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Kikuchi K.,Yame Public General Hospital | Uchikado H.,Kurume University | Miura N.,Kagoshima University | Morimoto Y.,Kagoshima University | And 11 more authors.
Experimental and Therapeutic Medicine | Year: 2011

Historically, clinical outcomes following spinal cord injury (SCI) have been dismal. Severe SCI leads to devastating neurological deficits, and there is no treatment available that restores the injury-induced loss of function to a degree that an independent life can be guaranteed. To address all the issues associated with SCI, a multidisciplinary approach is required, as it is unlikely that a single approach, such as surgical intervention, pharmacotherapy or cellular transplantation, will suffice. High mobility group box 1 (HMGB1) is an inflammatory cytokine. Various studies have shown that HMGB1 plays a critical role in SCI and that inhibition of HMGB1 release may be a novel therapeutic target for SCI and may support spinal cord repair. In addition, HMGB1 has been associated with graft rejection in the early phase. Therefore, HMGB1 may be a promising therapeutic target for SCI transplant. Source

Kikuchi K.,Yame Public General Hospital | Uchikado H.,Kurume University | Miyagi N.,Yame Public General Hospital | Morimoto Y.,Kagoshima University | And 10 more authors.
International Journal of Molecular Medicine | Year: 2011

Free radicals play major roles in the pathogenesis of tissue damage in many diseases and clinical conditions, and the removal of free radicals may offer a treatment option. Several modulators of free radical scavenger pathways have been developed and some have progressed to clinical trials. One such agent, edaravone, was approved in 2001 in Japan for the treatment of cerebral infarction. It has since been shown that edaravone can diffuse into many organs and, in addition to its effects on hydroxyl radical removal, edaravone modulates inflammatory processes, matrix metalloproteinase levels, nitric oxide production, apoptotic cell death, and necrotic cell death. Edaravone also exerts protective effects in a number of animal models of disease and tissue damage, including models of myocardial, lung, intestinal, liver, pancreatic and renal injury. Together with the proven safety of edaravone following 9 years of use as a modulator of free radical scavenging pathways in neurological disease, these additional effects of edaravone suggest that it may offer a novel treatment for several non-neurological diseases and clinical conditions in humans. Source

Naito Y.,Kurume University | Kusano H.,Kurume University | Nakashima O.,Kurume University | Sadashima E.,Kurume University | And 24 more authors.
World Journal of Gastroenterology | Year: 2012

AIM: To investigate the clinicopathological features of intraductal neoplasm of the intrahepatic bile duct (INihB). METHODS: Clinicopathological features of 24 cases of INihB, which were previously diagnosed as biliary papillomatosis or intraductal growth of intrahepatic biliary neoplasm, were reviewed. Mucin immunohistochemistry was performed for mucin (MUC)1, MUC2, MUC5AC and MUC6. Ki-67, P53 and β-catenin immunoreactivity were also examined. We categorized each tumor as adenoma (low grade), borderline (intermediate grade), and malignant (carcinoma in situ, high grade including tumors with microinvasion). RESULTS: Among 24 cases of INihB, we identified 24 tumors. Twenty of 24 tumors (83%) were composed of a papillary structure; the same feature observed in intraductal papillary neoplasm of the bile duct (IPNB). In contrast, the remaining four tumors (17%) showed both tubular and papillary structures. In three of the four tumors (75%), macroscopic mucin secretion was limited but microscopic intracellular mucin was evident. Histologically, 16 tumors (67%) were malignant, three (12%) were borderline, and five (21%) were adenoma. Microinvasion was found in four cases (17%). Immunohistochemical analysis revealed that MUC1 was not expressed in the borderline/adenoma group but was expressed only in malignant lesions (P = 0.0095). Ki-67 labeling index (LI) was significantly higher in the malignant group than in the borderline/adenoma group (22.2 ± 15.5 vs 7.5 ± 6.3, P < 0.01). In the 16 malignant cases, expression of MUC5AC showed borderline significant association with high Ki-67 LI (P = 0.0622). Nuclear expression of β-catenin was observed in two (8%) of the 24 tumors, and these two tumors also showed MUC1 expression. P53 was negative in all tumors. CONCLUSION: Some cases of INihB have a tubular structure, and are subcategorized as IPNB with tubular structure. MUC1 expression in INihB correlates positively with degree of malignancy. © 2012 Baishideng. All rights reserved. Source

Kikuchi K.,Yame Public General Hospital | Kawahara K.-I.,Kagoshima University | Miyagi N.,Yame Public General Hospital | Uchikado H.,Kurume University | And 18 more authors.
Medical Hypotheses | Year: 2010

Acute stroke, including acute ischemic stroke (AIS) and acute hemorrhagic stroke, (AHS) is a common medical problem with particular relevance to the demographic changes in industrialized societies. In recent years, treatments for AIS have emerged, including thrombolysis with tissue plasminogen activator (t-PA). Although t-PA is the most effective currently available therapy, it is limited by a narrow therapeutic time window and side effects, and only 3% of all AIS patients receive thrombolysis. Edaravone was originally developed as a potent free radical scavenger and, since 2001, has been widely used to treat AIS in Japan. It was shown that edaravone extended the narrow therapeutic time window of t-PA in rats. The therapeutic time window is very important for the treatment of AIS, and early edaravone treatment is more effective. Thus, more AIS patients might be rescued by administering edaravone with t-PA. Meanwhile, edaravone attenuates AHS-induced brain edema, neurologic deficits and oxidative injury in rats. Although edaravone treatment is currently only indicated for AIS, it does offer neuroprotective effects against AHS in rats. Therefore, we hypothesize that early administration of edaravone can rescue AHS patients as well as AIS patients. Taken together, our findings suggest that edaravone should be immediately administered on suspicion of acute stroke, including AIS and AHS. © 2010 Elsevier Ltd. Source

Matono S.,Kurume University | Fujita H.,Kurume University | Tanaka T.,Kurume University | Tanaka Y.,Kurume University | And 5 more authors.
Surgery Today | Year: 2011

We report the case of a 50-year-old man with a double aortic arch who underwent esophagectomy for cancer in the middle thoracic esophagus at clinical Stage IIA (T3N0M0), based on the TNM classification (UICC 2002). The patient underwent esophagectomy with three-field lymphadenectomy following neoadjuvant chemotherapy. In such a case, it is important to recognize the anatomy in the upper mediastinum, especially the relationship between the right and left aortic arch, and the recurrent laryngeal nerves using computed tomography (CT) and three-dimensional CT. At first, we performed a cervical lymphadenectomy in order to isolate the bilateral recurrent laryngeal nerves, then mediastinal lymphadenectomy through a right thoracotomy. However, we could not confirm the bilateral recurrent laryngeal nerves during mediastinal lymphadenectomy, and were thus unable to resect them. The postoperative course was uneventful. The patient died of multiple liver metastasis 4 years after the surgery, with no evidence of recurrence in any lymph node. © 2011 Springer. Source

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