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Biomedical subjects

M Robert-Guroff

Publications and source records attributed to M Robert-Guroff.

At least 91 records · Page 5Linked to original sources
PubMed1985

Racial and other characteristics of human T cell leukemia/lymphoma (HTLV-I) and AIDS (HTLV-III) in Trinidad.

Adult T cell leukaemia/lymphoma was first recognised as a clinical entity in southwest Japan. Subsequently the Caribbean has been found to be another area where the disease is endemic, and sporadic cases have been identified in different parts of the world. The human T cell leukaemia/lymphoma virus (HTLV-I) is causally related to adult T cell leukaemia/lymphoma. A subgroup of HTLV, designated HTLV-III, has recently been isolated from many patients with the acquired immunodeficiency syndrome (AIDS) and preAIDS, and there is now evidence that this variant is the primary cause of AIDS. This is the first report from Trinidad to describe 12 cases of adult T cell leukaemia/lymphoma and 14 of AIDS. All were in patients of African descent. No cases were seen in subjects of East Indian descent, who, like those of African descent, comprise as much as 40% of the population. West Indians of African descent may have increased susceptibility to infection with both HTLV-I and HTLV-III.

Acquired Immunodeficiency Syndrome↗
PubMed1985

A monoclonal antibody specific for a 52,000-molecular-weight human T-cell leukemia virus-associated glycoprotein expressed by infected cells.

A monoclonal antibody, designated HT462, is described which is specific for an antigen expressed in human T-cell leukemia/lymphoma virus (HTLV) preparations and by HTLV-infected cells. In indirect immunofluorescence assays, the antigen was detected on the surface of both HTLV-transformed producer and nonproducer cells, including cells infected in vitro with either HTLV subgroup I (HTLV-I) or HTLV-II. Normal human peripheral blood lymphocytes stimulated with phytohemagglutinin, cord blood T cells cultured with T-cell growth factor, and a variety of HTLV-negative T- and B-cell lines all lacked HT462 antigen expression. The HT462 antigen is a 52,000-molecular-weight glycoprotein, as shown by Western blotting procedures and treatment of viral preparations with neuraminidase, endoglycosidase F, and trypsin. The unglycosylated molecule is approximately 42,000 daltons. That the antigen is virus associated was demonstrated by its banding at the density of HTLV in gradients of metrizamide and by its concomitant synthesis with HTLV gag proteins after short-term culture of primary HTLV-positive leukemic cells. Differential expression of the HT462 antigen and HTLV gag-pol gene products was observed. In one case, low HT462 expression was correlated with the known inability of the particular cell line to produce syncytia in vitro. The properties of the HT462 antigen are most consistent with it being a gene product of the HTLV px region or else a cellular antigen specifically induced after viral infection. We cannot rule out, however, that the antigen is a variant cleavage product of the env gene. The monoclonal HT462 will be useful in further definition of the proteins and functions encoded by the env-px genetic sequence and in studying the biological properties of HTLV-transformed cells. Furthermore, the monoclonal, by recognizing HTLV-transformed nonproducers, will allow a greater spectrum of virus-infected cells to be detected.

Antibodies, Monoclonal↗
PubMed1985

Human T-cell leukemia-lymphoma virus type 1 and adult T-cell leukemia-lymphoma in Okinawa.

A serological survey for the presence of antibodies against the human T-cell leukemia virus, type 1 (HTLV-1) in patients seen at the Chubu Hospital in Okinawa was undertaken. All patients with the clinicopathological diagnosis of adult T-cell leukemia-lymphoma were positive. These cases had the characteristic features of adult T-cell leukemia-lymphoma: diffuse histology, often mixed cell or pleomorphic, and a high frequency of hypercalcemia, leukemic phase, diffuse visceral involvement, and opportunistic infections. The median survival of these patients was short, being only 18 weeks. Of the other patients with cancers screened, two of five other non-Hodgkin's lymphoma patients were positive and three of eight patients with other hematological cancers were positive. In addition, three of the four immediate family members of one adult T-cell leukemia-lymphoma case had antibodies. Of the other persons (both in- and outpatients) without hematological cancers, those under the age of 50 had a much lower antibody prevalence (4%) than those over 50 (30%). There was no significant difference in antibody prevalence between the two sexes in either the younger or older age group. These findings further document that Okinawa is an endemic area for HTLV-1. None of the 157 individuals screened for antibodies to HTLV-3 were positive, consistent with the fact that no cases of the acquired immune deficiency syndrome have been reported from Okinawa.

Acquired Immunodeficiency Syndrome↗
PubMed1985

Antigenicity of human T-cell leukemia virus-associated gp52: greater response in leukemia patients compared to healthy donors exposed to the virus.

Monoclonal antibody HT462 recognizes a human T-cell leukemia virus type I (HTLV-I)-associated Mr 52,000 glycoprotein (HA-gp52), which is found on the surface of HTLV-infected cells. Whether HA-gp52 is encoded by the virus or by the infected cells has not yet been established. Using monoclonal HT462 in a competitive binding assay, natural human antibodies specific for HA-gp52 were detected in 97% of the patients from the United States, the Caribbean, and Japan with adult T-cell leukemia but not in healthy donors not exposed to HTLV-I. In contrast, antibodies to HA-gp52 occur in healthy virus-exposed donors, but at a lower prevalence than that observed in patients. Among Japanese from HTLV-I-endemic areas and exposed to the virus as indicated by the presence of antibodies to disrupted HTLV-I, 93% of adult T-cell leukemia patients were also seropositive for HA-gp52 compared to only 16% of healthy individuals. Differing sensitivities in the methods of assaying antibodies to HTLV and HA-gp52 were not responsible for these observations as shown by the lack of correlation of HTLV-I antibody titer with the presence of antibody to HA-gp52. Among adult T-cell leukemia patients, antibody titers to HTLV-I and HA-gp52 also varied independently. These results indicate that HA-gp52 in humans is antigenic and correlated with disease. Detection of antibody to this protein in asymptomatic individuals may be indicative of a predisease condition.

Animals↗
PubMed1985

Detection of antibodies to HTLV-I and -III in sera from Japanese hemophiliacs.

Sera from 50 Japanese hemophiliacs were screened for antibodies to human T-lymphotropic retrovirus types I and III (HTLV-I and -III). As a whole, antibody to HTLV-I, antibody to HTLV-III, and antibodies to HTLV-I and -III were detected in sera from 2, 17, and 6 hemophiliacs, respectively. Among them, two hemophiliacs developed acquired immunodeficiency syndrome who were positive for both antibodies to HTLV-I and -III in sera. All of the others were asymptomatic. Most of the blood products transfused into these hemophiliacs were imported from abroad, whence the source of HTLV-III infection presumably originated. However, since quite a high percentage of these antibody-positive hemophiliacs was positive for antibody to HTLV-I, even though they are native residents in HTLV-I nonendemic areas of Japan, some special factors may have participated in HTLV-I infection. These special factors should be investigated in the future.

Acquired Immunodeficiency Syndrome↗
PubMed1985

Comparative seroepidemiology of HTLV-I and HTLV-III in the French West Indies and some African countries.

The prevalence of antibodies detected by ELISA against human T-lymphotropic viruses, type I (HTLV-I) and type III (HTLV-III-LAV), is described in a comparative serosurvey in the French West Indies and African countries. The data confirm that the Caribbean basin is endemic for HTLV-I. In this region, HTLV-I antibody prevalence varied from 3.4% to 5.2% among blood donors and increased with age to reach a value of 33% among elderly people from the Dominica Island. In French Guyana, a South American country bordering the Caribbean sea, differences in antibody distribution across three ethnic groups (black Bonis, Indian Wayanas, and Hmongs from Asia) provide clues for investigation of the mode of HTLV-I transmission. Africa appears to be an endemic continent for HTLV-I and HTLV-III. For both viruses, the antibody prevalence exhibited an increasing gradient from northern to equatorial through Sudanic areas. These preliminary data by showing that Africa represents an endemic reservoir of HTLVs and, possibly, of other human retroviruses should stimulate further investigations on the natural history and the geographical origin of these viruses.

Adolescent↗
PubMed1985

Natural antibodies in sera from Japanese individuals infected with HTLV-I do not recognize HTLV-III.

Seventy-one sera from Japanese individuals infected with human T cell leukemia virus type I (HTLV-I) were examined for the presence of antibodies to HTLV-III by an enzyme-linked immunosorbent assay (ELISA) and by a strip radioimmunoassay based on the Western blot technique. The sera were from 23 healthy carriers and from 48 patients, including 18 with smoldering adult T cell leukemia (ATL), 13 with chronic ATL, and 17 with acute ATL. All people tested lived in the southwestern part of Japan, a known endemic area for HTLV-I infection. Antibodies against HTLV-I were detected in all sera both by indirect immunofluorescent methods and strip radioimmunoassay using cell lysates. Six sera were reactive in the ELISA assay for HTLV-III. But these sera did not react specifically to HTLV-III-related proteins (p15, p24, gp41) when analyzed by strip radioimmunoassay. Our data suggest that coincidental infection of HTLV-I and HTLV-III is quite rare in Japan.

Antibodies, Viral↗
PubMed1984

Natural antibodies to human T-cell leukemia/lymphoma virus in healthy Venezuelan populations.

Serum samples of 769 healthy Venezuelan donors were assayed for natural antibodies to HTLV-I by the ELISA technique. Specific HTLV-I antibody prevalence was 6.8% but varied from 1% in Caracas to 13.7% in the Amazonas region and the State of Zulia. Adults infected with Trypanosoma cruzi had the highest HTLV-I antibody prevalence of 15%. Areas of high antibody prevalence were correlated most strongly with the presence of arthropod-borne diseases and to a lesser extent with socio-economic factors. Genetic factors were not correlated with antibody prevalence. Antibodies were seen in children as young as 3 years of age in the most endemic areas. Antibody titers increased with age, suggesting continuous exposure to the virus. The data provide clues for elucidation of the geographic variation in HTLV-I antibody prevalence seen Venezuela and other HTLV-I endemic areas. In addition, they further confirm the Caribbean region as being endemic for HTLV-I and extend this region to inland areas of South America.

Adolescent↗
PubMed1984

HTLV-I-specific antibody in AIDS patients and others at risk.

Serum samples from 440 acquired immunodeficiency syndrome (AIDS) patients or individuals at risk for AIDS were examined by the enzyme-linked immunosorbent assay technique for antibodies to HTLV-I core proteins. Specific antibodies were detected in 7% of AIDS patients, 7% of patients with lymphadenopathy, 0% of healthy homosexual men, and 12% of healthy Haitians. When findings in homosexual men were analysed separately, the prevalence for homosexual men with lymphadenopathy was 7% and for homosexuals with AIDS, 6%. Antibody titres ranged from 77 to 74 000. The antibody-positive cases included intravenous drug users, a Haitian AIDS patient, a recipient of multiple blood transfusions, and homosexual men. Haemophiliacs were not examined. Although HTLV-I-specific antibodies are more prevalent in AIDS patients than in healthy US donors, the difference is not sufficient to suggest an association of HTLV-I with the disease. The low rate may indicate an opportunisitic infection of AIDS patients by HTLV-I, or a crossreaction with the recently described HTLV variant, HTLV-III, believed to be the aetiological agent of AIDS. Whether HTLV-I normally exerts immune suppressive effects in vivo with biological consequences remains to be determined.

Acquired Immunodeficiency Syndrome↗
PubMed1984

Human T-cell leukemia virus (HTLV) in the United Kingdom.

Ten out of 26 leukaemic patients who had emigrated from the Caribbean region to the United Kingdom had adult T-cell leukaemia with associated serum antibodies to HTLV I. Antibodies to HTLV were also detected in sera from a small proportion of non-leukaemic Caribbean immigrants but not in any sera from other (non-ATL) T-cell leukaemias or a variety of control groups. The long period between immigration to the UK and diagnosis of leukaemia (up to 30 years) suggests that an extensive latent period in disease development may exist. Cell lines were isolated from two patients with HTLV antibody-positive ATL and were shown to be virus-positive by electron microscopy and immunofluorescence using antibodies to the p19 and p24 viral proteins. HTLV1 provirus integration and active transcription were demonstrated by Southern blotting of DNA and in situ hybridization respectively using molecularly cloned HTLV1 probes. Virus from one of these cell lines could be transmitted to normal T cells by co-cultivation.

Adolescent↗
PubMed1984

Location of human T-cell leukemia virus (HTLV) p19 antigen on virus-producing cells.

Mouse monoclonal antibody to HTLV p19 was used to locate HTLV p19 on the surface of cells and virions by immunofluorescence microscopy (IFM) and immunoelectron microscopy (IEM). When HTLV-producing cells HUT 102 (B2 clone), MT-2 and strain A were used as target cells, HTLV p19 was detected on the surface of cells and virions as spots or small sectors by both IFM and IEM. Cells infected with animal type-C retroviruses, e.g., gibbon ape leukemia virus, simian sarcoma virus, feline leukemia virus, and Gross murine leukemia virus, were completely negative for HTLVp19 expression. Other human T cells not producing HTLV, including HUT78 and HSB2-0, immature or pre-T cells (Molt-3) derived from leukemia patients, and fresh peripheral blood T cells from healthy persons, were also negative. In addition, B cells including Rob-B, IM-9, Raji, and BT-1 did not react with the monoclonal antibody to HTLV p19. In the light of the presence of HTLV p19 in the periphery of acetone-fixed HTLV-producing cells as shown by IFM, it seems most likely that HTLV p19 is an internal antigen of HTLV with part of its structure protruding out of the viral and cell membrane. The monoclonal antibody to HTLV p19 did not lyse HTLV-producing cells in the presence of complement, as expected, because the antibody is an IgG1. Antibody-dependent cell-mediated cytotoxicity was also studied by the 51Cr-release assay. No cytotoxicity was observed. Although HTLV p19 does not contribute to the destruction of malignant T cells for treatment and/or virions for prophylaxis, this protein is an important marker for diagnosis of HTLV infection. The patterns of HTLV p19 expression described above were exactly the same for American HTLV-producing HUT 102 (B2 clone), for strain A cells and for Japanese HTLV-producing MT-2 cells. These results further substantiate the close relationship of the Japanese and American HTLV isolates.

Antibodies, Monoclonal↗