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Yaizu, Japan

Fukasawa H.,Iwata City Hospital | Fujigaki Y.,Hamamatsu University School of Medicine | Yamamoto T.,Clinical Training Center | Hishida A.,Yaizu City Hospital | Kitagawa M.,Hamamatsu University School of Medicine
Current Medicinal Chemistry | Year: 2012

Abnormal and exaggerated deposition of extracellular matrix proteins is the common feature of fibrotic diseases. The resulting fibrosis disrupts the normal architecture of the affected organs and finally leads to their dysfunction and failure. At present, there are no effective therapies for fibrotic diseases. Protein degradation via the ubiquitin-proteasome system is the major pathway for non-lysosomal proteolysis and controls many critical cellular functions including cell-cycle progression, deoxyribonucleic acid repair, growth and differentiation. Therefore, aberration of the system leads to dysregulation of cellular homeostasis and development of many diseases such as cancers, degenerative diseases and fibrotic diseases. Although the ubiquitin-proteasome system has mainly been investigated in the field of cancers so far and several anti-cancer drugs that modulate the activity of the system have been used clinically, the recent findings regarding the system and fibrosis can provide a rational basis for the discovery of novel therapy for fibrotic diseases. In this article, we discuss (i) the basic mechanism of the ubiquitin-proteasome system and (ii) the recent findings regarding the association between the system and pathological organ fibrosis. These examples indicate that the ubiquitin-proteasome system plays diverse roles in the progression of fibrotic diseases, and further studies of the system are expected to reveal new strategies for overcoming pathological fibrosis. © 2012 Bentham Science Publishers. Source

Takahashi T.,Yaizu City Hospital
Kyobu geka. The Japanese journal of thoracic surgery | Year: 2013

A 56-year-old woman was referred to our hospital presenting high serum levels of calcium (Ca) and intact-parathyroid hormone (PTH) and an anterior mediastinal nodule of 18×13 mm in size on chest computed tomography (CT). Tumor was suspected of a parathyroid tumor. 99mTc-methoxy-isobutylisonitrile( MIBI) scintigram showed abnormal radioactive tracer accumulation in the lesion. 3 ml/kg of methylene blue was administered intravenously an hour before surgery, and the stained tumor was successfully resected by thoracoscopic surgery. Pathological diagnosis was parathyroid hyperplasia. Postoperative course was uneventful and serum levels of Ca and intact-PTH returned to normal ranges. Source

Takahashi K.,Toshiba General Hospital | Terada S.,Yaizu City Hospital | Kokuryu H.,Kyoto Katsura Hospital | Arai M.,Toshiba General Hospital | Mishiro S.,Toshiba General Hospital
Acta Hepatologica Japonica | Year: 2010

A peculiar nucleotide sequence of HEV RNA was recovered from a wild boar (Sus scrofa leucomystax) of male sex with about 10 kg of body weight, captured 1-Feb-2009 in the forest of Tenryu-ku, Hamamatsu, Shizuoka, Japan. The sequence (JBOAR135-Shiz09, accession number AB573435) showed only less than 80% nucleotide identity to so far reported sequences of HEV genotype 1 through 4 (72.7-76.4% vs G1, 75.5% vs G2, 71.2-78.2% vs G3, 74.9-78.2% vs G4) and also to the rabbit HEV isolates recently reported from China (75.5-77.3%). Since the rabbit HEV segregates to genotype 3 in the present phylogenetic analysis (CLUSTALW Unrooted N-J Tree Method), we propose our JBOAR135-Shiz09 isolate as the first member of new genetic group of HEV, "genotype 5". © 2010 The Japan Society of Hepatology. Source

Furuya R.,Iwata City Hospital | Kumagai H.,University of Shizuoka | Miyata T.,Tohoku University | Fukasawa H.,Iwata City Hospital | And 3 more authors.
Clinical and Experimental Nephrology | Year: 2012

Background Cardiovascular disease is a major complication in patients with end-stage renal disease (ESRD). The accumulation of advanced glycation end products (AGEs) is facilitated in these patients. The aim of this study was to investigate the relationship between circulating AGEs and cardiovascular events in hemodialysis patients. Methods The plasma level of pentosidine, a well-defined AGEs, was measured in 110 hemodialysis patients who were prospectively followed for 90 months. The relationship between plasma pentosidine level and cardiovascular events was assessed using Kaplan-Meier and Cox regression analysis. Results Thirty-nine cardiovascular events (14 coronary heart disease and 25 strokes) occurred during the follow-up period. Multivariable Cox proportional hazard analysis showed that plasma pentosidine levels (HR 1.040, 95% CI 1.022-1.058, P<0.01) were correlated to increased risk for cardiovascular events. When patients were divided into four groups according to plasma pentosidine levels, Kaplan-Meier analysis revealed that cardiovascular events in the highest pentosidine group were significantly greater than in the other groups (P<0.01 in lower and low, and P<0.05 in high pentosidine groups). Conclusion The plasma pentosidine level predicts cardiovascular events in hemodialysis patients. The effects of lowering circulating AGE levels on cardiovascular events should be examined in ESRD patients. © Japanese Society of Nephrology 2012. Source

Iimuro S.,University of Tokyo | Imai E.,Nagoya University | Watanabe T.,Fukushima Medical University | Nitta K.,Tokyo Womens Medical University | And 5 more authors.
Clinical Journal of the American Society of Nephrology | Year: 2013

Background and objectives Ambulatory BP monitoring (ABPM) allows a better risk stratification than office BP in hypertensive patients. However, the clinical relevance of ABPM has not been extensively investigated in the CKD population. Design, setting, participants, & measurements Within the Chronic Kidney Disease Japan Cohort study, 2977 patients enrolled (62% men, aged 60.8611.6 years) and ABPM was conducted in a subgroup of patients from September 2007 to April 2010. Data from 1075 patients (682 men) were analyzed to determine BP control and factors associated with the ABPM parameters. Results The prevalence of masked hypertension was 30.9%, whereas that of white-coat hypertension was 5.6%. With advancing CKD stage, the percentage of persistent hypertension increased from 21.7% to 36.1%. Diabetes, antihypertensive medicine use, and low estimated GFR (eGFR) were significantly associated with the difference between office BP and ambulatory BP (1.7 mmHg, 2.6 mmHg, and 0.6 mmHg per 10 ml/min per 1.73 m2, respectively). There tended to be fewer nondippers and risers in stage 3 than in stages 4 and 5. In the nocturia-negative group, low eGFR, diabetes, and summer season were identified as factors associated with lower nocturnal BP change (20.5 mmHg, 22.0 mmHg, and 22.8 mmHg, respectively). Morning BP change was greater with older age (0.2 mmHg per 10 years) and higher body mass index (0.6 mmHg per 1 kg/m2), and in winter (4.5 mmHg) versus summer. Conclusions Various factors including eGFR, diabetes, antihypertensive medication use, and season are associated with higher BP and abnormal BP patterns in CKD patients. © 2013 by the American Society of Nephrology. Source

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