Kendo Kiyosawa's research while affiliated with Aizawa Hospital and other places

Publications (422)

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Objective To clarify the impact of hepatic steatosis (HS) indexed by Fatty Liver Index (FLI) and high normal fasting plasma glucose (FPG) as risk factors for incident prediabetes in a non-obese cohort. Methods Data from 1,125 participants with ADA-defined normal glucose metabolism (NGM) (median age and BMI, 52 years and 23.1 kg/m 2, respectively)...
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A 78-year-old woman was admitted for examination and treatment of melena. Although upper and lower gastrointestinal endoscopy and abdominal computed tomography showed no bleeding lesions, oral double-balloon endoscopy revealed a long, slender polyp covered with normal mucosa and accompanied with erosions in the proximal jejunum. Surgical resection...
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Glecaprevir/pibrentasvir (G/P) are direct-acting antivirals (DAAs) that achieve a high sustained virological response (SVR) rate for hepatitis C virus (HCV) infection. We investigated G/P effectiveness for HCV patients based on real-world experience and the clinical features of retreatment cases. HCV patients (n = 182) were compared for clinical fe...
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A 62-year-old male forestry worker was referred to our hospital with general malaise and anorexia, as well as a high level of liver enzymes (AST 1559 U/L, ALT 2464 U/L). He was diagnosed with acute hepatitis E (HEV) after testing positive for IgA/IgM HEV antibodies and HEV RNA. He had not ingested untreated water and had not eaten raw meat or the v...
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Background/objectives: It has been unknown if attenuated insulin sensitivity (Si) in non-alcoholic fatty liver disease (NAFLD) is a cause or a result. We examined the impact of attenuated Si on NAFLD evolution. Subjects/methods: We observed 4856 NAFLD- and diabetes-free participants for a mean 2.9 years. Si was indexed by single point insulin se...
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Direct‐acting antiviral (DAA) treatment can achieve a high sustained virological response (SVR) rate in patients with hepatitis C virus (HCV) infection regardless of a history of hepatocellular carcinoma (HCC [+]). We examined 838 patients (370 men, median age: 69 years) who were treated with DAAs for comparisons of clinical findings between 79 HCC...
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Persistent hepatitis C virus (HCV) infection may induce autoimmune diseases and chronic hepatitis C is sometimes accompanied by autoimmune hepatitis (AIH). However, we are worried about the treatment for chronic hepatitis C-AIH overlap syndrome because interferon-based antiviral therapies may enhance autoimmunity and immunosuppressive corticosteroi...
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Background . A new agent, potassium-competitive acid blocker vonoprazan (VPZ) has potent acid-inhibitory effects and may offer advantages over conventional H. pylori eradication therapies. We aimed to compare the eradication rate between VPZ-based treatment and PPI-based one. Methods . This randomized controlled trial was designed to assign 141 pat...
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Background and aim: Past HBV infection is considered as a risk factor for hepatocarcinogenesis, but the clinicopathological characteristics of non-B non-C hepatocellular carcinoma (NBNC-HCC) excluding past HBV infection have not been investigated. This study aimed to clarify the clinicopathological features of strictly-defined NBNC-HCC. Methods:...
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Background: The number of hepatocellular carcinoma (HCC) patients with non-viral etiologies is increasing in Japan. We conducted a nation-wide survey to examine the characteristics of those patients. Methods: After we assessed the trend of patients who were first diagnosed with HCC at 53 tertiary care centers in Japan from 1991 to 2010, we colle...
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Natural killer cells play a key role in the immune control of viral infections. Killer immunoglobulin-like receptors (KIRs) regulate natural killer cell activation and inhibition through the recognition of their cognate HLA class I ligands. We assessed the predictive factors of a sustained virological response (SVR) in 200 Japanese patients with ch...
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A unique form of chronic pancreatitis characterized by elderly male preponderance, minimal abdominal pain, irregular narrowing of the pancreatic duct, and swelling of the pancreatic parenchyma has been referred to as autoimmune pancreatitis. Autoimmune pancreatitis is also characterized by hypergammaglobulinemia, histological evidence of lymphoplas...
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Unlabelled: The long-term outcome of patients with autoimmune hepatitis (AIH) in Japan has not been well-defined. The aim of this study was to clarify the outcome of this disease over a long follow-up period compared with that of the general Japanese population as well as that among patients. A total of 203 AIH patients were enrolled for a mean fo...
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This prospective, non-randomized, multicenter cohort study analyzed the safety and efficacy of a steroid-free immunosuppressive (IS) protocol for hepatitis C virus (HCV)-positive living donor liver transplant (LDLT) recipients in Japan. Of 68 patients enrolled from 13 transplant centers, 56 fulfilled the inclusion/exclusion criteria; 27 were assign...
Article
B型慢性肝炎に対するペグインターフェロンアルファ-2a(PEG-IFNα-2a)の有効性,安全性を検討した. HBe抗原陽性例はPEG-IFNα-2a 90 μg,180 μg/週の各々24週投与,48週投与又は天然型IFNα6 MIU週3回24週投与(HLBI群)の5群に無作為割付けし,投与終了後24週時のALT正常化,HBeセロコンバージョン及びHBV-DNA量抑制の複合評価で有効性を評価した. PEG-IFNα-2a群では用量,投与期間に応じて高い有効率を示した.PEG-IFNα-2a 48週併合群とHLBI群の有効率の差は11.3%(95%CI:0.0-22.6)とHLBI群に対し非劣性が検証され,安全に使用できた. HBe抗原陰性例に対するHBV-DNA抑制率は,180 μg,90...
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Immunoglobulin (Ig) G4-associated autoimmune hepatitis (AIH) is a recently identified and possibly new disease entity. However, the epidemiology and clinical features of IgG4-associated AIH remain uncertain. The aim of this study was to determine the prevalence and the clinical, serological, and histological characteristics of IgG4-associated AIH....
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A 42-year-old man was admitted to our hospital because of elevated liver enzymes (aspartate aminotransferase, 642 IU/L [normal range: 12-37]; alanine aminotransferase, 788 IU/L [normal range: 7-45]; alkaline phosphatase, 605 IU/L [normal range: 124-367]; c-glutamyl transpeptidase, 180 IU/L [normal range: 6-30]; and total bilirubin, 8.6 mg/dL [norma...
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To evaluate the long-term efficacy of entecavir in nucleoside-naïve chronic hepatitis B patients. One hundred and sixty-seven patients treated with entecavir 0.01mg, 0.1mg or 0.5mg for 24-52weeks in Phase II studies entered rollover study ETV-060 and received entecavir 0.5mg daily. Responses were evaluated among patients with available samples. Aft...
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The Japanese Liver Transplantation Society presented its first report on donor morbidity in 2003. The Society has been continuing to survey outcomes in living liver donors in Japan. By using a uniform comprehensive medical record review process, data were collected on 3565 living liver donors who had donated grafts by the end of December 2006 at 38...
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Entecavir (ETV) is a potent nucleoside analogue against hepatitis B virus (HBV), and emergence of drug resistance is rare in nucleoside-naive patients because development of ETV resistance (ETVr) requires at least three amino acid substitutions in HBV reverse transcriptase. We observed two cases of genotypic ETVr with viral rebound and biochemical...
Article
Alcoholic liver disease (ALD) is one of the leading causes of cirrhosis and yet efficient therapeutic strategies are lacking. Polyenephosphatidylcholine (PPC), a major component of essential phospholipids, prevented alcoholic liver fibrosis in baboons, but its precise mechanism remains uncertain. We aimed to explore the effects of PPC on ALD using...
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Hepatoprotective therapies that include regular glycyrrhizin injections (GIs) are beneficial for chronic hepatitis C patients, but are sometimes insufficient for normalizing serum alanine aminotransferase (ALT) levels. Here, we evaluated whether the addition of minor bloodletting, named petit phlebotomy (PP), prior to each GI could further reduce s...
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Acute respiratory distress syndrome (ARDS) and acute lung injury (ALI) are characterized by a high mortality rate; therefore, ARDS/ALI in humans is a leading cause of morbidity and mortality in critically ill patients. As previously reported, cytokines play a critical role as signaling molecules that initiate, amplify, and perpetuate inflammatory r...
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Primary liver cancer, 95% of which is hepatocellular carcinoma (HCC), is ranked third in men and fifth in women as a cause of death from malignant neoplasms in Japan. The number of deaths and death rate of HCC began to increase sharply in 1975. These numbers peaked at 34,510 and 27.4/100,000, respectively, in 2004, but decreased to 33,662 annual de...
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The interferon sensitivity determining region (ISDR) of the hepatitis C virus (HCV) and T-helper type 1 and type 2 (Th1/Th2) ratio were analyzed along with other host and viral factors for their ability to predict the response of patients with chronic hepatitis C to pegylated interferon alpha-2b (Peg-IFN) and ribavirin (RBV) combination therapy. A...
Article
Nonalcoholic fatty liver disease (NAFLD) is classified as nonalcoholic steatohepatitis (NASH) or simple steatosis (SS) according to histological findings. It is well recognized that NASH may develop into cirrhosis and hepatocellular carcinoma (HCC), both with unfavorable prognoses. Although the outlook of SS is reported to be better than that of NA...
Article
The activated mesangial cell is an important therapeutic target for the control of glomerulonephritis. The peroxisome proliferator-activated receptor alpha (PPARalpha) has attracted considerable attention for its anti-inflammatory effects; however, its roles in the mesangial cells remain unknown. To determine the anti-inflammatory function of PPARa...
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Hepatitis B virus (HBV) reactivation in patients with resolved HBV infection was found in 23 (4%) of 552 newly hepatitis B surface antigen-positive patients in Japan. Because one-fourth of cases develop into fulminant hepatic failure and mortality is 100%, management of HBV reactivation in patients with resolved HBV infection should be discussed.
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Aim: Autoimmune hepatitis (AIH) is an organ-specific autoimmune disease characterized by chronic inflammation of the liver. Although the HLA DR4 allele is associated with type 1 AIH in Japanese, the exact genetic etiology of AIH remains undefined. The cytotoxic T-lymphocyte antigen 4 (CTLA4) is an inhibitory receptor expressed by T-cells that acts...
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Citrin deficiency caused by SLC25A13 gene mutations develops into adult-onset type II citrullinemia (CTLN2) and may be accompanied with hepatic steatosis and steatohepatitis. As its clinical features remain unclear, we aimed to explore the characteristics of fatty liver disease associated with citrin deficiency. The prevalence of hepatic steatosis...
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Recent studies have demonstrated that n-3 polyunsaturated fatty acids ameliorate nonalcoholic fatty liver disease. Although eicosapentaenoic acid (EPA), one of the major components of n-3 polyunsaturated fatty acids, is widely used as an antilipidemic agent, its single efficacy for nonalcoholic steatohepatitis (NASH) remains unclear. As such, we ai...
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Since first being described in 1998, de novo autoimmune hepatitis (AIH) after liver transplantation has been reported in several cases suffering from non-autoimmune liver diseases and primary biliary cirrhosis (PBC). Glutathione S-transferase (GST) T1 genotype mismatches between donor and recipient have also been suggested to constitute a risk fact...
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Recent studies using transgenic mouse models have demonstrated that the presence of hepatitis C virus (HCV) singularly induces insulin resistance (IR). When evaluated in humans, the exclusion of other factors influencing IR, such as obesity, alcohol intake, hepatic inflammation and steatosis is needed, but only few studies have been performed to th...
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Intrahepatic expression of hepatitis B surface antigen (HBsAg) and hepatitis B core antigen (HBcAg) was investigated in 46 asymptomatic HBsAg carriers by a direct immuno-fluorescent method. In 21 HBeAg positive carriers, HBsAg was expressed diffusely on the membrane of hepatocytes, with associated cytoplasmic localization in a few scattered hepato-...
Article
Auto-antibodies including antinuclear antibody (ANA), antismooth muscle antibody, antimitochondrial antibody, rheumatoid factor, lupus erythematosus factor, antimicrosomal antibody and antithyroglobulin antibody were assayed in sera from 84 patients with hepatocellular carcinoma, 70 with liver cirrhosis, 50 with chronic hepatitis, 30 with cancer of...
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Transgenic mice expressing HCV core protein develop hepatic steatosis and hepatocellular carcinoma (HCC), but the mechanism underlying this process remains unclear. Because PPARalpha is a central regulator of triglyceride homeostasis and mediates hepatocarcinogenesis in rodents, we determined whether PPARalpha contributes to HCV core protein-induce...
Article
Autoimmune pancreatitis (AIP) is characterized by high serum IgG4 concentrations, lymphoplasmacytic inflammation, and a favorable response to corticosteroid treatment. Although the HLA DRB1*0405-DQB1*0401 haplotype and Fc receptor-like 3 polymorphisms have been associated with AIP, the role of other genetic factors is largely unknown. As cytotoxic...
Article
Fluorine-18 fluorodeoxyglucose positron emission tomography (FDG-PET) has been widely used for the diagnosis of pancreatic cancer. Because autoimmune pancreatitis is easily misdiagnosed as pancreatic cancer and can be tested for by FDG-PET analysis based on the presence of suspected pancreatic cancer, we attempted to clarify the differences in FDG-...
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The American Journal of Gastroenterology is published by Nature Publishing Group (NPG) on behalf of the American College of Gastroenterology (ACG). Ranked the #1 clinical journal covering gastroenterology and hepatology*, The American Journal of Gastroenterology (AJG) provides practical and professional support for clinicians dealing with the gastr...
Article
Persistent infection of hepatitis C virus (HCV) can lead to a high risk for hepatocellular carcinoma (HCC). HCV core protein plays important roles in HCV-related hepatocarcinogenesis, because mice carrying the core protein exhibit multicentric HCCs without hepatic inflammation and fibrosis. However, the precise mechanism of hepatocarcinogenesis in...
Article
BACKGROUND and objective: In Japan the prevalence of the hepatitis C virus (HCV) antibody is highest in the elderly population. Therefore, it is important for elderly patients to undergo interferon (IFN) therapy. In patients with HCV genotype 1b and a high viral load, the sustained virological response (SVR) rate is lower in older compared with you...
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A hepatic tumor (S4) was found by CT in a 64-year-old man with tenderness and swelling of abdominal wall at right hypochondrium. He had type 2 diabetes mellitus and a history of gastrectomy and pancreatoduodenostomy due to gastric cancer and chronic pancreatitis. His nutritional status was poor, and a hepatic malignant tumor was suspected initially...
Article
Fatty acids bound to albumin are filtered through glomeruli, reabsorbed by proximal tubular epithelial cells, and metabolized. Because albumin serves as a carrier, an increase in delivery of fatty acids to the proximal tubule may occur in proteinuric states, possibly leading to toxic effects. At present, the contribution of fatty acids to tubuloint...
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Autoimmune pancreatitis is a unique form of chronic pancreatitis characterized by irregular narrowing of the pancreatic duct, pancreatic swelling, and a favorable response to corticosteroids, in which the autoimmune mechanism is postulated in the pathogenesis. High serum immunoglobulin (Ig)G4 concentrations and various types of extrapancreatic invo...
Article
NK cell-type lymphoproliferative disease of granular lymphocytes can be subdivided into aggressive NK-cell leukemia (ANKL) and chronic NK-cell lymphocytosis (CNKL). Hepatosplenomegaly is observed in ANKL patients, and hepatic failure is a common cause of death. Significant numbers of ANKL cells were pathologically observed in sinusoidal and interlo...
Article
Primary liver cancer, 95% of which is hepatocellular carcinoma (HCC), has ranked third in men and fifth in women as a cause of death from malignant neoplasm in Japan. Although the number of deaths and death rates from HCC increased until 2002 in Japan, annual deaths (34 089) and the death rate (27.0/100 000) from liver cancer decreased in 2003. Hep...
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Aim: The clinical significance of hepatitis B virus (HBV) core-related antigen (HBcrAg) in predicting the reactivation of hepatitis after halting lamivudine administration was analyzed. Methods: A total of 34 patients with chronic hepatitis B were enrolled. Lamivudine was administered for at least 6 months before cessation, and reactivation of hepa...
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T-cell large granular lymphocyte (T-LGL) leukemia and chronic natural killer (NK) cell lymphocytosis (CNKL) are major subtypes of lymphoproliferative disease of granular lymphocytes (LDGL). To clarify the mechanism of LGL proliferation and the relationship with the chemokine system in LDGL, we enrolled 22 T-LGL leukemia patients and 8 CNKL cases, a...
Article
Autoimmune pancreatitis (AIP) is characterized by high serum immunoglobin (Ig) G4 concentrations, lymphoplasmacytic inflammation, and a favorable response to corticosteroid treatment. Since liver dysfunction is frequently seen in AIP patients, we investigated hepatic histopathology and its clinical significance in patients with AIP. We examined the...
Article
The efficacy and safety of peginterferon alpha-2a (40 KD) (peg-IFNalpha-2a) plus ribavirin has not been reported for Japanese patients with chronic hepatitis C. The aim of this study was to evaluate this combination in treatment-naïve patients and in non-responders or relapsers to interferon monotherapy. Overall, 201 treatment-naïve patients with h...
Article
The American Journal of Gastroenterology is published by Nature Publishing Group (NPG) on behalf of the American College of Gastroenterology (ACG). Ranked the #1 clinical journal covering gastroenterology and hepatology*, The American Journal of Gastroenterology (AJG) provides practical and professional support for clinicians dealing with the gastr...
Article
Autoimmune hepatitis (AIH) is an organ-specific autoimmune disease characterized by chronic inflammation of the liver. Although the HLA-DRB1*0405 allele is associated with type 1 AIH in Japanese, the exact genetic etiology of AIH remains undefined. Recently, polymorphisms of Fcgamma receptors (FcgammaR) and Fc receptor-like gene 3 (FCRL3) were link...
Article
Autoimmune pancreatitis is a unique form of chronic pancreatitis characterized by high serum IgG4 concentrations and abundant IgG4-bearing plasma cell infiltration in the pancreatic lesion, and it has been reported to be associated with a variety of extrapancreatic lesions, leading us to postulate the concept of a systemic inflammatory disease. To...
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Safety concerns about di-(2-ethylhexyl)phthalate (DEHP), a plasticizer and a probable endocrine disruptor, have attracted considerable public attention, but there are few studies about long-term exposure to DEHP. DEHP toxicity is thought to involve peroxisome proliferator-activated receptor alpha (PPARalpha), but this contention remains controversi...
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Unlabelled: Genetic predisposition to type 1 autoimmune hepatitis (AIH) is linked mainly to HLA class II genes. We previously searched the whole HLA region for AIH susceptibility genes using microsatellite markers and found only HLA-DR/DQ to be a candidate region for this suspected multifactorial disease. As such, the aim of this study was to broa...
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Iron reduction therapy (IRT) has been recognized as beneficial for chronic hepatitis C patients. However, its efficacy for hepatitis C virus-related liver cirrhosis (LC-C) has not been elucidated. We evaluated the efficacy and safety of IRT for LC-C patients. Twenty-two LC-C patients were treated with biweekly phlebotomy and low iron diet for 6 mon...
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We have previously reported that autoimmune pancreatitis (AIP) is a bioclinical entity characterized by high serum immunoglobulin G4 concentrations and association with the HLA-DRB1*0405-DQB1*0401 haplotype. However, the precise identity of gene(s) within this haplotype directly responsible for AIP pathogenesis is yet to be established. To dissect...
Chapter
Autoimmune pancreatitis is characterized by hypergammaglobulinemia, histologic evidence of lymphoplasmacytic inflammation and fibrosis, and a favorable response to glucocorticoid treatment. These findings suggest that autoimmune mechanisms are involved in the pathogenesis of this disease. Another characteristic feature of this disease is high serum...
Article
As detecting mild steatosis is difficult by abdominal ultrasonography (US), nonalcoholic steatohepatitis (NASH) with mild steatosis may sometimes be confused with cryptogenic chronic hepatitis. We aimed to test this possibility and to isolate factors that may indicate NASH. First, 53 Japanese patients diagnosed as having cryptogenic chronic hepatit...
Article
Under immunosuppressive conditions after hematopoietic stem cell transplantation (HSCT), even if hepatitis B virus (HBV) antigen is negative but hepatitis B surface antibody (HBsAb) or hepatitis B core antibody (HBcAb) is presented, HBV reactivates and sometimes causes fulminant hepatitis. However, it remains unclear which patients will develop ful...
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Changes in the serum hepatitis B virus (HBV) RNA level during lamivudine therapy were compared to those in the serum HBV DNA and HBV core-related antigen (HBVcrAg) levels in 24 patients with chronic hepatitis B. For measurement of HBV RNA, total nucleic acid was extracted from serum samples and treated with RNase-free DNase I. After cDNA synthesis...
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Pancreatic adenocarcinoma is an aggressive human malignancy and is characterized by resistance to apoptosis. Recently, NADPH oxidase (Nox) 4-mediated generation of intracellular reactive oxygen species (ROS) was proposed to confer antiapoptotic activity and thus a growth advantage to pancreatic cancer cells. The signaling mechanism by which Nox4 tr...
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Survival and death of Chara internodal cells were investigated in one of the alkali metal salts KCl, some of the alkali earth metal salts CaCl2, Ca(NO3)2, MgCl2, Mg(NO3)2, SrCl2, Sr(NO3)2, BaCl2 and Ba(NO3)2, potassium phosphate pH buffer solution (pH 7.0), Tris-maleate pH buffer solution (pH 7.0), HEPES (N-2-hydroxyethylpiperazine-N′-2-ethanesulph...
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The clinical usefulness of hepatitis B virus core-related antigen (HBVcrAg) assay was compared with that of HBV DNA assay in predicting the occurrence of lamivudine resistance in patients with chronic hepatitis B. Of a total of 81 patients who were treated with lamivudine, 25 (31%) developed lamivudine resistance during a median follow-up period of...
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Laparoscopic observation of the liver is important to diagnose liver conditions accurately. However, the laparoscopic findings of nonalcoholic steatohepatitis (NASH) have not been characterized. The aim of this study was to clarify the laparoscopic characteristics of NASH. Twenty-four patients were enrolled. The degrees of hepatomegaly, color and i...
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Adenovirus is one of the major causes of non-relapse morbidity and mortality after allogeneic hematopoietic stem cell transplantation for hematological malignancy. Fulminant hepatic failure is a rare manifestation of post-transplant complication with adenovirus. Extremely high mortality and aggressiveness of the clinical course have been posing cli...