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Biomedical subjects

R Ueda

Publications and source records attributed to R Ueda.

At least 163 records · Page 9Linked to original sources
PubMed1997

Immunostaining of PRAD1/cyclin D1 protein as a marker for the diagnosis of mantle cell lymphoma.

The overexpression of PRAD1/cyclin D1 gene activated by the 11q13 translocation and its molecular counterpart BCL-1 rearrangement is frequently associated with mantle cell lymphomas (MCLs). Recently, we produced a monoclonal antibody, 5D4, against the PRAD1/cyclin D1 product, and demonstrated that the positive nuclear staining by this antibody correlates with PRAD1/cyclin D1 mRNA overexpression in MCLs. In the present study, we have immunohistochemically examined the cyclin D1 protein in a large series of 315 malignant lymphomas including 39 MCLs on paraffin sections. The nuclear positive pattern was found in 35 (90%) of 39 MCLs with an exceptional case of immunocytoma among the B-cell lymphomas examined. In the other cases, the positivity was absent or appeared to lie within the cytoplasm without nuclear staining. We therefore propose that the immunolocalization of cyclin D1 protein is an essential marker for the definite diagnosis of MCL.

Biomarkers, Tumor↗
PubMed1997

Distinct regulation of two hydroxysteroid sulfotransferases, ST2A1 and ST2A2, by growth hormone: a unique type of growth hormone regulation in rats.

In the present study, changes in the mRNAs of two major forms of hydroxysteroid sulfotransferases (STs), ST2A1 and ST2A2, have been determined in different growth hormone (GH) states. Hepatic ST2A1 mRNA was detected in both sexes of mature Sprague-Dawley rats. The level was 5 times higher in the females than in the males. ST2A1 mRNA was undetectable in GH-deficient animals, such as hypophysectomized rats and spontaneous dwarf rats. Continuous infusion of GH (mimicking the female secretory pattern) increased hepatic levels of ST2A1 mRNA in both GH-deficient animals. ST2A2 mRNA was detected only in the livers of mature female rats and in both sexes of GH-deficient animals. Intermittent injection of GH (mimicking male secretory pattern) strongly suppressed hepatic levels of ST2A2 mRNA in both GH-deficient animals. These results indicate that pituitary GH independently regulates both ST2A1 and ST2A2 at the pretranslational levels. These differences in GH responses between ST2A1 and ST2A2 are in good agreement with their female-dominant and female-specific modes of expression in normal rats. Furthermore, the present study demonstrates a unique response of ST2A2 to the secretory pattern of GH among the drug-metabolizing enzymes in rat livers, in which ST2A2 mRNA levels are suppressed by the male secretory pattern but not by the female secretory pattern of GH.

Animals↗
PubMed1997

[Human parvovirus B19 infection mimicking systemic lupus erythematosus: case report].

Human parvovirus B19 (HPV-B19) has been known as the etiologic agents of erythema infectiosum in normal childhood, and chronic anemia and thrombocytopenia in immuno-compromised patients. Recently, this virus has been reported as the association with rheumatic manifestation such as rheumatoid arthritis and systemic lupus erythematosus (SLE). We described here a patient whose HPV-B19 infection was mimiking atypical symptoms of SLE at diagnosis, and was persistent because of immuno-suppressive therapy for SLE. A 34-year-old female was admitted to our hospital on 22 June 1995, presenting fever episode and cervical lymph node swelling. Before eighteen months, she was received methyl-predonisolone pulse therapy and plasma exchange by fresh frozen plasma for the treatment of Stevens-Johnson syndrome, and after several weeks these therapy she was suffered from viral infection with lymphadenopathies with a transient appearance of atypical lymphocytes in her peripheral blood smear. On laboratory examination at the present admission, her peripheral blood showed anemia, thrombocytopenia with atypical lymphocytes. Throughout her hospitalization, anti-nuclear antibody (ANA) suspected SLE including anti-DNA and anti-Sm antibody were all negative except of transient week positive ANA screening test. Her physical condition presented poor clinical course with fever elevation, increased ascites and renal dysfunction showing the elevation of CRP and circulating immune-complex (Clq binding method). Her serum was positive for IgM and IgG antibody against VP-1 and VP-2 antigen of HPV-B19 by ELISA in April 1996. And then, HPV-B19 DNA by polymerase chain reaction (PCR) was positive in bone marrow sample in March 1996, and also positive in spleen necropsy at death. We confirmed persistent chronic HPV-B19 infection by measurement of HPV-B19 IgM and IgG antibody by ELISA and HPV-B19 DNA by PCR. The plasmapheresis and administration of intravenous immunoglobulin showed the possible efficacy for her symptom throughout this clinical course. Moreover, bone marrow smear showed the finding of virus-associated hemophagocytic syndrome, and finally, she was died of cervical hemorrhage accompanied with disseminated intravascular coagulation syndrome on July 1996. HPV-B19 infection can present an atypical clinical picture that is highly suggestive of SLE. We suggest that the therapy of steroids and immuno-suppressive agents should be cautious, because these may potentially cause persistent chronic HPV-B19 infection and induced life-threatening clinical course.

Adult↗
PubMed1996

Subcellular localization and protein interaction of the human LIMK2 gene expressing alternative transcripts with tissue-specific regulation.

In our efforts to explore possible roles of proteins with a LIM domain, which is a cysteine-rich Zinc-binding motif, in differentiation and oncogenesis in the lung, we have cloned a human LIMK2 gene and identified two alternative transcripts, LIMK2a and LIMK2b, which are probably due to variation in transcriptional initiation. The former encodes a protein containing two LIM domains, a PDZ domain, and a kinase domain, while the latter has only one and half LIM domains. The predominance of the two transcripts appears to be regulated in a tissue-specific manner. Alteration of the regulation is also observed in some cancer cell lines. Transfection studies have shown an association of 63-kDa and 58-kDa proteins with the LIMK2a and LIMK2b protein; the former is distributed in the cytoplasm and nucleus and the latter occurs mainly in the cytoplasm and is scarcely translocated to the nucleus. In contrast, a truncated LIMK2-Kinase has a nuclear location, not showing the protein association.

Alternative Splicing↗
PubMed1996

Fusion of the MLL gene with two different genes, AF-6 and AF-5alpha, by a complex translocation involving chromosomes 5, 6, 8 and 11 in infant leukemia.

We analysed a complex translocation involving chromosomes 5, 6, 8 and 11 in a case of infant leukemia. Molecular analysis of the MLL gene revealed that MLL was fused with two different genes, AF-6 on chromosome 6q27 and AF-5alpha. AF-5alpha, the 11th partner gene fused with MLL, is a novel gene mapped to chromosome 5q12, which encodes a 31 kDa protein of 269 amino acids and contains a possible nuclear targeting sequence, a potential leucine zipper dimerization motif and an alpha-helical coiled-coil domain. In situ hybridization and molecular cloning analyses demonstrated that two different types of chromosomal recombination had occurred in the cells. One was a three-way translocation among chromosomes 6, 8 and 11, and the other was an insertion of a chromosome 5-derived segment into the breakpoint of chromosomes 8 and 11. Accordingly, the karyotype was defined as del(5)(q11.2q12), der(6)t(6;8) (q27;q11.2), der(8)(8pter-->8q11.2::5q11.2-->5q12::11q23-->++ +11qter), der(11)t(6;11) (q27;q23). Thus, the MLL gene created two different fusion mRNAs, since the chromosome 11 split into two different chromosomes 5 and 6. This is the first report demonstrating fusion of the MLL gene with two different genes by a complex translocation.

Base Sequence↗
PubMed1996

Identification of MLL and chimeric MLL gene products involved in 11q23 translocation and possible mechanisms of leukemogenesis by MLL truncation.

11q23 chromosome aberrations are frequently observed in infantile as well as therapy-related leukemias. The target gene at 11q23, MLL, is disrupted by the translocation and becomes fused to various translocation partner genes such as AF4/FEL, LTG9/AF9 and LTG19/ENL. The resulting chimeric mRNAs are fused in frame and have been predicted to encode leukemia-specific chimeric proteins. In the present study, we raised antibodies against MLL, LTG9 and LTG19 and demonstrated that MLL and chimeric MLL-LTG9 and MLL-LTG19 products are synthesized in vivo and are localized in the nuclei, using immunofluorescence and cell fractionation studies. The truncated N-terminal portion of the MLL product common to the various types of 11q23 translocation was also localized in the nuclei in a similar fashion. Murine 32Dc13 cells stably expressing the truncated N-terminal MLL protein exhibited an inhibition of differentiation and a growth advantage following stimulation by granulocyte-colony stimulating factor, although the IL-3 dependency was not significantly changed in comparison to the parental cells. These results suggest that the N-terminal portion common to various MLL-chimeric products plays an important role in leukemogenesis.

Amino Acid Sequence↗
PubMed1996

The Drosophila tamou gene, a component of the activating pathway of extramacrochaetae expression, encodes a protein homologous to mammalian cell-cell junction-associated protein ZO-1.

In Drosophila sensory organ development, the balance of activities between proneural genes and repressor genes defines a proneural cluster as a population of competent cells for neural development. In this study, we report the isolation and analysis of the tamou (tam) gene that encodes a cell-cell junction-associated protein, which is homologous to mammalian ZO-1, a member of the membrane-associated guanylate kinase homolog family. The tam mutation reduces the transcription of a repressor gene, extramacrochaetae, and causes enlargement of a proneural cluster where supernumerary precursor cells emerge, resulting in extra mechanosensory organs in the fly. These results suggest that the membrane-associated Tam protein is involved in the signaling pathway that activates emc expression.

Amino Acid Sequence↗
PubMed1996

Inactivation of multiple tumor-suppressor genes involved in negative regulation of the cell cycle, MTS1/p16INK4A/CDKN2, MTS2/p15INK4B, p53, and Rb genes in primary lymphoid malignancies.

It is now evident that the cell cycle machinery has a variety of elements negatively regulating cell cycle progression. However, among these negative regulators in cell cycle control, only 4 have been shown to be consistently involved in the development of human cancers as tumor suppressors: Rb (Retinoblastoma susceptibility protein), p53, and two recently identified cyclin-dependent kinase inhibitors, p16INK4A/MTS1 and p15INK4B/MTS2. Because there are functional interrelations among these negative regulators in the cell cycle machinery, it is particularly interesting to investigate the multiplicity of inactivations of these tumor suppressors in human cancers, including leukemias/lymphomas. To address this point, we examined inactivations of these four genes in primary lymphoid malignancies by Southern blot and polymerase chain reaction-single-strand conformation polymorphism analyses. We also analyzed Rb protein expression by Western blot analysis. The p16INK4A and p15INK4B genes were homozygously deleted in 45 and 42 of 230 lymphoid tumor specimens, respectively. Inactivations of the Rb and p53 genes were 27 of 91 and 9 of 173 specimens, respectively. Forty-one (45.1%) of 91 samples examined for inactivations of all four tumor suppressors had one or more abnormalities of these four tumor-suppressor genes, indicating that dysregulation of cell cycle control is important for tumor development. Statistical analysis of interrelations among impairments of these four genes indicated that inactivations of the individual tumor-suppressor genes might occur almost independently. In some patients, disruptions of multiple tumor-suppressor genes occurred; 4 cases with p16INK4A, p15INK4B, and Rb inactivations; 2 cases with p16INK4A, p15INK4B, and p53 inactivations; and 1 case with Rb and p53 inactivations. It is suggested that disruptions of multiple tumor suppressors in a tumor cell confer an additional growth advantage on the tumor.

Adolescent↗
PubMed1996

Allelic-expression imbalance of the insulin-like growth factor 2 gene in hepatocellular carcinoma and underlying disease.

It has been well documented that the liver is an exceptional organ in which the monoallelic expression of insulin-like growth factor 2 (IGF2) due to genomic imprinting is relaxed during the postnatal period, resulting in biallelic expression thereafter. In the present study, changes in the status of genomic imprinting were examined in 15 hepatocellular carcinomas (HCCs) as well as in 29 liver biopsies of chronic hepatitis or liver cirrhosis without clinical evidence of HCC, following screening for heterozygotes with an ApaI polymorphism in IGF2 in 34 HCCs and 80 such non-HCC cases. Extreme allelic-expression imbalance, leading to restoration of monoallelic IGF2 expression, was observed in 15 (100%) of 15 informative HCCs for the polymorphism with this monoallelic IGF2 expression appearing to be non-random from the paternal allele. Interestingly, the same allelic-expression imbalance was also present in a significant fraction of noncancerous liver specimens of patients with underlying disease known to be associated with HCC development. In contrast, the status of genomic imprinting of H19, another gene closely mapped at 11p15 under opposite imprinting, was strictly maintained in seven (100%) of seven cases informative for an RsaI polymorphism of H19. Together with the previous reports on altered genomic imprinting of IGF2 and H19 in embryonal lesions such as Wilms tumors as well as in lung cancers, the results suggest that perturbations of imprinting status occur as locus and tumor-type specific events in the development of human cancers.

Alleles↗
PubMed1996

11q23 aberration is an additional chromosomal change in de novo acute leukemia after treatment with etoposide and mitoxantrone.

We report on 2 patients with acute leukemia who had an 11q23 chromosomal aberration as an additional change after treatment with etoposide and mitoxantrone, agents that affect topoisomerase II (Topo II). One patient with Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (L2) received chemotherapy, including 1,000 mg of etoposide and 75 mg of mitoxantrone. She relapsed 10 months later. Analysis at time of relapse showed a chromosomal aberration of del(11)(q23) as an additional cytogenetic change. The other patient was diagnosed with acute monoblastic leukemia (M5a) and received two autologous peripheral blood stem-cell transplantations. Her cumulative doses of etoposide and mitoxantrone were 6,000 mg and 42 mg, respectively. She also relapsed, and analysis at that time revealed del(11)(q23) as an additional chromosomal aberration. The mixed lineage leukemia/myeloid-lymphoid leukemia (MLL) gene was not rearranged in either case, making these cases distinct from previously described therapy-related leukemias caused by Topo II inhibitors. Based on these two cases, it may be that Topo II inhibitors can cause clonal evolution affecting chromosome band 11q23.

Adult↗
PubMed1996

Expression of CD10/neutral endopeptidase in normal and malignant tissues of the human stomach and colon.

The expression of common acute lymphoblastic leukemia antigen (CALLA; CD10), which is identical to neutral endopeptidase (NEP, EC3.424.11), was examined in the malignant and adjacent noninvaded tissues of the human stomach and colon (n = 27). All of 27 normal and 18 well or moderately differentiated adenocarcioma tissue specimens were positive for monoclonal antibody (mAb) NL-1 against CD10/NEP, whereas the expression level was clearly decreased in all of 9 specimens of poorly differentiated adenocarcinoma. In addition, all of 7 gastric or colorectal carcinoma cell lines tested showed decreased expression of CD10/NEP. Sodium dodecylsulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and Western blot analysis of the crude antigen J5 from the normal colon tissue lysate by mAb J5 detected a single band of approximately 100 kDa that was consistent with that of NALM-6 cells used as a positive control. These findings suggest that CD10/NEP is expressed in normal epithelial cells of the human stomach and colon, whereas the expression level is decreased in the poorly differentiated type of adenocarcinoma.

Adenocarcinoma↗
PubMed1996

Translocation (9;11;22)(p22;q23;q11). A new type of complex variant translocation of t(9;11)(p22;q23) with MLL rearrangement.

We describe a patient with acute monocytic leukemia (M5a, FAB classification) associated with a new type of variant translocation (9;11). Southern blot analysis showed the rearrangement of the MLL (ALL-1/HRX) gene at 11q23. Fluorescence in situ hybridization (FISH) with painting probes of chromosomes 9, 11, and 22 revealed the translocation as t(9;11;22) (p22;q23;q11). This is more evidence that the production of chimeric mRNA following the translocation of the LTG9 (MLLT3/AF9) gene at 9p22 to 11q is a critical event in this leukemia subtype.

Adult↗
PubMed1996

GB virus C/hepatitis G virus infection among Japanese patients with chronic liver diseases and blood donors.

Recently, a novel hepatitis virus, GB virus C/hepatitis G virus (GBV-C/HGV), has been isolated. To elucidate the seroprevalence of chronic GBV-C/HGV infection in Japan and the phylogenetic relationship between Japanese strains and the strains previously reported, serum GBV-C/HGV RNA was detected by reverse transcription polymerase chain reaction (RT-PCR) in 203 patients with chronic liver diseases and 200 samples of voluntary blood donors. RT-PCR was performed with primers derived from the 5'-untranslated region which were conserved between GBV-C and HGV and distant from other flaviviruses including hepatitis C virus (HCV). The nucleotide sequences were determined by the dideoxy chain termination method. The phylogenetic analysis was performed by the neighbor-joining method. In 10 (4.7%) of 203 patients with chronic liver diseases and in 1 (0.5%) of 200 blood donor samples, serum GBV-C/HGV RNA was detected. Of 10 patients, 9 patients were positive for anti-HCV and negative for HBsAg, and 1 patient was positive for HBsAg and negative for anti-HCV. The phylogenetic analysis indicated that there were three major groups which were group 1 (GBV-C), group 2 (HGV), and group 3 (a group of Japanese strains). These data indicated that (1) there was a low prevalence of GBV-C/HGV infection in Japanese patients with chronic liver diseases, (2) a high proportion of patients with GBV-C/HGV infection had chronic HCV infection however, and (3) there were at least three groups in strains of GBV-C/HGV.

Adult↗
PubMed1996

A novel human leukaemic cell line, CTS, has a t(6;11) chromosomal translocation and characteristics of pluripotent stem cells.

A novel human leukaemic cell line, designated CTS, was established from the peripheral blood of a 13-year-old girl suffering from acute myeloblastic leukaemia (AML) in relapse. CTS cells expressed CD7, CD13, CD33, CD34 and HLA-DR antigens, and showed ultrastructural myeloperoxidase activity. In addition, CTS cells showed DNA rearrangements of the immunoglobulin heavy chain gene and the light kappa chain gene, and deletions of the T-cell receptor delta 1 gene. Cytogenetic analysis revealed a human female diploid karyotype with a t(6;11)(q27;q23) chromosomal translocation. Molecular studies demonstrated a DNA rearrangement of the MLL gene, the expression of a truncated 11.0 kb MLL mRNA and the detection of the MLL/AF-6 fusion transcript in CTS cells. To our knowledge, this cell line is the first report of a human leukaemic cell line with a t(6;11) chromosomal translocation. CTS cells showed no significant proliferative response to the cytokines, IL-2, IL-3, IL-6, IL-11, GM-CSF, G-CSF, EPO, SCF, but were induced to differentiate to the T-cell, B-cell, erythroid or megakaryocytic lineage in the presence of particular cytokines. This CTS cell line may provide a useful tool in the study of the oncogenesis of mixed lineage leukaemia with 11q23 abnormalities and for the analysis of growth and differentiation of pluripotent stem cells.

Adolescent↗
PubMed1996

Inconsistent association of Epstein-Barr virus with CD56 (NCAM)-positive angiocentric lymphoma occuring in sites other than the upper and lower respiratory tract.

We previously described nine cases of angiocentric lymphoma of a possible natural killer (NK)-cell lineage with a surface CD3-CD56+ phenotype occurring in sites other than the upper and lower respiratory tract. This study was performed to investigate the association of Epstein-Barr virus (EBV) with these lymphomas, using the polymerase chain reaction (PCR) for the presence of EBV-DNA, in situ hybridization (ISH) for EBV-encoded small RNAs (EBERs) and immunohistology for EBV-determined nuclear antigen-2 (EBNA-2) and latent membrane protein-1 (LMP-1) in paraffin sections. PCR and ISH produced almost identical results, and EBERs were identified in the nuclei of the lymphoma cells of three cases, two of which exhibited LMP-1 in the cytoplasm of tumour cells without EBNA-2 expression. Molecular genetic analysis revealed EBV to be incorporated into these three EBER-positive cases either clonally or biclonally. It was revealed by re-evaluation of their morphology with the established EBV status on each case that, in contrast to the rather variable and irregular cellular composition of the EBV-positive tumours, the EBV-negative tumours stood out because of their remarkably uniform 'blastoid' appearance, and could be grouped as blastic NK-cell lymphoma. The relationship of the EBV-positive cases with nasal NK-cell tumours has yet to be clarified.

Adult↗
PubMed1996

Effect of jinkoh-eremol and agarospirol from agarwood on the central nervous system in mice.

Agarwood (Jinkoh in Japanese), one of the Oriental medicines, is used as a sedative. The benzene extract of this medicine showed a prolonged effect on the hexobarbital-induced sleeping time, and hypothermic effects in terms of rectal temperature, a suppressive effect on acetic acid-writhing, and a reduction of the spontaneous motility in mice. By repeated fractionation, oral administration in mice, and pharmacological screening, the active principles, jinkoh-eremol and agarospirol, were obtained from the benzene extract. They also gave positive effects on the central nervous system by peritoneal and intracerebroventricular administration. They decreased both methamphetamine- and apomorphine-induced spontaneous motility. The level of homovanillic acid in the brain was increased by them, while the levels of monoamines and other metabolites were unchanged. Similar results were seen in chlorpromazine-administered mice. Therefore, jinkoh-eremol and agarospirol can be considered to be neuroleptic.

Animals↗
PubMed1996

Modification of chemo-radiosensitivity of a human lung cancer cell line by introduction of the glutathione S-transferase pi gene.

Recent studies have suggested that glutathione S-transferase pi (GST-pi) may play a role in determining tumor sensitivities to cytotoxic drugs. In order to better understand the role of this enzyme in chemo- and/or radioresistance of lung cancer cells, we examined whether introduction of GST-pi cDNA into a chemo- and radiosensitive lung cancer cell line altered its sensitivities to various chemotherapeutic agents and/or ionizing radiation, which are often used in the management of lung cancers. Modestly increased resistance of the GST-pi transfectants preferentially to sublethal damage caused by ionizing radiation as well as to adriamycin (ADM) was observed. In contrast, resistances to cisplatin (CDDP), etoposide (VP-16), irinotecan hydrochloride (CPT-11) and paclitaxel were virtually unaltered. These results suggest that GST-pi may not play a major role in chemo- and radioresistance of lung cancers, although it could afford selective and limited protection against ADM- and ionizing radiation-induced damage.

Antineoplastic Agents↗