Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Epstein-Barr virus (EBV) is associated with B-cell malignancy in immunosuppressed humans and SCID mice receiving human peripheral blood leukocyte grafts (hu-PBL-SCID). We have further characterized the process of lymphoma development in hu-PBL-SCID mice. We report that EBV-seropositive donors differ markedly in the capacity of their PBL to give rise to immunoblastic lymphomas in SCID mice; some donors (high incidence) generated tumors rapidly in all hu-PBL-SCID mice, other donors (intermediate-low incidence) gave rise to sporadic tumors after a longer latent period (greater than 10 weeks), and some donors failed to produce tumors. B-cell lymphomas arising from high incidence donors were multiclonal in origin, and EBV replication was detected in all tumors. Tumors derived from intermediate-low incidence donors were monoclonal or oligoclonal and often had no evidence of viral replication. All tumors, regardless of the donor, resembled EBV-transformed lymphoblastoid cell lines in surface phenotype but differed from lymphoblastoid cell lines by having less Epstein-Barr nuclear antigen 2 and CD23 expression. The variable patterns of lymphomagenesis seen among different EBV-sero-positive donors may be explained by lower levels of specific immunity to EBV in high incidence donors, permitting activation of EBV replication and potential transformation of secondary B-cell targets. In addition, there may be differences in the transforming potential of EBV infecting different donors. The use of the hu-PBL-SCID model may help predict patients at high risk for posttransplant or acquired immunodeficiency syndrome-associated lymphomas.
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PMID:Heterogeneity among Epstein-Barr virus-seropositive donors in the generation of immunoblastic B-cell lymphomas in SCID mice receiving human peripheral blood leukocyte grafts. 131 93

As previously described, proliferation of Kaposi sarcoma (KS)-derived cells in vitro is dependent on the presence of platelet-derived growth factor (PDGF). To test the hypothesis that PDGF may also be a major growth factor for KS cells in vivo, we performed in situ hybridization and immunohistochemical staining for PDGF and PDGF receptors in tissue sections of AIDS-related KS. The data suggest that KS consists of two types of tumor cells. (i) The main population are spindle-shaped cells with elongated nuclei (KS-s cells). They reveal a strong expression of PDGF beta receptors but do not express the PDGF-A and PDGF-B isoforms. (ii) A minor population of KS cells express PDGF beta receptor as well as PDGF-A and PDGF-B (KS-p cells). These cells are often grouped in whorls and surrounding vascular slits. They reveal spherical nuclei with evenly distributed chromatin and inconspicuous nucleoli. PDGF alpha receptor is not expressed in either form of KS cells. The results suggest that the isoforms of PDGF and the PDGF beta receptor are differentially expressed in two different cell types in KS and that PDGF isoforms may contribute to the pathogenesis of KS.
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PMID:Expression of platelet-derived growth factor and its receptor in AIDS-related Kaposi sarcoma in vivo suggests paracrine and autocrine mechanisms of tumor maintenance. 132 24

The prevalence of Epstein-Barr virus (EBV) and human immunodeficiency virus (HIV) in acquired immunodeficiency syndrome (AIDS)-related primary central nervous system (CNS) lymphoma was examined. Deoxyribonucleic acid (DNA) extracted from 12 formalin-fixed, paraffin-embedded tumors was used as substrate for the polymerase chain reaction (PCR). Targets for amplification were the EBNA-1 region of EBV, the gag region of HIV, and a single copy cellular sequence as a control. The cases studied were autopsy and surgical specimens collected between the years 1985 and 1989. By the working formulation for non-Hodgkin's lymphomas, five had large cell, four had mixed large and small cleaved cell, two had small cleaved cell, and one had an unclassified histology. Epstein-Barr virus was detected in 6 of 12 tumors studied. Human immunodeficiency virus was not detected in any of the tumors. The presence of EBV was not correlated with any particular histologic tumor type. It is concluded that EBV, not HIV, can be detected in a large percentage (50%) of AIDS-related primary central nervous system (CNS) lymphomas. This viral association may be significant in light of the demonstrated ability of EBV to induce lymphoid tumors in experimental mammalian systems.
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PMID:Epstein-Barr and human immunodeficiency viruses in acquired immunodeficiency syndrome-related primary central nervous system lymphoma. 132 21

The data presented here indicate that the pathogenesis of AIDS-NHL is variably associated with multiple genetic alterations including monoclonal EBV infection, oncogene activation (c-myc, N-, Ki-ras) and tumor suppressor gene (p53) inactivation. Up to three (3 cases) or four (1 case) different lesions have been observed in the same tumor. The distribution of these lesions among the various histotypes is heterogeneous, although some preferential associations have been found either between lesion and histotype or between lesions. The most notable case involves p53 mutations/loss that is exclusively associated with the SNCC lymphoma subtype. Since alterations of the c-myc gene occur at very high frequency in this same histotype it is possible that both lesions may be required for the pathogenesis of the BL phenotype. The consistent negativity of p53 lesions in other NHLs associated or non associated with HIV infection (18) reinforces this hypothesis. Finally, we note that the frequency of p53 mutations is significantly higher in AIDS-BL than in non HIV-related BL (18), although the significancy of this difference remains to be assessed. This study confirms the relatively low frequency of EBV infection in systemic AIDS-NHL in general, but reinforces the notion that EBV may be required for the pathogenesis of AIDS-LC-IBP, as recently suggested by the high frequency of EBV positivity in primary CNS AIDS-NHL which are mostly represented by LC-IBP (2). Conversely, the low frequency of EBV sequences in the AIDS-SNCC lymphomas appears similar to that observed in sBL. Only in a small minority of cases were ras oncogene mutations found, mostly associated with the BL type.(ABSTRACT TRUNCATED AT 250 WORDS)
AIDS Res Hum Retroviruses 1992 May
PMID:Molecular pathogenesis of HIV-associated lymphomas. 132 69

A recent addition to the lymphokine network is human IL-10 (hIL-10). This novel lymphokine has striking homology to BCRF1 protein, the product of a previously uncharacterized open-reading frame in the Epstein-Barr virus (EBV) genome. To date, IL-10 expression has been described in several T clones induced with anti-CD3 and phorbol myristate acetate (PMA), in monocytes stimulated with lipopolysaccharide (LPS), and in murine B-cell lymphomas. We sought to determine whether human B cells express hIL-10 and, if so, its relationship to EBV and to other B-cell lymphokines. We studied 21 EBV-positive B-cell lines derived from patients with acquired immunodeficiency syndrome (AIDS) and Burkitt's lymphoma (n = 6), American Burkitt's (n = 3), African Burkitt's (n = 5), and normal lymphoblastoid cell lines (n = 7), in comparison with seven EBV-negative cell lines. All cell lines were activated with the tumor promoters PMA and teleocidin and were studied by Northern blot analysis, reverse transcription-polymerase chain reaction (RT-PCR), and enzyme-linked immunoadsorbent assay (ELISA). We demonstrated that EBV-positive cell lines derived from patients with American Burkitt's lymphoma, and especially those from patients with AIDS, constitutively express large quantities of hIL-10 by Northern blot analysis and ELISA (range, 3,101 to 25,915 pg/mL), and that both teleocidin and PMA induce hIL-10 in these cell lines. In contrast, six of seven EBV-negative cell lines did not express hIL-10 even by RT-PCR, and hIL-10 was not triggered by PMA or teleocidin. To assure that the 350 bp amplified by PCR was hIL-10 and not BCRF1, we used PCR primers, which do not amplify a fragment from plasmid templates containing BCRF1. Cloning and sequencing of the 350 bp product also demonstrated that B-cell IL-10 is identical to hIL-10 from the T-cell clone B21. Correlation of hIL-10 with other B-cell lymphokines secreted by these B-cell lines demonstrated that hIL-10 secretor cell lines also constitutively secrete or can be induced to secrete IL-6, although to a much lesser amount. Since both lymphokines influence B-cell growth and differentiation, we suggest that hIL-10 may contribute to the polyclonal B-cell activation and hyperglobulinemia seen in AIDS patients. Finally, several reports support the hypothesis that EBV is an important cofactor in the development of human immunodeficiency virus type 1 (HIV-1)-related B-cell lymphomas. Detection of large quantities of hIL-10 in B-cell lines derived from AIDS patients, the close association between EBV and hIL-10 shown in this report, and the ability of BCRF1 to capture hIL-10 activities, make hIL-10/BCRF1 an attractive candidate as a factor causing B-cell growth and immortalization in patients with AIDS and B-cell lymphomas.
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PMID:Human B-cell interleukin-10: B-cell lines derived from patients with acquired immunodeficiency syndrome and Burkitt's lymphoma constitutively secrete large quantities of interleukin-10. 842 93

Interest in the human cytomegalovirus (HCMV) mainly derives from its associations with congenital malformations, mental retardation, and severe or fatal infections in immunosuppressed individuals such as transplant patients, tumor and AIDS patients. It is evidenced that there has been a need for a rapid and sensitive methods to detect an ongoing acute infection. The recent studies showed that high titers of antibody to the glycoprotein 52kd are present in sera of patients undergoing acute HCMV infection. However, purification of individual glycoprotein from HCMV-infected cells is a daunting prospect. HCMV glycoprotein 52 kd expressed via recombinant DNA techniques are a promising approach to solve this problem. In order to evaluate the diagnostic value of the recombinant glycoprotein 52 kd antigenic code region for HCMV infection, we have used the polymerase chain reaction (PCR) and recombinant DNA techniques to construct successfully the high-level expression plasmid pHCMV containing the HCMV GP-52 kd antigenic code region, with the predicted protein at levels up to 20% in total bacterial protein. The expressed protein was purified from SDS-PAGE, used as an antigen in Western-blot, and reacted with 12 cases of the positive sera, 4 cases of the negative sera, following by reaction with HRP-labelled horse IgG antibody against human. The results indicated that the approach we are using to detect antibody to HCMV acute infection are as sensitive as general serological methods such as ELISA, with the advantages of easy preparation of antigen with high quantity, and clinical practicability.
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PMID:[Preliminary use of recombinant glycoprotein 52kd as an antigen in the diagnosis of human cytomegalovirus infection]. 132 25

A cDNA encoding UDP-GlcNAc:Gal beta 1-3GalNAc-R (GlcNAc to GalNAc) beta 1-6GlcNAc transferase (EC 2.4.1.102), which forms critical branches in O-glycans, has been isolated by an expression cloning approach using Chinese hamster ovary (CHO) cells. Increased activity of this enzyme and the concomitant occurrence of the O-glycan core 2 structure [Gal beta 1-3(GlcNAc beta 1-6)GalNAc] has been observed in a variety of biological processes, such as T-cell activation and immunodeficiency due to the Wiskott-Aldrich syndrome and AIDS. Since CHO cells do not express this enzyme, CHO cell lines were established to stably express polyoma large tumor (T) antigen, which enables transient expression cloning. Because the antibody used was found to detect most efficiently the oligosaccharide products attached to leukosialin, the CHO cells were also stably transfected with leukosialin cDNA. By using this particular CHO cell line, a cDNA that encodes a protein determining the formation of the core 2 structure was isolated from an HL-60 cDNA library. The cDNA sequence predicts a protein with type II membrane topology, as has been found for all other mammalian glycosyltransferases cloned to date. The expression of the presumed catalytic domain as a fusion protein with the IgG binding domain of protein A enabled us to demonstrate unequivocally that the cDNA encodes the core 2 beta-1,6-N-acetylglucosaminyltransferase, the enzyme responsible for the formation of Gal beta 1-3(GlcNAc beta 1-6)GalNAc structures. No activity with this enzyme was detected toward the acceptors for other beta 1-6GlcNAc transferases.
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PMID:Expression cloning of a cDNA encoding UDP-GlcNAc:Gal beta 1-3-GalNAc-R (GlcNAc to GalNAc) beta 1-6GlcNAc transferase by gene transfer into CHO cells expressing polyoma large tumor antigen. 132 93

Human T-cell leukemia virus type (HTLV-I) is a type C retrovirus that has been linked to both adult T-cell leukemia and neurological disorders in humans. Baboons and other Old World non-human primates harbor a related virus termed simian T-cell leukemia virus type 1 (STLV-I), which may also be associated with neoplastic disease. To explore the utility of the baboon as a model for HTLV-I infection and disease, 329 baboons from a colony of 3200 at the Southwest Foundation for Biomedical Research (SFBR) were analyzed for the presence of antibodies against STLV-I. An overall seroprevalence rate of > 40% was found, with higher rates in females versus males. Furthermore, seroprevalence rates increased dramatically with age, reaching greater than 80% in animals over the age of 16. Molecular and antigenic analysis of proviral DNA isolated from both tumor tissue and a cell line isolated from a baboon with non-Hodgkin's lymphoma (NHL) indicates that STLV-I in this colony is closely related to HTLV-I. Furthermore, monoclonally integrated provirus isolated from lymphoma tissue was detected, strongly implicating STLV-I in the etiology of this malignancy. DNA primer pairs homologous to HTLV-I sequences amplified both HTLV-I and STLV-I, but not HTLV-II, providing further evidence for a close genetic relationship between baboon-derived STLV-I and HTLV-I. The detailed study of a large population of naturally infected baboons may therefore shed some light into the complex processes required for the induction of disease associated with HTLV-I infection in humans.
AIDS Res Hum Retroviruses 1992 Sep
PMID:Simian T-cell leukemia virus type I infection in captive baboons. 133 79

Bronchopulmonary lavage (BAL) has provided a fresh dimension for the investigation of pulmonary and multisystem disorders. BAL fluid may be analysed for cells and chemical mediators in the diagnosis and also serially for the management of several granulomatous disorders including sarcoidosis, extrinsic allergic alveolitis, chronic beryllium disease, talc granulomatosis, tuberculosis, Langerhans' histiocytosis-x and Crohn's disease. It may also provide information in fibrosing alveolitis, collagen vascular disease, occupational and drug-induced lung disease, acquired immune deficiency syndrome, bronchial asthma, neoplasia, transplantation, pulmonary alveolar proteinosis and eosinophilic lung disease. This survey analyses the value of BAL and how it has provided a new window for the chest physician.
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PMID:Bronchopulmonary lavage (BAL). A window of the lungs. 134 40

In the USA, Kaposi's sarcoma associated with the acquired immunodeficiency syndrome (AIDS-KS) is ten times more common in homosexual or bisexual men than in heterosexual men with AIDS. One explanation for this finding is that AIDS-KS may be caused by an infectious agent. Because there is a high incidence of human papillomavirus (HPV) infection, especially HPV-16, in homosexual men, we have sought HPV DNA sequences in Kaposi's sarcoma. We used the polymerase chain reaction with a primer pair specific for the highly conserved E6 region of HPV-16 to detect HPV-16 homologous DNA fragments in tumour tissues from 97 patients with KS and in KS-derived cell cultures. HPV DNA sequences were found in 11 of 69 KS skin tumours from homosexual men with AIDS-KS, in 3 of 11 KS biopsy specimens from homosexual men who had no clinical or laboratory evidence of HIV-infection, and in 5 of 17 KS skin lesions from HIV-1-negative elderly men and women with classic KS. The same primer pair amplified HPV-16 homologous fragments from two different continuous cell cultures derived from pleural effusion fluid of patients with pulmonary AIDS-KS and two continuous cell cultures derived from KS skin lesions. The findings suggest that HPV-16-related DNA sequences are associated with different forms of KS and may have a role in the pathogenesis of this neoplasm.
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PMID:HPV-16-related DNA sequences in Kaposi's sarcoma. 135 72


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