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Biomedical subjects

Y Hinuma

Publications and source records attributed to Y Hinuma.

At least 91 records · Page 5Linked to original sources

A novel agglutination test for the human immunodeficiency virus antibody: a comparative study with enzyme-linked immunosorbent assay and immunofluorescence.

A new serological test, the gelatin particle agglutination (PA) test, was developed for the detection of antibody to human immunodeficiency virus (HIV). The sensitivity of the PA test was the same as that of enzyme-linked immunosorbent assay (ELISA) among 761 US and Japanese sera tested. However, false-positive cases were found in 1.2% of all sera in ELISA but in 0% in the PA test (P less than 0.05). There was 100% agreement of seropositivity between PA and a confirmatory indirect immunofluorescence (IF) test. In addition, the agglutination test was reproducible. Thus, the test should be useful for the mass screening of anti-HIV antibody in blood donors.

Acquired Immunodeficiency Syndrome↗

A glycoprotein antigen detected with new monoclonal antibodies on the surface of human lymphocytes infected with human T-cell leukemia virus type-I (HTLV-I).

We have prepared two new mouse monoclonal antibodies (MAbs) named TARM-34 (IgM) and TAG-34 (IgG1), that react with surface antigens of lines of human lymphocytes bearing a human T-cell leukemia virus type-I (HTLV-I). The characters of these antibodies are compared with those of anti-HTLV-1 gp21 MAb (TA-21, IgG1), anti-HTLV-I p19 MAb (GIN-14, IgG1) and human antibodies from patients with adult T-cell leukemia (ATL). An indirect membrane immunofluorescence assay showed that TARM-34, TAG-34 and TA-21 all reacted specifically with cell-surface antigens of HTLV-I-positive T- and B-cell lines and cultured peripheral blood lymphocytes from HTLV-I-infected adults. Radioimmunoassay showed that serum antibodies from the ATL patients interfered with the binding of TA-21 antibody to cells of the HTLV-I-positive T-cell line MT-2, but not with the bindings of TARM-34 and TAG-34 antibodies. TARM-34 and TAG-34 both precipitated a 34-kd glycoprotein (gP34), while TA-21 precipitated gp21 from a lysate of 3H-glucosamine-labelled MT-2 cells. TARM-34 and TAG-34 also precipitated the 34-kd protein from lysates of MT-2 and HUT 102 cells labelled with 125I- or 35S-cysteine. Interestingly, TARM-34 and TAG-34 also precipitated 35-kd protein from a lysate of other HTLV-I-positive cells (F-Taj cell line) derived from an ATL patient. TA-21 precipitated the 21-kd protein from the lysates of 35S-cysteine-labelled HTLV-IMT-2 virions, but TARM-34 and TAG-34 did not precipitate any protein from this lysate. TARM-34 lysed HTLV-I-bearing cells in the presence of rabbit complement. These results indicate that TARM-34 and TAG-34 both recognize a glycoprotein antigen that is expressed on the surface of HTLV-I-infected cells.

Animals↗

Production of cytotoxic factor(s) in human T cell lines transformed by a human retrovirus.

Human T cell lines, MT-2, TCL-Ter, TCL-Haz, and TCL-Kan which were transformed by a human retrovirus, constitutively produced cytotoxic factor(s) (CF) in the culture supernatants. In these cell lines, MT-2 produced the largest amount of CF. The amount of CF produced by MT-2 was 9-10 or 3-4 times larger than that produced by a human B cell line, RPMI 1788, or normal peripheral blood leukocytes stimulated with mitogens and phorbol ester. The kinetics of the production by MT-2 was similar in media with and without serum. The activity was stable at 56 degrees C for 30 min but was lost at 80 degrees C for 30 min and at pH 2 for 20 hr. On gel filtration, the molecular weight of the factor produced by MT-2 was approximately 90,000. On isoelectric focusing, the activity was recovered in the fraction at pH 6.5-7.0.

Cell Line↗

Effect of human serum anti-HTLV antibodies on viral antigen induction in vitro cultured peripheral lymphocytes from adult T-cell leukemia patients and healthy virus carriers.

Leukemic cells of adult T-cell leukemia (ATL) patients contain human T-cell leukemia virus type I (HTLV-I) genomes. However, viral antigens (HTLV-A) are not usually expressed in vivo. It has been shown that HTLV-I antigens are spontaneously induced after culture of peripheral blood lymphocytes (PBL) from patients with ATL and healthy carriers (HC), who are viral antibody-positive. In the present communication, we show the suppressive effect of human serum antibodies against HTLV-I on viral antigen expression in PBL derived from ATL patients and HC. Viral antigen synthesis in various PBL specimens is variable in terms of frequencies and kinetics. (1) Low concentrations (2%) of antibody-positive but not of antibody-negative sera efficiently suppressed HTLV antigen induction in lymphocytes from both ATL patients and HC. (2) An inhibitory effect was exerted by HTLV-I-specific antibodies which originated from either ATL, HC or even HTLV-I-positive monkeys. (3) Sera showed a fairly wide range of suppressive activity in view of their concentrations. (4) At the late stage of cultures even continuous presence of antibodies frequently failed to suppress antigen synthesis in lymphocytes. (5) Antibodies were less effective in suppressing the increase of antigens if they were added to cultures which had already HTLV-A-positive lymphocytes in antibody-free media. (6) Pretreatment with protein A completely abolished the activities of the suppressive plasmas. (7) Antibodies did not affect the inhibition of spontaneous or chemical induction of HTLV-A in 2 HTLV-I-positive cell lines. These results suggest that HTLV-I antigen expression in leukemic cells from patients with ATL in vivo and in vitro is partly regulated by antibodies to HTLV-I. Furthermore, at least 2 different pathways, one antibody-sensitive and the other -insensitive, might exist to express HTLV-A.

Antibodies, Viral↗

Incidence of adult T-cell leukemia-lymphoma and its familial clustering.

The yearly incidence of ATLL in the Uwajima district is 6.6 patients per 100,000 inhabitants aged over 40. The yearly morbidity rate from ATLL of persons in this district who are positive for HTLV-antibody and older than 40 is 1 patient per 1,631. Familial occurrence was observed in 9/38 families available for pedigree analyses. Even in the endemic area, the existence of positive HTLV antibody is remarkably high in ATLL families, suggesting that HTLV has been transmitted from generation to generation mainly within these particular families.

Adult↗

Interleukin 2 inhibits in vitro growth of human T cell lines carrying retrovirus.

Four human T cell lines, TL-Mor, TL-Su, TL-TerI, and TL-OmI, carrying human T cell leukemia virus (HTLV), were established previously. TL-Mor, TL-Su, and TL-TerI were derived from interleukin 2 (IL-2)-dependent parental cell lines cloned from peripheral blood leukocytes (PBL) of three healthy HTLV carriers, while TL-OmI was directly established from PBL of a patient with adult T cell leukemia. These four TL cell lines grow autonomously without IL-2. When they were cultured in the presence of IL-2, their growth was inhibited after a few days. This growth inhibition depended on the dose of IL-2, and the effective dose significantly promoted growth of their parental IL-2-dependent cell lines. The growth inhibition is demonstrated to be due to specific binding of IL-2 to receptors on the TL cells.

Cell Line↗

Prevalence of a human retrovirus in native Japanese: evidence for a possible ancient origin.

The origin of a human retrovirus (ATLV or HTLV-I) is, at present, unknown although carriers of the virus have been found in Japan, the Caribbean basin and Africa. By means of a sero-epidemiological study, the Ainu people of Hokkaido, located in the northernmost island of Japan, were shown to have antibody to the virus in high frequency. Since the Ainu are regarded as descendants of the pre-agriculture native population of northern Japan, this finding appears to indicate that the retrovirus was already present in the aboriginal Japanese of prehistoric times.

Adolescent↗

Survey of the prevalence of AIDS-associated virus (LAV) infection in Japan.

An indirect immunofluorescence method was developed for the assay of antibodies to lymphadenopathy-associated virus (LAV) which is known to be associated with the aetiology of the acquired immunodeficiency syndrome (AIDS). Samples of serum or plasma from 1353 healthy volunteer blood donors, 53 homosexual males, 29 patients who had received multiple blood transfusions and 163 haemophiliacs in Japan were tested for antibody to LAV. Results showed that 47 (29%) of the haemophiliacs, who had been treated largely with factor VIII or IX produced in the USA, were anti-LAV antibody positive, whereas all other subjects were anti-LAV antibody negative. The incidence of antibodies to Adult T-cell leukaemia virus or Human T-cell leukaemia virus I (ATLV or HTLV-I) in these subjects was high.

Acquired Immunodeficiency Syndrome↗

Production of plasminogen activators by human T-cell leukaemia virus-transformed human T cell lines.

Six human T cell lines HAMA, KUN, KAN, TCL-Haz, TCL-Ter, and TCL-Mor, which were transformed by a retrovirus, human T-cell leukaemia virus (HTLV), constitutively produced plasminogen activators (PAs) in culture supernatants. The amount of PAs produced varied among the cell lines. The PAs were distinguished by immunochemical analysis between two types: urokinase (UK)-type and non-UK-type. KUN, TCL-Ter, and HAMA mainly produced UK-type PA, whereas the other cell lines produced both types. Thus, HTLV-transformed T cell lines differ in the quality and quantity of the PAs they produce. The PAs in the culture supernatants of each cell line were separated into several mol. w forms on sodium dodecyl sulfate polyacrylamide gel electrophoresis. The results indicate that the same cell line produces PAs of different mol. wt. PA production by these cell lines was affected by treatment with phorbol miristate acetate, concanavalin A, and phytohaemagglutinin; the effects were substantially different in each cell line. The data described here indicate that HTLV-transformed T cell lines constitutively produce PAs which are very heterogeneous in both quality and quantity.

Cell Line↗

A field study of infection with human T-cell leukemia virus among asian primates.

Asian nonhuman primates were surveyed seroepidemiologically for natural infection with human T-cell leukemia virus (ATLV/HTLV) or a closely related agent. Materials from various primates (three genera [Macaca, Presbytis, and Hylobates], 17 species, totalling 1,079 animals) under natural conditions were obtained in the field study. Virus infection was determined by the indirect immunofluorescence test using HTLV-specific antigens. Animals seropositive for HTLV were found only among macaques originating from various localities, toque monkeys in Sri Lanka (17.5%), crab-eating macaques in Thailand (1.3%), stumptailed macaques in Thailand (1.5%), rhesus monkeys in Thailand (3.3%), and Celebes macaques in Indonesia (16.9%). Langurs and gibbons were seronegative. Thus the wide distribution of HTLV in nature among various macaques suggests that the introduction of this virus into primates occurred in ancient times.

Animals↗

Distribution of the level of antibody to AIDS-associated virus (LAV) in sera from AIDS or AIDS related complex and Japanese hemophiliacs infected with AIDS-associated virus.

The level of antibody to AIDS-associated virus (LAV) in sera from patients with AIDS or AIDS related diseases (AIDS related complex; ARC) and Japanese hemophiliacs was studied using indirect immunofluorescence. Titer of anti-LAV antibody in sera from 89 patients with AIDS or ARC ranged between 10 and 40,960 (median: 1,280) and that of 83 Japanese hemophiliacs ranged from 20 to 20,480 (median: 640). The distribution of the level of anti-LAV antibody in hemophiliacs was similar to that of patients with AIDS or ARC, and no correlation between the titer of antibody and the presence of symptoms of AIDS was observed. Our results suggested that hemophiliacs in Japan might have been infected with live LAV rather than been immunized with inactivated LAV by injection of factor VIII or IX concentrate, and more hemophiliacs in Japan might show symptoms of AIDS in the future as in the United States.

Acquired Immunodeficiency Syndrome↗

Distinct reactivities of four monoclonal antibodies with human interleukin 2 receptor.

Two new murine monoclonal IgG1 antibodies, H-31 and H-A26, were characterized in comparison with two previously obtained monoclonal antibodies against human interleukin 2 (IL-2) receptor (IL-2 R), anti-Tac and HIEI. In immunofluorescence assays with various human hematopoietic cells, H-31 and H-A26 antibodies both reacted with only IL-2 R-positive cells, and they precipitated IL-2 R molecules, glycoproteins with molecular weights of 60K and 53K daltons (gp60/gp53), from human T-cell leukemia virus type I (HTLV-I)-carrying MT-2 cells, as demonstrated by sequential immunoprecipitation after absorption of IL-2 R with anti-Tac. Antibody-binding competition assays showed that H-31 and anti-Tac, and H-A26 and HIEI, respectively, competed reciprocally in binding to the cells, and that anti-Tac also inhibited the binding of HIEI but not vice versa. H-31, like anti-Tac, strongly inhibited the IL-2-dependent proliferation of normal activated T-cells, absorption of IL-2 and direct binding of IL-2 to the cells, while H-A26, like HIEI, inhibited those processes only weakly. The spectra of reactivities of these antibodies with various simian cell lines derived by HTLV-I infection were different, as revealed by immunofluorescence studies. Human IL-2 R was shown to express a unique antigenic determinant, detected with HIEI, that was not detectable in IL-2 R molecules of Old and New World monkeys, and also to express determinants common to simian IL-2 R molecules. These observations indicate that H-31 and H-A26 recognize human IL-2 R molecules and that the antigenic sites on the IL-2 R molecule defined by H-31, H-A26, anti-Tac, and HIEI are different.

Animals↗

trans-Activation of the human T-cell leukemia virus long terminal repeat correlates with expression of the x-lor protein.

Cell lines established directly from adult T-cell leukemia-lymphoma patients or immortalized by human T-cell leukemia virus type I (HTLV-I) in vitro that do not produce complete HTLV virions were characterized both for the content of viral proteins and for the presence of trans-acting factors activating gene expression under the control of the HTLV long terminal repeat. The expression of the 42-kilodalton HTLV x-lor product correlated with trans-activation of the long terminal repeat. The implications of this study for understanding the role of the HTLV x-lor product in the initiation and maintenance of T-lymphocyte transformation are discussed.

Deltaretrovirus↗

Seroepidemiology of adult T-cell leukemia virus in Taiwan.

A survey of carriers of adult T-cell leukemia virus (ATLV) detected as anti-ATLV associated antigens was made in Taiwan. Among 2545 adults aged 30 years or more examined, seropositive donors amounted to 0.9% in the Han Chinese but none in the aborigines.

Adult↗

Human T-cell leukemia virus I induction by 5-iodo-2'-deoxyuridine and N-methyl-N'-nitro-N-nitrosoguanidine: inhibition by retinoids, L-ascorbic acid, and DL-alpha-tocopherol.

Human T-cell leukemia virus type I was induced by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) and 5-iodo-2'-deoxyuridine (ldUrd) in the MT-1 cell line. Virus expression was monitored by immunofluorescence microscopy with GIN-14, mouse monoclonal antibodies directed toward Mr 19,000 and Mr 28,000 protein-specific virus polypeptides. MNNG (0.1 micrograms/ml) and ldUrd (50 micrograms/ml) both induced virus synthesis in MT-1 cells. MNNG-induced virus expression peaked between 24 and 48 h of incubation, whereas ldUrd induced maximum virus expression between 48 and 72 h of incubation. Superinduction resulted when MNNG was added to cells induced 48 h previously with ldUrd, but not with concomitant treatment. 13-cis-Retinoic acid, retinol, retinol aldehyde, and retinol acetate (10(-6) to 10(-9)M) were concomitantly added with ldUrd to MT-1 cells for 24, 48, and 72 h incubation. All inhibited virus induction to various degrees. The retinoids were ranked as to inhibitory activity: retinol greater than retinoic acid greater than retinol aldehyde greater than retinol acetate. The most sensitive period for inhibiting ldUrd induction by retinoic acid was 24 h postinduction or with concomitant treatment. Vitamin C and vitamin E inhibited ldUrd induction most effectively with 48 h incubation. Retinol and vitamin C also inhibited virus induction by MNNG. None of the retinoids, vitamin C, or vitamin E significantly inhibited virus expression in noninduced cells or were toxic to the cells at the concentrations used in these experiments.

Antigens, Viral↗