Kumamoto University

About: Kumamoto University is a education organization based out in Kumamoto, Kumamoto, Japan. It is known for research contribution in the topics: Population & Cancer. The organization has 19602 authors who have published 35513 publications receiving 901260 citations. The organization is also known as: Kumamoto Daigaku.

A Pathological Study of Minamata Disease in Japan

Abstract: The pathological features and experimental results of Minamata disease are summarized. This disease is an unusual neurological disorder resulting from eating a large amount of fish and shellfish of Minamata bay in Japan. Minamata disease is a toxic encephalopathy characterized by cerebellar atrophy of granule-cell type, preferential injury of both calcarine regions and degenerative disturbances, to a lesser degree, of other cortical areas. Other parts of the nervous system may occasionally be disturbed. There are little or no remarkable changes in organs other than the nervous system, except for an occasional fatty degeneration of the liver and kidney, erosion in the digestive tract, and hypoplasia of the bone marrow.

Proteolytic release of CD44 intracellular domain and its role in the CD44 signaling pathway

Abstract: CD44 is a widely distributed cell surface adhesion molecule and is implicated in diverse biological processes. However, the nature of intracellular signaling triggered by CD44 remains to be elucidated. Here, we show that CD44 undergoes sequential proteolytic cleavage in the ectodomain and intracellular domain, resulting in the release of a CD44 intracellular domain (ICD) fragment. Consequently, CD44ICD acts as a signal transduction molecule, where it translocates to the nucleus and activates transcription mediated through the 12-O-tetradecanoylphorbol 13-acetate–responsive element, which is found in numerous genes involved in diverse cellular processes. Expression of an uncleavable CD44 mutant as well as metalloprotease inhibitor treatment blocks CD44-mediated transcriptional activation. In search of the underlying mechanism, we have found that CD44ICD potentiates transactivation mediated by the transcriptional coactivator CBP/p300. Furthermore, we show that cells expressing CD44ICD produce high levels of CD44 messenger RNA, suggesting that the CD44 gene is one of the potential targets for transcriptional activation by CD44ICD. These observations establish a novel CD44 signaling pathway and shed new light on the functional link between proteolytic processing of an adhesion molecule at the cell surface and transcriptional activation in the nucleus.

Nitric Oxide Activity Is Deficient in Spasm Arteries of Patients With Coronary Spastic Angina

Abstract: Background Coronary spasm can be induced by acetylcholine, serotonin, ergonovine, or histamine, all of which cause vasodilation when the endothelium is intact by releasing nitric oxide (NO). Coronary spasm is promptly relieved by nitroglycerin, which vasodilates through its conversion to NO. It is thus possible that NO release may be deficient in the spasm arteries in patients with coronary spastic angina (CSA). The aim of this study was to determine whether NO release is deficient in coronary arteries of patients with CSA. Methods and ResultsNG-monomethyl-l-arginine (L-NMMA), an inhibitor of NO synthase, was infused into coronary arteries in 21 patients with coronary spastic angina (CSA) and in 28 control patients. Coronary spasm was induced by intracoronary injection of acetylcholine and was documented angiographically in all patients with CSA. L-NMMA dose-dependently decreased basal luminal diameter of coronary arteries in control patients, whereas it had no effect on basal diameter of the spasm arteri...

Posttherapeutic Intraaxial Brain Tumor: The Value of Perfusion-sensitive Contrast-enhanced MR Imaging for Differentiating Tumor Recurrence from Nonneoplastic Contrast-enhancing Tissue

Abstract: BACKGROUND AND PURPOSE: Differentiation of tumor recurrence from treatment-related changes may be difficult with conventional MR imaging when newly enhancing lesions appear. Our aim was to determine the value of perfusion-sensitive contrast-enhanced MR imaging for differentiating recurrent neoplasm from nonneoplastic contrast-enhancing tissue. METHODS: Twenty patients in whom new enhancing lesions developed within irradiated regions were examined prospectively with perfusion-sensitive contrast-enhanced MR imaging. Twelve of them also underwent thallous chloride Tl 201 single-photon emission tomography (201Tl-SPECT). Normalized relative cerebral blood volume (rCBV) ratios and thallium indexes were evaluated to determine whether the new enhancing lesions were recurrent or not. Five instances of tumor recurrence and one of radiation necrosis were verified histologically; in the others, tumor recurrence was distinguished by lesions that progressively increased in size on serial MR examinations over at least 5 months, and nonneoplastic contrast-enhancing tissue was distinguished by lesions that disappeared or decreased in size on serial MR studies over at least 9 months. RESULTS: When normalized rCBV ratios were higher than 2.6 or lower than 0.6, enhancing lesions were either recurrent (n = 5) or nonneoplastic contrast-enhancing tissue (n = 3), respectively. All nonneoplastic contrast-enhancing tissue had a low thallium index, whereas three of four recurrent lesions had a high index. CONCLUSION: An enhancing lesion with a normalized rCBV ratio higher than 2.6 or lower than 0.6 may suggest tumor recurrence or nonneoplastic contrast-enhancing tissue, respectively. In these cases, further examination with 201Tl-SPECT may not be necessary. However, when the normalized rCBV ratio is between 0.6 and 2.6, 201Tl-SPECT may be useful in making the differentiation.

Sall1 is a transcriptional regulator defining microglia identity and function

Abstract: Microglia are the resident macrophages of the central nervous system (CNS). Gene expression profiling has identified Sall1, which encodes a transcriptional regulator, as a microglial signature gene. We found that Sall1 was expressed by microglia but not by other members of the mononuclear phagocyte system or by other CNS-resident cells. Using Sall1 for microglia-specific gene targeting, we found that the cytokine receptor CSF1R was involved in the maintenance of adult microglia and that the receptor for the cytokine TGF-β suppressed activation of microglia. We then used the microglia-specific expression of Sall1 to inducibly inactivate the murine Sall1 locus in vivo, which resulted in the conversion of microglia from resting tissue macrophages into inflammatory phagocytes, leading to altered neurogenesis and disturbed tissue homeostasis. Collectively, our results show that transcriptional regulation by Sall1 maintains microglial identity and physiological properties in the CNS and allows microglia-specific manipulation in vivo.