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Iwata, 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

Fukasawa H.,Iwata City Hospital
Clinical and Experimental Nephrology | Year: 2012

Proteins in mammalian cells are continually being degraded and synthesized. Protein degradation via the ubiquitin-proteasome system (UPS) is the major pathway for non-lysosomal proteolysis of intracellular proteins and plays important roles in a variety of fundamental cellular processes such as regulation of cell cycle progression, differentiation, apoptosis, sodium channel function, and modulation of inflammatory responses. The central element of this system is the covalent linkage of ubiquitins to targeted proteins, which are then recognized by the 26S proteasome composed of adenosine triphosphate- dependent, multi-catalytic proteases. Damaged or misfolded proteins, as well as regulatory proteins that control many critical cellular functions, are among the targets of this degradation process. Consequently, aberration of the system leads to dysregulation of cellular homeostasis and development of many diseases. Based on the findings, it is not surprising that abnormalities of the system are also associated with the pathogenesis of kidney diseases. In this review, I discuss (1) the basic mechanism of the UPS, and (2) the association between the pathogenesis of kidney diseases and the UPS. Diverse roles of the UPS are implicated in the development of kidney diseases, and further studies on this system may reveal new strategies for overcoming kidney diseases. © 2012 Japanese Society of Nephrology. Source

Shimizu K.,Iwata City Hospital
Kyobu geka. The Japanese journal of thoracic surgery | Year: 2012

A 56-year-old woman admitted to our hospital because of injury by a road accident. A chest X-ray film and computed tomography (CT) scan showed multiple left rib fractures, hemothorax in the left pleural cavity, and obscurity of the left diaphragm. The stomach and injured spleen were also shown to shift to the left thoracic cavity. The patient was diagnosed as having diaphragmatic rupture with hemothorax in the left pleural cavity due to splenic injury. Emergent surgery was performed and massive bleeding was observed in the thoracic and abdominal cavities. After performing splenectomy and replacing the stomach in the abdominal cavity, the diaphragm was repaired. The patient was discharged 66 days after the surgery. Since traumatic diaphragm rupture can lead to hemorrhagic shock associated with injuries to adjacent organs, it is important to establish an accurate diagnosis and to performed appropriate surgical treatment without delay. Source

Suzuki A.,Hamamatsu University School of Medicine | Sakaguchi T.,Hamamatsu University School of Medicine | Inaba K.,Hamamatsu University School of Medicine | Suzuki S.,Iwata City Hospital | Konno H.,Hamamatsu University School of Medicine
Journal of Surgical Research | Year: 2012

Background: The number of elderly patients with hepatobiliary malignancies has increased with the steady growth of elderly population. However, the safety of major hepatectomy for elderly patients remains controversial. This study investigated the effect of aging on the hepatic regenerative response after partial resection of livers subjected to ischemic insult. Methods: Two-thirds hepatectomy following 1-h hepatic ischemia was performed in young (12-wk-old) and old (18-mo-old) rats under portosystemic shunt establishment by subcutaneous transposition of the spleen. Results: The survival rate 48 h after hepatectomy of the old rats was significantly lower (20%) than that of the young rats (53%), whereas all animals without hepatic ischemia were alive at 48 h. Hepatic necrosis and hepatocyte apoptosis during the early post-hepatectomy phase were more severe in the aged livers, which also showed delayed Akt activation. Liver mass restoration was significantly retarded in the old rats, despite higher plasma IL-6 levels, rapid and prolonged activation of hepatic STAT3, and increased hepatocyte nuclear cyclin D1 levels. In the young livers, cyclin E, which is essential for G1/S transition, and cyclin A, a marker of S phase, were observed in the nucleus from 24 h, reaching peaks 48 h after hepatectomy. In contrast, the old livers showed greatly delayed and decreased nuclear cyclin E and cyclin A levels. Conclusion: Age-related reductions in the regenerative ability of ischemically damaged livers may be caused by cell cycle disruption at either the late G1 phase or the G1/S transition, despite increased cyclin D1 levels and compensatory IL-6/STAT3 activation. © 2012 Elsevier Inc. All rights reserved. Source

Yamazaki K.,Iwata City Hospital
Clinical calcium | Year: 2013

Previous studies have demonstrated close associations between QUS parameters and osteoporotic status. However, due to the ambiguities in assessing accuracy of QUS and the moderate correlation of DXA and QUS results, currently there is no agreement on how results of QUS devices should be interpreted in order to diagnose osteoporosis. However, I could recommend for clinical application that QUS should be used as the predictor of the risk of osteoporotic fractures. Good portability and low cost of QUS technique might make QUS an attractive technology for assessing risk of fractures in large populations. Source

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