PubMed Health⌕ Search

Biomedical subjects

M Popovic

Publications and source records attributed to M Popovic.

At least 145 records · Page 8Linked to original sources
PubMed1983

Isolation of human T-cell leukemia virus in acquired immune deficiency syndrome (AIDS).

Several isolates of a human type-C retrovirus belonging to one group, known as human T-cell leukemia virus (HTLV), have previously been obtained from patients with adult T-cell leukemia or lymphoma. The T-cell tropism of HTLV and its prevalence in the Caribbean basin prompted a search for it in patients with the epidemic T-cell immune deficiency disorder known as AIDS. Peripheral blood lymphocytes from one patient in the United States and two in France were cultured with T-cell growth factor (TCGF) an shown to express HTLV antigens. Virus from the U.S. patient was isolated and characterized and shown to be related to HTLV subgroup I. The virus was also transmitted into normal human T cells from umbilical cord blood of a newborn. Whether or not HTLV-I or other retroviruses of this family with T-cell tropism cause AIDS, it is possible that patients from whom the virus can be isolated can also transmit it to others. If the target cell of AIDS is the mature T cell as suspected, the methods used in these studies may prove useful for the long-term growth of these cells and for the identification of antigens specific for the etiological agent of AIDS.

Acquired Immunodeficiency Syndrome↗
PubMed1983

Relatedness by nucleic acid hybridization of new isolates of human T-cell leukemia-lymphoma virus (HTLV) and demonstration of provirus in uncultured leukemic blood cells.

Human T-cell leukemia-lymphoma virus (HTLV) has now been isolated from many different patients with cutaneous T-cell lymphoma and leukemia, as judged by detection of media reverse transcriptase and virus particles and of antigenic determinants related to those of viral structural proteins p24 and p19. Molecular hybridization experiments with HTLV cDNA to viral mRNA or proviral DNA to ascertain the relatedness of four of these new isolates to the first HTLV isolate have been used. By these assays, three appear virtually indistinguishable from the original isolate, HTLV-I(CR), the second U.S. isolate (HTLV-I[MB]), and the Japanese ATLV isolates. Proviral sequences indistinguishable from those of HTLV-I(CR) were also detected in uncultured leukemic blood leukocytes from a patient of Japanese origin with adult T-cell leukemia. These viral isolates thus form a closely related virus group, HTLV-I. In contrast, however, RNA and DNA from one cell line derived from a patient with a T-cell variant of hairy cell leukemia, which expresses media reverse transcriptase and antigenic determinants related to but distinguishable from HTLV p24, did not hybridize substantially with HTLV cDNA. This latter virus appears to represent a second type of HTLV (HTLV-II), related to but substantially different from HTLV-I.

Cell Line↗
PubMed1983

Infection and transformation of fresh human umbilical cord blood cells by multiple sources of human T-cell leukemia-lymphoma virus (HTLV).

Human T-cell leukemia-lymphoma virus (HTLV) was first isolated from sporadic patients with adult T-cell malignancies in the United States and subsequently from T-lymphocytes established in culture from additional T-cell leukemia-lymphoma patients living in different geographical areas of the world. Co-cultivation of normal umbilical cord blood with lethally irradiated, HTLV-positive lymphocytes established in culture from many of these patients resulted in the productive infection of the cord blood T-lymphocytes which grew in suspension culture in the absence of exogenous TCGF. These transformed cord blood cells have morphological and cytochemical properties similar to HTLV-positive fresh and cultured tumor T-cells and are distinguishable from virus donor cells by HLA haplotype and chromosomal markers. These cells express HTLV proteins, release type-C virus particles and contain surface receptors for TCGF. These results demonstrate that HTLV isolated from T-cell leukemic donors from different parts of the world can productively infect and transform fresh human cord blood T-lymphocytes, and that the transformed cells share many similarities with fresh or cultured leukemic cells.

Animals↗
PubMed1983

Isolation and transmission of human retrovirus (human t-cell leukemia virus).

Nine new isolates of human T-cell leukemia-lymphoma virus (HTLV) were obtained from cells of seven patients with malignancies of mature T cells and from two clinically normal relatives of a T-cell leukemia patient. These people were from the United States, Israel, the West Indies, and Japan. The virus was detected in the fresh T cells and was isolated from the established T-cell lines. Each isolate is closely related to the first HTLV isolate, and all the new HTLV isolates were transmitted into normal human T cells obtained from the umbilical cord blood of newborns.

Cell Line↗
PubMed1983

Evidence for human T cell lymphoma-leukemia virus infection of family members of human T cell lymphoma-leukemia virus positive T cell leukemia-lymphoma patients.

Sera of family members of patients from the United States, the Caribbean, and Japan, with human T cell lymphoma-leukemia virus (HTLV) associated T cell malignancies, possess HTLV-specific antibodies directed against internal structural components of HTLV, p24 and p19. The prevalence of antibodies to HTLV is greater in family members than in random healthy donors, which supports the infectious nature of HTLV and its association with particular aggressive T cell malignancies. Expression of HTLV p24 and p19 has also been observed in cultured T cells of some healthy relatives, and intact virus particles have been released from cells of one possibly pre-leukemic family member.

Antibodies, Neoplasm↗
PubMed1983

Abundant transcription of a cellular gene in T cells infected with human T-cell leukemia-lymphoma virus.

Human T-cell leukemia-lymphoma virus (HTLV) is a type C retrovirus associated with a subtype of mature T-cell malignancy in humans. HTLV also infects normal human cord blood mature T lymphocytes in vitro and induces a number of phenotypic changes in these cells, including their continuous growth and partial or complete independence of T-cell growth factor (TCGF). As part of our initial study designed to analyze gene(s) specifically activated by HTLV infection, we have isolated a recombinant DNA clone by differential screening of a cDNA library made from mRNA of a human T-cell lymphoma cell line producing HTLV. This cDNA identifies a single-copy gene in all human DNAs and a single mRNA species of 2.3 kilobases expressed at several hundred copies per cell in five HTLV-positive neoplastic T-cell lines. In addition, cord blood T lymphocytes infected with HTLV, but not the uninfected counterparts, express high levels of mRNA from this gene. A survey of different human hematopoietic cell types showed that this gene is expressed at low or undetectable levels (less than 10 copies) in human T, B, myeloid, or erythroid cell lines; in moderate amounts in lymphoid precursor (immature) cell lines; and in high amounts in lectin-activated mature T-cells, comparable to those of HTLV-infected T-cell lines. The precise function of this gene has not yet been determined.

Animals↗
PubMed1983

Transformation of human umbilical cord blood T cells by human T-cell leukemia/lymphoma virus.

Several isolates of human T-cell leukemia/lymphoma virus (HTLV) were transmitted to normal human T cells obtained from the umbilical cord blood of newborns. T cells from seven specimens were immortalized by infection with different HTLV isolates and their properties were compared with those of activated uninfected normal T cells grown in the presence of T-cell growth factor (TCGF) and with those of HTLV-positive neoplastic T-cell lines derived from patients with T-cell malignancies. The HTLV-infected cells generally belonged to a class of mature T cells (OKT4+ and Leu 3A+) and differed from the normal uninfected cells in that they could be propagated in culture indefinitely; possessed altered morphology, including convoluted nuclei and some bi- and multinucleated giant cells; formed large clumps in culture; demonstrated a diminished requirement for TCGF; had an increased density of TCGF receptors; often became completely independent of exogenous TCGF; and expressed HLA-DR determinants. These properties of the HTLV-infected cord blood T cells contrasted to those of uncultured cord blood T cells and of cord blood cells stimulated with mitogen and grown with TCGF but resembled the characteristics of T-cell lines established previously from patients with HTLV-associated T-cell malignancies. This in vitro system offers a unique opportunity to study the basic mechanism involved in abnormal growth and neoplastic transformation of a specific class of human T cells.

Cell Division↗
PubMed1983

High incidence of human type-C retrovirus (HTLV) in family members of a HTLV-positive Japanese T-cell leukemia patient.

Sera and peripheral blood cells of an adult T-cell leukemia patient and several clinically normal members of his family from the northwest coast of Japan were examined for evidence of infection with human T-cell leukemia (lymphoma) virus (HTLV). The sera of the patient and his parents had antibodies to HTLV, whereas these antibodies were absent in the sera of the patient's brother and sister. T-cell lines were established from the peripheral blood lymphocytes of all of the family members, and all except the patient's sister expressed HTLV antigens (p19, p24, and reverse transcriptase) and type-C virus particles. Not only the fresh peripheral blood lymphocytes from the patient but also those from his clinically normal mother showed abnormal morphology of the kind characteristic of some patients with T-cell leukemia. These studies are consistent with previous evidence indicative of a high rate of HTLV infection within families, and they show that people whose sera are negative for antibodies may still be infected by HTLV. In addition, the results indicate that infection of T cells by HTLV can be associated with morphological transformation of the cells without other signs of leukemia.

Humans↗
PubMed1983

Human T-cell leukemia/lymphoma virus: the retrovirus of adult T-cell leukemia/lymphoma.

Human T (thymus-derived)-cell leukemia/lymphoma virus (HTLV) is a new retrovirus first isolated from T-cell lines from a patient with cutaneous T-cell lymphoma from the southeastern United States. Closely related viruses have since been isolated from several patients with adult T-cell leukemia and lymphoma (and some normal persons) from different areas of the world. HTLV is not a genetically transmitted endogenous virus of humans, but it rather is acquired by postzygotic infection. Natural antibodies to several purified viral proteins have been observed in infected individuals. HTLV is transmissible in vitro to human cord blood T cells, and infection results in an increased growth rate, a reduced requirement for (and often independence from) T-cell growth factor, and an abrogation of the crisis period that usually occurs a month after the establishment of normal T-cell cultures. These data suggest that HTLV is the etiologic agent in some human cases of leukemia and lymphoma.

Antibodies, Viral↗
PubMed1983

Cell surface antigen expression in newborn cord blood lymphocytes infected with HTLV.

Human T cell lymphocyte lines, established from lymphoid tissues from patients with adult T cell malignancies infected with the human T cell lymphoma virus (HTLV), were used in co-culture experiments to infect newborn cord blood lymphocytes (CBL). The infected and non-infected CBL cell lines were typed for HLA alloantigen determinants and tested for cell surface antigens using selected monoclonal antibodies. Infected cord blood lymphocytes showed inappropriate expression of alloantigenic determinants of the HLA-A and -B alleles. The monoclonal antibody 4D12, detecting an antigen common to the HLA-B5 cross-reactive group, was reactive with all infected cultures; this determinant appeared de novo in CBL cells lacking B5 cross-reactive group antigens in the uninfected state, and it increased in density in the infected cultures where the HLA-B5 cross-reactive alloantigens were present in uninfected CBL. HLA-DR was expressed in low levels or not detected on non-infected cultured cord blood lymphocytes and was present on all infected cells. OKT4 positive cells predominated in infected cultures, whereas OKT8 positive cells decreased in number or were absent. The TCGF receptor also increased both in density and in percent positive cells in all infected cell lines. The results suggest that HTLV may be tropic for a subset of T cells expressing mature T cell markers and that viral infections directly affect expression of cell surface antigens controlled by the human major histocompatibility complex (MHC).

Adult↗
PubMed1982

Identification of the RPMI 8226 retrovirus and its dissemination as a significant contaminant of some widely used human and marmoset cell lines.

A retrovirus designated RPMI 8226V, isolated in 1973 from the human myeloma cell line RPMI 8226 has been characterized by competition radioimmunoassay (RIA) for the major viral structural protein and by nucleic acid hybridization analysis using cDNA of the virus. The virus is highly related to the squirrel monkey type D retrovirus, SMRV. In the homologous RIA using rabbit anti-RPMI 8226V and 125I-labelled p37 of RPMI 8226V, RPMI 8226V and SMRV exhibited competition of 81% and 73% respectively. Similarly, in the homologous system for SMRV p36, these viruses competed 98 and 100%. Reagents made from the type D retrovirus. Mason Pfizer Monkey Virus (MPMV), known to be related but distinct from SMRV, were used in assays designed to detect interspecies determinants of type D retroviruses. In assays using goat anti-MPMVp26 vs SMRV 125I-p36, RPMI 8226V, SMRV and MPMV competed to the same extent (93%). Hybridization analysis of RPMI 8226V cDNA showed significant homology to cellular RNA and DNA of mink, bat, and human cell infected with RPMI 8226V and to DNA or SMRV infected cells but not to uninfected cells or cells infected with other viruses. These results taken together clearly indicate that RPMI 8226V and SMRV are very closely related to each other. The finding of a type D retrovirus in this human myeloma cell line that had been used in EBV studies (the usual source of EBV being the marmoset cell line B95-8) prompted a survey of RPMI 8226V in some human and marmoset cell lines. The assays included the RIA for p36, nucleic acid hybridization using cDNA of RPMI 8226V, reverse transcriptase analysis and electron microscopy (EM). The results clearly show that in addition to RPMI 8226, human Burkitt lymphoma cells BJAB/B-95-8/K which were supertransformed by EBV from B-95-8/K marmoset cells as well as marmoset cell lines [(B-95-8/K and B-95-8/N) obtained from Stockholm and Uppsala, Sweden] were positive for the RPMI 8226V. Similar lines obtained elsewhere were negative. The results obtained clearly indicate that RPMI 8226V is a serious laboratory contamination in some widely used human cell lines. The possible impact of this viral contamination for some virological and cell biological studies is discussed.

Animals↗
PubMed1981

Immunoprecipitation of membrane proteins of cultured human sarcoma cells.

Human sarcoma associated antigens (HSAA) have previously been identified by indirect immune fluorescence in human sarcoma cells in culture using sera from patients bearing different types of sarcoma. To further characterize these HSAA, surface proteins of cultured cells were labeled with 125Iodine, [3H]-glucosamine and [35S]-methionine and solubilized. After immunoprecipitation labeled proteins were detected in immune complexes by SDS polyacrylamide gel electrophoresis and autoradiography, which allowed comparison with antigens described by other groups. A surface protein (Mr 96 000) was precipitated with sera from sarcoma bearing patients, and two glycoproteins (Mr 115 000 and 85 000) were preferentially precipitated with antisera from rabbits immunized with membranes from two human sarcoma cell lines. At least two of these proteins were found in each of five human sarcoma cell lines studied (U-4SS, U-3930S, U-20S, B-5GT and B-6FS). None of the proteins were precipitated with three human control sera, and only occasionally a faint band was observed in immunoprecipitates from control cells (B-25F, B-41B, B-42FC, U-2S, and U-393S with the immune sera. These proteins are probably some of the antigens responsible for the immune fluorescence observed in determination of HSAA. However, purification of the proteins and competition experiments are needed before this can be finally established.

Antigens, Neoplasm↗
PubMed1980

Radioimmunoassay for major internal structural protein (p21) of the bovine leukemia virus; antibodies detection and viruses identification.

The major internal protein of bovine leukemia virus (BLV p24) was isolated using ion exchange chromatography on phosphocellulose and gel filtration. The specificity of the BLV p24 isolated was checked by both the radioimmunoprecipitation (RIP) and the competitive radioimmunoassay (RIA). No cross reactivity between BLV p25 and the mammalian viruses of type C and D and the retrovirus isolated from human myeloma cells RPMI8226 [8, 17] was detected. The analysis of 429 leukemia-suspected bovine blood sera resulted in the detection of 165 (38.5%) positive and 264 (61.5%) negative blood sera. A correlation of the results of radioimmunoprecipitation reaction of major internal protein p24 and immunodiffusion test on the glycoprotein antigen of BLV was observed.

Animals↗