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T Nosaka

Publications and source records attributed to T Nosaka.

At least 73 records · Page 4Linked to original sources
PubMed1991

Functional conversion from HIV-1 Rev to HTLV-1 Rex by mutation.

A nucleolar localizing rev gene mutant M10 of human immunodeficiency virus type 1 (HIV-1) lost a Rev function completely, instead, gained a Rex activity of human T cell leukemia virus type 1 (HTLV-1). The obtained compatibility between Rev M10 and Rex with their own nucleolar targeting signal (NOS) suggests a common molecular mechanism of their post-transcriptional regulation, despite no sequence similarities of both proteins and their responsive RNA elements, respectively.

Amino Acid Sequence↗
PubMed1991

The nucleolar localisation signal of the HTLV-I protein p27rex is important for stabilisation of IL-2 receptor alpha subunit mRNA by p27rex.

In this study we investigated the mechanism of stabilisation of IL-2 receptor alpha subunit mRNA by the HTLV-I protein p27rex. We tested the role of the nucleolar targetting signal in rex by introducing mutations. Three deletion mutants could not express rex protein in the nucleolus and although protein was still expressed in the nucleoplasm none of the mutants could stabilise IL-2R alpha mRNA. A substitution mutant could be expressed in the nucleolus and could also stabilise IL-2R alpha mRNA. The data show that the nucleolar targetting signal is crucial for stabilisation of IL-2R alpha mRNA by rex and raise the possibility that transport of mRNA from nucleus to cytoplasm can involve the nucleolus.

Animals↗
PubMed1991

Induction of c-fos and c-myc mRNA expression by immunoglobulin G from patients with Graves' disease in thyrotrophin-dependent rat thyroid cell line (FRTL5).

The present study was conducted to evaluate effects of autoantibodies in patients with Graves' disease on induction of c-fos and c-myc mRNA expression in rat thyroid cell line (FRTL5). IgG fractions were isolated from 11 patients with Graves' disease, and six healthy subjects, with protein A-Sepharose. FRTL5 cells which had been grown to subconfluency and deprived of TSH for a week were exposed to the IgG for an hour. Expression of c-fos and c-myc mRNAs was examined by the Northern blot method using nick-translated v-fos and c-myc probes. C-fos and c-myc transcripts were induced by IgGs from two patients with Graves' disease, which displayed much higher activities in assays for TSH binding inhibitor immunoglobulins, thyroid stimulating antibodies and thyroid growth-stimulating immunoglobulins, assessed by measuring inhibition of 125I-TSH binding to the TSH-receptor, cAMP production and 3H-thymidine incorporation in FRTL5 cells, respectively, compared with those in the remaining patients. The induction of c-fos and c-myc mRNAs by IgG from a patient with Graves' disease was suppressed by preincubation with IgGs from two patients with primary myxoedema who were known to have a blocking type TSH-receptor antibody. These data suggest that the binding of the antibodies to the TSH-receptor followed by cAMP production is related to the induction of c-fos and c-myc mRNAs and, thus, to the growth of FRTL5 cells. To our knowledge, this is the first report demonstrating that autoantibodies induce proto-oncogene mRNA expression.

Adolescent↗
PubMed1991

Effects of chimeric mutants of human immunodeficiency virus type 1 Rev and human T-cell leukemia virus type I Rex on nucleolar targeting signals.

Two chimeric mutant genes derived from rev of human immunodeficiency virus type 1 and rex of human T-cell leukemia virus type I were constructed to investigate the functions of the nucleolar-targeting signals (NOS) in Rev and Rex proteins. A chimeric Rex protein whose NOS region was substituted with the NOS of Rev was located predominantly in the cell nucleolus and functioned like the wild-type protein in the Rex assay system. However, a chimeric Rev with the NOS of Rex abolished Rev function despite its nucleolar localization. This nonfunctional nucleolar-targeting chimeric protein inhibited the function of both Rex and Rev. In the same experimental conditions, this mutant interfered with the localization of the functional Rex in the nucleolus.

Amino Acid Sequence↗
PubMed1990

Protein kinase inhibitor H-7 blocks accumulation of unspliced mRNA of human T-cell leukemia virus type I (HTLV-I).

Rex, the post-transcriptional regulator of human T-cell leukemia virus type I (HTLV-I), is known to induce accumulation of the unspliced viral gag-pol mRNA. Rex is a phosphoprotein found in the cell nucleolus, whose function may be regulated by its localization and phosphorylation. We have examined the role of phosphorylation on Rex function by using a protein kinase inhibitor, H-7 [1-(5-isoquinolinyl-sulfonyl)-2-methylpiperazine]. Treatment of an HTLV-I infected human T-cell line with H-7 blocked specifically accumulation of the unspliced gag-pol mRNA, resulting in the decreased Gag protein synthesis that corresponds with the decreased in vivo phosphorylation of Rex. In contrast, other viral and cellular products have not been influenced by the level of H-7 used. Therefore, the phosphorylation of Rex is required for the viral RNA partition of HTLV-I.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1990

HTLV-1 p27rex stabilizes human interleukin-2 receptor alpha chain mRNA.

Expression of the pX gene products (p40tax, p27rex and p21X-III) of human T cell leukemia virus type 1 (HTLV-1), which is known to be a causative agent of adult T cell lymphoma/leukemia, induces expression of the interleukin-2 receptor alpha chain (IL-2R alpha) on infected T cells. Comparison of IL-2R alpha promoter activities has revealed that the transcriptional activation of the promoter alone cannot explain the large numbers of IL-2R alpha expressed on HTLV-1 infected cells. We found that the rates of the IL-2R alpha mRNA degradation were greatly reduced in pX-positive cells as compared with pX-negative cells. Simultaneous transfection of the expression vector plasmid containing IL-2R alpha cDNA and similar plasmids containing various pX sequences showed that p27rex elongated the half life of IL-2R alpha mRNA. As p27rex did not affect the transport of the IL-2R alpha mRNA from nucleus to cytoplasm, prolongation of the IL-2R alpha mRNA half life by p27rex is ascribed to stabilization of the mRNA. Experiments using deletion mutants and chimeric constructs of the IL-2R alpha cDNA demonstrated that the coding sequence but not the 5' or 3' untranslated region of the IL-2R alpha mRNA sequence is responsible for its protection by p27rex.

Cell Line↗
PubMed1990

Genetic heterogeneity in blast crisis of chronic myelocytic leukemia.

Fourteen patients with lymphoid and mixed blast crisis (BC) of chronic myelocytic leukemia were studied by immunophenotyping and genotyping. Rearrangements of immunoglobulin heavy chain (IgH), T-cell receptor (TcR) gamma and TcR beta genes were detected in all 14, in nine and in four patients, respectively. Interestingly, more than two rearranged bands of IgH gene in three lymphoid BC and two rearranged bands with germ line band in 1 biphenotypic BC indicated the genetic heterogeneity of the blasts. Some blastic transformations are thought to occur at a more immature stage of hematopoietic differentiation than that indicated by the phenotype and genotype of BC cells.

Antigens, Differentiation↗
PubMed1990

Oncogenic transformation by the tax gene of human T-cell leukemia virus type I in vitro.

Human T-cell leukemia virus type I (HTLV-I) is a causative agent of adult T-cell leukemia (ATL). To elucidate the role of HTLV-I in leukemogenesis, we examined the biological activity of a defective HTLV-I provirus with the env-pX 3' long terminal repeat region cloned from leukemic cells of an ATL patient. Transfection experiments showed growth stimulation of NIH 3T3 cells--growing beyond the saturation density and growing in soft agar. Since the pX sequence is known to encode three proteins, Tax, Rex, and p21x, the biological activity of each pX gene was examined separately. The growth-stimulating activity was induced only by the tax gene in NIH 3T3 cells and Rat-1 cells. Furthermore, the tax gene induced tumorigenicity in nude mice when introduced into Rat-1 cells. Thus, a transcriptional transactivator gene of HTLV-I, tax, is clearly identified as a viral oncogene without a cellular homolog. The transforming activity of tax, possibly via a transcriptional deregulation of cell growth control, may play an important role in leukemogenesis of ATL in addition to its aberrant stimulation of the interleukin 2 system.

Animals↗
PubMed1990

Frequent expression of myeloid antigen (CD13) on immature T cells in culture.

Leukemic cells from 12 patients with lymphoblastic lymphoma (LBL) and T cell acute lymphoblastic leukemia (T-ALL) were studied to determine the inducibility of myeloid antigens in culture in the presence and absence of 12-O-tetradecanoylphorbol-13-acetate (TPA) in association with discrete phenotypic and genotypic analyses on these cells. The investigation revealed that leukemic cells corresponding to common or mature thymocytes were never induced to express any myeloid antigens, and showed rearrangements of T cell antigen receptor (TcR) beta and gamma chain genes. Concomitant examination on leukemic cells from mature T cell malignancies, including adult T cell leukemia (ATL), T cell chronic lymphocytic leukemia (T-CLL) and T cell non-Hodgkin's lymphoma (T-NHL), also failed to express myeloid antigens in culture. By contrast, one of the panmyeloid antigens, CD13 (MCS-2) antigen was induced on leukemic cells corresponding to early thymocytes in 5 out of 7 cases in TPA-added culture and in 3 cases even in TPA-free culture. All of these CD13 antigen inducible cases exhibited the germ line configurations of TcR beta and gamma chain genes except for one case of T-ALL with sole TcR gamma chain gene rearrangement. These findings suggest that primitive T cells, still not undergoing TcR gene rearrangements, retain the characteristics of multipotent progenitor cells to possess different lineage markers and are able to express myeloid antigen not exceptionally. Both phenotypically and genotypically immature thymocytes are considered to be less restricted in the differentiation pathway of hematopoietic cells committed to T cell lineage.

Antigens, Differentiation, Myelomonocytic↗
PubMed1989

Nucleolar targeting signal of human T-cell leukemia virus type I rex-encoded protein is essential for cytoplasmic accumulation of unspliced viral mRNA.

The posttranscriptional regulator (rex) of human T-cell leukemia virus type I is known to be located predominantly in the cell nucleolus and to induce the accumulation of gag and env viral mRNAs. The N-terminal 19 amino acids of rex-encoded protein (Rex) has been shown to be sufficient to direct hybrid proteins to the cell nucleolus. We have studied the function of the nucleolar targeting signal (NOS) of rex by using full-length proviral DNA and mutant rex expression plasmids. Partial deletions of the NOS sequence abolished the accumulation of unspliced cytoplasmic mRNA, although the gene products of rex mutants were found in the nucleoplasm. These results indicate that NOS sequence, or nucleolar localization of Rex, is essential for Rex function.

Animals↗
PubMed1989

Effects of exercise training on biochemical and biomechanical properties of rat aorta.

The authors studied the effect of prolonged physical exercise on the mechanical properties of rat aorta in relation to the amounts and qualities of arterial connective tissue fibrous proteins. Twelve male rats were divided into two groups: 6 sedentary rats (S) and 6 training rats (T), which were forced to swim from nine weeks to twenty-five weeks of age. The ultimate tensile stress and the ultimate tensile extension ratio of ring specimens at the descending thoracic aorta were larger in T than in S (192.3 +/- 47.9 g/mm2, mean +/- SD, vs 147.8 +/- 26.0, p less than 0.05; 3.52 +/- 0.13 vs 3.18 +/- 0.27, p less than 0.05; respectively). The elasticity parameter, calculated by fitting stress-strain curves to exponential function in the stress level of 0-20 g/mm2, was lower in T than in S (1.79 +/- 0.15 vs 2.13 +/- 0.24, p less than 0.01). The contents of elastin (alkali-insoluble elastin preparation) and collagen were higher in T than in S (0.44 +/- 0.11 g/g dry aorta vs 0.30 +/- 0.06, p less than 0.05; 0.15 +/- 0.04 g/g dry aorta vs 0.11 +/- 0.04, NS, respectively). Although the aortic calcium content did not significantly change in the training rats (T 1.17 +/- 0.23 mg/g dry aorta, S 0.95 +/- 0.34), the content of calcium in elastin was lower in T than in S (1.75 +/- 0.51 mg/g dry elastin vs 2.63 +/- 1.00, p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acids↗
PubMed1989

A mechanism for cross-lineage gene rearrangements in B-cell neoplasm.

The organization of immunoglobulin heavy chain (IgH) gene of B precursor cell acute lymphoblastic leukemia (ALL) was examined in order to elucidate the mechanism causing simultaneous TCR gene rearrangements. Study using a 5'D probe lying 20 kb upstream of IgH D region genes was useful to distinguish diversity(D)-joining(J) recombination(DJ) from variable(V)-DJ recombination(VDJ). Indeed, IgH gene structures determined by 5'D study well correlated to those recognized by DJ or VDJ transcripts. IgH gene rearrangements of B precursor cell ALL showed developmentally restricted gene recombination; DJ/DJ genotype in the most immature stage and VDJ/VDJ genotype in the relatively mature stage. B precursor cell ALL with simultaneous rearrangements were frequently found in relatively mature cells, i.e., CD20 expressing cells on their surface. Furthermore, most of such dual genotypic ALL showed that at least one allele of IgH genes was VDJ recombination. This finding suggests that dual genotype was the incidental product by a putative common recombinase during the process of VH gene rearrangements. Moreover, since IgH gene rearrangements of acute unclassified leukemia with dual genotype were DQ52 genotype, which indicates abortive gene rearrangements, it was also thought that dual genotype occurred due to the pluripotentiality of the stem cell.

Burkitt Lymphoma↗
PubMed1989

Cross-lineage gene rearrangements in human leukemic B-precursor cells occur frequently with V-DJ rearrangements of IgH genes.

Gene configurations of immunoglobulin (Ig), T-cell antigen receptor (TCR) beta chain, and T-cell rearranging gene gamma (TRG gamma) were studied in human B-precursor lymphoblastic leukemic cells. These cells were phenotypically classified into three developmental stages (stages II through IV) according to Nadler's criteria. All of them showed the Ig heavy chain (IgH) gene rearrangement, and 67% of the cells in stage IV had the rearranged TRG gamma, albeit seldom in other stages. We further analyzed IgH gene rearrangements in detail using upstream to DH (diversity region of IgH) region probe to distinguish DJ from V-DJ recombination. All dual genotyped cells in each stage except one case in stage II showed the V-DJ rearrangements. This suggests the cross-lineage involvement of the putative recombinase, particularly in the process of V-DJ rearrangements. We next examined the transcriptional status of Ig genes as an indirect reflection of the accessibility of these genes to the recombinase. Properly spliced IgH transcripts of normal size were observed in stage IV and surface Ig positive stage, but not in stage II nor III. However, IgH transcripts of aberrant sizes were seen in stage II, III, and also IV. Cross-lineage gene rearrangements were shown to occur frequently when normally spliced IgH gene begins to be transcribed or just before this. These findings may implicate that V-DJ or V-VDJ gene rearrangements forming functional IgH genes, induce frequently TCR or TRG gene rearrangements. We propose these dual genotypes are different in origin from those observed in stem cell leukemia.

Antigens, Differentiation, B-Lymphocyte↗
PubMed1988

Fulminant clonal expansion of large granular lymphocytes. Characterization of their morphology, phenotype, genotype, and function.

A 39-year-old woman exhibited abrupt malignant transformation of the large granular lymphocytes (LGL) after a chronic course of T gamma-lymphoproliferative disease (T gamma-LPD). The T gamma-lymphocytes were CD2+, CD3-, CD8-, CD16+, Leu7-, and Leu19+ with morphologic characteristics of LGL. Newly appearing LGL were much larger and had more prominent azurophilic granules. Although fundamentally they had the same phenotype as the LGL in chronic stage, they showed increased Ia-like antigen and decreased CD16 antigen expressions. Immunoglobulin (Ig) G-kappa type monoclonal component was detected in the patient's serum. The LGL showed a germ-line configuration for T-cell receptor (TCR) beta and gamma chain genes, whereas the clonal chromosomal abnormalities indicated the neoplastic nature of the LGL. The LGL exhibited competent natural killer (NK), interleukin 2 (IL2) activated killer (AK), and antibody-dependent cell-mediated cytotoxicity (ADCC) activities. The LGL may have derived from NK cells at their mature stage with prethymic phenotype and may have influenced the homeostasis of the patient's humoral immune response.

Adult↗
PubMed1988

Sequence requirements for nucleolar localization of human T cell leukemia virus type I pX protein, which regulates viral RNA processing.

The posttranscriptional regulator (p27x-III) of human T cell leukemia virus type I (HTLV-I) is located predominantly in the cell nucleolus. A highly basic amino-terminal sequence (NH2-Met-Pro-Lys-Thr-Arg-Arg-Arg-Pro-Arg-Arg-Ser-Gln-Arg-Lys-Arg-Pro-Pro -Thr- Pro) in this protein, when fused to the amino termini of beta-galactosidase and p40x of HTLV-I, acts as an autonomous signal capable of directing the hybrid proteins to the cell nucleolus.

Amino Acid Sequence↗
PubMed1988

Two major subgroups of human T-cell leukemia virus-1 in Japan.

T lymphocytes of patients with human T-cell leukemia virus type 1 (HTLV-1)-associated myelopathy (HAM) were cultured. After cultivating for several months, HAM-derived cell lines were tested for the presence of HTLV-1 proviral genome. We have found two major subgroups, the SacI type and the PstI type, of HTLV-1 by the restriction map analysis. They were almost equally distributed among HAM patients. We have also found two types of the provirus in DNA derived from fresh peripheral blood lymphocytes (PBL) or lymph node cells of adult T-cell leukemia/lymphoma (ATL) patients. The PstI type proviruses were predominant in ATL patients. It was concluded that two major subgroups of HTLV-1 exist in Japan and both types have an ability to cause either of two diseases, ATL or HAM.

Cell Line↗