Biomedical subjects

Ryuzo Ueda

Publications and source records attributed to Ryuzo Ueda.

At least 109 records · Page 6Linked to original sources

PubMed2003

Frequent coinfection with hepatitis B virus strains of distinct genotypes detected by hybridization with type-specific probes immobilized on a solid-phase support.

A genotype-specific probes assay (GSPA) was developed for distinguishing the seven genotypes (A-G) of hepatitis B virus (HBV). Nucleotide (nt) sequences corresponding to preS1 region were amplified by PCR with a primer labeled with biotin, and delivered to eight wells on which complementary sequences specific to one or other genotype had been immobilized. Thereafter, hybridization of HBV DNA sequences amplified from the test serum was detected by colorimetry. When 256 sera from HBV carriers in Bangladesh, Cameroon, Japan, South Africa, USA and Uzbekistan were subjected to GSPA, genotypes were concordant with those of ELISA with monoclonal antibodies to epitopes on preS2-region products in 242 (94.6%) of them; 8 sera (3.1%) were not genotypeable by either method. Cloning analysis confirmed the presence of two distinct HBV genotypes in the seven selected sera with coinfection. There were 7 (2.7%) sera with discordant genotyping results between GSPA and ELISA. When HBV DNA clones propagated from these sera were sequenced and analyzed phylogenetically, the genotypes determined by GSPA were verified. Coinfection with HBV strains of two distinct genotypes was identified by GSPA in 28 (10.9%) sera, while it was suggested by ELISA in only 2 (0.8%) sera. The GSPA method would be particularly useful for detecting the coinfection with distinct HBV genotypes of any clinical relevance, which seems to be more frequent than reported previously.

Biotin↗

PubMed2003

Impact of interleukin-1beta genetic polymorphisms on the development of hepatitis C virus-related hepatocellular carcinoma in Japan.

To examine the effects of polymorphisms in the gene encoding proinflammatory interleukin (IL)-1beta in patients infected with hepatitis C virus (HCV) in Japan, we studied 364 patients with chronic HCV infection (146 of whom had hepatocellular carcinoma [HCC] and 218 of whom did not) and 230 healthy control subjects. IL-1B-511 and IL-1RN genotypes were ascertained, and IL-1B-511 genotype T/T was found to be significant risk factors for the development of HCC, indicating that polymorphism in the IL-1B-511 genetic locus is one of the possible determinants of progression of hepatitis C to HCC.

Aged↗

PubMed2003

Distribution of astrocytic plaques in the corticobasal degeneration brain and comparison with tuft-shaped astrocytes in the progressive supranuclear palsy brain.

Corticobasal degeneration (CBD) and progressive supranuclear palsy (PSP) have some clinical and pathological features in common. Each, however, has been shown to have specific astrocytic inclusions. CBD is characterized by astrocytic plaques, and PSP is characterized by tuft-shaped astrocytes. To clarify differences between these inclusions, we investigated intracerebral distribution of astrocytic plaques and tuft-shaped astrocytes in autopsied brains of patients with either CBD or PSP. Specimens from ten patients with CBD and five patients with PSP were stained by the Gallyas-Braak method. Densities of the astrocytic plaques and tuft-shaped astrocytes were determined for 11 cerebral cortical regions, 6 subcortical nuclei, 5 brain stem regions, the cerebellar cortex and the dentate nucleus. Astrocytic plaques were most abundant in the prefrontal and premotor areas in the cerebral cortex of CBD brains, whereas tuft-shaped astrocytes were most prominent in the precentral gyrus and premotor area of PSP brains. Many astrocytic plaques were observed in the caudate nucleus of CBD brains, whereas tuft-shaped astrocytes were abundant in both the caudate and putamen and moderate in number in the globus pallidus, subthalamic nucleus and thalamus in PSP brains. Very slight accumulation of astrocytic plaques was seen in the brain stem of CBD brains, whereas numerous tuft-shaped astrocytes were found in the red nucleus and superior colliculus of PSP brains. Distribution of the astrocytic plaques and tuft-shaped astrocytes differed greatly. Thus, CBD and PSP can be considered different entities.

Aged↗

PubMed2003

Detection of t(11;18)(q21;q21) in marginal zone lymphoma of mucosa-associated lymphocytic tissue type on paraffin-embedded tissue sections by using fluorescence in situ hybridization.

A chromosomal t(11;18)(q21;q21) recurrently found in marginal zone lymphomas of mucosa-associated lymphocytic tissue (MALT) type is one of the key determinants of their treatment and outcome because t(11;18)-positive cases are resistant to Helicobacter pylori eradication therapy. To detect t(11;18) on paraffin-embedded tissue sections, we established a method of dual-color fluorescence in situ hybridization (D-FISH) using DNA probes directly labeled with SpectrumGreen and SpectrumOrange (tissue-FISH [T-FISH]). T-FISH detected the t(11;18) as colocalized signals between the band-specific yeast artificial chromosome (YAC) clones y966e4 (11q21) and y943b8 (18q21) on the der(11)t(11;18). The t(11;18) was detected in four of 22 patients with marginal zone lymphoma of MALT type in 72%-78% of the cells. In both patients studied, the percentage of t(11;18)-positive cells was much higher in tissue-FISH analysis than in interphase-FISH: 74% versus 30% in patient 1 and 75% versus 31% in patient 4. None of the 12 patients with diffuse large B-cell lymphoma of the stomach showed the t(11;18). Tissue-FISH is a powerful tool for the diagnosis of marginal zone lymphoma of MALT type because it can be applied not only to small specimens obtained from endoscopic biopsy samples but also to archival materials, hence facilitating the delineation of subtypes in marginal zone lymphoma of MALT type.

Adult↗

PubMed2003

Genotype, serotype, and phylogenetic characterization of the complete genome sequence of hepatitis B virus isolates from Malawian chronic carriers of the virus.

Hepatitis B virus (HBV) genotypes have distinct geographical distribution. HBV sequences among hepatitis B carriers in Malawi have not been evaluated thus far. HBsAg serotype and genotype of HBV was determined in 20 serum samples from Malawian chronic HBV carriers, and two complete genomes and 13 entire pre-S2/S genes were sequenced directly. Genotype A HBV isolates were found in all of the samples, and serotype with adw2 and ayw2 were detected in three and 17 samples, respectively. In phylogenetic analyses, two complete genomes were classified into a subgroup A' that was described previously in South African isolates of the virus, and were separated from HBV isolates in Western countries with nucleotide differences ranging from 4.1-6.2%. The separation of subgroup A' was also evident in the tree topology of the entire pre-S1/S2, X and precore/core region, but not evident in the small-S region. The nucleotide divergences in subgroup A' were higher than those among genotype A without subgroup A' in the complete genomes as well as each of four open reading frames. All of the 13 pre-S2/S sequences were classified into the subgroup A', and clustered with known HBV isolates with ayw2 in carriers from South Africa and Zimbabwe. Three amino acids in the pre-S2/S gene were characteristic of subgroup A' with ayw2. In conclusion, unique HBV isolates of subgroup A' with ayw2 are prevalent in Malawi, and subgroup A' with a relatively higher nucleotide diversity may be a HBV isolate characteristic of the indigenous population of some African countries.

Antibodies, Monoclonal↗

PubMed2003

Distribution of hepatitis B virus (HBV) genotypes among HBV carriers in the Cote d'Ivoire: complete genome sequence and phylogenetic relatedness of HBV genotype E.

The characteristics of hepatitis B virus (HBV) genotype E are not well known because only a few studies have been carried out by complete genome analysis. The aim of this study was to elucidate the distribution of HBV genotypes in Cote d'Ivoire, and to clarify the genotype-related characteristics of genotype E. The distribution of HBV genotypes among 48 HBV carriers in Cote d'Ivoire was determined using serological and genetic methods. The characteristics of genotype E were evaluated by complete genome sequences, and further investigations of small S gene, basic core promoter (BCP) mutation, and precore mutation were undertaken. HBV genotype distribution among the 48 carriers was 6.3% for genotype A, 6.3% for genotype D, and 87.4% for genotype E. Complete genomes of two genotype E strains were sequenced, and found to have 98.2% to 99.2% homology at the nucleotide level when compared with genotype E strains reported previously. In 24 genotype E carriers, the precore mutation was detected in 75% of the patients without HBeAg, in contrast to only 25% of the patients with HBeAg (P < 0.05). All 24 strains have T at nucleotide 1858 in the precore region. In contrast, BCP double mutation was detected in 17% of the patients with HBeAg, and 33% of the patients without HBeAg. These results indicated as the following: (1) genotypes A, D, and E of HBV exist in Cote d'Ivoire and genotype E is the most prevalent; (2) genotype E spread with low genetic diversity over the complete genome in West Africa; (3) HBV precore and/or BCP double variants were common among the patients with genotype E infections.

Amino Acid Sequence↗

PubMed2003

Influence of hepatitis B virus genotypes on the development of preS deletions and advanced liver disease.

Hepatitis B virus (HBV) mutants with deletions in the preS region have not been evaluated for association with viral genotypes. In a case-control study, HBV DNA samples collected from 80 each of carriers infected with HBV genotype B or C were examined for preS deletions. PreS deletion mutants were found in a total of 37 of 160 (23%) HBV carriers. Carriers with preS deletion mutants were older (56.0 +/- 12.7 vs 49.3 +/- 16.9 years, P < 0.05), were infected more frequently with HBV genotype C (84% vs 40%, P < 0.05), and had more advanced disease, such as liver cirrhosis and hepatocellular carcinoma (54% vs 31%; P < 0.05), than did those without such mutants. In a multivariate analysis, genotype C (odds ratio [OR] = 9.3, P < 0.001) and advanced liver disease (OR = 3.1, P < 0.01) were the most significant variables in association with preS deletions. A direct repeat sequence (TCAGG) was found at the start or at the end of preS1 deletions in 6 of the 20 (30%) cases examined, and preS2 deletions in these cases were clustered over the 5'-terminal half of this region. These results indicate that the development of preS deletion mutants depends on HBV genotypes and that it may be associated with progressive liver disease.

Adult↗

PubMed2003

Loss of hepatitis C virus RNA after parturition in female patients with chronic HCV infection.

It is unclear whether pregnancy has any influence on chronic hepatitis C virus (HCV) infection. The aim of this study was to investigate the relationship between pregnancy and parturition with HCV viremia levels and the natural resolution of HCV RNA. Twenty-two pregnant patients and 120 nonpregnant control female patients, both positive for anti-HCV and HCV RNA, were studied. The HCV core protein levels were quantified by enzyme immunoassay, and HCV RNA was detected by reverse transcription-polymerase chain reaction (RT-PCR). Of the pregnant group, two females whose HCV RNA was negative continuously for more than 6 months lost HCV RNA permanently after parturition, and one female whose level of HCV core protein was intermittently under the limit of detection level lost HCV RNA intermittently. In the control group, only one female lost HCV RNA persistently, and one lost HCV RNA intermittently after she developed liver cirrhosis. At 3 months after parturition, the HCV core protein level was <15 fmol/L in all patients who lost HCV RNA, while the HCV core protein level was >/=15 fmol/L in 81.3% of the patients who persistently had HCV RNA (P = 0.03). Significantly more pregnant patients lost HCV RNA than did nonpregnant controls. These findings suggest that pregnancy and parturition appear to influence the clinical course of HCV infection.

Adult↗

PubMed2003

Multistep tumorigenesis of multiple myeloma: its molecular delineation.

Multiple myeloma (MM) is an incurable malignant neoplasm affecting terminally differentiated B-cells. It derives from post-germinal center B-cells and develops as a result of multistep tumorigenic events, because approximately one third of all MM cases have a history of preceding monoclonal gammopathy of undetermined significance (MGUS) or smoldering myeloma. MM terminates in the formation of extramedullary invasion or in secondary plasma cell leukemia. To account for this clinical experience, investigators have found that intrinsic chromosomal instability followed by complex chromosomal translocations/deletions plays a crucial role in the development from MGUS to MM. Representative aberrations include chromosomal rearrangements involving 14q32 loci and deletion at the long arm of chromosome 13. Contributing to the progression of MM itself are genomic instability and altered methylation of the specific gene promoters. The former results in activation of specific oncogenes such as RAS and FGFR3 or in inactivation of p53, and the latter results in inactivation of tumor suppressor genes, including p16. An accurate understanding of each of these molecular events should help clarify the development of specific molecular targeting therapies based on the differences in dysfunctional signaling pathways found in the cells of all MM patients.

Cell Transformation, Neoplastic↗

PubMed2003

T-cell acute lymphoblastic leukemia as a secondary leukemia after a 3-year remission of acute myelocytic leukemia.

Therapy-related myelodysplastic syndrome and therapy-related acute myelocytic leukemia (AML) are now recognized as hematologic malignancies that occur a few years after chemotherapy for primary malignancy with alkylating agents or topoisomerase II inhibitors. The secondary leukemia is usually AML and sometimes is preceded by a myelodysplastic syndrome. Acute lymphoblastic leukemia (ALL) as a secondary leukemia is quite rare, and secondary T-cell ALL after AML is even rarer. We report a case of a 56-year-old woman who developed T-cell ALL after a 3-year remission of AML (M2). We thought that this case would be extremely valuable for studying the etiology and biological characteristics of T-cell ALL as a secondary leukemia after AML.

Chromosomes, Human, Pair 14↗

PubMed2003

Autonomic dysfunctions in dementia with Lewy bodies.

Twenty-nine cases of both clinically and neuropathologically diagnosed dementia with Lewy bodies (DLB) were retrospectively examined for autonomic symptoms. Twenty-eight cases showed some kind of autonomic dysfunction. Urinary incontinence (97 %) and constipation (83 %) were the two most common. Although urinary retention and episodic hypotension causing syncopal attacks were less common, the frequency was still high (28 % each). There were 18 cases (62 %) with severe autonomic failure. These 28 cases showed similar tendencies, with no significant differences between the subtypes of DLB (brainstem, limbic, and neocortical types or common and pure forms). We found that DLB of all pathological subtypes exhibits some kind and level of autonomic symptoms.

Aged↗

PubMed2003

API2-MALT1 fusion defines a distinctive clinicopathologic subtype in pulmonary extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue.

t(11;18)(q21;q21) is associated with mucosa-associated lymphoid tissue (MALT)-type lymphoma and results in API2-MALT1 fusion. However, its clinicopathologic significance remains unclarified. API2-MALT1 fusion is detected most frequently in MALT lymphomas primarily involving the lung. We therefore screened 51 cases of pulmonary MALT lymphoma for API2-MALT1 fusion, and studied its relationship with clinicopathologic factors including the immunohistochemical expression of BCL10, another MALT lymphoma-associated molecule. The API2-MALT1 fusion transcript was detected in 21 of 51 (41%) cases, and was correlated with the absence of any underlying autoimmune disease, and with a normal serum lactate dehydrogenase, a "typical" histology without marked plasmacytic differentiation or an increased number of large cells, and aberrant nuclear BCL10 expression. However, its prognostic impact was not identified in the limited follow-up (6 to 187 months, median 27). These data suggest that the API2-MALT1 fusion may be a causative gene abnormality unrelated to autoimmune disease. In addition, this alteration may define a homogeneous MALT lymphoma subtype that is clinically more indolent and histologically more "typical." Aberrant nuclear BCL10 expression may have a possible role as a tool to screen for this API2-MALT1 fusion. A large-scale study with a long follow-up is necessary to establish the prognostic significance of API2-MALT1 fusion.

Adult↗

PubMed2003

Potential limitations in using minor histocompatibility antigen-specific cytotoxic T cells for targeting solid tumor cells.

We have shown previously that KIAA0223, a gene encoding a minor histocompatibility antigen, HA-1, whose expression was believed to be restricted to the hematopoietic cells, is aberrantly expressed in some solid tumor cell lines. However, its significance in tumor immunity needs to be determined. Cytotoxic activity of HA-1(H)-specific cytotoxic T lymphocytes (CTLs) was assessed against solid tumor cell lines expressing KIAA0223 using (51)Cr release assays. Five of seven cell lines were lysed when HLA-A*0201 was adequately expressed. One of the two CTL-resistant cell lines became susceptible after treatment with IFN-gamma and TNF-alpha, while the other was lysed only after pulsing with HA-1(H) peptide. In most cell lines tested, HA-1(H) peptide was properly generated and presented for recognition by the CTL. However, impaired antigen processing and presentation observed in this study may result in escape from CTL recognition in vivo, as well as in vitro, as observed in this study.

Gene Expression Regulation, Neoplastic↗

PubMed2003

Radioimmunoscintigraphy of intracranial glioma xenograft with a technetium-99m-labeled mouse monoclonal antibody specifically recognizing type III mutant epidermal growth factor receptor.

The type III mutant epidermal growth factor receptor (EGFR) is expressed on the cell surface of a subset of glioma, but not of normal tissues. In this study, we investigated the in vivo kinetics of 3C10 mouse monoclonal antibody (mAb), specifically recognizing the type III mutant EGFR (EGFRvIII), using athymic nude mice bearing the intracranial glioma xenograft overexpressing the EGFRvIII. Human glioma cell line, U87MG, expressing the wild type EGFR and the transfectant, named U87MG x deltaEGFR, expressing the EGFRvIII, were transplanted subcutaneously or intracranially to nude mice. 3C10 mAb labeled with a technetium-99m (99mTc) was intravenously injected into these nude mice and then the mice were sacrificed at 24 h later, and the 99mTc-uptake by xenografts and major normal organs was measured to determine the biodistribution of mAb. Furthermore, at 3, 6 and 24 h after injection of 99mTc-labeled 3C10 mAb, whole-body scintigraphy was obtained with a gamma camera to localize the tumor site. 3C10 mAb significantly accumulated to U87MG x deltaEGFR xenografts transplanted subcutaneously or intracranially in nude mice, showing high tumor-to-blood ratio of 10.30 and 4.01, respectively. In contrast, uptake of control antibody in the intracranial tumor was as low as 0.43. In scintigrams, intracranially transplanted U87MG x deltaEGFR xenografts were detectable at 3 h after injection of 99mTc-labeled 3C10 mAb. These results suggest that intravenously injected 3C10 mAb specifically accumulated to the subcutaneous or intracranial glioma xenograft expressing the EGFRvIII and 3C10 mAb is a potential diagnostic and therapeutic agent for patients with gliomas expressing the EGFRvIII.

Animals↗

PubMed2003

Transforming growth factor-beta-1 genetic polymorphism in Japanese patients with chronic hepatitis C virus infection.

BACKGROUND AND AIM: Transforming growth factor beta-1 (TGF-beta1) is one of the most dominant fibrogenic cytokines in hepatic fibrosis. The aim of the present study was to examine the effects of TGF-beta1 polymorphisms in Japanese patients with chronic hepatitis C virus (HCV) infection and in healthy control subjects. METHODS: The TGF-beta1 genotypes at codon 10 and codon 25 were determined in 206 Japanese patients with chronic HCV infection and in 101 Japanese healthy control subjects. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used for the detection of these polymorphisms. The degree of hepatic fibrosis was assessed by liver biopsy and graded according to the New Inuyama Classification for chronic hepatitis graded F0-4. RESULTS: The authors found no significant differences in genotype distributions and allele frequency between the HCV patients and the healthy control subjects. The frequencies of the TT, TC, and CC genotypes of codon 10 were 24%, 42% and 35%, respectively, among the patients of the F0-2 group, and 31%, 40% and 29%, respectively, among those of the F3-4 group. No significant differences were shown between the TGF-beta1 polymorphism at codon 10 and the stage of hepatic fibrosis. In contrast, no genetic alteration of codon 25 was found in healthy controls and patients with chronic HCV infection. CONCLUSION: These results suggest that there may not be a significant relationship between polymorphism at codon 10 and the development of progressive hepatic fibrosis in the Japanese population.

Codon↗

PubMed2003

Evaluation of loss of heterozygosity before and after interferon therapy in patients with hepatitis C virus infection who developed hepatocellular carcinoma during follow up.

BACKGROUND AND AIM: The aim of the present study was to determine whether evaluating the status of loss of heterozygosity (LOH) before interferon (IFN) therapy is predictive for development of hepatocellular carcinoma (HCC) in chronic hepatitis and liver cirrhosis patients. METHODS: Eighteen patients with hepatitis C virus were studied, nine of whom developed HCC (HCC group) after IFN therapy and nine whom did not (non-HCC group). Samples before IFN therapy from both groups (pre-IFN-N and pre-IFN-H samples from the non-HCC and HCC groups, respectively) were analyzed for LOH using 12 microsatellite markers. To evaluate the LOH incidence in different steps in HCC patients, paired samples of cancerous tissue (CT) and adjacent non-CT (ANCT) obtained from the HCC group were also analyzed. RESULTS: Frequency of LOH in the pre-IFN-H samples was significantly higher than that in the pre-IFN-N samples regardless of the response to IFN therapy. Interestingly, in the HCC group, there is no significant difference in the frequency of LOH among the pre-IFN-H, ANCT and CT samples. CONCLUSIONS: The present results suggest the theory that genetic instability, such as LOH, had already accumulated at stages before the development of HCC. The authors propose that the status of LOH in chronic hepatitis and liver cirrhosis patients before IFN therapy could be a potential predictor for the development of HCC.

Adult↗

PubMed2003

Further investigation of the epitope recognized by the new monoclonal antibody 2C9.

OBJECTIVE: We established a new monoclonal antibody (2C9) that reacted with prostate tissue. The immunohistochemical reactivity of this antibody is similar to anti-prostate-specific membrane antigen (PSMA). Herein, we report the antigenic determinant of 2C9 antibody. METHODS: The reactivity of the antibody was characterized by immunohistochemical staining and the antigen target was characterized by amino acid sequencing after immuno-affinity purification from an LNCaP cell lysate and cloning of a cDNA using a mammalian expression cDNA cloning system. RESULTS: The amino acid and nucleotide sequences for the antigen molecule recognized with 2C9 monoclonal antibody demonstrated identity with PSMA. CONCLUSION: The target molecule of the 2C9 monoclonal antibody is PSMA, pointing to future diagnostic and therapeutic applications.

Amino Acid Sequence↗

PubMed2003

Epidemiologic and virologic characteristics of hepatitis B virus genotype B having the recombination with genotype C.

BACKGROUND & AIMS: Hepatitis B virus (HBV) isolates of genotype B (HBV/B) with or without the recombination with genotype C over the precore region plus core gene have been reported. METHODS: All the 41 HBV/B isolates having the recombination with genotype C (HBV/Ba) possessed the nucleotide 1838 of A in contrast to that of G in all 29 of those without the recombination (HBV/Bj). Taking advantage of this single nucleotide polymorphism, a restriction fragment length polymorphism method was developed that distinguished HBV/Ba from HBV/Bj. RESULTS: HBV/Bj was detected in 90 of the 97 (93%) carriers of HBV/B from Japan, whereas HBV/Ba occurred in all 177 carriers of HBV/B from other countries (China, 20; Hong Kong, 45; Taiwan, 32; Thailand, 30; Vietnam, 30; and the United States, 20 [all of an Asian ethnicity]). In a case-control study, hepatitis B e antigen (HBeAg) and the double mutation in the core promoter (T1762/A1764) were significantly more frequent in 80 carriers each of HBV/Ba than HBV/Bj (35% vs. 18%, P < 0.05 and 33% vs. 15%, P < 0.05, respectively). Differences in the prevalence of HBeAg were more conspicuous between the carriers of HBV/Bj and HBV/Ba older than 30 years (5 of 66 or 8% vs. 16 of 62 or 26%, P < 0.01). CONCLUSIONS: HBV/B having the recombination with genotype C is frequent in Asia, except in Japan, and HBeAg is more prevalent in carriers of HBV/Ba than HBV/Bj.

Adult↗