.5% of the mononuclear cells and had the immunophenotype CD10-CD19 +CD20-CD21-CD23-CD34 -CD38++HLA-DR+. Although the level of interleukin 6 was not increased, the presence of activated T-cells with an inverted CD4/CD8 ratio and high levels of soluble interleukin 2 receptor and neopterin indicated a marked immune response to acute hepatitis A. The patient's plasma cells had almost disappeared from the blood by hospital day 16. This report may represent the first described case of reactive peripheral blood plasmacytosis in acute hepatitis A. © 2007 The Japanese Society of Hematology. 続きを見る
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Iwata, Yasunori ; Wada, Takashi ; Yokoyama, Hitoshi ; Toyama, Tadashi ; Kitajima, Shinji ; Okumura, Toshiya ; Hara, Akinori ; Yamahana, Junya ; Nakaya, Izaya ; Kobayashi, Motoo ; Kitagawa, Kiyoki ; Kokubo, Satoshi ; Yoshimoto, Keiichi ; Shimizu, Kazuaki ; Sakai, Norihiko ; Furuichi, Kengo ; Koshino, Yoshitaka ; Takaeda, Chikako ; Takeda, Shinichi ; Takasawa, Kazuya ; Ohta, Satoshi ; Takaeda, Masayoshi ; Kaneko, Shuichi
出版情報: Internal Medicine.  46  pp.447-452,  2007-04-08.  日本内科学会
URL: http://hdl.handle.net/2297/6249
概要: 金沢大学保健管理センター<br />金沢大学大学院医学系研究科<br />金沢大学附属病院<br />Background: In hemodialysis patients, adynamic bone disease has been reported to be closely associated with low levels of parathyroid hormone (PTH) due to exposure to high levels of serum calcium following the administration of calcium carbonate (CaCO3) or vitamin D agents. This study was conducted to clarify the therapeutic effect of a non-calcemic phosphate binder, sevelamer hydrochloride (sevelamer), for hypoparathyroidism in hemodialysis patients with or without diabetes mellitus. Methods: Based on entry criteria, 40 Japanese chronic hemodialysis patients (22 males and 18 females with a mean age of 60.6, 14 diabetic patients and 26 non-diabetic patients) were switched from CaCO3 to sevelamer for 48 weeks. Serum calcium, phosphate, intact (i) PTH and PTH-(1-84) were analyzed. Bone remodeling activity was evaluated by determining intact osteocalcine (iOC), bone-specific alkaline phosphatase (BAP). Results: The switch from CaCO3 to sevelamer significantly decreased the serum levels of calcium, resulting in the elevation of iPTH levels from 31±18 pg/mL to 95±96 pg/mL by 48 weeks. In contrast, serum phosphate levels remained similar to those in patients with CaCO3 treatment. Concomitantly, the levels of BAP and iOC were elevated. Further, these beneficial effects on bone turnover were observed in both diabetic and non-diabetic patients. Conclusion: Sevelamer reduced the calcium concentration and thereby increased PTH levels, resulting in the improvement of markers of bone turnover. The administration of sevelamer is of therapeutic benefit for the improvement of bone remodeling activity even in hemodialysis patients with diabetes. © 2007 The Japanese Society of Internal Medicine. 続きを見る
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Sakurai, Masaru ; Takamura, Toshinari ; Miura, Katsuyuki ; Kaneko, Shuichi ; Nakagawa, Hideaki
出版情報: Internal Medicine.  48  pp.1573-1574,  2009-01-01.  Japanese Society of Internal Medicine = 日本内科学会
URL: http://hdl.handle.net/2297/19772
概要: 金沢大学医薬保健研究域医学系
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Kurita, Seiichiro ; Takamura, Toshinari ; Ota, Tsuguhito ; Matsuzawa-Nagata, Naoto ; Kita, Yuki ; Uno, Masafumi ; Nabemoto, Satoko ; Ishikura, Kazuhide ; Misu, Hirofumi ; Ando, Hitoshi ; Zen, Yoh ; Nakanuma, Yasuni ; Kaneko, Shuichi
出版情報: European Journal of Pharmacology.  588  2008-07-07.  Elsevier
URL: http://hdl.handle.net/2297/10979
概要: 金沢大学大学院医学系研究科<br />金沢大学医薬保健研究域医学系<br />Insulin resistance is a major pathological condition associated with obesity and metabolic syndrome. Insulin resistance and the renin-angiotensin system are intimately linked. We evaluated the role of the renin-angiotensin system in the pathogenesis of insulin resistance-associated, non-alcoholic steatohepatitis by using the angiotensin II type 1 receptor blocker olmesartan medoxomil in a diabetic rat model. The effects of olmesartan on methionine- and choline-deficient (MCD) diet-induced steatohepatitis were investigated in obese, diabetic Otsuka Long-Evans Tokushima Fatty (OLETF) rats and control Long-Evans Tokushima Otsuka (LETO) rats. Components of the renin-angiotensin system were up-regulated in the livers of OLETF rats, compared with LETO rats. In OLETF, but not LETO, rats, oral administration of olmesartan for 8 weeks ameliorated insulin resistance. Moreover, olmesartan suppressed MCD diet-induced hepatic steatosis and the hepatic expression of lipogenic genes (sterol regulatory element-binding protein-1c and fatty acid synthase) in OLETF, but not LETO, rats. In both OLETF and LETO rats, olmesartan inhibited hepatic oxidative stress (4-hydroxy-2-nonenal-modified protein) and expression of NADPH oxidase. Olmesartan also inhibited hepatic fibrosis, stellate cell activation, and expression of fibrogenic genes (transforming growth factor-β, α1 [I] procollagen, plasminogen activator inhibitor-1) in both OLETF and LETO rats. In conclusion, pharmacological blockade of the angiotensin II type 1 receptor slows the development of steatohepatitis in the OLETF rat model. This angiotensin II type 1 receptor blocker may exert insulin resistance-associated effects against hepatic steatosis and inflammation as well as direct effects against the generation of reactive oxygen species and fibrogenesis. © 2008 Elsevier B.V. All rights reserved. 続きを見る
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Takashima, Shinichiro ; Sugimoto, Naotoshi ; Takuwa, Noriko ; Okamoto, Yasuo ; Yoshioka, Kazuaki ; Takamura, Masayuki ; Takata, Shigeo ; Kaneko, Shuichi ; Takuwa, Yoh
出版情報: Cardiovascular Research.  79  pp.689-697,  2008-09-01.  Elsevier
URL: http://hdl.handle.net/2297/12043
概要: 金沢大学医薬保健研究域医学系<br />Aims: The lysophospholipid mediator sphingosine-1-phosphate (S1P) activates G protein-coupled receptors (GPCRs) to induce potent inhibition of platelet-derived growth factor (PDGF)-induced Rac activation and, thereby, chemotaxis in rat vascular smooth muscle cells (VSMCs). We explored the heterotrimeric G protein and the downstream mechanism that mediated S1P inhibition of Rac and cell migration in VSMCs. Methods and results: S1P inhibition of PDGF-induced cell migration and Rac activation in VSMCs was abolished by the selective S1P2 receptor antagonist JTE-013. The C-terminal peptides of Gα subunits (Gα-CTs) act as specific inhibitors of respective G protein-GPCR coupling. Adenovirus-mediated expression of Gα12-CT, Gα13-CT, and Gα q-CT, but not that of Gαs-CT or LacZ or pertussis toxin treatment, abrogated S1P inhibition of PDGF-induced Rac activation and migration, indicating that both G12/13 and Gq classes are necessary for the S1P inhibition. The expression of Gαq-CT as well as Gα12-CT and Gα13-CT also abolished S1P-induced Rho stimulation. C3 toxin, but not a Rho kinase inhibitor or a dominant negative form of Rho kinase, abolished S1P inhibition of PDGF-induced Rac activation and cell migration. The angiotensin II receptor AT1, which robustly couples to Gq, did not mediate either Rho activation or inhibition of PDGF-induced Rac activation or migration, suggesting that activation of Gq alone was not sufficient for Rho activation and resultant Rac inhibition. However, the AT1 receptor fused to Gα12 was able to induce not only Rho stimulation but also inhibition of PDGF-induced Rac activation and migration. Phospholipase C inhibition did not affect S1P-induced Rho activation, and protein kinase C activation by a phorbol ester did not mimic S1P action, suggesting that S1P inhibition of migration or Rac was not dependent on the phospholipase C pathway. Conclusion: These observations together suggest that S1P2 mediates inhibition of Rac and migration through the coordinated action of G 12/13 and Gq for Rho activation in VSMCs. © The Author 2008.. 続きを見る
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Sakurai, Masaru ; Takamura, Toshinari ; Miura, Katsuyuki ; Kaneko, Shuichi ; Nakagawa, Hideaki
出版情報: Metabolism: Clinical and Experimental.  58  pp.456-459,  2009-04-01.  Elsevier
URL: http://hdl.handle.net/2297/17359
概要: 金沢大学医薬保健研究域医学系<br />We attempted to determine sex differences in obesity-related metabolic abnormalities in a rela tively large middle-aged Japanese population. The study population consisted of 2935 men and 1622 women who were 35 to 59 years old. Metabolic abnormalities were determined using the Japanese criteria for metabolic syndrome, and we evaluated the number of metabolic abnormalities discriminated by waist circumference. In men, the mean number of metabolic abnormalities increased as the waist circumference increased. In women, although the mean number of metabolic abnormalities increased as the waist circumference increased, the mean number was less than 1 even in those with a waist circumference of at least 95 cm. According to the receiver operating characteristic curve, the cutoff levels yielding the maximal sensitivity plus specificity for predicting the prevalence of one or more obesity-related metabolic abnormalities were 80 cm in men and 73 cm in women. However, the positive predictive value was as low as 28.8% in men and 7.1% in women, which may not be suitable for a screening test, especially in women. Middle-aged Japanese women seem to be resistant to obesity-induced metabolic abnormalities, and waist circumference would not effectively predict the existence of metabolic syndrome. In setting the cutoff points in guidelines, a greater emphasis should be placed on the absolute risk of having abnormalities or diseases. © 2009 Elsevier Inc. All rights reserved. 続きを見る
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Sakurai, Sho ; Miura, K. ; Takamura, Toshinari ; Ishizaki, Masao ; Morikawa, Y. ; Nakamura, K. ; Yoshita, Katsushi ; Kido, Teruhiko ; Naruse, Yuchi ; Kaneko, Shuichi ; Nakagawa, H.
出版情報: Diabetic Medicine.  26  pp.753-759,  2009-08-01.  Blackwell Publishing
URL: http://hdl.handle.net/2297/19144
概要: 金沢大学医薬保健研究域医学系<br />金沢医科大学健康増進予防医学(公衆衛生学)<br />Aims This study investigated the relationship between waist c ircumference and the subsequent incidence of Type 2 diabetes and the association with insulin resistance and pancreatic B-cell function in relatively lean Japanese individuals. Methods The study participants were 3992 employees (2533 men and 1459 women, aged 35-55 years) of a metal-products factory in Japan. The incidence of diabetes was determined in annual medical examinations during an 8-year follow-up. We calculated age- and sex-adjusted hazard ratios (HRs) according to the sex-specific quintile of waist circumference at baseline. Differences in baseline insulin resistance [homeostatis model assessment (HOMA)-IR] and pancreatic B-cell function (HOMA-B) were compared between participants who developed diabetes and those who did not. Results During the follow-up, 218 participants developed diabetes. Age- and sex-adjusted HRs across the quintiles of waist circumference were 1.78, 1.00 (reference), 1.59, 3.11 and 3.30, respectively (P for trend, < 0.0001). The HR for the lowest quintile was significantly higher than that for the second quintile. Among participants with waist circumference of the lowest quintile, HOMA-B was lower in those who developed diabetes than in those who did not [33.1 (24.1-45.0) vs. 54.3 (37.9-74.6) median (interquartile range), P < 0.0001], but HOMA-IR did not differ between these groups. Conclusions There was a J-shaped relationship between waist circumference and subsequent risk for Type 2 diabetes in relatively lean Japanese individuals; lower pancreatic B-cell function may also increase the risk of diabetes in very lean Japanese people. © 2009 Diabetes UK. 続きを見る
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Matsuzawa-Nagata, Naoto ; Takamura, Toshinari ; Ando, Hitoshi ; Nakamura, Seiji ; Kurita, Seiichiro ; Misu, Hirofumi ; Ota, Tsuguhito ; Yokoyama, Masayoshi ; Honda, Masao ; Miyamoto, Ken-ichi ; Kaneko, Shuichi
出版情報: Metabolism: Clinical and Experimental.  57  pp.1071-1077,  2008-08-01.  Elsevier
URL: http://hdl.handle.net/2297/11570
概要: 金沢大学医薬保健研究域医学系<br />Insulin resistance is a key pathophysiological feature of metabolic syndrome. However, the ini tial events triggering the development of insulin resistance and its causal relations with dysregulation of glucose and fatty acids metabolism remain unclear. We investigated biological pathways that have the potential to induce insulin resistance in mice fed a high-fat diet (HFD). We demonstrate that the pathways for reactive oxygen species (ROS) production and oxidative stress are coordinately up-regulated in both the liver and adipose tissue of mice fed an HFD before the onset of insulin resistance through discrete mechanism. In the liver, an HFD up-regulated genes involved in sterol regulatory element binding protein 1c-related fatty acid synthesis and peroxisome proliferator-activated receptor α-related fatty acid oxidation. In the adipose tissue, however, the HFD down-regulated genes involved in fatty acid synthesis and up-regulated nicotinamide adenine dinucleotide phosphate (NADPH) oxidase complex. Furthermore, increased ROS production preceded the elevation of tumor necrosis factor-α and free fatty acids in the plasma and liver. The ROS may be an initial key event triggering HFD-induced insulin resistance. © 2008 Elsevier Inc. All rights reserved. 続きを見る
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Takeshita, Yumie ; Takamura, Toshinari ; Minato, Hiroshi ; Misu, Hirofumi ; Ando, Hitoshi ; Yamashita, Tatsuya ; Ikeda, Hiroko ; Nakanuma, Yasuni ; Kaneko, Shuichi
出版情報: Internal Medicine.  47  pp.1709-1712,  2008-01-01.  日本内科学会 = the Japanese Society of Internal Medicine
URL: http://hdl.handle.net/2297/14444
概要: 金沢大学医薬保健研究域医学系<br />金沢大学医薬保健研究域医学系恒常性制御学<br />Multiple liver metastases were incidentally detected in the lo be of the liver of an 81-year-old woman following total thyroidectomy and ablative radioactive iodine administration for the treatment of papillary thyroid carcinoma. A biopsy specimen taken from the metastatic liver tumor was histologically diagnosed as anaplastic carcinoma. Immunohistochemical staining for p53 was positive in both the primary tumor and liver biopsy specimens. We considered this to have been caused by anaplastic transformation from papillary thyroid carcinoma during treatment. We report a rare case of multiple liver metastases from a papillary thyroid carcinoma, which we believe to be the result of anaplastic transformation during postoperative radioactive iodine-131 therapy. © 2008 The Japanese Society of Internal Medicine. 続きを見る
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Hara, Akinori ; Wada, Takashi ; Kitajima, Shinji ; Toyama, Tadashi ; Okumura, Toshiya ; Kitagawa, Kiyoki ; Iwata, Yasunori ; Sakai, Norihiko ; Furuichi, Kengo ; Higuchi, Masato ; Kaneko, Shuichi
出版情報: American Journal of Hematology.  83  pp.750-752,  2008-09-01.  John Wiley & Sons
URL: http://hdl.handle.net/2297/11836
概要: 金沢大学医薬保健研究域医学系<br />A 42-year-old woman with systemic lupus erythematosus was admitted to our hospital because of severe anemia. Her bone marrow was almost normocellular and erythroblasts were nearly absent. Laboratory data showed elevated levels of lactate dehydrogenase and positive findings on Coombs' tests. On the basis of these findings, her anemia was diagnosed as the overlap of pure red cell aplasia with autoimmune hemolytic anemia. Radioimmunoprecipitation assay revealed that her serum was positive for anti-erythropoietin antibodies before therapy. Furthermore, the autoantibodies inhibited proliferation of an erythropoietin-dependent cell line in a dose-dependent manner. Immunosuppressive treatment improved the anemia accompanied with disappearance of the autoantibodies. © 2008 Wiley-Liss, Inc. 続きを見る