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Biomedical subjects

Y Sei

Publications and source records attributed to Y Sei.

At least 73 records · Page 4Linked to original sources

Inhibition of calcium mobilization is an early event in opiate-induced immunosuppression.

Morphine administered as a subcutaneous implant inhibits the initial increase in cytoplasmic free-calcium [Ca2+]i induced by mitogens in mouse splenocytes. This effect was not reproduced by incubation of splenocytes with morphine (10(-8)-10(-4) M). Analysis of splenocyte subpopulations demonstrates that this effect was manifest in both B and T cells. However, within T cell subpopulations, CD4+ but not CD8+ cells were affected. Adrenalectomy abolished this effect of morphine in CD4+ T but not CD4-, CD8- spleen cells (most likely Thy 1.2- B cells). Moreover, simultaneous administration of the opiate antagonist naltrexone blocked the effect of morphine in CD4-, CD8- spleen cells, but not in CD4+ T cells. These data indicate that the effects of morphine on mitogen-stimulated increase in [Ca2+]i may be mediated through distinct glucocorticoid-dependent and -independent mechanisms. The morphine-induced inhibition of an increase in [Ca2+]i in immune cells reported here may be an early event mediating opiate-induced immunosuppression.

Animals↗

Characterization of human B cell (DK) and promonocyte (U937) clones after HIV-1 exposure: accumulation of viral reverse transcriptase activity in cells and early syncytia induction against SupT1 cells.

The kinetics of HIV-1 infection were compared among human B (DK), promonocyte (U937), T-B hybrid (CEMX174), and T (H9) cell lines. Just like H9 cells, CEMX174 cells exhibited strong syncytia induction capacity against highly HIV-1-sensitive CD4+ T cells (SupT1) and had high reverse transcriptase (RT) release in the supernatant. DK and U937 cells showed syncytia induction capacity by 72 hr, but RT activity in the culture supernatant (extracellular RT) increased much later. RT activity in cell lysates (intracellular RT) became detectable at 12-15 days. The inverted extracellular/intracellular RT ratio and syncytia induction capacity were also observed in chronically infected DK (DK-IIIB) and U937 (U937-IIIB) cell lines and subclones from U937-IIIB. Further, the coculture of H9 with DK-IIIB (which indicates no detectable extracellular RT release) showed remarkable amplification of extracellular RT with significant increase of T-B double marker hybrids (H9-DK-IIIB). Our results suggest that B cells and/or monocytes/macrophages may acquire fusing capacity against CD4+ T cells in early stages of the infection and that these cell-to-cell interactions may also lead to a reduction in the number of CD4+ T cells. Further, these T-B and T monocyte hybrids may serve as temporal sites for viral replication. These in vitro studies may provide clues to the possible immunopathological roles of HIV-1-infected B cells and monocytes/macrophages and may help in understanding the mechanisms of viral burden on an infected host.

B-Lymphocytes↗

Biochemical basis of prolidase deficiency. Polypeptide and RNA phenotypes and the relation to clinical phenotypes.

Cultured skin fibroblasts or lymphoblastoid cells from eight patients with clinical symptoms of prolidase deficiency were analyzed in terms of enzyme activity, presence of material crossreacting with specific antibodies, biosynthesis of the polypeptide, and mRNA corresponding to the enzyme. There are at least two enzymes that hydrolyze imidodipeptides in these cells and these two enzymes could be separated by an immunochemical procedure. The specific assay for prolidase showed that the enzyme activity was virtually absent in six cell strains and was markedly reduced in two (less than 3% of controls). The activities of the labile enzyme that did not immunoprecipitate with the anti-prolidase antibody were decreased in the cells (30-60% of controls). Cell strains with residual activities of prolidase had immunological polypeptides crossreacting with a Mr 56,000, similar to findings in the normal enzyme. The polypeptide biosynthesis in these cells and the controls was similar. Northern blot analyses revealed the presence of mRNA in the polypeptide-positive cells, yet it was absent in the polypeptide-negative cells. The substrate specificities analyzed in the partially purified enzymes from the polypeptide-positive cell strains differed, presumably due to different mutations. Thus, there seems to be a molecular heterogeneity in prolidase deficiency. There was no apparent relation between the clinical symptoms and the biochemical phenotypes, except that mental retardation was present in the polypeptide-negative patients. The activities of the labile enzyme may not be a major factor in modifying the clinical symptoms.

Adolescent↗

Opiate-induced inhibition of calcium flux in immune cells.

Administration of morphine as a subcutaneous implant inhibits the initial influx of calcium (Ca2+) induced by mitogens in mouse splenocytes. This effect was not reproduced by incubation of splenocytes with morphine (10(-8)-10(-4)M). Within T cell subpopulations, CD4+, but not CD8+ cells were affected. Adrenalectomy abolished this effect of morphine in CD4+ but not B cells. Moreover, simultaneous administration of the opiate antagonist naltrexone blocked the effect of morphine in B cells, but not in CD4+ cells. These data indicate that inhibition of Ca2+ influx by morphine may be mediated through distinct glucocorticoid-dependent and independent mechanisms. The morphine-induced inhibition of Ca2+ influx in immune cells reported here may be an early event mediating opiate-induced immunosuppression.

Adrenalectomy↗

Evaluation of the effects of erythro-9(2-hydroxy-3-nonyl) adenine (EHNA) on HIV-1 production in vitro.

Effects of erythro-9(2-hydroxy-3-nonyl) adenine (EHNA), an inhibitor of the common Adenosine deaminase (adenosine aminohydrolase, EC 3.5.4.4.), on HIV-1 production was evaluated in vitro. Reverse transcriptase (RT) activity in the supernatant was inhibited by nearly 50% in EHNA-treated HIV-1 infected H9 cells, when compared with untreated but infected H9 cells. There was also a significant decrease in cell viability, but this was reversed following the addition of deoxycytidine (dC) to these cultures. The combined treatment was also effective in suppressing HIV-1 release from HIV-1-infected U937 cells. This combined EHNA plus dC treatment had no effect on RT activity in the cell lysates, suggesting that the inhibition of HIV-1 production may be due to the disturbance of virus release from infected cells.

Adenine↗

Inverse relationship between HIV-1 p24 antigenemia, anti-p24 antibody and neutralizing antibody response in all stages of HIV-1 infection.

A double blind cohort study was conducted on 149 homosexual males and 36 patients with AIDS to investigate the relationship between HIV-1 antigenemia, the presence of neutralizing antibody (NA) activity and specific anti-viral core protein (p24) antibody (Ab) in the sera of HIV infected individuals during their progression to AIDS. All AIDS patients and 68% (101/149) of the homosexual males were HIV seropositive upon entering the study. Of those 48 (32%) homosexuals who were HIV negative at the onset, three seroconverted during the two year observation period. Retrospective studies of the HIV(-) subjects' sequentially stored serum samples demonstrated an early transient appearance of gag encoded p24 antigen (Ag) which preceded their production of NA and specific anti-p24 Ab. Following their seroconversion, no more circulating p24 Ag could be detected. Among the 101 HIV positive homosexuals, 16% rapidly progressed to AIDS and seven of these 16 (44%) subjects eventually died during the two year observation period. In this group of individuals with poor prognosis, presence of NA and anti-p24 Ab commenced at the onset reaching peak levels just prior to developing AIDS and began to decline as the clinical course worsened. Their circulating level of p24 Ag remained undetectable as long as there was quantifiable NA and anti-p24 Ab in their sera. Reappearance of circulatory p24 Ag, on the other hand, was associated with high risk for progression to AIDS.2+hus, while only 11

Acquired Immunodeficiency Syndrome↗

Presence of HIV-1 reverse transcriptase inhibitory antibodies in the sera of some HTLV-1 carriers and absence of neutralizing antibodies against HIV-1 in the sera of HTLV-1 carriers.

We have detected inhibitory antibody against HIV-1 reverse transcriptase (RT) in the sera of HTLV-1 carriers, although the lack of immunological cross reaction between HIV-RT and other mammalian retroviruses, including HTLV-1, has been reported elsewhere (1). Sera from 72 HTLV-1 carriers in the southern part of Kyushu in Japan and 61 controls from the same district were studied and controlled for age and sex. One of the 72 HTLV-1 carriers was HTLV-1 antibody-positive, while the others were HIV-1 antibody-negative by ELISA and Western blot method. Sera from two HTLV-1 carriers and one hemophiliac with combined HIV-1 and HTLV-1 infections were found to inhibit HIV-1 RT activity. The inhibition ratios were 72, 65 and 72%, respectively. Protein A effluents of inhibitory sera retained no inhibitory capacity. These results might suggest that HTLV-1 and HIV-1 reverse transcriptase may share common or similar epitopes and that antibodies raised to the HTLV-1 RT react with that of HIV-1 RT in an inhibitory mode. However, the RT inhibitory antibody-positive sera had no neutralizing capacity against HIV-1 infection, supporting the idea that HIV-1 RT inhibitory antibody may not contribute to neutralization against HIV-1. The results also suggest that previous exposure to HTLV-1 does not contribute to neutralizing antibodies against HIV-1 in HIV-1 infected individuals.

Blotting, Western↗

Neutralizing antibodies as a prognostic indicator in the progression of acquired immune deficiency syndrome (AIDS)-related disorders: a double-blind study.

A double-blind longitudinal study for the presence of human immunodeficiency virus type 1 (HIV-1) neutralizing antibodies (NAb) in the sera of 36 patients with acquired immune deficiency syndrome (AIDS), 149 prodromal homosexual subjects, and 33 heterosexual subjects has been carried out. All AIDS patients and 68% of prodromal homosexual subjects (101/149) were found to be HIV-1 antibody positive by Western blot assay. All heterosexual subjects were HIV-1 antibody negative. Neutralizing antibody(s) was determined by testing the protective activity of sera against HIV-1 infection of human T-cell line H9. Study subjects were divided into NAb(+) (antibody titer, greater than 1:40) and NAb(-) (antibody titer, less than 1:40) groups. During the 24-month observation period 2 of 80 (3%) HIV-1(+) NAb(+) individuals progressed to AIDS and died, as compared to 5 of 21 (24%) of HIV-1(+) NAb(-) subjects who progressed to AIDS. Similarly, among the NAb(+) AIDS patients 8 of 23 (35%) died, while 10 of 13 (77%) of the NAb(-) patients died during the course of the study. In addition, the absence or reduction of HIV-1 p17 and p24 antibodies directed against HIV-1 antigens as well as the low titer or absence of NAb appears to be closely related to the clinical progression of the disease. These studies suggest that a decrease in the virus neutralization capacity of the sera and a decrease or complete loss of HIV-1 p17 and p24 antibodies may be useful as prognostic indicators for the progression of disease in HIV-1-seropositive patients.

AIDS-Related Complex↗

Isoprinosine-induced modulation of T-helper-cell subsets and antigen-presenting monocytes (Leu M3 + Ia +) resulted in improvement of T- and B-lymphocyte functions, in vitro in ARC and AIDS patients.

Peripheral blood leukocytes from ARC and AIDS patients were analyzed following phytohemagglutinin- and pokeweed mitogen-induced lymphocyte transformation by dual-color flow cytometry using monoclonal antibodies that identify developmental (HLA-DR) and functional (Leu8) subsets of T cells and monocytes. Significant decreases in both the suppressor regulating helper T subset (Leu3+ Leu8+) and the reciprocal inducer helper T subset (Leu3+ Leu8-) responsible for inducing differentiation of B cells were observed. Simultaneously, the percentages of the effector suppressor T cells and the precursor suppressor T cells were increased, both of which were required for generation of suppression of cell-mediated immunity. There was also a progressive selection of Ia+ cells bearing the Leu2 (Ts) markers and a concurrent reduction of the percentage of antigen-presenting monocytes and activated helper T cells. These results suggest that the functional deficiencies in AIDS may be caused by defects in T-cell activation as well as antigen presentation by monocytes. Isoprinosine induced an increase in both regulator Th (Leu3+ Leu8+) and inducer Th (Leu3+ Leu8+) subsets of helper T cells while potentiating the expression of Ia antigen on helper T cells and monocytes during mitogen-driven DNA synthesis. These events initiated a cascade of cellular interactions leading to partial restoration of cell-mediated immune responses. These interferences with the defective helper/suppressor regulatory pathways may have important therapeutic implications.

AIDS-Related Complex↗

Multiple dysfunctions in developmental and activational stages of T lymphocytes, B lymphocytes and monocytes in ARC and AIDS patients.

Peripheral blood leukocytes from ARC and AIDS patients were examined before and after phytohemagglutinin (PHA) stimulation by dual color flow cytometry and monoclonal antibodies which identify developmental and activational stages of T lymphocytes, B cells and monocytes. There was a persistent elevation in the total number of circulating Ia+ lymphocytes with progressive selection for B1+ Ia+ lymphocytes and T suppressor cells and a concurrent reduction in the antigen-presenting monocytes. Following PHA stimulation there was a marked decrease in all subsets of Ia+ lymphocytes and monocytes. These results indicate (a) multicellular dysfunctions in the immunosurveillance mechanisms in AIDS, and (b) that many functional subsets of circulating lymphocytes and monocytes were already activated and therefore poorly responsive to additional antigenic or mitogenic stimuli.

AIDS-Related Complex↗

Management of wounds treated by thrombin coagulation.

Thrombin solution was applied to skin-graft donor sites following skin removal with a Reese dermatome. Immediately after the blood was clotted by the thrombin solution, sheets of silicone gauze were applied to the clotting site. Forty-eight hours after the operation, the coagulated blood had disappeared spontaneously. In a total of 21 operations, the wounds treated by the above method healed completely without infection.

Bandages↗

Monocytes in AIDS.

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Acquired Immunodeficiency Syndrome↗

Healthy HTLV-I carriers in Japan: the haematological and immunological characteristics.

The haematological and immunological characteristics of 34 healthy anti-HTLV-I antibody-positive individuals (HTLV-I carriers) in southwestern Japan were examined. No significant difference was noted between carriers and the controls in counts of RBC, WBC and the absolute number of lymphocytes. The serum IgG in the carriers was higher than that of the controls. The percentages of OKT4, OKT8, OKIa1 and B1-positive cells were found to be normal in the peripheral blood of the carriers, whereas the percentages of OKT11 and anti-Tac-positive cells were significantly higher in the carriers than in the controls. A correlation was observed between the percentages of anti-Tac-positive cells and the titres of anti-HTLV-I antibody in the carriers. After a 72 h incubation of peripheral blood lymphocytes with medium alone, the percentage of anti-Tac-positive cells tended to decrease in the controls, but to increase in carriers, with the appearance of large blastoid cells resembling blastic transformed lymphocytes cultured with mitogen. Tac and Ia antigens were markedly expressed on these large blastoid cells.

Acute Disease↗

Cell surface antigen expression in cultured lymphocytes derived from healthy HTLV-I carriers.

We studied cell surface antigens on fresh and cultured peripheral blood lymphocytes (PBL) of healthy HTLV-I carriers. OKT4, OKT8 and OKIa1-positive cells were found to be within the normal range as compared with controls both in fresh and in cultured PBL. The percentage of Tac positive cells in HTLV-I carriers was shown to be higher in fresh PBL than that of controls. Furthermore the value increased significantly during cell culture in vitro and large blastoid cells appeared. The results suggested that HTLV-I proliferation in infected lymphocytes is activated in a serum-free environment and that small resting lymphocytes are transformed into Tac-positive large blastoid cells.

Aged↗

Defect of OKT4 antigen epitopes on normal human lymphocytes found in Japan.

Membrane surface antigens on peripheral blood lymphocytes were analyzed by a laser flow cytometry system using monoclonal antibodies. Four normal subjects among 1,998 normal and diseased groups were found whose lymphocytes were not detected by OKT4 monoclonal antibody, while Leu3a and KOLT-1, which were also specific for helper/inducer T-lymphocytes as OKT4, were present in these subjects. The cases with the defect of the OKT4 antigen suggest that there is some modification of the antigen, lack of epitopes, or genetic polymorphism in the appearance of the OKT4+ cell surface antigen on normal human lymphocyte.

Adult↗