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Masao Honda

Publications and source records attributed to Masao Honda.

At least 19 recordsLinked to original sources
PubMed2025

The SELENOP Polymorphism rs7579 Predicts Hepatic Steatosis in Females With Insulin Resistance in the General Population.

CONTEXT: Selenoprotein P is a hepatokine associated with several metabolic processes. Rs7579 (C > T) is a SeP-related functional single nucleotide polymorphism. OBJECTIVE: In this study, we aimed to identify the environmental factors affecting the relationship between rs7579 and metabolic diseases, such as metabolic dysfunction-associated steatotic liver disease, in the general population. METHODS: This cross-sectional study was based on the Shika Study, a survey of residents in the Noto Peninsula of Ishikawa Prefecture. We analyzed a total of 900 adults, measuring full-length selenoprotein P (FL-SeP) serum levels using a sol-particle homogeneous immunoassay. RESULTS: We observed that selenium and FL-SeP serum levels were associated with dyslipidemia. In males, serum selenium was associated with dyslipidemia and hepatic steatosis. However, in females, FL-SeP tended to be associated with diabetes. Participants carrying the TT genotype and hepatic steatosis exhibited higher levels of liver enzymes, insulin, the homeostatic model assessment of insulin resistance (HOMA-IR), and the homeostasis model assessment of β-cell function than those without hepatic steatosis or with other genotypes. In females carrying the TT genotype of rs7579, hepatic steatosis, hypertension, diabetes, obesity, and metabolic syndrome were associated with higher HOMA-IR levels. CONCLUSION: In this study, we revealed that the association between metabolic diseases and HOMA-IR differed single nucleotide polymorphism genotype and sex dependently. In females carrying the TT genotype of rs7579, hepatic steatosis-associated metabolic disorders (diabetes, hypertension, obesity, and metabolic syndrome) were associated with higher HOMA-IR. The results of this study open the way to genetic signatures-based personalized preventive medicines.

CCDC152↗
PubMed2006

Expression profiling of peripheral-blood mononuclear cells from patients with chronic hepatitis C undergoing interferon therapy.

BACKGROUND: Interferon (IFN) is now the standard treatment for chronic hepatitis C (CH-C); however, treatment efficacy is unpredictable before IFN therapy is started. METHODS: We investigated the gene-expression profiles of peripheral-blood mononuclear cells (PBMCs) from patients with CH-C showing different responses to IFN. Gene-expression profiles of PBMCs were analyzed in 21 patients with CH-C treated with IFN alone or in combination with ribavirin as well as in 6 healthy volunteers. Serial changes in the gene-expression profiles of PBMCs from individual patients were evaluated before treatment, 2 weeks after the start of IFN therapy, and 6 months after the completion of IFN therapy. RESULTS: Interestingly, the gene-expression profiles of PBMCs from patients with CH-C and healthy volunteers differed substantially; early T cell-activation antigen CD69 was significantly up-regulated in patients with CH-C, but immune-related molecules such as chemokine (C-C motif) receptor 2 and interleukin 7 receptor were significantly down-regulated. Selected combinations of expressed genes obtained before treatment and during IFN therapy by use of a fuzzy neural network combined with the SWEEP operator method predicted the outcome of IFN therapy with peak accuracies of 91.0% and 90.2%, respectively. CONCLUSIONS: These findings suggest that the gene-expression profiles of PBMCs from patients with CH-C may be useful biomarkers for IFN therapy.

Adult↗
PubMed2006

Virological effects and safety of combined double filtration plasmapheresis (DFPP) and interferon therapy in patients with chronic hepatitis C: A preliminary study.

PURPOSE: In patients with chronic genotype 1b hepatitis C and a high viral load, the viral load was reduced by double filtration plasmapheresis (DFPP), followed by combined interferon and ribavirin therapy. The safety and virological effects of this treatment method were preliminarily investigated. METHODS: In nine patients with chronic hepatitis C, DFPP was performed three times on days 1, 2, and 4, and the administration of interferon and ribavirin was initiated immediately after DFPP on day 1. RESULT: The HCV RNA was undetectable in all patients after the plasma was passed through a plasma fractionator (second filter) in the DFPP circuit. After 2 weeks, the HCV RNA tended to decrease in the DFPP group more than in the control group (-2.45+/-1.12 versus -1.57+/-0.95, P=0.073). However, this decrease was not attributable to a sustained virological response (SVR) (22.2% versus 18.2%, P=0.822). Most of the adverse events were caused by the interferon and ribavirin combination therapy. CONCLUSION: DFPP can be safely performed concomitantly with interferon and ribavirin combination therapy in chronic hepatitis C patients. The combination may contribute to an early virological response. The effect of DFPP on the SVR and its significance remain to be clarified.

Journal Article↗
PubMed2006

Different signaling pathways in the livers of patients with chronic hepatitis B or chronic hepatitis C.

The clinical manifestations of chronic hepatitis B (CH-B) and chronic hepatitis C (CH-C) are different. We previously reported differences in the gene expression profiles of liver tissue infected with CH-B or CH-C; however, the signaling pathways underlying each condition have yet to be clarified. Using a newly constructed cDNA microarray consisting of 9614 clones selected from 256,550 tags of hepatic serial analysis of gene expression (SAGE) libraries, we compared the gene expression profiles of liver tissue from 24 CH-B patients with those of 23 CH-C patients. Laser capture microdissection was used to isolate hepatocytes from liver lobules and infiltrating lymphoid cells from the portal area, from 16 patients, for gene expression analysis. Furthermore, the comprehensive gene network was analyzed using SAGE libraries of CH-B and CH-C. Supervised and nonsupervised learning methods revealed that gene expression was correlated more with the infecting virus than any other clinical parameters such as histological stage and disease activity. Pro-apoptotic and DNA repair responses were predominant in CH-B with p53 and 14-3-3 interacting genes having an important role. In contrast, inflammatory and anti-apoptotic phenotypes were predominant in CH-C. These differences would evoke different oncogenic factors in CH-B and CH-C. In conclusion, we describe the different signaling pathways induced in the livers of patients with CH-B or CH-C. The results might be useful in guiding therapeutic strategies to prevent the development of hepatocellular carcinoma in cases of CH-B and CH-C.

Adolescent↗
PubMed2006

The development and clinical features of splenic aneurysm associated with liver cirrhosis.

OBJECTIVES: Splenic artery aneurysm (SAA) is usually asymptomatic, but can be fatal if it ruptures. Portal hypertensive patients with varix or splenomegaly are sometimes complicated by SAA. However, there have been no large-scale clinical studies regarding whether liver cirrhosis itself is associated with splenic aneurysm regardless of varix or splenomegaly. METHODS: In the present study, we retrospectively analyzed 303 cirrhotic patients examined with arteriography. The diagnosis and characteristics of SAAs were determined, and the relation with splenic artery diameter was evaluated. RESULTS: Nine patients (2.97%) had 12 complicated SAAs. The aneurysms, which measured 4-22 mm in diameter, were all saccular, and occurred commonly in the splenic hilum (50.0%). A correlation was noted between splenic artery diameter and aneurysm diameter (R(2)=0.706). Aneurysm growth was strongly associated with an increase in diameter of the splenic artery trunk (R(2)=0.705), which is closely related to arterial flow. CONCLUSIONS: SAA is considered a complication of cirrhosis. The increase in splenic artery diameter may result in SAA enlargement and rupture. Elective procedures should be considered based on the follow-up of main trunk or diameter of the splenic artery in addition to SAA size, a known risk factor of aneurysmal rupture.

Adult↗
PubMed2006

Effect of hepatitis C virus (HCV) NS5B-nucleolin interaction on HCV replication with HCV subgenomic replicon.

We previously reported that nucleolin, a representative nucleolar marker, interacts with nonstructural protein 5B (NS5B) of hepatitis C virus (HCV) through two independent regions of NS5B, amino acids 208 to 214 and 500 to 506. We also showed that truncated nucleolin that harbors the NS5B-binding region inhibited the RNA-dependent RNA polymerase activity of NS5B in vitro, suggesting that nucleolin may be involved in HCV replication. To address this question, we focused on NS5B amino acids 208 to 214. We constructed one alanine-substituted clustered mutant (CM) replicon, in which all the amino acids in this region were changed to alanine, as well as seven different point mutant (PM) replicons, each of which harbored an alanine substitution at one of the amino acids in the region. After transfection into Huh7 cells, the CM replicon and the PM replicon containing NS5B W208A could not replicate, whereas the remaining PM replicons were able to replicate. In vivo immunoprecipitation also showed that the W208 residue of NS5B was essential for its interaction with nucleolin, strongly suggesting that this interaction is essential for HCV replication. To gain further insight into the role of nucleolin in HCV replication, we utilized the small interfering RNA (siRNA) technique to investigate the knockdown effect of nucleolin on HCV replication. Cotransfection of replicon RNA and nucleolin siRNA into Huh7 cells moderately inhibited HCV replication, although suppression of nucleolin did not affect cell proliferation. Taken together, our findings strongly suggest that nucleolin is a host component that interacts with HCV NS5B and is indispensable for HCV replication.

Alanine↗
PubMed2005

cDNA microarray analysis of autoimmune hepatitis, primary biliary cirrhosis and consecutive disease manifestation.

While autoimmune hepatitis (AIH) and primary biliary cirrhosis (PBC) usually have distinct clinical manifestations, some patients present with features of both conditions. Using cDNA microarrays, we analyzed and compared gene expression profiles in 8 patients with AIH, 9 with PBC, 8 with chronic hepatitis C (CHC), 8 with non-alcoholic steatohepatitis (NASH) and 9 with normal livers. We subsequently applied this method to a tissue sample from a 61-year-old woman with overlapping features of both AIH and PBC. A 61-year-old woman was admitted to our hospital for evaluation of elevated serum alkaline phosphatase. A liver biopsy showed accumulation of mononuclear cells around the bile duct cells, a feature characteristic of chronic non-suppurative destructive cholangitis (CNSDC). Three years later, her serum alanine aminotransferase (ALT) level had increased, and a liver biopsy demonstrated evidence of a severe form of hepatitis. A cDNA microarray analysis of both biopsies identified the molecular events associated with her altered histology. The expression profile of this patient, which was originally different from that of the other PBC patients, changed to an AIH pattern. Our results suggest that this patient has characteristics of both AIH and PBC.

Aged↗
PubMed2005

Differential gene alteration among hepatoma cell lines demonstrated by cDNA microarray-based comparative genomic hybridization.

We assayed chromosomal abnormalities in hepatoma cell lines using the microarray-based comparative genomic hybridization (array-CGH) method and investigated the relationship between genomic copy number alterations and expression profiles in these hepatoma cell lines. We modified a cDNA array-CGH assay to compare genomic DNAs from seven hepatoma cell lines, as well as DNA from two non-hepatoma cell lines and from normal cells. The mRNA expression of each sample was assayed in parallel by cDNA microarray. We identified small amplified or deleted chromosomal regions, as well as alterations in DNA copy number not previously described. We predominantly found alterations of apoptosis-related genes in Hep3B and HepG2, cell adhesion and receptor molecules in HLE, and cytokine-related genes in PLC/PRF/5. About 40% of the genes showing amplification or loss showed altered levels of mRNA (p < 0.05). Hierarchical clustering analysis showed that the expression of these genes allows differentiation between alpha-fetoprotein (AFP)-producing and AFP-negative cell lines. cDNA array-CGH is a sensitive method that can be used to detect alterations in genomic copy number in tumor cells. Differences in DNA copy alterations between AFP-producing and AFP-negative cells may lead to differential gene expression and may be related to the phenotype of these cells.

Apoptosis↗
PubMed2005

La protein is a potent regulator of replication of hepatitis C virus in patients with chronic hepatitis C through internal ribosomal entry site-directed translation.

BACKGROUND AND AIMS: Translation of hepatitis C virus is an essential step of viral replication and is mediated by an internal ribosome entry site. We previously reported that the hepatitis C virus internal ribosome entry site is most active during the synthetic (S) or mitotic (M) phases and lowest during quiescent (G 0 ) phase. Here, we investigated host factors responsible for the regulation of the hepatitis C virus internal ribosome entry site. METHODS: We synchronized the cell-cycle progression and evaluated gene-expression dynamics of host factors and kinetics of hepatitis C virus internal ribosome entry site activity in cells at various points during the cell cycle by using a complementary DNA microarray. We also validated the significance of identified host factors on hepatitis C virus replication in vivo. RESULTS: Hepatitis C virus internal ribosome entry site activity correlated with a gene cluster induced in the S and G 2 /M phases. It is interesting to note that most initiation factors known to bind or interact with the hepatitis C virus internal ribosome entry site [poly(rC)-binding protein 2, polypyrimidine tract binding protein, eukaryotic initiation factor 3, eukaryotic initiation factor 2gamma, eukaryotic initiation factor 2beta, La protein, and heterogenous nuclear ribonucleoprotein L] were induced during the S and G 2 /M phases. Expression of La protein, polypyrimidine tract binding protein, and eukaryotic initiation factor 3 (p116, p170) were predominantly repressed in G 0 phase and induced in S and G 2 /M phases. Suppression or overexpression of La protein and polypyrimidine tract binding protein in RCF-26 significantly changed hepatitis C virus internal ribosome entry site activity. In the livers of patients with chronic hepatitis C, expression of La protein was significantly increased and correlated with the amount of hepatitis C virus RNA. CONCLUSIONS: Hepatitis C virus uses host factors induced during cell division but not during quiescence for replication. Of these, La protein is a potent regulator and enhances hepatitis C virus replication in regenerating hepatocytes in patients with chronic hepatitis C.

Autoantigens↗
PubMed2005

Differential gene expression profiles in stage I primary biliary cirrhosis.

OBJECTIVES: Primary biliary cirrhosis (PBC) is a progressive disease. However, little is understood about the molecular mechanisms underlying its features. METHODS: We analyzed gene expression profiles of liver biopsy samples from 16 patients with PBC, seven with autoimmune hepatitis, eight with chronic hepatitis C, and eight normal control livers. In addition to whole liver samples, we selectively analyzed chronic nonsuppurative destructive cholangitis (CNSDC) lesions by laser capture microdissection. RESULTS: Hierarchical clustering analysis using only early-stage liver disease demonstrated 85 genes were upregulated in stage I PBC specifically. Surprisingly, the expression of these genes was not maintained in advanced-stage PBC, while other gene clusters were upregulated. Expression analysis of CNSDC lesions in stage I PBC showed the presence of active inflammatory changes, characterized by the significant elevation of interferon-gamma and the development and maturation of lymphocytes. Expression of these genes was diminished in lymphoid cells aggregation in stage III PBC, and genes reflecting hepatocyte damage were upregulated with disease progression. CONCLUSION: Gene expression patterns in stage I PBC are different from others. There are distinct changes in molecular pathology from early- to late-stage PBC, which might be a clue to reveal the etiology and progression of PBC.

Aged↗
PubMed2004

An open-label study of administration of EH0202, a health-food additive, to patients with chronic hepatitis C.

BACKGROUND: In this study, we examined the effect of EH0202, a mixture of four herbal extracts that are known to induce interferons, on hepatitis C virus (HCV)-RNA levels in patients with chronic hepatitis C. METHODS: This was an open-label uncontrolled study. The study subjects ingested food containing EH0202 daily for 3 months, which was equivalent to 1 g of desiccated herbs daily. Clinical symptoms, hematology and biochemical examinations, urine, and HCV-RNA levels were examined before, during (1 month), and after the EH0202 treatment (3 months). RESULTS: Among the 35 patients who successfully completed the study, there were improvements in malaise (seen in 6 patients before and in 2 after EH0202 treatment), bloating sensation in the abdomen (seen in 2 before and in none after treatment), and nausea and vomiting (seen in 2 before and in 1 after treatment). There were no changes in hematology or biochemical examination parameters. There was a statistically significant decrease in HCV-RNA levels in patients with high viral titers after 3 months of EH0202 administration. No serious adverse events were observed with the EH0202 treatment. CONCLUSIONS: These findings suggest that EH0202 may be safe and useful in the treatment of patients with chronic hepatitis C. Further studies are, however, needed to obtain a definitive conclusion.

Adult↗
PubMed2004

Genome-wide transcriptome mapping analysis identifies organ-specific gene expression patterns along human chromosomes.

The Human Genome Project has revealed that there about 32,000 protein-encoding genes, which are distributed throughout the genome. It is unclear, however, whether genes are distributed on the chromosomes according to patterns linked to organ specificity. To explore the relationship between genes actively transcribed in normal tissues and their chromosomal locations, we analyzed serial analysis of gene expression libraries of normal human liver, brain, breast, and colon tissues. Transcriptome mapping analysis revealed that transcriptional activity in each tissue varied according to the chromosomal domains, and a weak positive correlation was observed between transcription density and gene density. We identified six liver-related and five colon-related chromosomal domains highly transcribed in each tissue, whereas no brain-related or breast-related chromosomal domains were identified. Representative genes located on these chromosomal domains were associated with the function of each organ and were highly conserved in both mouse and rat genomes. These data revealed that the transcriptional activities of normal human tissues are well orchestrated at chromosomal levels, suggesting that highly expressed genes may share physical proximity.

Chromosome Mapping↗
PubMed2003

Enhanced antitumor effects of a bicistronic adenovirus vector expressing both herpes simplex virus thymidine kinase and monocyte chemoattractant protein-1 against hepatocellular carcinoma.

The efficacy of the suicide gene therapy using the herpes simplex virus thymidine kinase/ganciclovir (HSV-tk/GCV) system for the treatment of cancer is limited because of the insufficient gene transfer and the low killing activity. To enhance the antitumor activity, we determined whether recombinant adenovirus vector (rAd)s expressing both HSV-tk and monocyte chemoattractant protein-1 (MCP-1) genes could potentiate the destruction of hepatocellular carcinoma (HCC). The rAd Ad-tk-MCP1 harboring HSV-tk and MCP-1 genes in sequence under the universal CAG promoter was constructed with a bicistronic unit including the encephalomyocarditis virus-internal ribosomal entry site. The levels of HSV-tk expression and GCV-sensitive tumoricidal activity of Ad-tk-MCP1 were comparable to those of rAd expressing HSV-tk alone. The growth of subcutaneous tumors in athymic nude mice was markedly suppressed when tumors were treated with Ad-tk-MCP1 as opposed to another bicistronic vector Ad-MCP1-tk, rAd expressing either HSV-tk or MCP-1, or both of these vectors. The antitumor effects of Ad-tkMCP1 may be dependent on the activation of macrophages, since the recruitment of macrophages was observed tumor necrosis factor-alpha production was enhanced in the tumor tissue. Furthermore, the enhanced antitumor effect was abolished by inactivating macrophages with carrageenan treatment. These results demonstrated that a bicistronic rAd harboring both suicide and chemokine genes in sequence exerted the enhanced, macrophage-dependent, antitumor effects in a model of HCC and support the use of this strategy for the treatment of HCC.

Adenoviridae↗
PubMed2003

Detection of hepatitis B virus DNA in sera from patients with chronic hepatitis B virus infection by DNA microarray method.

We have developed a sensitive and quantitative assay using a DNA microarray for the detection of hepatitis B virus (HBV) DNA in serum. Fluorescently labeled target cDNA prepared from cloned HBV DNA or serum HBV DNA was hybridized to capture DNA on a slide. A linear relationship was obtained between the intensities of the array spot and the amount of the cloned or serum HBV DNA, indicating the quantitative accuracy of this assay system. In addition, there was a significant correlation between the number of molecules of serum HBV DNA determined by the DNA microarray and that determined by a branched-DNA assay (n = 21, r = 0.89). Given these results, we conclude that the DNA microarray assay system may be useful as a diagnostic technique in the clinical laboratory.

Branched DNA Signal Amplification Assay↗
PubMed2002

Enantioselective analysis of glufosinate using precolumn derivatization with (+)-1-(9-fluorenyl)ethyl chloroformate and reversed-phase liquid chromatography.

We have developed a new analytical method to quantify the DL-homoalanine-4-yl(methyl)phosphinate (DL-GLUF) enantiomers in biological specimens using a reversed-phase high-performance liquid chromatography system with a fluorescence detection system. The derivatization of DL-GLUF enantiomers with (+)-1-(9-fluorenyl)ethyl chloroformate was carried out under mild conditions (40 degrees C for 30 min) without inducing racemization. The lower limit of quantitation was 0.01 microg/ml for both D-GLUF and L-GLUF, and the detection limit was 5 ng/ml. When DL-GLUF enantiomers were added to serum to produce concentrations between 0.1 and 100 microg/ml, the mean recovery rate was at least 93.8%. The recovery rate from urine was also satisfactory.

Aminobutyrates↗