Hepatitis: Osaka

Takehara T, Hayashi N. · Department of Molecular Therapeutics, Osaka University Graduate School of Medicine, Osaka, Japan. · Clin Gastroenterol Hepatol. · Pubmed #16234066 No free full text.

Abstract: Natural killer (NK) cells are specialized lymphocytes that provide a first line of defense through their ability to kill pathogen-infected cells and transformed cells. The function of NK cells is regulated by a fine balance of inhibitory and activating signals, which are mediated by a diverse array of cell-surface receptors. We recently found that expression of the inhibitory receptor CD94/NKG2A is up-regulated on NK cells in patients with chronic hepatitis C. HLA-E, a ligand for NKG2A, was expressed in all human hepatoma cell lines tested as well as in nontransformed hepatocytes, but not in K562 cells, a classic NK-sensitive target. NK cells isolated from patients with chronic hepatitis C (HCV-NK) were less capable of killing hepatoma cells and of producing interferon-gamma in response to hepatoma cells than those from healthy donors, whereas there was no significant difference in NK responsiveness toward K562 cells. Of note is the finding that maturation and activation of monocyte-derived dendritic cells were negatively modulated in the presence of HCV-NK and hepatoma cells, which were restored by the addition of anti-NKG2A antibody during the coculture of HCV-NK and hepatoma cells. Research revealed that dendritic cells recognize danger signals from microorganisms by monitoring pathogen-associated molecular patterns via Toll-like receptors. Our findings have shed light on NK receptors as an important interface that transmits danger signals from abnormal cells to immune systems. Aberrant expression of CD94/NKG2A should have negative impact on innate resistance and subsequent adaptive immunity toward HCV-infected or transformed cells in chronic hepatitis C.

Kasahara A, Hiraide A, Tomita N, Iwahashi H, Imagawa A, Ohguro N, Yamamoto S, Mita E, Hayashi N. · Department of General Medicine, Osaka University Graduate School of Medicine, 2-15 Yamada-Oka, 565-0871, Suita, Japan. · J Gastroenterol. · Pubmed #15580406 No free full text.

Abstract: Retinal abnormalities, including retinal hemorrhage and "cotton-wool" spots, often occur within the first 8 weeks in the course of interferon therapy in patients with chronic hepatitis C. Here, we describe a case of Vogt-Koyanagi-Harada disease occurring 4 months after the start of interferon alpha treatment, probably induced by the immunomodulatory effects of interferon. Therefore, we conclude that chronic hepatitis C patients, especially people with darkly pigmented skin, need to be closely monitored for ophthalmologic complications, by periodic check-up of the optic fundi, for a prolonged period, during interferon treatment.

Kubo S, Tanaka H, Shuto T, Takemura S, Uenishi T, Tanaka S, Hirohashi K. · Department of Gastroenterological and Hepato-Biliary-Pancreatic Surgery, Osaka City University Graduate School of Medicine, Osaka, Japan. · Nippon Geka Gakkai Zasshi. · Pubmed #15521384 No free full text.

Abstract: Despite improvements in the preoperative assessment of liver function and advances in surgical techniques, liver resection for hepatocellular carcinoma still holds a risk for postoperative hepatic failure, especially in patients with cirrhosis. Physiologic characteristics in patients with cirrhosis include hyperdynamic state of the systemic circulation, decrease in hepatic blood flow, portal hypertension, metabolic disorders, dysfunction of the reticuloendothelial system, and thrombocytopenia. Surgical stress including massive bleeding, disturbance of hepatic circulation, and infection are risk factors for postoperative hepatic failure. The risk of hepatic failure also correlates with the severity of active hepatitis and the degree of hepatic fibrosis. To prevent postoperative hepatic failure, dopamine, prostaglandin, and hydrocortisone have been used. Although various treatments including plasma exchange have been tried in hepatic failure, the results have often been unsatisfactory. Careful preoperative evaluation of the hepatic functional reserve and the severity of active hepatitis, and adequate selection of surgical method are important to prevent postoperative hepatic failure.

Nishiguchi S, Tamori A, Tanaka T. · Department of Hepatology, Osaka City University Graduate School of Medicine. · Nippon Rinsho. · Pubmed #15453350 No free full text.

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Yuki N, Kato M. · Department of Gastroenterology, Osaka National Hospital. · Nippon Rinsho. · Pubmed #15453280 No free full text.

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Murakami T, Hori M, Kim T, Kawata S, Abe H, Nakamura H. · Department of Radiology, Osaka University Graduate School of Medicine, Suita City, Osaka, Japan. · Intervirology. · Pubmed #15383731 No free full text.

Abstract: It is important to diagnose hepatocellular carcinoma (HCC) correctly and in early stage, because viral hepatitis and liver cirrhosis are often complicated by HCC. Noncontrast and enhanced CT and MRI are very useful to visualize and diagnose HCC objectively. Especially, CT and MR imaging with dynamic study is essential to diagnose HCC, because it is usually hypervascular. Dynamic CT and MR study also improve differential diagnosis in the characterization of the tumor. However, to perform useful dynamic study, it is necessary to use a CT unit which can make a helical scan, or a MR system with fast imaging technique available that can obtain more than 15 slices within a single breath hold. Tissue specific contrast medium, such as superparamagnetic iron oxide that is available only on MRI, is also useful for diagnosis of HCC.

Tamori A, Nishiguchi S. · Department of Hepatology, Osaka City University Graduate School of Medicine. · Nippon Rinsho. · Pubmed #15359882 No free full text.

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Hiramatsu N, Kasahara A, Hayashi N, Imai Y. · Department of Gastroenterology, Osaka University School of Medicine. · Nippon Rinsho. · Pubmed #15359876 No free full text.

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Tanaka T, Hirota Y, Nishiguchi S. · Department of Public Health, Graduate School of Medicine, Osaka City University. · Nippon Rinsho. · Pubmed #15359870 No free full text.

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Nishiguchi S, Kubo S, Shiomi S. · Department of Hepatology, Graduate School of Medicine, Osaka City University. · Nippon Rinsho. · Pubmed #15359868 No free full text.

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Iyoda K, Kato M. · Department of Gastroenterology, Osaka National Hospital. · Nippon Rinsho. · Pubmed #15359850 No free full text.

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Kato M, Yuki N, Iyoda K, Yamamoto K, Hayashi N. · Department of Gastroenterology, Osaka National Hospital. · Nippon Rinsho. · Pubmed #15359849 No free full text.

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Fukuda A. · First Department of Internal Medicine, Osaka Medical College. · Nippon Rinsho. · Pubmed #15359848 No free full text.

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Takehara T, Kuzushita N, Hayashi N. · Department of Molecular Therapeutics, Osaka University Graduate School of Medicine. · Nippon Rinsho. · Pubmed #15359826 No free full text.

This publication has no abstract.

Miyoshi Y, Etani Y, Mushiake S, Ozono K, Tajiri H. · Department of Developmental Medicine (Pediatrics), Faculty of Medicine, Osaka University Graduate School of Medicine. · Nippon Rinsho. · Pubmed #15359807 No free full text.

This publication has no abstract.

Moriishi K, Limn CK, Matsuura Y. · Research Center for Emerging Infectious Diseases, Research Institute for Microbial Diseases, Osaka University. · Nippon Rinsho. · Pubmed #15359791 No free full text.

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Kanto T, Hayashi N. · Department of Dendritic Cell Biology and Clinical Application, Osaka University Graduate School of Medicine. · Nippon Rinsho. · Pubmed #15359787 No free full text.

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Abe T, Moriishi K, Matsuura Y. · Research Center for Emerging Infectious Diseases, Research Institute for Microbial Diseases, Osaka University. · Nippon Rinsho. · Pubmed #15359780 No free full text.

This publication has no abstract.

Kanto T, Hayashi N. · Department of Molecular Therapeutics, Osaka University Graduate School of Medicine, 2-2 Yamada-oka, 565-0871 Suita, Japan. · J Gastroenterol. · Pubmed #15338363 No free full text.

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Yamada T, Ueda M, Seno M, Kondo A, Tanizawa K, Kuroda S. · Institute of Scientific and Industrial Research, Osaka University, 8-1 Mihogaoka, Ibaraki, Osaka, 567-0047, Japan. · Curr Drug Targets Infect Disord. · Pubmed #15180463 No free full text.

Abstract: The hepatitis B virus (HBV) surface antigen (HBsAg) L particle is a hollow nano-scale particle. HBsAg L particles have many properties that make them useful for in vivo gene transfer vectors and drug delivery systems. Gene therapy so far has required the in vivo pinpoint delivery of genetic materials into the target organs and cells. Gene transfer by HBsAg L particles might be an attractive method, since their tropism is the same as that of HBV. The HBsAg L particles are able to deliver therapeutic payloads with high specificity to human hepatocytes. In addition, the specificity of L particle can be altered by displaying various cell-binding molecules on the surface. Our results indicate that the L particle is suitable for a cell- and tissue-specific gene/drug transfer vector. In this review, we discuss HBsAg L particles as a gene/drug transfer vector and its potential for the treatment of infectious diseases.

Uchiyama-Tanaka Y, Mori Y, Kishimoto N, Nose A, Kijima Y, Nagata T, Umeda Y, Masaki H, Matsubara H, Iwasaka T. · Renal Division, Department of Medicine II, Kansai Medical University, Moriguchi, Osaka, Japan. · Clin Nephrol. · Pubmed #14989635 No free full text.

Abstract: We describe the case of a 51-year-old man with hepatitis C virus (HCV) infection and a 3-month history of facial edema. Laboratory tests upon admission for renal biopsy showed normal renal function and normocomplementemia. Serum HCV antibody (Ab) and cryoglobulin were positive. Renal biopsy specimens showed features of membranous glomerulonephritis. The likely cause was immune complex-mediated glomerulonephritis associated with HCV infection. Reports of similar cases in the literature show the normocomplementemia and negative or slightly positive cryoglobulins observed in our case as well as seropositivity for circulating immune complexes containing HCV RNA. In our case, electron microscopic examination of the subepithelial glomerular lesions revealed massive virus-like particles within unusual multilayers of electron-dense deposits (EDDs), suggesting the existence of HCV in the glomeruli. In the addition to the unique histopathological feature the presence of La/SS-B antibody in his serum indicated an abnormal immune response associated with HCV. We advise him to undergo the therapy with new type of IFN such as pegIFN-alpha2a and/or anti-viral agent like ribavirin to achieve clinical and histopathological improvement.

Moriishi K, Matsuura Y. · Research Centre for Emerging Infectious Diseases, Research Institute for Microbial Diseases, Osaka University, Osaka 565-0871, Japan. · Antivir Chem Chemother. · Pubmed #14968935 No free full text.

Abstract: Hepatitis C virus (HCV) is the major causative agent of chronic non-A, non-B hepatitis. The life cycle of HCV is largely unknown because a reliable culture system has not yet been established. HCV presumably binds to specific receptor(s) and enters cells through endocytosis, as do other members of Flaviviridae. The viral genome is translated into a precursor polyprotein after uncoating, and viral RNA is synthesized by a virus-encoded polymerase complex. Progeny viral particles are released into the luminal side of the endoplasmic reticulum and secreted from the cell after passage through the Golgi apparatus. Understanding the mechanisms of HCV infection is essential to the development of effective new therapies for chronic HCV infection. Several host membrane proteins have been identified as receptor candidates for HCV. Recent advances using pseudotype virus systems have provided information surrounding the initial steps of HCV infection. An HCV RNA replicon system has been useful for elucidating the replication mechanism of HCV. In this review, we summarize our current understanding of the mechanisms of HCV infection and discuss potential antiviral strategies against HCV infection.

Ogawa M, Morisada A. · Preclinical Research Department, Research & Development Division, Schering-Plough K.K., 2-3-7 Hiranomachi, Chuo-ku, Osaka 541-0046, Japan. · Nippon Yakurigaku Zasshi. · Pubmed #12528471 No free full text.

Abstract: Ribavirin (Rebetol) is an antiviral agent used in combination with interferon alpha-2b (IFN alpha-2b) for the treatment of chronic hepatitis C. Ribavirin has been reported to have a broad-spectrum antiviral activity mainly against RNA viruses. The effect of ribavirin was potentiated when administered in combination with IFN alpha-2b in an antiviral assay using bovine viral diarrhea virus as a surrogate for hepatitis C virus (HCV). Inhibition of host inosine monophosphate dehydrogenase and inhibition of RNA-dependent RNA polymerase (RdRp) of RNA viruses have been reported as the modes of action of ribavirin. Recently, ribavirin has been shown to induce mutation as template for newly generated RNA after uptake in RNA by RdRp of poliovirus, which is an RNA virus as in the case of HCV. It has also been shown that the infectivity of viruses is drastically reduced by the very slight increase in mutations induced by ribavirin. This effect as a mutagen on RNA viruses is a novel mode of ribavirin, and it is thought necessary to classify ribavirin into a new antiviral drug class.

Matsuura Y. · Research Center for Emerging Infectious Diseases, Research Institute for Microbial Diseases, Osaka University. · Uirusu. · Pubmed #12227171 No free full text.

This publication has no abstract.

Imanishi T, Obika S. · Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871, Japan. · Nippon Yakurigaku Zasshi. · Pubmed #12187626 No free full text.

Abstract: We recently developed a novel nucleic acid analogue, Bridged Nucleic Acid (BNA), one of the most promising artificial nucleic acids for antisense and/or antigene methodology. The antisense effects of BNA modified oligonucleotides targeting the Internal Ribosomal Entry Site (IRES) in Hepatitis C Virus (HCV) RNA were evaluated. As a result, it was found that the antisense BNA oligonucleotides efficiently suppressed the targeted gene-expression in a sequence specific manner. Although the stem region in the mRNA is generally thought to be out of target for the antisense strategy, BNA oligonucleotide targeting the stem region in the HCV-IRES gave a positive antisense effect, also. It is quite noteworthy.