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Institution

Kumamoto University

EducationKumamoto, Kumamoto, Japan
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.


Papers
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Journal ArticleDOI
TL;DR: The metabolism of rabeprazole is less dependent on CYP2C19 and therefore is the least affected by this genetic polymorphism and the therapeutic effectiveness of proton pump inhibitors during the treatment of acid‐related diseases.
Abstract: The proton pump inhibitors rabeprazole, omeprazole, lansoprazole, and pantoprazole undergo an extensive hepatic biotransformation. In the liver, they are metabolized to varying degree by several cytochrome P450 (CYP) isoenzymes which are further categorized into subfamilies of related polymorphic gene products. The principal isoenzymes involved in the metabolism of proton pump inhibitors are CYP2C19 and CYP3A4. Of these two, minor mutations in CYP2C19 affect its activity in the liver and, in turn, the metabolic and pharmacokinetic profiles of the proton pump inhibitors. The metabolism of rabeprazole is less dependent on CYP2C19 and therefore is the least affected by this genetic polymorphism. Recent studies have brought to light the important role that this polymorphism plays in the therapeutic effectiveness of proton pump inhibitors during the treatment of acid-related diseases.

424 citations

Journal ArticleDOI
TL;DR: In this article, peroxynitrite and GSH-dependent proMMP activation was found to be a potent oxidizing agent formed during inflammatory processes, and extensive S-glutathiolation of the pro-MMP protein occurred during activation.

423 citations

Journal ArticleDOI
TL;DR: Evidence is provided that AGE-modified beta 2M is a dominant constituent of the amyloid deposits in hemodialysis-associated amyloidsosis.
Abstract: beta 2-Microglobulin (beta 2M) is a major constituent of amyloid fibrils in hemodialysis-associated amyloidosis, a complication of long-term hemodialysis patients. Amyloid fibril proteins were isolated from connective tissues forming carpal tunnels in hemodialysis patients with carpal tunnel syndrome. Two-dimensional polyacrylamide gel electrophoresis and Western blotting demonstrated that most of the beta 2M forming amyloid fibrils exhibited a more acidic pI value than normal beta 2M. This acidic beta 2M was also found in a small fraction of beta 2M in sera and urine from these patients, whereas heterogeneity was not observed in healthy individuals. We purified acidic and normal beta 2M from the urine of long-term hemodialysis patients and compared their physicochemical and immunochemical properties. Acidic beta 2M, but not normal beta 2M, was brown in color and fluoresced, both of which are characteristics of advanced glycation end products (AGEs) of the Maillard reaction. Immunochemical studies showed that acidic beta 2M reacted with anti-AGE antibody and also with an antibody against an Amadori product, an early product of the Maillard reaction, but normal beta 2M did not react with either antibody. Incubating normal beta 2M with glucose in vitro resulted in a shift to a more acidic pI, generation of fluorescence, and immunoreactivity to the anti-AGE antibody. The beta 2M forming amyloid fibrils also reacted with anti-AGE antibody. These data provided evidence that AGE-modified beta 2M is a dominant constituent of the amyloid deposits in hemodialysis-associated amyloidosis.

423 citations

Journal ArticleDOI
TL;DR: The role of TAMs in human malignant tumors and the cell–cell interactions between TAMs and tumor cells are discussed.
Abstract: The fact that various immune cells, including macrophages, can be found in tumor tissue has long been known. With the recent introduction of the novel concept of macrophage differentiation into a classically activated phenotype (M1) and an alternatively activated phenotype (M2), the role of tumor-associated macrophages (TAMs) is gradually beginning to be elucidated. Specifically, in human malignant tumors, TAMs that have differentiated into M2 macrophages act as “protumoral macrophages” and contribute to the progression of disease. Based on recent basic and preclinical research, TAMs that have differentiated into protumoral or M2 macrophages are believed to be intimately involved in the angiogenesis, immunosuppression, and activation of tumor cells. In this paper, we specifically discuss both the role of TAMs in human malignant tumors and the cell–cell interactions between TAMs and tumor cells.

423 citations

Journal ArticleDOI
01 Jan 2004-Nature
TL;DR: It is shown that TLX maintains adult neural stem cells in an undifferentiated, proliferative state and can silence glia-specific expression of the astrocyte marker GFAP in Neural stem cells, suggesting that transcriptional repression may be crucial in maintaining the undifferentiation state of these cells.
Abstract: The finding of neurogenesis in the adult brain led to the discovery of adult neural stem cells. TLX was initially identified as an orphan nuclear receptor expressed in vertebrate forebrains and is highly expressed in the adult brain. The brains of TLX-null mice have been reported to have no obvious defects during embryogenesis; however, mature mice suffer from retinopathies, severe limbic defects, aggressiveness, reduced copulation and progressively violent behaviour. Here we show that TLX maintains adult neural stem cells in an undifferentiated, proliferative state. We show that TLX-expressing cells isolated by fluorescence-activated cell sorting (FACS) from adult brains can proliferate, self-renew and differentiate into all neural cell types in vitro. By contrast, TLX-null cells isolated from adult mutant brains fail to proliferate. Reintroducing TLX into FACS-sorted TLX-null cells rescues their ability to proliferate and to self-renew. In vivo, TLX mutant mice show a loss of cell proliferation and reduced labelling of nestin in neurogenic areas in the adult brain. TLX can silence glia-specific expression of the astrocyte marker GFAP in neural stem cells, suggesting that transcriptional repression may be crucial in maintaining the undifferentiated state of these cells.

419 citations


Authors

Showing all 19645 results

NameH-indexPapersCitations
Fred H. Gage216967185732
George D. Yancopoulos15849693955
Kenji Kangawa1531117110059
Tasuku Honjo14171288428
Hideo Yagita13794670623
Masashi Yanagisawa13052483631
Kazuwa Nakao128104170812
Kouji Matsushima12459056995
Thomas E. Mallouk12254952593
Toshio Hirano12040155721
Eisuke Nishida11234945918
Hiroaki Shimokawa11194948822
Bernd Bukau11127138446
Kazuo Tsubota105137948991
Toshio Suda10458041069
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Performance
Metrics
No. of papers from the Institution in previous years
YearPapers
202315
202297
20211,701
20201,654
20191,511
20181,330