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Biomedical subjects

M Yasukawa

Publications and source records attributed to M Yasukawa.

At least 19 recordsLinked to original sources
PubMed1998

Neoplastic involvement of granulocytic lineage, not granulocytic-monocytic, monocytic, or erythrocytic lineage, in a patient with chronic neutrophilic leukemia.

Chronic neutrophilic leukemia (CNL) is a very rare myeloproliferative disorder. To determine the neoplastic origin of CNL, morphological and cytogenetical studies were made of colonies derived from hematopoietic progenitors of a patient with CNL. The patient's hematopoietic progenitors spontaneously formed colonies consisting of mature granulocytes, and cytogenetical study of the colonies indicated chromosome abnormalities identical to those in the patient's bone marrow cells. Analysis of colonies consisting of granulocytes and macrophages, macrophages, or erythrocytes disclosed a normal karyotype. These results demonstrated that the neoplastic process in this patient with CNL originated in hematopoietic progenitors capable of differentiating only into granulocytes, and not granulocytes and monocytes, monocytes, or erythrocytes.

Cell Lineage↗
PubMed1998

Deleted HTLV provirus in peripheral blood cells of a patient with T-cell prolymphocytic leukaemia.

We describe the first case of T-cell prolymphocytic leukaemia (T-PLL) in which the peripheral blood cells contained a human T-lymphotropic virus (HTLV) related tax sequence. Serum screening tests for anti-HTLV-I/II antibodies were negative. Polymerase chain reaction disclosed the presence of an HTLV-I tax sequence in the peripheral blood. Other sets of oligonucleotide primers for HTLV-I gag, pol, env and the long terminal repeat regions and for the HTLV-II pol region were negative in the DNA of the cells. Although patients with T-PLL have been reported to be seronegative for HTLV-I, our findings point to the possibility that HTLV-I infection might be involved in the aetiology of at least some cases of T-PLL and that there may be alternative mechanisms involved in HTLV-associated leukaemogenesis.

Base Sequence↗
PubMed1998

Apoptosis of CD4+ T lymphocytes in human herpesvirus-6 infection.

The present authors have recently reported that inoculation with human herpesvirus-6 (HHV-6) renders CD4+ T lymphocytes susceptible to apoptosis in vitro. In order to confirm that apoptosis of CD4+ T lymphocytes also occurs in HHV-6 infection in vivo, apoptosis of lymphocytes isolated from nine patients with exanthem subitum and from an adult patient with severe HHV-6 infection was examined. Peripheral blood mononuclear cells were cultured for 3 days and apoptosis of lymphocytes was then examined by flow cytometry of propidium iodide-stained DNA. The percentages of hypodiploid DNA, indicating apoptosis, in lymphocytes from 10 patients with HHV-6 infection were significantly higher than those from five infant patients with noninfectious diseases and five healthy adults (P < 0-0002). DNA fragmentation was also detected by agarose gel electrophoresis in lymphocytes from patients with HHV-6 infection. Apoptosis appeared to occur predominantly in CD4+ T lymphocytes and HHV-6 was isolated from the CD4+ T lymphocyte fraction. These data demonstrate that HHV-6 renders CD4+ T lymphocytes susceptible to apoptosis in vivo.

Adult↗
PubMed1998

[HHV-7 infection of CD4 gene-transduced cells].

It has been reported recently that CD4 is a major component of the receptor for human herpesvirus-7 (HHV-7), which has been newly identified as a T-lymphotropic virus. To investigate further the role of CD4 in HHV-7 infection, we examined the susceptibility to HHV-7 infection of various CD4-negative or weakly positive cell lines into which the cDNA for CD4 was transferred using an adenovirus vector. Out of 13 cell lines transduced with a CD4 gene, one T-lymphoid cell line, one monocytoid cell line, and two myeloid cell lines showed high susceptibility to HHV-7 infection. Taken together with previous studies, these data suggest strongly that CD4 is a major component of the binding receptor for HHV-7.

Adenoviridae↗
PubMed1997

Isolation of a T-cell clone showing HLA-DRB1*0405-restricted cytotoxicity for hematopoietic cells in a patient with aplastic anemia.

The existence of T cells capable of inhibiting in vitro hematopoiesis has been shown in aplastic anemia (AA), although whether such inhibition is mediated by a specific immune reaction involving an HLA allele remained unknown. We isolated a CD4+ Vbeta21+ T-cell clone that was most dominant among Vbeta21+ T cells in the bone marrow (BM) of an AA patient whose HLA-DRB1 alleles included 1501 and 0405. The T-cell clone named NT4.2 lysed an autologous Epstein-Barr virus-transformed lymphoblastoid cell line (LCL) and phytohemagglutinin-stimulated lymphocytes (PHA-blasts) as well as allogeneic LCLs sharing HLA-DRB1*0405. Cytotoxicity against LCL cells and PHA-blasts by NT4.2 was blocked by anti-HLA-DR monoclonal antibody (MoAb) or anti-CD3 MoAb. NT4.2 also lysed autologous BM mononuclear cells enriched with CD34+ cells that had been cultured for one week in the presence of colony-stimulating factors as well as allogeneic CD34+ cells of a normal individual carrying HLA-DRB1*0405, cultured in the same way. Moreover, NT4.2 strongly inhibited colony formation by hematopoietic progenitor cells derived from cultured CD34+ cells sharing HLA-DRB1*0405. These results indicate that the AA patient has T cells capable of killing hematopoietic cells in an HLA-DRB1*0405-restricted manner and that such cytotoxic T cells may contribute to the pathogenesis of AA.

Aged↗
PubMed1997

Membrane tumor necrosis factor-alpha (TNF-alpha) expressed on HTLV-I-infected T cells mediates a costimulatory signal for B cell activation--characterization of membrane TNF-alpha.

The 26-kDa membrane tumor necrosis factor-alpha (TNF-alpha) expressed on activated CD4(+) T cells is a novel candidate for the functional membrane molecule in T-B cell interactions. We found that normal human T cells, when infected with human T cell lymphotropic virus type I (HTLV-I) in vitro, were induced to express the 26-kDa membrane TNF-alpha. The infected T cells, through this molecule, activated autologous B cells to produce immunoglobulin (Ig)M in a contact-dependent manner, which was partially inhibited by anti-TNF-alpha antibody (Ab). IgG synthesis was not stimulated, however, probably because of lack of CD40 ligand expression on the infected T cells. Anti-TNF-alpha Ab treatment stimulated the secretion of interleukin (IL)-2 and interferon gamma (IFN-gamma) in the infected T cells. These effects were not induced by anti-TNF receptor Ab treatment. Anti-TNF-alpha Ab also induced the elevation of intracellular calcium concentration in the infected T cells. These results suggest that T cells expressing membrane TNF-alpha can be directly stimulated through this molecule. Thus, it is suggested that the 26-kDa membrane TNF-alpha on HTLV-I-infected T cells plays a role in polyclonal B cell activation and may be involved in the pathogenesis of some HTLV-I-associated diseases. Additionally, our results suggest a novel mechanism by which cytokine production can be modulated in these T cells through membrane TNF-alpha on their surface.

Antigen Presentation↗
PubMed1997

Sequential changes of urinary pyridinoline and deoxypyridinoline as markers of metastatic bone tumor in patients with prostate cancer: a preliminary study.

Urinary concentration of pyridinoline and deoxypyridinoline, novel markers of bone resorption, was measured serially in patients with prostate cancer as markers of metastatic bone tumor. In 11 patients, five without bone metastasis and six with bone metastasis, pyridinoline and deoxypyridinoline were serially monitored for between 6 and 24 months. All patients received some hormonal therapy with or without radical prostatectomy. Pyridinoline and deoxypyridinoline were measured by ion-paired high-performance liquid chromatography and were adjusted according to urinary creatinine concentration. The sequential changes of pyridinoline and deoxypyridinoline were compared with those of prostatic specific antigen and alkaline phosphatase as well as with the findings of bone scintigrams. During the observation periods, no metastatic bone lesion developed and no significant changes in pyridinoline and deoxypyridinoline occurred in the five patients without bone metastasis. In the six patients with bone metastasis, the levels of prostatic-specific antigen showed relatively rapid decreases after starting therapy. In contrast, the levels of pyridinoline, deoxypyridinoline and alkaline phosphatase showed transient increases followed by gradual decreases in most cases. Correlations were observed between the changes of pyridinoline and deoxypyridinoline and the findings of bone scintigrams. The data suggest that serial monitoring of pyridinoline and deoxypyridinoline could be clinically useful as markers of metastatic bone tumors and may allow less frequent bone scintigrams during patient followup.

Aged↗
PubMed1997

Human herpesvirus 7 infection of lymphoid and myeloid cell lines transduced with an adenovirus vector containing the CD4 gene.

It has been reported recently that CD4 is a major component of the receptor for human herpesvirus 7 (HHV-7), which has been newly identified as a T-lymphotropic virus. To investigate further the role of CD4 in HHV-7 infection, we examined the susceptibility to HHV-7 infection of various CD4-negative or weakly positive cell lines into which the cDNA for CD4 was transferred using an adenovirus vector (Adex1CACD4). Of 13 cell lines transduced with Adex1CACD4, including T-lymphoid, B-lymphoid, monocytoid, and myeloid cell lines, one T-lymphoid cell line, one monocytoid cell line, and two cell lines established from the blast crisis of chronic myelogenous leukemia showed high susceptibility to HHV-7 infection. Taken together with the results of previous studies, these data suggest strongly that CD4 is a major component of the binding receptor for HHV-7. This study also shows that HHV-7 may be able to infect CD4-positive hematopoietic precursor cells as well as T lymphocytes.

Adenoviridae↗
PubMed1997

Induction of T-cell apoptosis by human herpesvirus 6.

The mechanisms of cell death in CD4+ T cells mediated by human herpesvirus 6 (HHV-6) were investigated. The frequency of cell death in the human CD4+ T-cell line JJHAN, which had been inoculated with HHV-6 variant A or B, appeared to be augmented by tumor necrosis factor alpha (TNF-alpha). Agarose gel electrophoresis of DNA from HHV-6-inoculated cells showed DNA fragmentation in multiples of the oligonucleosome length unit. The degree of DNA fragmentation increased when HHV-6-inoculated cells were cultured in the presence of TNF-alpha. Flow cytometry and Scatchard analysis of TNF receptors revealed an increase in the number of the p55 form of TNF receptors on JJHAN cells after HHV-6 inoculation. It also appeared that treatment with anti-Fas monoclonal antibody (MAb) induced marked apoptosis in HHV-6-inoculated cells. Transmission electron microscopy showed characteristics of apoptosis, such as chromatin condensation and fragmentation of nuclei, but virus particles were hardly detected in apoptotic cells. Two-color flow cytometric analysis using anti-HHV-6 MAb and propidium iodide revealed that DNA fragmentation was present predominantly in uninfected cells but not in productively HHV-6-infected cells. In addition, JJHAN cells incubated with UV light-irradiated and ultracentrifuged culture supernatant of HHV-6-infected cells appeared to undergo apoptosis. The present study demonstrated that both HHV-6 variants A and B induce apoptosis in CD4+ T cells by indirect mechanisms, as reported recently in human immunodeficiency virus type 1 infection.

Apoptosis↗
PubMed1997

[Treatment of transfusion-associated graft-versus-host disease].

Transfusion-associated graft-versus-host disease (TA-GVHD) in immunocompetent patients is mediated by activated lymphocytes derived from the donor directed against host allogeneic HLA antigens. When considering this pathogenesis, the target of TA -GVHD treatment should be focused on the cytotoxic T cells (CTL) directed against host HLA. The combination therapy of anti-CD3 monoclonal antibody, OKT3, cyclosporin A, and corticosteroid may be effective to inhibit the cytotoxic activity of CTL. In addition to these immunosuppressive agents, monoclonal antibodies against functional cell surface molecules, such as LFA-1, ICAM-1, Fas, and Fas ligand, must be effective for treatment of TA-GVHD. Since the effective standard therapy of TA -GVHD has not been established, the prevention by gamma irradiation of cellular blood components is most important.

Adult↗
PubMed1997

[Clinical findings of neurogenic bladder in patients with Parkinson's disease, multiple sclerosis and spinocerebellar degeneration].

Clinical symptoms, urodynamic findings, and urological treatment of 35 patients with neurogenic bladder dysfunction caused by Parkinson's disease (11 patients), multiple sclerosis (10 patients), and spinocerebellar degeneration (14 patients) were reviewed retrospectively. Most of the patients had a relatively low stage of disease, when they were first seen by their urologists. Chief urological complaints were of irritation in 63.6% of Parkinson's disease and 64.3% of spinocerebellar degeneration cases, compared with obstruction in 80.0% of multiple sclerosis cases. Cystometry revealed underactive detrusor function in 69.2% of the patients with spinocerebellar degeneration but no abnormalities in the patients with Parkinson's disease or multiple sclerosis. Of 34 patients, excluding one patient lost to follow-up, the period of urological management ranged from one to 44 weeks with a mean of 11.0. The final methods of urinary drainage in 34 patients consisted of voluntary voiding in 20, clean intermittent catheterization in 11 including eight by self catheterization, incontinence into diaper in two, and indwelling catheter in one. Five patients were compelled to change urinary drainage method from voluntary voiding to clean intermittent catheterization because of increasing residual volume in four and progressing bladder deformity in one. However, none of them showed the clinical signs of primary disease progression. These findings indicate that in patients with Parkinson's disease, multiple sclerosis, and spinocerebellar degeneration, the urological symptoms can appear even in the early stage of disease. In addition, close follow-up is important in the urological management of neurogenic bladder patients with these diseases, because the disorders of the lower urinary tract may progress regardless of the status of the primary disease.

Activities of Daily Living↗
PubMed1996

SFA-2, a novel bZIP transcription factor induced by human T-cell leukemia virus type I, is highly expressed in mature lymphocytes.

A novel cellular gene, SFA-2, was isolated by differential hybridization of a cDNA library, using probes obtained from an adult T-cell leukemia cell line in comparison with normal CD4+ T cells and MOLT-4 cell line. The mRNA of the SFA-2 gene is approximately 0.9-kb in size and encodes a protein of 125 amino acids, containing a basic region-leucine zipper DNA-binding domain. The N-terminal region of SFA-2 is rich in serine and contains a consensus sequence for casein kinase II phosphorylation. The SFA-2 gene was strongly expressed in mature T and B lymphocytes, and was up-regulated after transformation by human T-cell leukemia virus type I. The SFA-2 did not homodimerize efficiently but formed heterodimer preferentially with c-Jun. The SFA-2/c-Jun heterodimer bound preferentially to the AP-1 and CRE sites.

Amino Acid Sequence↗
PubMed1996

Two distinct mechanisms of cytotoxicity mediated by herpes simplex virus-specific CD4+ human cytotoxic T cell clones.

The present study was undertaken to elucidate the mechanisms responsible for the cytotoxicity of herpes simplex virus (HSV)-specific CD4+ human cytotoxic T lymphocyte (CTL) clones, focusing on perforin and membrane-bound lymphotoxin (LT) (tumor necrosis factor-beta). Two HSV-specific CD4+ CTL clones, which expressed both perforin and membrane-bound LT, exerted HSV-specific cytotoxicity and cytotoxicity against LT-sensitive L929 cells. These CD4+ CTL clones lysed HSV-infected cells directly in an HLA class II-restricted manner and did not exhibit "bystander killing." The culture supernatants of these clones stimulated with HSV antigen showed no cytotoxicity against HSV-infected cells or L929 cells, suggesting that adhesion to target cells is essential to their antigen-specific and antigen-nonspecific cytotoxicities. The cytotoxicities of these clones against HSV-infected autologous cells were inhibited by an anti-CD3 monoclonal antibody but not by an anti-LT antibody. Conversely, their cytotoxicities against L929 cells appeared to be partially inhibited by the anti-LT antibody but not by the anti-CD3 monoclonal antibody. Furthermore, target cell DNA fragmentation induced by these CD4+ CTL clones was apparently observed in L929 cells but only faintly detected in HSV-infected autologous cells. L929 cell DNA fragmentation was also inhibited by adding the anti-LT antibody to CD4+ CTL cultures. These data suggest that some CD4+ CTL possess at least two cytolytic mediators, i.e., perforin and membrane-bound LT simultaneously, and can exert both antigen-specific cytotoxicity via two distinct mechanisms, necrosis and apoptosis.

Antibodies, Monoclonal↗
PubMed1996

Molecular cloning of a cDNA encoding enolase from the filamentous fungus, Aspergillus oryzae.

A 1.6-kbp full-length cDNA for the Aspergillus oryzae enolase gene (enoA) was cloned. The sequenced insert contained a continuous open reading frame of 1314 bp encoding a protein of molecular weight 47 405. Among all enolases sequenced to-date, the deduced amino-acid sequence showed the highest homology (74.9%) with Candida albicans enolase (ENO1). Strong codon biases and multiple transcription start sites downstream from CT-blocks in the 5'-flanking region suggested strong expression. enoA mRNA was found to occupy approximately 3% (w/w) of total mRNA of A. oryzae by quantitative RT-PCR. This strong transcription was dependent on the carbon source in the medium and correlated with the growth rate of the mycelium.

Amino Acid Sequence↗
PubMed1996

Diverse effects of tumor necrosis factor-alpha on three subclones from human myelomonocytic leukemia cell line ME-1 exhibiting different differentiation stages.

The effects of tumor necrosis factor-alpha (TNF-alpha) were examined in three subclone cells from human myelomonocytic leukemia cell line ME-1. These three subclone cells exhibit different differentiation stages of the myelomonocytic lineage. TNF-alpha exerted a growth-suppressive effect on the least mature subclone cells, ME-F2 cells. On the other hand, TNF-alpha induced the most mature ME-F1 cells and intermediate ME-F3 cells to differentiate along the monocytic pathway. TNF-alpha also enhanced interferon-gamma (IFN-gamma)-induced complement C2 production by ME-F1 and ME-F3 cells but did not affect production by differentiated ME-F1 and ME-F3 cells. These results suggest that the diversity of the effects of TNF on subclone cells from ME-1 depends on the stage of cell differentiation.

Cell Differentiation↗
PubMed1996

Human herpesvirus 7 infection of CD4+(+) T cells does not require expression of the OKT4 epitope.

To evaluate the role of the OKT4 epitope in human herpesvirus 7 (HHV-7) infection, we studied the susceptibility to HHV-7 infection of CD4+ T cells isolated from two individuals with OKT4 epitope deficiency. HHV-7-infected OKT4-Leu3a+ T cells exhibited the characteristic cytopathic effect, reactivity with HHV-7-seropositive serum by immunofluorescence and down-modulation of surface CD4 in a manner similar to HHV-7-infected OKT4+Leu3a+ T cells. A semiquantitative PCR revealed that the amounts of HHV-7 replicated in OKT4+Leu3a+ T cells and OKT4-Leu3a+ T cells were not significantly different. Although it has been reported that OKT4 monoclonal antibody efficiently inhibits HHV-7 infection, the present study demonstrated that the interaction of HHV-7 with CD4+ T cells does not require participation of the epitope defined by OKT4 monoclonal antibody.

Antibodies, Monoclonal↗
PubMed1996

Detection of human herpesvirus 6 and human herpesvirus 7 in the submandibular gland, parotid gland, and lip salivary gland by PCR.

In order to define the major sites of persistence of human herpesvirus 6 (HHV-6) and HHV-7, PCR with DNAs from more than 100 specimens of 3 different salivary glands was performed. HHV-6 DNA was detected in 52 (88.1%) of 59 submandibular gland, 17 (63.0%) of 27 parotid gland, and 9 (52.9%) of 17 lip salivary gland specimens. On the other hand, HHV-7 DNA was detected in 59 (100%) of 59 submandibular gland, 23 (85.2%) of 27 parotid gland, and 10 (58.8%) of 17 lip salivary gland specimens. These findings demonstrate that salivary glands are a site of persistent infection of both HHV-6 and HHV-7 and that among the three types of salivary gland examined, the submandibular gland is the primary one in which these herpesviruses, especially HHV-7, persist.

Herpesvirus 6, Human↗