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Iizuka, Japan

Koshikawa N.,Tokyo Medical University | Mizushima H.,Osaka University | Minegishi T.,Tokyo Medical University | Eguchi F.,Aso Iizuka Hospital | And 5 more authors.
Cancer Science | Year: 2011

Increased expression of heparin-binding EGF-like growth factor (HB-EGF) and membrane-type matrix metalloproteinase-1 (MT1-MMP) is frequently associated with various types of malignant tumor. HB EGF-like growth factor has been reported to promote the malignant progression of ovarian carcinoma. Based on this finding, inhibition of HB-EGF activity with CRM197 is now under phase I clinical evaluation. On the other hand, MT1-MMP expressed in ovarian carcinoma cells is thought to promote invasion and growth of tumor cells by degrading the extracellular matrix. However, we recently demonstrated that co-expression of MT1-MMP and HB-EGF in gastric carcinoma cells leads to cleavage of HB-EGF within its N-terminal heparin-binding region, converting it into a potent heparin-independent growth factor. In this study, we evaluated the importance of regulation of HB-EGF by MT1-MMP in clinical samples of ovarian carcinoma. We detected co-expression of HB-EGF and MT1-MMP in clear cell ovarian carcinoma tissues, particularly at the invasion front and in tumor cells that had disseminated into the ascites, whereas HB-EGF alone was expressed in non-invasive borderline ovarian tumor tissue. Furthermore, a soluble HB-EGF fragment that corresponds to that processed by MT1-MMP was detected in malignant ascites obtained from patients with metastatic ovarian carcinoma. Ovarian carcinoma cells that express MT1-MMP and HB-EGF exhibited enhanced cell growth in a 3D-collagen matrix and anchorage-independent growth in suspension. These results indicate that MT1-MMP co-expressed with HB-EGF in ovarian carcinoma cells potentiates the activity of HB-EGF to promote invasive tumor growth and spreading in vivo. © 2010 Japanese Cancer Association. Source

Kikkawa Y.,Kyushu University | Natori Y.,Aso Iizuka Hospital | Sasaki T.,Kyushu University
Neurologia Medico-Chirurgica | Year: 2012

A 42-year-old male presented with a rare case of delayed aneurysmal formation of the intracranial ophthalmic artery after closed head injury manifesting as subarachnoid hemorrhage. Initial magnetic resonance angiography revealed no aneurysmal formation, but angiography 7 days after the injury demonstrated an intracranial ophthalmic artery aneurysm. Follow-up computed tomography angiography demonstrated enlargement of the aneurysm. The aneurysm was successfully treated by surgical resection. Histological examination revealed that the aneurysm was a pseudoaneurysm. Traumatic intracranial aneurysm (TICA) is rare and usually occurs in the peripheral arteries of the cerebral circulation or the basal portion of the internal carotid artery. The present case shows that failure to demonstrate an aneurysm on the initial angiography in the acute stage does not exclude the presence of traumatic aneurysm. This case clearly shows the time course of development of a TICA of the ophthalmic artery after closed head injury. Source

Ueno T.,University of Tsukuba | Takeda K.,Aso Iizuka Hospital | Nagata M.,University of Tsukuba
Nephrology Dialysis Transplantation | Year: 2012

Background. Renal AA amyloidosis presents as a life-threatening disease in patients with rheumatoid arthritis (RA). Although several newly developed immunosuppressive drugs have been tried, patients often progress to end-stage renal failure with unsatisfactory survival rate. Methods. A total of nine consecutive cases of severe nephrotic renal AA amyloidosis presented to us. Complete remission of proteinuria was observed in four cases (responders), and the remaining five reached the end point of haemodialysis or death (non-responders); these groups were retrospectively compared. The patients were treated with immunosuppressants, biological drugs and anti-hypertensive drugs. Levels of serum creatinine (S-Cr), urinary protein-creatinine ratio (UP/UCr), blood pressure (BP) and C-reactive protein (CRP) were measured. Histological characteristics of renal amyloid deposition and extent of kidney injury were also scored. Results. Prior to treatment, clinical data (S-Cr, UP/UCr, BP and CRP) and histological severity (glomerular sclerosis, tubulointerstitial injury and extent of amyloid deposition) observed in the renal biopsy specimen were not significantly different between the groups. Following therapeutic intervention, proteinuria disappeared (UP/UCr <0.3) in responders within 12 ± 5.4 months but persisted in non-responders. Consequently, renal function stabilized in responders, but it deteriorated in all non-responders. Strict inflammatory control along with optimal control of hypertension was achieved in responders during the treatment. Conclusion. Regardless of histological severity, intensive therapeutic intervention that includes strict inflammatory control and optimal control of hypertension may change the histology-predicted prognosis of RA-associated renal AA amyloidosis. © 2011 The Author. Source

Yamazaki Y.,Hiroshima University | Matsubara T.,Aso Iizuka Hospital | Takahashi T.,Hiroshima University | Kurashige T.,Hiroshima University | And 5 more authors.
PLoS ONE | Year: 2011

Background: Granulovacuolar degeneration (GVD) is one of the pathological hallmarks of Alzheimer's disease (AD), and it is defined as electron-dense granules within double membrane-bound cytoplasmic vacuoles. Several lines of evidence have suggested that GVDs appear within hippocampal pyramidal neurons in AD when phosphorylated tau begins to aggregate into early-stage neurofibrillary tangles. The aim of this study is to investigate the association of GVDs with phosphorylated tau pathology to determine whether GVDs and phosphorylated tau coexist among different non-AD neurodegenerative disorders. Methods: An autopsied series of 28 patients with a variety of neurodegenerative disorders and 9 control patients were evaluated. Standard histological stains along with immunohistochemistry using protein markers for GVD and confocal microscopy were utilized. Results: The number of neurons with GVDs significantly increased with the level of phosphorylated tau accumulation in the hippocampal regions in non-AD neurodegenerative disorders. At the cellular level, diffuse staining for phosphorylated tau was detected in neurons with GVDs. Conclusions: Our data suggest that GVDs appear in relation to hippocampal phosphorylated tau accumulation in various neurodegenerative disorders, while the presence of phosphorylated tau in GVD-harbouring neurons in non-AD neurodegenerative disorders was indistinguishable from age-related accumulation of phosphorylated tau. Although GVDs in non-AD neurodegenerative disorders have not been studied thoroughly, our results suggest that they are not incidental findings, but rather they appear in relation to phosphorylated tau accumulation, further highlighting the role of GVD in the process of phosphorylated tau accumulation. © 2011 Yamazaki et al. Source

Akahoshi K.,Aso Iizuka Hospital | Akahane H.,Fujifilm Co. | Motomura Y.,Aso Iizuka Hospital | Kubokawa M.,Aso Iizuka Hospital | And 5 more authors.
Digestion | Year: 2012

Endoscopic submucosal dissection (ESD) is accepted as minimally invasive therapy for early stage digestive tract tumors. It has allowed the achievement of histologically curative en-bloc resection of early stage digestive tract tumors regardless of size, including the resection of previously non-resectable tumors. Although numerous electrosurgical knives have been developed for ESD, technical difficulties and high complication rates (bleeding and perforation) have limited their use worldwide. Furthermore, conventional ESD usually needs several devices for each session. We developed the Clutch Cutter® (CC), which can grasp and incise the targeted tissue using electrosurgical current, to resolve such ESD-related problems. The ESD procedure using the CC is as follows: after marking using the CC and the injection of a solution into the submucosa, the lesion is separated from the surrounding normal mucosa by complete incision around the lesion using the CC. A piece of submucosal tissue is grasped and cut with the CC using electrosurgical current to achieve submucosal exfoliation. Intraoperative bleeding is also treated by the CC. Reported clinical studies showed that ESD using the CC is a safe, simple, easy-to-learn, technically efficient (en-bloc resection rate 100%), and a single-device method for the dissection of early stage digestive tract tumors. This new approach is promising to become the worldwide method of choice for early stage digestive tract tumors because it is technically simple and safe to perform. Copyright © 2012 S. Karger AG, Basel. Source

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