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Biomedical subjects

Ryuzo Ueda

Publications and source records attributed to Ryuzo Ueda.

At least 73 records · Page 4Linked to original sources

Diffuse large B-cell lymphoma with extra Bcl-2 gene signals detected by FISH analysis is associated with a "non-germinal center phenotype".

Amplification and translocation of the Bcl-2 gene has been detected in a certain subset of diffuse large B-cell lymphomas (DLBCL). The correlations among Bcl-2 protein expression, gene translocation or amplification, and the molecular signature determined by cDNA array are poorly understood. This study examined 25 cases with de novo nodal DLBCL. Interphase fluorescence in situ hybridization (FISH) analysis was performed to evaluate the Bcl-2 gene using IGH/BCL2 and CEP18 centromere probes (Vysis). When extra Bcl-2 gene signals were observed in each tumor cell and when these signals were in proportion to the extra CEP18 probe signals, we regarded the findings as indicating the presence of an additional chromosome 18; when extra Bcl-2 signals were observed but additional CEP18 signals were not, we regarded the findings as indicating the presence of gene amplification. A panel of 3 antigens (CD10, Bcl-6, and MUM-1) was applied to categorize each case as either a "germinal center B-cell (GCB) phenotype" or a "non-GCB phenotype." Of the 25 cases examined, 8 cases (32%) were classified as "GCB phenotype" and 17 cases (68%) were classified as "non-GCB phenotype." A FISH analysis revealed that t(14;18) was detected in 2 of the 8 cases (25%) with the "GCB phenotype" but in none of the 17 "non-GCB phenotype" cases. Extra Bcl-2 gene signals were detected in 7 of the 25 (28%) cases examined: n = 5 for an additional chromosome 18, n = 1 for gene amplification, and n = 1 for additional chromosome 18 + gene amplification. Extra Bcl-2 gene signals were exclusively detected in DLBCL with the "non-GCB phenotype"; these cases, with the exception of one, stained strongly positive for Bcl-2. The DLBCLs with Bcl-2 protein overexpression were classified into at least two heterogeneous molecular groups, based on the results of the FISH analysis.

Adult↗

[Clinical course of the disease and the level of WT1 mRNA in 191 patients with acute myeloid leukemia (AML): joint research by 23 institutions in Japan].

We evaluated the clinical course of acute myeloid leukemia (AML) and the levels of WT1 mRNA in 191 AML patients. Of 114 previously untreated patients with AML, 107 cases were positive for WT1 mRNA (93.9% : 107/114). WT1 mRNA expression-levels declined to below 50 copies/microg RNA ("negative") after remission was achieved in all 66 patients who achieved remission and 84.8% (47/54) cases were "negative" at the end of the follow-up periods. On the other hand, WT1 mRNA was expressed in 87.0% of non-remission cases (47/54), maintaining 50 copies/microg of RNA or higher ("positive"). In all 29 cases who relapsed during the follow-up observation period after achieving remission, WT1 mRNA levels declined transiently approximately around the time of achieving remission and then rose again when the disease relapsed. Moreover, we determined the time of elevation of WT1 mRNA in 29 relapsed cases. In 79.3% of relapsed cases (23/29), WT1 mRNA levels rose above 200 copies/microg RNA, 43 days (median) before the diagnosis of "relapse". Given the percent of the correct diagnosis, WT1 mRNA at 200 copies/microg RNA appeared to be a reasonable cut-off level for early detection of AML-relapse. The WT1 mRNA level reflected the clinical condition. Taken together, these findings indicate that WT1 mRNA levels allow us to detect the presence of so-called "minimal residual disease" (leukemic cells) that cannot be detected by morphological examination. Besides these promising data, this kit is suitable for routine monitoring of AML because this kit utilizes peripheral blood as a test specimen, reducing the patient's burden at the time of collection of clinical samples as compared with bone marrow aspirate.

Adult↗

Efficacy of docetaxel as a second-line chemotherapy for thymic carcinoma.

Thymic carcinoma is a rare and aggressive tumor, and the efficacy of second-line chemotherapy is still unclear. Here, we reported a case of thymic carcinoma that responded well to the administration of docetaxel alone as a second-line chemotherapy. A 64-year-old woman was diagnosed with thymic carcinoma (squamous cell type) with bone metastasis, and she, therefore, received nedaplatin combined with etoposide and ifosfamide. She responded partially, after which she received irradiation for bone metastasis. Two months after chemotherapy, the thymic carcinoma exhibited gradual regrowth and she experienced shoulder pain. We treated this with docetaxel alone (60 mg/m2 every 4 weeks). After three courses of docetaxel, we observed a partial response and her shoulder pain disappeared. This case demonstrated that docetaxel is effective as a second-line chemotherapy for thymic carcinoma.

Antineoplastic Agents, Phytogenic↗

The CC chemokine receptor 4 as a novel specific molecular target for immunotherapy in adult T-Cell leukemia/lymphoma.

Adult T-cell leukemia/lymphoma (ATLL) is a peripheral T-cell neoplasm with dismal prognosis, and no optimal therapy has been developed. We tested the defucosylated chimeric anti-CC chemokine receptor 4 (CCR4) monoclonal antibody, KM2760, to develop a novel immunotherapy for this refractory tumor. In the presence of peripheral blood mononuclear cells (PBMCs) from healthy adult donors, KM2760 induced CCR4-specific antibody-dependent cellular cytotoxicity (ADCC) against CCR4-positive ATLL cell lines and primary tumor cells obtained from ATLL patients. We next examined the KM2760-induced ADCC against primary ATLL cells in an autologous setting. Antibody-dependent cellular cytotoxicity mediated by autologous effector cells was generally lower than that mediated by allogeneic control effector cells. However, a robust ADCC activity was induced in some cases, which was comparable with that mediated by allogeneic effector cells. It suggests that the ATLL patients' PBMCs retain substantial ADCC-effector function, although the optimal conditions for maximal effect have not yet been determined. In addition, we also found a high expression of FoxP3 mRNA and protein, a hallmark of regulatory T cells, in ATLL cells, indicating the possibility that ATLL cells originated from regulatory T cells. KM2760 reduced FoxP3 mRNA expression in normal PBMCs along with CCR4 mRNA by lysis of CCR4+ T cells in vitro. Our data suggest not only that the CCR4 molecule could be a suitable target for the novel antibody-based therapy for patients with ATLL but also that KM2760 may induce effective tumor immunity by reducing the number of regulatory T cells.

Antibodies, Monoclonal↗

Distribution of CXCR3- or CCR4-positive cells in interstitial pneumonia associated with primary Sjogren's syndrome.

Patients with primary Sjogren's syndrome (SS) occasionally develop interstitial pneumonia (SS-IP), the prognosis of which is less grave compared with that of idiopathic pulmonary fibrosis (IPF). We examined distribution of helper T-cell subsets in open lung biopsy specimens from seven patients with SS-IP and, for comparison, ten patients with IPF. The expression of CXCR3 and CCR4, chemokine receptors associated in vitro with Th1 and Th2 cells, respectively, was analyzed in the mononuclear infiltrate using immunohistochemistry. The expression of CD4, CD8, and CD20 in the infiltrate was similarly examined. The positive cells were semiquantified in fibrosing areas and lymphoid clusters of both SS-IP and IPF. In fibrosing areas, CXCR3-positive cells were dominant over CCR4-positive cells in all cases of SS-IP, whereas the two types of cells showed no such difference in cases of IPF. Each of the CXCR3/CD4 and CXCR3/CCR4 ratios was significantly higher in SS-IP than in IPF ( P<0.05 and P<0.05, respectively). The CCR4/CD4 ratio showed a significantly lower value in SS-IP than in IPF ( P<0.05). In lymphoid clusters, prominent in SS-IP and few and small in IPF, CXCR3-positive cells predominated over CCR4-positive cells in both lung lesions. There was no significant difference of CXCR3/CCR4 ratio in lymphoid clusters between SS-IP and IPF ( P=0.33). These findings in SS-IP are in accordance with those reported in previous studies of the salivary glands of SS patients, where most of the infiltrating lymphocytes expressed CXCR3, and the expression of interferon-gamma was upregulated. In contrast, the Th2 cell dominance was reported in IPF in the previous studies. The present findings suggest that the pathogenesis of interstitial pneumonia is different between SS-IP and IPF in regard to the roles of helper T-cell subsets.

Aged↗

CXC chemokine receptor 3 and CC chemokine receptor 4 expression in T-cell and NK-cell lymphomas with special reference to clinicopathological significance for peripheral T-cell lymphoma, unspecified.

We recently reported expression of the chemokine receptors CXC chemokine receptor 3 (CXCR3) and CC chemokine receptor 4 (CCR4) in adult T-cell leukemia/lymphoma and showed a preferential expression of CCR4 and its association with an unfavorable outcome. In the present study, we extend our adult T-cell leukemia/lymphoma study to other subtypes of T- and NK-cell lymphoma, to clarify whether a characteristic chemokine receptor expression pattern is obtained for each of the subtypes defined by the WHO classification. CXCR3 and CCR4 were rarely expressed in three well-defined subtypes, precursor T-lymphoblastic lymphoma, anaplastic lymphoma kinase-positive anaplastic large cell lymphoma, and extranodal NK/T-cell lymphoma. A CXCR3-dominant expression pattern was observed in angioimmunoblastic T-cell lymphoma, while a CCR4-dominant expression pattern was observed in mycosis fungoides in transformation and in anaplastic lymphoma kinase-negative anaplastic large cell lymphoma. CXCR3 and CCR4 were heterogeneously expressed in peripheral T-cell lymphomas, unspecified (PTCLU). We next focused on PTCLU and analyzed the clinical significance of the chemokine receptors and their association with FoxP3, a hallmark of immunoregulatory T (Treg) cells. Multivariate analysis showed that CCR4 expression was an independent and significant unfavorable prognostic factor (P < 0.001). A significant correlation was found between mRNA expression of CCR4 and FoxP3, suggesting a possible association of CCR4-positive tumors with Treg cells and thereby with an immunocompromised state. Chemokine receptors may be useful not only for further characterization of the T- and NK-cell lymphomas but also in predicting clinical outcomes for patients. We suggest that a specific therapy targeting the CCR4 molecule may be developed as an alternative treatment for patients with CCR4-positive tumors.

Adolescent↗

Genotype and phylogenetic characterization of hepatitis B virus among multi-ethnic cohort in Hawaii.

AIM: Hepatitis B virus (HBV) genomes in carriers from Hawaii have not been evaluated previously. The aim of the present study was to evaluate the distribution of HBV genotypes and their clinical relevance in Hawaii. METHODS: Genotyping of HBV among 61 multi-ethnic carriers in Hawaii was performed by genetic methods. Three complete genomes and 61 core promoter/precore regions of HBV were sequenced directly. RESULTS: HBV genotype distribution among the 61 carriers was 23.0% for genotype A, 14.7% for genotype B and 62.3% for genotype C. Genotypes A, B and C were obtained from the carriers whose ethnicities were Filipino and Caucasian, Southeast Asian, and various Asian and Micronesian, respectively. All cases of genotype B were composed of recombinant strains with genotype C in the precore plus core region named genotype Ba. HBeAg was detected more frequently in genotype C than in genotype B (68.4% vs 33.3%, P<0.05) and basal core promoter (BCP) mutation (T1762/A1764) was more frequently found in genotype C than in genotype B. Twelve of the 38 genotype C strains possessed C at nucleotide (nt) position 1858 (C-1858). However there was no significant difference in clinical characteristics between C-1858 and T-1858 variants. Based on complete genome sequences, phylogenetic analysis revealed one patient of Micronesian ethnicity as having C-1858 clustered with two isolates from Polynesia with T-1858. In addition, two strains from Asian ethnicities were clustered with known isolates in carriers from Southeast Asia. CONCLUSION: Genotypes A, B and C are predominant types among multi-ethnic HBV carriers in Hawaii, and distribution of HBV genotypes is dependent on the ethnic background of the carriers in Hawaii.

Adult↗

Two subtypes of genotype B (Ba and Bj) of hepatitis B virus in Japan.

We have previously reported 2 subtypes of hepatitis B virus (HBV) genotype B, one of which has the recombination with genotype C over the precore region plus core gene (Ba) and the other of which does not (Bj). A restriction fragment-length polymorphism method with 2 endonucleases was newly developed for distinguishing between subtypes Ba and Bj and was applied to 313 carriers of HBV genotype B in Japan. Subtype Ba was detected in 38 (12%) and subtype Bj in 275 (88%) of the carriers of HBV genotype B. Hepatitis B e antigen in serum was found more frequently in patients with chronic infection with subtype Ba than in those with chronic infection with subtype Bj (8 [32%] of 25 vs. 25 [9%] of 273; P<.01). The new method for distinguishing between Ba and Bj by restriction fragment-length polymorphism would be useful in examining the distribution of these 2 subtypes in situations in which HBV genotype B is prevalent.

Acute Disease↗

Gene-environment interactions between the smoking habit and polymorphisms in the DNA repair genes, APE1 Asp148Glu and XRCC1 Arg399Gln, in Japanese lung cancer risk.

APE1 (apurinic/apyrimidinic endonuclease 1) and XRCC1 (X-ray cross-complementing group 1) are DNA repair proteins that play important roles in the base excision repair (BER) pathway. Polymorphisms in their encoding genes are associated with altered DNA repair capacity and thus may impact on cancer risk. In the present case-control study with 178 Japanese incident lung cancer cases and 449 age- and sex-matched controls, we investigated the gene-environment interaction among APE1 Asp148Glu, XRCC1 Arg399Gln and smoking habit in lung cancer risk. The results were analyzed by using conditional logistic regression models, adjusted for age, sex and smoking status. The adjusted odds ratio for the current smokers with APE1 148Asp/Asp, Asp/Glu and Glu/Glu genotype as compared with the never smokers with the Asp/Asp genotype were 3.01 (95% CI 1.39-6.51, P = 0.005), 2.73 (95% CI 1.29-5.77, P = 0.008) and 7.33 (95% CI 2.93-18.3, P < 0.001), respectively. The gene-environment interaction between current smoking and APE1 148Glu/Glu genotype was statistically significant (OR 3.59, 95% CI 1.28-10.1, P = 0.015). When APE1 Asp148Glu and XRCC1 Arg399Gln polymorphisms were evaluated together, the adjusted odds ratios for the current smokers with 0-1, 2 and 3-4 of APE1 148Glu or XRCC1 399Gln alleles as compared with never smokers with the 0 of these alleles were 2.96 (95% CI 1.57-5.58, P = 0.001), 3.86 (95% CI 1.85-8.05, P < 0.001) and 6.01 (95% CI 2.25-16.1, P < 0.001), respectively. The gene-environment interaction between current smoking and three or more APE1 148Glu or XRCC1 399Gln alleles was statistically significant (OR 2.44, 95% CI 1.00-9.22, P = 0.049). The OR for the gene-environment interaction of Glu/Glu genotype of APE1 codon 148 with heavy smoking was 1.04 (95% CI 0.38-2.90, P = 0.936) and that with light smoking was 2.67 (95% CI 1.00-7.68, P = 0.049). These results suggest that APE1 Asp148Glu and XRCC1 Arg399Gln polymorphisms might modify the risk of lung cancer attributable to cigarette smoking exposure.

Adult↗

Defucosylated chimeric anti-CC chemokine receptor 4 IgG1 with enhanced antibody-dependent cellular cytotoxicity shows potent therapeutic activity to T-cell leukemia and lymphoma.

Human IgG1 antibodies with low fucose contents in their asparagine-linked oligosaccharides have been shown recently to exhibit potent antibody-dependent cellular cytotoxicity (ADCC) in vitro. To additionally investigate the efficacy of the human IgG1 with enhanced ADCC, we generated the defucosylated chimeric anti-CC chemokine receptor 4 (CCR4) IgG1 antibody KM2760. KM2760 exhibited much higher ADCC using human peripheral blood mononuclear cells (PBMCs) as effector cells compared with the highly fucosylated, but otherwise identical IgG1, KM3060. In addition, KM2760 also exhibited potent ADCC in the presence of lower concentrations of human PBMCs than KM3060. Because CCR4 is a selective marker of T-cell leukemia/lymphoma, the effectiveness of KM2760 for T-cell malignancy was evaluated in several mouse models. First, to compare the antitumor activity of KM2760 and KM3060, we constructed a human PBMC-engrafted mouse model to determine ADCC efficacy with human effector cells. In this model, KM2760 showed significantly higher antitumor efficacy than KM3060, indicating that KM2760 retains its high potency in vivo. Second, KM2760 suppressed tumor growth in both syngeneic and xenograft mouse models in which human PBMCs were not engrafted. Although murine effector cells exhibited marginal ADCC mediated by KM2760 and KM3060, KM2760 unexpectedly showed higher efficacy than KM3060 in a syngeneic mouse model, suggesting that KM2760 functions in murine effector system in vivo via an unknown mechanism that differs from that in human. These results indicate that defucosylated antibodies with enhanced ADCC as well as potent antitumor activity in vivo are promising candidates for the novel antibody-based therapy.

Animals↗

Familial essential thrombocythemia associated with a dominant-positive activating mutation of the c-MPL gene, which encodes for the receptor for thrombopoietin.

One Japanese pedigree of familial essential thrombocythemia (FET) inherited in an autosomal-dominant manner is presented. A unique point mutation, serine 505 to asparagine 505 (Ser505Asn), was identified in the transmembrane domain of the c-MPL gene in all of the 8 members with thrombocythemia, but in none of the other 8 unaffected members in this FET family. The Ba/F3 cells expressing the mutant Asn505 acquired interleukin 3 (IL-3)-independent survival capacity, whereas those expressing wild-type Ser505 did not. The autonomous phosphorylation of Mek1/2 and Stat5b was observed in the mutant Ba/F3 cells in the absence of IL-3. The former was also found in platelets derived from the affected individual in the absence of thrombopoietin. These results show that the Asn505 is an activating mutation with respect to the intracellular signaling and survival of the cells. This is the first report of FET deriving from a dominant-positive activating mutation of the c-MPL gene.

Cells, Cultured↗

Predicting relapse after cessation of Lamivudine monotherapy for chronic hepatitis B virus infection.

There have been reports of relapse after cessation of lamivudine monotherapy for hepatitis B virus (HBV) infection. The aim of this study was to examine factors that predict posttreatment relapse. Comparison 22 patients who experienced relapse with 11 who did not after cessation of therapy showed that predictive factors for nonrelapse were hepatitis B e antigen seroconversion and duration of undetectable HBV DNA load (<0.7 log IU/mL), as determined by HBV real-time detection direct testing. However, 7 of 12 patients with seroconversion experienced relapse after cessation of therapy. Multivariate analysis revealed that the duration of an undetectable HBV DNA load was the only independent predictive factor for nonrelapse (odds ratio, 0.50; 95% confidence interval, 0.27-0.9). More-prolonged lamivudine therapy is required after seroconversion, and persistent duration of an HBV DNA level of <0.7 log IU/mL for >6 months can more accurately aid in the decision of when to stop lamivudine therapy.

Adult↗

Eight genotypes (A-H) of hepatitis B virus infecting patients from San Francisco and their demographic, clinical, and virological characteristics.

Clinical lines of evidence have been accumulated that hepatitis B virus (HBV) genotypes have characteristic geographical distributions and distinct clinical impact on liver diseases. The distribution of HBV genotypes was determined with reference to hepatitis B e antigen (HBeAg) and alanine aminotransferase (ALT) levels in 165 patients with hepatitis B in San Francisco. HBV genotypes were determined by enzyme-linked immunosorbent assay (ELISA) and the unclassified samples were sequenced within the S region for phylogenetic analysis. Genotype A occurred in 60 (36%) patients, B in 16 (10%), C in 56 (34%), D in 19 (12%), E in 1 (1%), F in 1 (1%), G in 8 (5%), and H in 4 (2%). Caucasians were infected predominantly with HBV genotype A (HBV/A) (38 of 57 [67%]), Asians with HBV/C (45 of 63 [71%]), and Hispanics with HBV/F and HBV/H (4 of 9 [44%]). Serum ALT levels were higher in the patients infected with HBV/A (P = 0.03) or HBV/G (P = 0.02) than HBV/C. HBeAg was more frequent in patients infected with HBV/G than HBV/C or HBV/D (7 of 8 [88%] vs. 25 of 56 [45%] or 6 of 19 [32%], P = 0.03 or 0.01). In conclusion, eight genotypes (A-H) were identified in San Francisco in association with various ethnicities and then influenced ALT levels as well as the prevalence of serum HBeAg. HBV genotype H might be identified by combination of preS2 serotpe bksf and HBsAg serotype adw.

Adult↗

Matrix metalloproteinase-1 polymorphism of promoter region in sarcoidosis and tuberculosis patients.

BACKGROUND AND AIM OF THE WORK: Matrix metalloproteinases (MMPs) are associated with several diseases. MMP-1 is one of the interstitial collagenases and the most highly expressed. Recent studies have found that a single nucleotide polymorphism located in the promoter region of the MMP-1 gene affects transcriptional activity. This polymorphism, 1G/2G, has been reported to associate with several malignant tumors and lung diseases. In this study, we investigated whether this polymorphism is associated with sarcoidosis or tuberculosis. METHODS: Polymerase chain reaction-restriction fragment length polymorphism was used to determine the MMP-1 genotypes of 103 sarcoidosis patients, 105 tuberculosis patients and 106 healthy control subjects. RESULTS: We found no differences in genotype distributions and allele frequency between sarcoidosis or tuberculosis patients and healthy control subjects. In sarcoidosis patients with ocular involvement, a significant increase in 1G/1G or 1G/2G genotype was observed compared with patients without (p = 0.009, odds ratio (OR) = 3.22, 95% confidence interval (CI): 1.34-7.71). In sarcoidosis patients with three or more organs involved, 1G/1G type tended to increase compared with patients without (p = 0.035, OR = 5.17, 95% CI: 1.12-23.9). In tuberculosis patients with cavity formation, an increasing trend of 1G/1G type was observed compared with patients without (p = 0.064, OR = 7.69, 95% CI: 0.89-66.3). CONCLUSIONS: Although MMP-1 polymorphism was not associated with onset risk of sarcoidosis and tuberculosis, the clinical characteristics of both diseases were affected by this polymorphism.

Adult↗

A randomized controlled trial of consensus interferon with or without lactoferrin for chronic hepatitis C patients with genotype 1b and high viral load.

Recently, lactoferrin has been reported to have anti-HCV effects. The aim of this study was to investigate the effect of combination therapy using consensus interferon (CIFN) and lactoferrin in patients with chronic hepatitis C. Twenty-one patients with chronic HCV infection, who were positive for HCV-RNA genotype 1b with serum viral loads from 100 to 700KIU/ml, were randomly assigned to two groups; the CIFN + Lac group received CIFN with lactoferrin and the CIFN group received CIFN alone. Nine patients in each group completed this trial; the other patients dropped out because of side effects. Three, two and four patients were categorized as complete responders, relapsers and non-responders, respectively, in the CIFN + Lac group, and four, one and four in the CIFN group, respectively. There was no statistically significant difference in virologic response between the two groups. During the follow up after CIFN therapy with continued lactoferrin, there were two relapsers in the CIFN + Lac group and their HCV-RNA titers before treatment were over 400KIU/ml. In conclusion, the combination therapy of CIFN and lactoferrin did not increase the response rate or prevent relapse after discontinuation of IFN.

Journal Article↗

Spontaneous regression of hepatocellular carcinoma: two case reports and a literature review.

Spontaneous regression of a malignant tumor is extremely rare. Here we report two cases of spontaneous regression of hepatocellular carcinoma (HCC), and review the associated literature. Case 1 was a 77-year-old male with HCC in the right lobe and multiple lung metastases. alpha-fetoprotein (AFP) and protein induced by vitamin K deficiency or antagonist II (PIVKA-II) were >50,000ng/ml and 21,500mAU/ml, respectively. He and his family refused further treatment, and he was discharged. Four months after the diagnosis, dramatic diminution of HCC and lung metastases was noted, and the HCC had disappeared completely 12 months later. Case 2 was a 72-year-old male with multiple nodular regions with enhanced circumference in the right lobe, the largest of which was 8cm in diameter, referred to the gastroenterology unit of our hospital. Laboratory analyses showed positive for hepatitis C virus antibody, and AFP and PIVKA-II were 936.3ng/ml and 2,380mAU/ml, respectively. However, he and his family refused further treatment, and he was followed-up as an outpatient by a local clinic. Two years later, radiological investigations revealed remarkable regression of HCC. Laboratory analyses showed that PIVKA-II had decreased to the normal range, while AFP had increased to double the original value.

Journal Article↗

Hepatitis B virus genotype G is an extremely rare genotype in Japan.

BACKGROUND:: Hepatitis B virus (HBV) has been classified into seven genotypes (A-G). HBV genotypes have a geographically characteristic distribution. Since HBV genotype G (HBV/G) was identified recently, little is known about the distribution of HBV/G in Japan. The aim of this study was to clarify this issue. PATIENTS AND METHODS:: Seven hundred and twenty-one serum samples obtained from patients with HBV in Japan were investigated. The patients included 149 asymptomatic carriers, 325 with chronic hepatitis, 129 with liver cirrhosis, and 118 with hepatocellular carcinoma. Six HBV genotypes (A-F) were determined by restriction fragment length polymorphim targeting to the S region of the HBV genome. Furthermore, HBV/G was investigated by polymerase chain reaction with hemi-nested primers derived from an HBV/G-specific nucleotide sequence. RESULTS:: Of the 721 serum samples investigated, 12 subjects were classified as having HBV/A, 88 HBV/B, 610 HBV/C, 3 HBV/D, and 1 HBV/F. Seven subjects had a mixed infection with distinct genotypes, two with HBV/A and HBV/D, and five with HBV/B and HBV/C. HBV/G was not identified among the 721 samples. CONCLUSION:: HBV/G was not identified in a large cohort of patients with HBV, either single or dual infection. HBV/G seems to be an extremely rare genotype in Japan.

Journal Article↗