Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A method is presented whereby antigenic determinants recognized by specific monoclonal antibodies can be mapped to specific sites on a protein sequence with high resolution. Short DNase I-generated DNA fragments encoding portions of the protein of interest are molecularly cloned into the EcoRI site of the beta-galactosidase gene of phage lambda Charon 16 so as to obtain expression of random protein fragments as fusion proteins. The monoclonal antibody is used to screen the phage library to isolate phage expressing the specific antigenic determinant. DNA of immunoreactive phage can be analyzed rapidly and subcloned to allow DNA sequence determination. The method is generally applicable and permits antigenic determinants of functionally interesting monoclonal antibodies to be mapped and related to specific protein sequences. We have used this procedure to determine the region of the feline leukemia virus envelope protein gp70 recognized by a virus-neutralizing monoclonal antibody, cl.25. Antibody binding was mapped to a 14-amino acid region in the amino-terminal half of gp70. This region may be directly involved in an essential function of the gp70 protein, perhaps in gp70-mediated host recognition functions. Synthetic peptides derived from this region may provide useful vaccine antigens for the prevention of feline leukemia virus-associated disease in cats.
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PMID:Method to map antigenic determinants recognized by monoclonal antibodies: localization of a determinant of virus neutralization on the feline leukemia virus envelope protein gp70. 620 25

Two regions of the gene for the human T-cell leukemia virus subgroup I (HTLV-I) envelope were expressed in Escherichia coli by use of the vector pJLA16. One corresponds to the carboxyl terminal region of the major envelope protein p46, and the other corresponds to the transmembrane protein p21E. Reactivity of the expressed protein with human serum was tested by the Western blot procedure. Each of 11 sera tested that had been shown to contain antibodies to HTLV-I or HTLV-II by an enzyme-linked immunosorbent assay recognized the bacterially synthesized envelope proteins. There was no reaction detected when 17 control sera were tested. This system will be useful for large-scale seroepidemiological surveys for HTLV-I and related human retroviruses.
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PMID:Diagnostic potential for human malignancies of bacterially produced HTLV-I envelope protein. 620 12

T cell responses to Moloney virus involve cytolytic and helper lymphocytes. In contrast to specific cytolytic T lymphocytes, few studies have been devoted to the characteristics of helper T cells for antibody production. The present experiments describe an assay for Moloney virus-specific help for B cells using dinitrophenylated virus. This method, using the Moloney virus as a carrier in a hapten-carrier system, allows to definition of the specific helper function of antibody responses. T helper cells were induced in murine sarcoma virus or inactivated Moloney murine leukemia virus-primed spleens or lymph nodes. T helper function was due to Thy-1.2, Lyt-1+2- cells and was macrophage-dependent. It was stimulated by whole virus of Moloney gp71 envelope protein but not Moloney p30 internal protein. Cross-reactive stimuli were obtained with other dinitrophenylated type C viruses. High and low responses were correlated respectively with resistance and susceptibility to Moloney leukemia virus. Cultures of helper T cells with preserved activity have been established and maintained for one month.
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PMID:Genetic control of sensitivity to moloney leukemia virus in mice. VI. Involvement of virus-specific T helper cells collaborating with B cells. 621 12

Sera of breast cancer patients from the United States, India, East Africa and China as well as from their families and from healthy women were assayed for antibodies reactive with the murine mammary tumor virus (MuMTV). Detection was by an enzyme-linked immunoassay recently developed in our laboratory. In the women with breast cancer, 62% of the East Africans, 28% of the Indians, 19% of the Americans but only 5% of the Chinese had antibody to MuMTV. Among healthy women, 21% of the Africans, 3% of the Americans and 5% of the Chinese possessed this antibody. Several family members of breast cancer patients, males as well as females, had increased levels of MuMTV antibody. The MuMTV-reactive antibody was removed by absorption with MuMTV, deglycosylated MuMTV and gp52, the major MuMTV envelope protein. It was not absorbed out by murine leukemia viruses, red blood cells from various species, fetal calf serum or carbohydrates. The results suggest that there may be more than one form of breast cancer, definable by reactivity to MuMTV. The murine mammary tumor virus (MuMTV) is the etiological agent of breast cancer in mice. The induction of mammary tumorigenesis, however, is dependent upon the genetic makeup, hormonal status, and diet of the infected mouse. Thus, even in a situation where a known single cause for breast cancer exists, disease manifestation is subordinate to diverse factors in the individual host.
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PMID:Geographic and family studies of immunological responses to antigens of the murine mammary tumor virus in sera of patients with breast cancer. 626 56

We investigated the nature of a common tumor rejection antigen(s) in chemically induced murine fibrosarcomas. Two methylcholanthrene-induced fibrosarcomas, previously demonstrated to contain a common tumor rejection antigen(s), released infectious ecotropic murine leukemia virus and expressed the murine leukemia virus proteins, a glycoprotein with a molecular weight of 70,000 (gp70) and an envelope protein with a molecular weight of 15,000. To determine whether an antigen(s) specified by a murine leukemia virus might serve as a common tumor rejection antigen(s), primary cultures of syngeneic embryo cells or cultures of an allogeneic embryo cell line were infected with an endogenous ecotropic murine leukemia virus obtained from one of the cross-reacting fibrosarcomas; expression of infectious virus and/or viral proteins by infected and uninfected embryo cells was monitored and correlated with the results of transplantation protection tests. Uninfected allogeneic embryo cells (SC-1) did not release infectious virus or the viral protein gp70; mice immunized with SC-1 cells did not inhibit tumor growth. Uninfected syngeneic embryo cells did not release infectious virus but did release micrograms quantities of gp70 into supernatant fluids; mice immunized with uninfected syngeneic cells inhibited tumor growth in two of seven experiments. Virus-infected syngeneic and allogeneic embryo cells released both infectious ecotropic murine leukemia virus and gp70; mice immunized with virus-infected cells inhibited tumor growth in 11 of 11 experiments. Growth of the two cross-reacting fibrosarcomas was inhibited in mice immunized with virus-infected embryo cells. The results indicate that antigens coded for by endogenous murine leukemia virus may function as common tumor rejection antigen on chemically induced murine fibrosarcomas.
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PMID:Immunoprophylaxis of transplantable methylcholanthrene-induced murine fibrosarcomas by immunization with embryo cells expressing endogenous murine leukemia virus antigens. 627 79

Sixteen mouse and rat monoclonal antibodies reactive with gag or env proteins of Friend murine leukemia virus (F-MuLV) or recombinant MCF viruses related to F-MuLV were derived. Specificity of these was determined by immunofluorescence, immunoprecipitation, and reactivity with viral proteins blotted onto nitrocellulose paper. Seven antibodies reacted with envelope protein antigens of certain nonecotropic viruses only. Nine antibodies reacted with both ecotropic and nonecotropic viruses. Of this latter group, three were antienvelope, four were anti-p15, one was anti-p12, and one was anti-p30 in specificity. When tested as a panel against 10 strains of F-MuLV, these antibodies could distinguish seven different antigenic patterns. However, all 10 strains retained reactivity for three anti-gp70 antibodies uniquely specific for Friend and Rauscher MuLVs. Our antibody panel could also identify MCF viruses isolated from mice neonatally inoculated with F-MuLV as recombinants related to a particular F-MuLV strain based on identity of p15 gag antigenic profiles. However, recombinant viruses lacked several envelope antigens always associated with F-MuLV and instead had new envelope reactivities. These anti-MCF monoclonal antibodies detected no shared envelope antigens between MCF and xenotropic viruses isolated from mice inoculated with F-MuLV, however many of them did react with MCF viruses derived from AKR mice and NFS mice congenic for endogenous ecotropic virus loci.
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PMID:Characterization of monoclonal antibodies reactive with murine leukemia viruses: use in analysis of strains of friend MCF and Friend ecotropic murine leukemia virus. 630 11

Passage of human tumors in athymic mice is accompanied by an increase in serum levels of the Mr 70,000 murine leukemia virus envelope protein, gp70. Elevated levels of gp70 can be detected in tissues of the hematopoietic systems of mice bearing human xenografts, but there is no evidence of synthesis of gp70 in these tissues. By far, the highest concentration of gp70 is in the human xenografts themselves. When assayed for gp70, 8 human xenografts and 12 cell lines established from human xenografts were all positive. In the plasma membrane of the human astrocytoma xenograft, T24, the gp70 was found to be approximately 10% of the total membrane protein. In contrast, the concentration of the Mr 30,000 viral core protein, p30, was 17-fold less. Only trace amounts of complete infectious virus could be detected. A human prostate carcinoma line that had not been grown in the athymic mice was found to have no gp70, but was shown to be able to synthesize gp70 after a single passage in the athymic mice.
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PMID:Amplification of the murine leukemia virus Mr 70,000 glycoprotein gene product by human xenografts in athymic mice. 630 13

Immunosuppression is commonly associated with retrovirus-induced animal tumors. Studies in the murine and feline retrovirus systems suggest that the 15,000-dalton envelope protein (p15E) of the virion may contribute to immunosuppression by interfering with normal lymphocyte function. We examined the effect of inactivated feline leukemia virus (UV-FeLV) and p15E derived from this virus on concanavalin A (Con A) driven human T cell proliferation. Virus and p15E markedly suppressed mononuclear cell proliferative response to Con A. Suppression was not due to inhibition of monocyte accessory cell function, or interleukin 1 (IL 1) secretion. In fact, the presence of monocytes partially protected T cells from UV-FeLV suppression. UV-FeLV, however, suppressed T cell secretion of and response to interleukin 2 (IL 2). We conclude that UV-FeLV and derived p15E inhibit T cell proliferation by direct inhibition of T cell function. These findings, extended to the in vivo situations, suggest that retrovirus-associated suppression of the immune response involves the induction of T cell but not monocyte dysfunction.
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PMID:The mechanism of retrovirus suppression of human T cell proliferation in vitro. 631 4

The effects of concentrated ultraviolet-inactivated feline leukemia virus (FeLV), the purified Mr 15,000 envelope protein (p15E) of FeLV, or the purified Mr 27,000 structural protein (p27) of FeLV on feline bone marrow mononuclear cells were studied in vitro in methylcellulose cultures. Whole virus and purified viral proteins were from the Kawakami-Theilen isolate of FeLV, which induces erythroid aplasia in cats. Bone marrow mononuclear cells from FeLV-negative young adult cats were preincubated with a medium control, ultraviolet-inactivated whole virus, or the p15E or p27 of FeLV, incubated in methylcellulose cultures for 2 days, and then observed for the formation of colony-forming units-erythroid (CFU-E) and colony-forming units-granulocyte/macrophage. The ultraviolet-inactivated Kawakami-Theilen isolate of FeLV at concentrations of 10 or 20 micrograms of viral protein/5 X 10(4) cells suppressed CFU-E to 66 to 56% of control values but had no significant effect on proliferation of colony-forming units-granulocyte/macrophage. p15E at concentrations of 0.1 to 0.2 micrograms/5 X 10(4) cells decreased CFU-E numbers to 0 to 1% of control values, whereas the same concentration of p27 did not alter CFU-E growth when compared with controls. Neither p15E nor p27 had a significant effect on growth of colony-forming units-granulocyte/macrophage. The erythrosuppressive effects of whole virus and an envelope-derived protein but not a structural core protein suggest that FeLV envelope proteins are important in the selective inhibition of erythrogenesis observed in vivo in FeLV-infected cats.
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PMID:Inhibition of erythroid colony-forming cells by a Mr 15,000 protein of feline leukemia virus. 632 79

Tumour cells share with normal cells antigens characteristic of defined states of differentiation. Is there anything else? An example of tumour antigens not expressed anywhere in normal tissue is the set of tumour-specific transplantation antigens (TSTA) of murine chemically induced sarcomas. There is evidence that at least one TSTA specificity is retrovirus-derived, is carried on the envelope protein gp70, and probably arises by the recombination events that yield the diverse gp70s of the MCF strains of murine leukaemia viruses. Whether a similar mechanism can generate human tumour antigens depends on the yet unanswered question of whether human cells have retroviruses in their genomes capable of recombination. Aside from this, the only other mechanism known for antigen expression on tumours is via their oncogenes, which seem to make normal cell products. Such products, or secondary consequences of their production, were they normally expressed only at an early stage of development, would be candidates for 'fetal antigens'. While only the two mechanisms mentioned above seem the ready sources of 'tumour-associated antigens', it would be too early--in the face of ever more startling information about gene mobility and rearrangements--to think we have exhausted possible mechanisms for generating tumour antigens.
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PMID:How are tumour antigens related to normal antigens? 634 8


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