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Biomedical subjects

T Akagi

Publications and source records attributed to T Akagi.

At least 127 records · Page 7Linked to original sources
PubMed1997

Characterization of peripheral blood T-lymphocytes transduced with HTLV-I Tax mutants with different trans-activating phenotypes.

Tax1, a transcriptional trans-activator of the Human T-cell leukemia virus type I (HTLV-I), induces the expression of many cellular genes through interaction with at least three distinct cellular transcription factors; CREB/ATF, NF-kappaB, and SRF. This Tax1-induced activation of cellular genes is considered to be a critical event in T-cell transformation by HTLV-I. To elucidate the role of each Tax1-inducible transcriptional pathway in T-cell transformation, we introduced Tax1 mutants with different trans-activating phenotypes into peripheral blood lymphocytes (PBL) by retroviral vectors. Analysis of these PBLs revealed that activation of the NF-kappaB pathway is sufficient to promote the growth response to IL-2. However, for the clonal expansion of CD4+ T-cells, which is a characteristic result of HTLV-I infection, activation of the CREB/ATF and SRF pathways is also required.

CD4-Positive T-Lymphocytes↗
PubMed1997

Suppression of signalling through transcription factor NF-AT by interactions between calcineurin and Bcl-2.

It is not known how the protein Bcl-2 inhibits cell death induced by calcium signalling and growth-factor withdrawal. Here we report that Bcl-2 forms a tight complex with calcineurin, resulting in the targeting of calcineurin to Bcl-2 sites on cytoplasmic membranes, and show that this interaction is dependent on the BH4 domain of Bcl-2. Calcineurin bound to Bcl-2 is an active phosphatase but is unable to promote the nuclear translocation of NF-AT, a transcription-factor required for induction of interleukin-2 expression, suggesting a mechanism by which Bcl-2 suppresses NF-AT activity. We also show that Bax, a pro-apoptotic member of the Bcl-2 family, interferes with interactions between calcineurin and Bcl-2. We propose that the ability of Bcl-2 to block NF-AT signalling is due to the sequestering of active calcineurin to the same domain of Bcl-2 which associates with Rad-1 (ref. 5), and that calcineurin may act in Bcl-2-regulated functions.

Amino Acid Sequence↗
PubMed1997

Aberrant expression and function of p53 in T-cells immortalized by HTLV-I Tax1.

The expression and function of p53 tumor suppressor protein was investigated in T-cells immortalized by the Tax1 protein of HTLV-I. Conformationally wild-type p53 was expressed at elevated levels in Tax1-immortalized T-cells by post-transcriptional mechanisms when compared with normal T-cells. Luciferase assays with a reporter plasmid containing p53-binding sites revealed an impairment in the transactivating function of p53 in Tax1-immortalized T-cells. Our results suggest an important role for Tax1 in the aberrant expression and function of p53 observed in many HTLV-I transformed cells.

CD4-Positive T-Lymphocytes↗
PubMed1997

Expression of Fas ligand mRNA in germinal centres of the human tonsil.

Fas ligand (FasL), a cell surface molecule belonging to the tumour necrosis family, induces apoptosis through its receptor, Fas antigen (Fas). Germinal centre B cells strongly express Fas, but the role of the Fas-FasL system in B-cell selection in the germinal centre remains unclear. In the present study, FasL mRNA in the tonsils was examined by RNA in situ hybridization. FasL mRNA was detected in the lymphocytes of both germinal centres and interfollicular areas, but much more intensively in the former. The distribution of cells strongly expressing FasL mRNA in the germinal centres was quite similar to that of CD45RO-positive T cells. Immunohistochemically, however, most of the germinal centre cells were positive for FasL. Flow cytometric analysis demonstrated that FasL-positive cells of the tonsils included not only CD3-positive/CD45RO-positive T cells, but also CD19-positive B cells. This finding therefore suggests either that germinal centre B cells can produce FasL, although the level of mRNA was equivocal, or that the soluble form of FasL may be released from FasL-positive T cells in the germinal centres and then bind to Fas-positive germinal centre B cells. Thus, the Fas-FasL system may participate in the positive selection of B cells.

Antigens, Surface↗
PubMed1997

Coil occlusion of patent ductus arteriosus with detachable coils.

Twenty-five patients (mean age 7.0 +/- 4.8 years) underwent transcatheter coil occlusion of patent ductus arteriosus with detachable coils. The minimum diameter of the ductus arteriosus ranged from 1.0 to 4.2 mm (mean 2.6 +/- 0.9 mm). A single-coil technique was used in 17 patients, double- (six patients) or triple-coil (two patients) techniques were used in eight patients. The coil was not detached until sufficient shape and position of implanted coils were confirmed. All patients had successful implantation of coils regardless of the morphologic characteristics of the ductus. Immediately after the occlusion, heart murmurs were abolished in all patients. Color-flow mapping showed complete closure in 16 (64%) patients immediately after and 20 (80%) patients 1 month after the procedure. No significant complications occurred. The advantages of this detachable coil system may reduce coil migration and allow safer and more reliable execution of this procedure.

Adolescent↗
PubMed1997

Anti-CD53 monoclonal antibody induced LFA-1/ICAM-1-dependent and -independent lymphocyte homotypic cell aggregation.

CD53 is a pan-leukocyte glycoprotein and belongs to a member of the tetraspan family of cell membrane proteins. The predicted structure and functional characteristics of CD53 suggest that it may play important roles in transmembrane signaling, but its roles in cell adhesion have not been clarified. The present study shows that anti-CD53 monoclonal antibody (mAb), HI29 induced homotypic cell aggregation of lymphoid cell lines including a B cell line from a patient with leukocyte adhesion deficiency syndrome (LAD). The homotypic cell aggregation was blocked by another anti-CD53 mAb, MEM53, in all the examined cell lines and by anti-LFA-1 (CD11a/CD18) or anti-ICAM-1 (CD54) mAbs in the cell lines except for the LAD line, but it was not blocked by anti-CD44 or anti-CD49d mAb. The induced homotypic cell aggregation was energy-dependent. These findings suggest that CD53 relates to LFA-1/ICAM-1-dependent and -independent pathways of homotypic cell aggregation of lymphocytes and that it plays an important role in lymphocyte activation and cell adhesion.

Antibodies, Blocking↗
PubMed1997

Malignant lymphoma induction of rabbits with oral spray of Epstein-Barr virus-related herpesvirus from Si-IIA cells (HTLV-II-transformed Cynomolgus cell line): a possible animal model for Epstein-Barr virus infection and subsequent virus-related tumors in humans.

Malignant lymphoma (ML) was induced in eight of nine rabbits inoculated by oral spray of the cell-free pellets from Si-IIA culture (HTLV-II-transformed leukocyte cell line of the Cynomolgus-producing Epstein-Barr virus (EBV)-related herpesvirus) after 64-141 days. None of the rabbits inoculated with EBV from B-95-8 cells or HTLV-II from MOT cells developed ML. Malignant lymphomas were usually of diffuse, large-cell or mixed type. HTLV-II infection was excluded by the polymerase chain reaction (PCR) and the particle agglutination test. EBV-encoded RNA-1 and EBV-related DNA were detected in the tumor tissues by in situ hybridization and PCR, respectively. Anti-viral capsid antigen of EBV antibody (anti-VCA) was observed 3 weeks after oral inoculation of Si-IIA cell-free pellets. Polymerase chain reaction revealed continuous detection of EBV-related virus DNA in the peripheral blood leukocytes from 3 days after oral inoculation. These results show that ML induced orally with Si-IIA cell-free pellets was caused by EBV-related herpesvirus harbored by Si-IIA cells. Oral spray of EBV from B-95-8 also induced EBV infection in rabbits, which was confirmed both by the presence of anti-VCA and by PCR. These oral infection and malignant lymphoma induction systems of rabbit using EBV-related virus from Si-IIA or human EBV are useful animal models for the study of EBV infection and EBV-related lymphomas in humans.

Administration, Oral↗
PubMed1997

Evaluation of biological responses to polymeric biomaterials by RT-PCR analysis. II: Study of HSP 70 mRNA expression.

In order to investigate how cells recognize biomaterials, mRNA that was expressed in attached HeLa S3 cells on various substrates was evaluated. As culture substrates, cellulose, ethylene-vinyl alcohol copolymer (EVAL), nylon, tissue culture polystyrene (TCPS), high-density polyethylene (PE), silicone rubber, and tetrafluoroethylene-hexafluoropropylene copolymer (6F) were used. HeLa S3 cells were cultured on these substrates for 24 h. The expressed HSP 70s mRNA was then isolated and detected using the RT-PCR method. As a result, the expression of HSP 70B mRNA was largely induced in cells that adhered to hydrophilic surfaces. On the other hand, on hydrophobic surfaces, the HSP 70B mRNA expression was low. It is concluded that HSP 70B mRNA expression is sensitive to differences in the hydrophilicity-hydrophobicity of the substrates.

Biocompatible Materials↗
PubMed1997

Coil occlusion for patent ductus arteriosus in Japan.

We surveyed Japanese experience of coil occlusion of patent ductus arteriosus up to 30 September 1996 by sending questionnaires to 175 hospitals. Thirty-four hospitals reported outcome data for 231 procedures in 218 patients. Successful implantation was achieved in 94% and acute complete closure of the ductus occurred in 71% of those in whom implantation of the coil was successful. Of the latter, 83% reported late complete closure. When those patients who underwent reocclusion for residual shunt are included, 89% attained complete closure. No life-threatening complications have occurred so far. Late reopening was reported in 3 cases. Although the angiographic type of ductus was significantly related to successful implantation (p < 0.01), there was no significant correlation with complete occlusion. Ductuses with a minimum diameter greater than 3 mm had a decreased chance of successful implantation, whereas those less than 2 mm had a greater incidence of complete closure.

Child↗
PubMed1997

Analysis of the genome of an Epstein-Barr-virus (EBV)-related herpesvirus in a cynomolgus monkey cell line (Si-IIA).

A simian cell line, Si-IIA, harboring Epstein-Barr-virus (EBV)-related herpesvirus (Si-IIA-EBV), produces malignant lymphoma in rabbits when administered by intravenous inoculation. In this study, we analyzed the Si-IIA-EBV genome and compared it with human EBV and herpesvirus macaca fascicularis 1 (HVMF 1), which is associated with B-cell lymphoma developing in SIV-infected immunosuppressed monkeys. DNA from Si-IIA-EBV was amplified by the polymerase chain reaction using three different primer pairs complementary to human EBV (B95-8) DNA; two of the primer pairs covered part of the long internal repeat 1 region (IR 1) and the third covered part of the BRRF 1 region. Direct sequencing of the three PCR products revealed that Si-IIA-EBV DNA had about 82% nucleotide homology to the human EBV DNA in all three regions and 92.4% homology to HVMF1 in the IR1 region. The blotting pattern by Southern blot analysis was different between Si-IIA-EBV and human EBV.

Animals↗
PubMed1997

Malignant lymphoma induction in rabbits by oral inoculation of crude virus fraction prepared from Ts-B6 cells (cynomolgus B-lymphoblastoid cells harboring Epstein-Barr virus-related simian herpesvirus).

Malignant lymphoma was induced in Japanese (JWY), New Zealand (NZY) and Dutch (DUY) white rabbits by oral spray of cell-free pellets of culture fluid (crude virus fraction) of Ts-B6 cells (cynomolgus monkey B-lymphoblastoid cells harboring Epstein Barr virus-related simian herpesvirus or Cyno-EBV). Nine of 11 inoculated rabbits developed malignant lymphomas within 42-160 days after oral inoculation (JWY, 2/3; NZY, 5/6; DUY, 2/2). In contrast, none of the control rabbits inoculated in the same fashion with B95-8 (EBV-producing marmoset cell line) cell-free pellets developed malignant lymphoma. Most rabbits showed increased anti-VCA IgG and anti-EA-DR IgG antibody titers after inoculation by oral spray of Ts-B6 cell-free pellets. EBV-encoded RNA-1 was revealed in the tumor cells by in situ hybridization. EBV DNA was detected in the rabbit peripheral blood leukocytes (PBL) by polymerase chain reaction; the earliest positive result was obtained only two days after oral inoculation. These data suggest that orally administered Cyno-EBV in Ts-B6 cells infects PBL and then induces malignant lymphoma in rabbits. The availability of this animal model promises to clarify the role of EBV in human lymphoma and provides a means for studying prophylactic and therapeutic regimens.

Administration, Oral↗
PubMed1997

[Hematological characteristics of hypoplastic MDS patients with chromosomal abnormalities, who had been followed for aplastic anemia with normal karyotypes].

During 1990 to 1993, five patients who had been treated in our hospital for aplastic anemia (AA) with a normal karyotype, were found to have hypoplastic myelodysplastic syndromes (hMDS); three patients with RA, one RAEB, and one RAEB-T, and all of them have chromosomal abnormalities. The mean age of the hMDS patients (4 men, 1 woman) was 51.0 years (range 31-61). We retrospectively studied the hematological features of the 5 cases in the early stage without chromosomal abnormalities. They showed, 1) appearance of erythroblasts (3/5), 2) more reticulocyte counts than typical AA (mean 7.8 x 10(4)/microliter), 3) macrocytic anemia (mean MCV 106fl) in peripheral blood, 4) relative erythroid hyperplasia (M/E ratio 0.2-1.5), and 5) low lymphocyte counts (mean percentage of lymphocytes 32, 8%) in bone marrow. Considering about the differences or transformation between AA and hMDS, it is interesting that all five patients have initially had a normal karyotype and subsequently developed chromosomal abnormalities.

Adult↗
PubMed1996

Long-term consequences of Kawasaki disease. A 10- to 21-year follow-up study of 594 patients.

BACKGROUND: The long-term consequences of the cardiovascular sequelae in Kawasaki disease remain uncertain. METHODS AND RESULTS: We identified 594 consecutive children with acute Kawasaki disease between 1973 and 1983, and this cohort was followed up for 10 to 21 years (mean, 13.6 years). In all patients, we evaluated coronary lesions by coronary angiography just after the acute stage. One hundred and forty-six patients (24.6%) were diagnosed as having coronary aneurysms. A second angiogram was performed 1 to 2 years later in all 146 patients who previously had coronary aneurysms, which demonstrated that 72 (49.3%) of these 146 had regression in the coronary aneurysm. A third angiogram was performed for 62 patients, a fourth for 29, and a fifth for 17. By 10 to 21 years after the onset of the illness, stenosis in the coronary aneurysm had developed in 28 patients. Myocardial infarction occurred in 11 patients, 5 of whom died. In the 26 patients with giant coronary aneurysms, stenotic lesions developed in 12, and no regression occurred. The 448 patients with normal findings at the first angiogram subsequently never developed any abnormal cardiac findings. Systemic artery aneurysms developed in 13 patients (2.2%), and valvular heart disease appeared in 7 (1.2%). CONCLUSIONS: The incidence of coronary aneurysm in acute Kawasaki disease was 25%, 55% of which showed regression. During follow-up, ischemic heart disease developed in 4.7% and myocardial infarction in 1.9%. Death occurred in 0.8%.

Aneurysm↗
PubMed1996

Tyrosine kinase inhibitor herbimycin A reduces the stability of cyclin-dependent kinase Cdk6 protein in T-cells.

The Cdk6 protein level rapidly decreased after treatment with the tyrosine kinase inhibitor herbimycin A in human T-cell lines. This decrease is fairly specific, because the level of other Cdks such as Cdk2 and Cdk4 and cyclins such as cyclin D2, cyclin E and cyclin A, did not change significantly even after 24 h treatment with herbimycin A. Pulse-chase analysis revealed that the decrease in the Cdk6 protein level results from reduced stability of the protein. Our results suggest that herbimycin A-sensitive protein tyrosine kinase(s) are involved in the regulation of the Cdk6 protein level.

Animals↗
PubMed1996

Epstein-Barr virus infection in the neoplastic and nonneoplastic cells of lymphoid malignancies.

BACKGROUND: The Epstein-Barr virus (EBV) has been frequently detected in lymphoid malignancies. However, EBV infection in the nonneoplastic cells of lymphoid malignancies has not been extensively studied. METHODS: Four hundred nine cases of lymphoid malignancies including 377 non-Hodgkin's lymphoma (NHL) and 32 Hodgkin's disease (HD) were examined for EBV infection by EBER-1 in situ hybridization (EBER-ISH), immunostaining against LMP-1, Epstein-Barr nuclear antigen 2 (EBNA2) and ZEBRA, and Southern hybridization using a BamHIW fragment as a probe. Double staining with EBER-ISH and immunostaining against CD20, CD45RO, and LMP-1 was performed in selected cases. RESULTS: Although EBER-1-positive cells (EPCs) were detected in 49 of 276 B-cell lymphomas, 31 of 100 T-cell lymphomas, 1 of 1 natural killer-cell lymphoma, and 17 of 32 HDs, almost all of the tumor cells were exclusively EBER-1-positive in the 10 NHL cases. Some EPCs were of different cell lineages than the tumor cells in 15 of the 26 NHLs examined by double staining. LMP-1, EBNA2, and ZEBRA were detected in 22, 4, and 3 cases, respectively. In 4 LMP-1-positive HDs, double staining revealed that some EBER-1-positive Reed-Sternberg cells were negative for LMP-1, EBV genomic DNA was detected in 8 of the 39 examined cases. CONCLUSIONS: T-cell lymphomas contained EPCs more frequently than B-cell lymphomas. Nonneoplastic lymphocytes were infected with EBV more frequently than lymphoma cells. Rowe's latency II may be unstable in lymphoid malignancies. Some NHLs, especially T-cell lymphoma, may provide favorable conditions for EBV infection of nonneoplastic lymphocytes.

Antigens, Viral↗
PubMed1996

Expression of cell-cycle regulatory genes in HTLV-I infected T-cell lines: possible involvement of Tax1 in the altered expression of cyclin D2, p18Ink4 and p21Waf1/Cip1/Sdi1.

To understand how the growth of T-cells transformed by Human T-cell leukemia virus type I (HTLV-I) is deregulated, we analysed the expression of cell-cycle regulatory genes in HTLV-I infected and non-infected T-cell lines. We investigated the gene for 6 cyclins, 4 cyclin-dependent kinases, and 5 cyclin-dependent kinase inhibitors, and found the following: (1) HTLV-I infected T-cell lines preferentially expressed cyclin D2, whereas cyclin D3 was the major D-type cyclin in HTLV-I negative T-cell lines; (2) HTLV-I infected T-cell lines expressed strikingly low levels of p18Ink4 compared with those that were HTLV-I negative; (3) HTLV-I infected T-cell lines expressed high levels of p21Waf1/Cip1/Sdi1, whereas p21Waf1/Cip1/Sdi1 was undetectable in HTLV-I negative T-cell lines. These features were also found in T-cells immortalized by Tax1, which we established. Therefore, it is strongly suggested that Tax1 alters the expression of these cell-cycle regulatory genes.

Carrier Proteins↗