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Biomedical subjects

H Moriuchi

Publications and source records attributed to H Moriuchi.

At least 37 records · Page 2Linked to original sources
PubMed2000

Class I-unrestricted noncytotoxic anti-HTLV-I activity of CD8(+) T cells.

Although it is widely believed that viral clearance is mediated principally by the destruction of infected cells by cytotoxic T cells, noncytolytic antiviral activity of CD8(+) T cells may play a role in preventing the progression to disease in infections with immunodeficiency viruses and hepatitis B virus. We demonstrate here that (1) replication of human T-lymphotropic virus type I (HTLV-I) is more readily detected from CD8(+) T-cell-depleted (CD8(-)) peripheral blood mononuclear cells (PBMCs) of healthy HTLV-I carriers than from unfractionated PBMCs, (2) cocultures of CD8(-) PBMCs with autologous or allogeneic CD8(+) T cells suppressed HTLV-I replication, and (3) CD8(+) T-cell anti-HTLV-I activity is not abrogated in trans-well cultures in which CD8(+) cells are separated from CD8(-) PBMCs by a permeable membrane filter. These results suggest that class I-unrestricted noncytolytic anti-HTLV-I activity is mediated, at least in part by a soluble factor(s), and may play a role in the pathogenesis of HTLV-I infection. (Blood. 2000;96:1994-1995)

Antiviral Agents↗
PubMed2000

Involvement of K(+) channel in procainamide-induced relaxation of bovine tracheal smooth muscle.

The relaxant effect of procainamide, a class Ia antiarrhythmic agent, was examined in bovine tracheal smooth muscle. Procainamide produced concentration-dependent decreases in tension and full relaxation in the preparations contracted with methacholine (0.3 microM). By comparison, in preparations contracted with 40 mM K(+), procainamide had only slight relaxant effects. The relaxant effects of cromakalim and salbutamol on 40 mM K(+)-contracted preparations were significantly (P<0.01) smaller than those on 0.3 microM methacholine-contracted ones. On the other hand, the concentration-response relationships for quinidine, lidocaine, mexiletine and propafenone were not so dramatically different between 0.3 microM methacholine- and 40 mM K(+)-contracted preparations. Tetraethylammonium (300 microM), iberiotoxin (30 nM) and Ba(2+) (1 mM) significantly (P<0.05) attenuated the relaxant effects of procainamide on methacholine-induced contractions, whereas apamin (100 nM), 4-aminopyridine (300 microM), and glibenclamide (10 microM) did not affect them. The inhibitory effect of a combination of iberiotoxin and Ba(2+) was greater than that of iberiotoxin or Ba(2+) alone (P<0.01). These results suggest that the activation of at least two types of K(+) (maxi-K(+) and inward rectifier K(+)) channels contributes to the procainamide-induced relaxation of bovine tracheal smooth muscle.

Albuterol↗
PubMed2000

In vitro reactivation of human immunodeficiency virus 1 from latently infected, resting CD4+ T cells after bacterial stimulation.

Microbial coinfections have been associated with transient bursts of human immunodeficiency virus (HIV) viremia in patients. In this study, we have investigated whether microbial coinfections can induce replication of HIV-1 in latently infected CD4(+) T cells derived from HIV-infected patients who are receiving highly active antiretroviral therapy and in whom plasma viremia is undetectable by sensitive assays. We demonstrate that supernatants from macrophages exposed to the bacterial product lipopolysaccharide can induce in vitro activation of HIV-1 from latently infected, resting CD4(+) T cells obtained from HIV-infected individuals. Depletion of proinflammatory cytokines from the supernatant markedly reduced-whereas depletion of ss chemokines increased--the ability of the supernatant to induce replication of HIV-1. Our results suggest that coinfection with microbial pathogens such as bacteria may induce viral replication in the latent viral reservoirs in vivo.

Anti-HIV Agents↗
PubMed2000

Y-27632 potentiates relaxant effects of beta 2-adrenoceptor agonists in bovine tracheal smooth muscle.

We examined how (+)-(R)-trans-4-(1-aminoethyl)-N-(4-pyridyl)cyclohexanecarboxamide (Y-27632), an inhibitor of Rho-associated coiled coil-forming protein kinase (ROCK I) and Rho kinase (ROCK II), affects the relaxant responses to beta(2)-adrenoceptor agonists in bovine tracheal smooth muscle preparations precontracted with methacholine. Y-27632 (0.3-30 microM) caused a concentration-dependent attenuation of precontraction with methacholine (0.3-3 microM). Pretreatment with Y-27632 (1 microM) significantly (P<0.05) augmented salbutamol (0.3-100 nM) and terbutaline (0.3 nM-1 microM)-induced relaxations. These results suggest that the ROCK inhibitor could become a new type bronchodilator and its combination with beta(2)-adrenoceptor agonists may become a novel strategy for the long-term treatment of asthma.

Adrenergic beta-Agonists↗
PubMed2000

Inefficient formation of a complex among CXCR4, CD4 and gp120 in U937 clones resistant to X4 gp120-gp41-mediated fusion.

Certain subclones (designated as minus clones) of the promonocytic U937 cell line do not support efficient infection and fusion mediated by T cell line adapted (TCLA) X4 HIV-1 gp120-gp41 (Env) although the CXCR4 and CD4 concentrations at their surfaces are similar to those at the surfaces of clones susceptible to HIV-1 entry (plus clones) (H. Moriuchi et al., J. Virol. 71, 9664-9671, 1997). To test the hypothesis that inefficient formation of gp120-CD4-CXCR4 complexes could contribute to the mechanism of resistance to Env-mediated fusion in the minus clones, we incubated plus and minus cells with HIV-1 LAI gp120 and coimmunoprecipitated CD4 by using anti-CXCR4 antibodies. The gp120 induced inefficient coimmunoprecipitation of CD4 in the minus clones but not in the plus ones. Overexpression of CD4 resulted in significant restoration of the minus clones' susceptibility to fusion in parallel with an increase in the amount of the gp120-CD4-CXCR4 complexes. These results not only suggest that the resistance to TCLA X4 HIV-1 entry in the U937 minus clones is due to the inability of these cells to efficiently form complexes among CD4, gp120, and CXCR4, but also provide a direct evidence for the correlation between fusion and the cell surface concentration of the complexes among CXCR4, CD4, and gp120. These data and similar recent observations in macrophages suggest that inefficient complex formation among CXCR4, CD4, and gp120 could be a general mechanism of cell resistance to gp120-gp41-mediated fusion and a major determinant of HIV-1 evolution in vivo.

CD4 Antigens↗
PubMed2000

Lidocaine potentiates the relaxant effects of cAMP-elevating agents in bovine tracheal smooth muscle.

The effect of lidocaine on the relaxation and accumulation of adenosine 3',5'-cyclic monophosphate (cAMP) induced by salbutamol, forskolin and 3-isobutyl-1-methylxanthine (IBMX) was examined in bovine tracheal smooth muscle preparations precontracted with methacholine (0.3 microM). Lidocaine attenuated the methacholine-induced contraction in a concentration-dependent manner. Pretreatment of the preparations with lidocaine (100 microM) caused significant leftwards shifts of concentration/response curves for the relaxant responses to salbutamol, forskolin, and IBMX, whereas it did not change the responses to diltiazem. Similar leftwards shifts were observed when the preparations were treated with procaine (6 microM) or bupivacaine (40 microM). Lidocaine (100 microM) augmented cAMP accumulation induced by salbutamol (10 nM) and forskolin (1 microM). These results suggest that lidocaine augments the relaxant responses to cAMP-elevating agents through enhancement of cAMP accumulation.

1-Methyl-3-isobutylxanthine↗
PubMed2000

Qualitative and quantitative characterization of Fas (CD95) expression and its role in primary human acute leukemia cells.

Fas antigen, a cell surface molecule, directly mediates apoptosis, and is expressed on a limited number of human tissues. Blood or bone marrow samples from patients with acute myelogenous leukemia (AML), acute lymphoblastic leukemia (ALL) and mixed leukemia were examined qualitatively and quantitatively for the expression of Fas as well as its function using flow cytometry and the annexin V staining method. Fas expression was flow cytometrically unimodal with heterogeneous density, and showed quantitatively characteristic features in different diseases: undetectable in mixed leukemia, faint to weak in ALL, low in M0 and M1, and variable (low to strong) in M2, M3, M4, and M5. Both the full-length and the alternatively spliced truncated mRNAs were detected constitutively even in acute leukemia cells with qualitatively negative and quantitatively faint Fas, and the band density of the former transcripts detected by RT-PCR was correlated with the level of expression of the Fas protein. Short-term culturing of freshly isolated leukemia cells gave rise to an increase of Fas density. In acute leukemia cells, the apoptosis induced by anti-Fas MoAb was compared with that induced by etoposide (a topoisomerase II inhibitor). We found that fresh ALL and AML cells were resistant to the anti-Fas IgM antibody, while etoposide could trigger apoptosis in all types of leukemia tested. The combined effects of the anti-Fas MoAb and etoposide were not always synergistic. These results suggest that Fas is a biological marker for characterizing ALL and AML cells, and provide insight into creating a new therapeutic modality using cytotoxic drugs and cytokines together with modulation of Fas.

Acute Disease↗
PubMed2000

Cathepsin G, a neutrophil-derived serine protease, increases susceptibility of macrophages to acute human immunodeficiency virus type 1 infection.

Neutrophils dominate acute inflammatory responses that generally evolve into chronic inflammatory reactions mediated by monocyte/macrophages and lymphocytes. The latter cell types also serve as major targets for human immunodeficiency virus type 1 (HIV-1). In this study we have investigated the role of neutrophil products, particularly cathepsin G, in HIV infection. Cathepsin G induced chemotaxis and production of proinflammatory cytokines by macrophages but not CD4(+) T cells. Pretreatment with cathepsin G markedly increased susceptibility of macrophages but not CD4(+) T cells to acute HIV-1 infection. When macrophages were exposed to pertussis toxin prior to cathepsin G treatment, the cathepsin G-mediated effect was almost abrogated, suggesting that enhancement of HIV-1 replication by cathepsin G requires Gi protein-mediated signal transduction. Although prolonged exposure to cathepsin G suppressed HIV infection of macrophages, serine protease inhibitors, which are exuded from the bloodstream later during inflammatory processes, neutralized the inhibitory effect. Neutrophil extracts or supernatants from neutrophil cultures, which contain cathepsin G, had effects similar to purified cathepsin G. Thus, cathepsin G, and possibly other neutrophil-derived serine proteases, may have multiple activities in HIV-1 infection of macrophages, including chemoattraction of monocyte/macrophages (HIV-1 targets) to inflamed tissue, activation of target cells, and increase in their susceptibility to acute HIV-1 infection.

CD4-Positive T-Lymphocytes↗
PubMed1999

Induction of HIV-1 replication by allogeneic stimulation.

Allogeneic stimulation presents an immunologic challenge during pregnancy, blood transfusions, and transplantations, and has been associated with reactivation of latently infected virus such as CMV. Since HIV-1 is transmitted vertically, sexually, or via contaminated blood, we have tested the effects of allostimulation on HIV-1 infection. 1) We show that allostimulated lymphocytes are highly susceptible to acute infection with T cell-tropic or dual-tropic HIV-1. 2) We show that allostimulation has dichotomous effects on replication of macrophage-tropic HIV-1; it activates HIV expression in already infected cells but inhibits HIV entry by secreting HIV-suppressive CC chemokines. 3) We show that allogeneic stimulation of latently infected, resting CD4+ T cells induced replication of HIV-1 in these cells. These observations suggest that allogeneic stimulation may play a role in the transmission, replication, and phenotypic transition of HIV-1.

CD4-Positive T-Lymphocytes↗
PubMed1999

HTLV type I Tax activation of the CXCR4 promoter by association with nuclear respiratory factor 1.

Human T lymphotropic virus type I trans-activator Tax protein regulates expression of several cellular genes that are involved in cellular activation, proliferation, and transformation. Tax mediates its regulatory activity through interaction with cellular transcription factors such as members of the cAMP-responsive element-binding factors/ATF family or the NF-kappaB/Rel family. In this study we have demonstrated that Tax trans-activates the promoter for CXCR4, a coreceptor for T cell-tropic HIV-1 through its association with nuclear respiratory factor 1 (NRF1). The promoter region for CXCR4 contains an NRF1-binding site, which is crucial for basal and Tax-induced activity. Glutathione S-transferase (GST) pull-down experiments showed association of GST-Tax fusion protein with NRF1 in vitro. Expression of Tax, in addition to stimulation with phorbol myristate acetate and ionomycin, increased formation of the NRF1 complex in a gel-mobility shift assay, indicating that Tax association with NRF1 in vivo facilitates its DNA binding. HTLV-I Tax activation of CXCR4 may contribute to the rapid progression of HIV disease observed in certain coinfected individuals.

Cell Line↗
PubMed1999

USF/c-Myc enhances, while Yin-Yang 1 suppresses, the promoter activity of CXCR4, a coreceptor for HIV-1 entry.

Transcription factors USF1 and USF2 up-regulate gene expression (i.e. , HIV-1 long terminal repeats) via interaction with an E box on their target promoters, which is also a binding site for c-Myc. The c-Myc oncoprotein is important in control of cellular proliferation and differentiation, while Yin-Yang 1 (YY1) has been shown to control the expression of a number of cellular and viral genes. These two proteins physically interact with each other and mutually inhibit their respective biological functions. In this study, we show that USF/c-Myc up-regulates, while YY1 down-regulates the promoter activity of CXCR4, a coreceptor for T cell-tropic HIV-1 entry. We have identified an E box around -260 and a YY1 binding site around -300 relative to the transcription start site. Mutation of the E box abolished USF/c-Myc-mediated up-regulation of CXCR4 promoter activity, and mutation of the YY1 binding site was associated with unresponsiveness to YY1-mediated inhibition. These data suggest that USF/c-Myc and YY1 may play an important role in the HIV-1-replicative cycle, by modulating both the viral fusion/entry process and viral expression.

Base Sequence↗