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Tochigi, Japan

Jichi Medical University is a private university in Shimotsuke, Tochigi, Japan, established in 1972.In 2008 the Gates Foundation awarded $100,000 to Hiroyuki Matsuoka, a medical researcher at the university, to do research on flying syringes. Wikipedia.

Okamoto H.,Jichi Medical University
Virus Research | Year: 2011

Early studies reported the propagation of hepatitis E virus (HEV) in either primary hepatocytes or several established cell lines, but replication was inefficient. Efficient cell culture systems for HEV in PLC/PRF/5 and A549 cells have recently been established, using inoculum of fecal suspensions with high HEV loads, originally obtained from patients with genotype 3 HEV (the JE03-1760F strain, 2.0×10 7copies/ml) or genotype 4 HEV (the HE-JF5/15F strain, 1.3×10 7copies/ml), and many generations were successfully propagated in serial passages of culture supernatant. In addition, a full-length infectious cDNA clone (pJE03-1760F/wt) of the JE03-1760F strain was constructed, which can replicate efficiently in PLC/PRF/5 and A549 cells. A derivative ORF3-deficient mutant revealed that the ORF3 protein of HEV is responsible for virion egress from infected cells and is present on the surface of released HEV particles, which is associated with lipids. Various HEV strains with high loads of ≥10 5copies/ml in circulating blood were also propagated efficiently in PLC/PRF/5 and A549 cells. This paper reviews the road map toward the development of efficient cell culture systems for a wide variety of HEV strains and introduces the current knowledge on virion egress obtained by cell culture models. © 2011 Elsevier B.V.

Takahashi M.,Jichi Medical University
Circulation Journal | Year: 2010

Myocardial infarction (MI) is accompanied by an inflammatory response, leading to the recruitment of leukocytes and subsequent myocardial injury and healing. Chemokines are potent chemoattractant cytokines that regulate leukocyte trafficking in inflammatory processes. Recent evidence indicates that chemokines play a role not only in leukocyte trafficking but also in angiogenesis and cardioprotection. In particular, stromal cell-derived factor-1α (SDF-1α) has generated considerable interest for its role in the pathophysiology of MI. This review will focus on the role of SDF-1 and its receptor CXC chemokine receptor 4 (CXCR4; ie, the SDF-1/CXCR4 system) in the pathophysiology of MI and discuss their potential as therapeutic targets for MI.

Takahashi M.,Jichi Medical University
International Heart Journal | Year: 2014

Inflammasomes are multiple protein complexes that serve as molecular platforms to activate caspase-1 and regulate maturation of a potent proinflammatory cytokine, interleukin (IL)-1β, as well as proinflammatory cell death, pyroptosis. Although several types of inflammasomes have been reported so far, recent investigations indicate that the NLRP3 inflammasome recognizes non-microbial danger signals and leads to sterile inflammatory responses in various disease conditions. Sterile inflammatory responses are also implicated in the development of myocardial infarction (MI). In particular, IL-1β is an early and prominent mediator of inflammatory responses in MI, suggesting the pathophysiologic role of NLRP3 inflammasomes in MI. This review highlights the current state of knowledge regarding the role of NLRP3 inflammasomes in MI.

Okamoto H.,Jichi Medical University
Journal of Gastroenterology | Year: 2013

The lack of an efficient cell culture system for hepatitis E virus (HEV) has greatly hampered detailed analyses of this virus. The first efficient cell culture systems for HEV that were developed were capable of secreting infectious HEV progenies in high titers into culture media, using PLC/PRF/5 cells derived from human hepatocellular carcinoma and A549 cells derived fromhuman lung cancer as host cells. The success achieved with the original genotype 3 JE03-1760F strain has now been extended to various HEV strains in fecal and serum samples obtained from hepatitis E patients and to HEV strains in fecal and serum samples and liver tissues obtained from pigs and wild boar across species barriers. In addition, infectious HEV cDNA clones of the wild-type JE03-1760F strain and its variants have been engineered. Cell culture-generated HEV particles and those in circulating blood were found to be associated with lipids and open reading frame 3 (ORF3) protein, thereby likely contributing to the assembly and release of HEV from infected cells both in vivo and in vitro. The ORF3 protein interacts with the tumor susceptibility gene 101, a critical cellular protein required for the budding of enveloped viruses, through the Pro, Ser, Ala, and Pro (PSAP) motif in infected cells; ORF3 is co-localized with multivesicular bodies (MVBs) in the cytoplasm of infected cells, thus suggesting that HEV requires theMVB pathway for the egress of virus particles. This article reviews the development of efficient cell culture systems for a wide variety of infectious HEV strains obtained from humans, pigs, and wild boar, and also provides details of a new model for virion egress. © Springer 2012.

Kario K.,Jichi Medical University
Nature Reviews Nephrology | Year: 2013

Orthostatic hypertension - a condition characterized by a hyperactive pressor response to orthostatic stress - is an emerging risk factor for cardiovascular disease and is associated with hypertensive target-organ damage (resulting in silent cerebrovascular disease, left ventricular hypertrophy, carotid atherosclerosis and/or chronic kidney disease) and cardiovascular events (such as coronary artery disease and lacunar stroke). The condition is also considered to be a form of prehypertension as it precedes hypertension in young, normotensive adults. Orthostatic blood pressure changes can be assessed using orthostatic stress tests, including clinic active standing tests, home blood pressure monitoring and the head-up tilting test. Devices for home and for ambulatory blood pressure monitoring that are equipped with position sensors and do not induce a white-coat effect have increased the sensitivity and specificity of diagnosis of out-of-clinic orthostatic hypertension. Potential major mechanisms of orthostatic hypertension are sympathetic hyperactivity (as a result of hypersensitivity of the cardiopulmonary and arterial baroreceptor reflex) and α-adrenergic hyperactivation. Orthostatic hypertension is also associated with morning blood pressure surge and extreme nocturnal blood pressure dipping, both of which increase the pulsatile haemodynamic stress of central arterial pressure and blood flow in patients with systemic haemodynamic atherothrombotic syndrome. © 2013 Macmillan Publishers Limited. All rights reserved.

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