Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0021051 (immunodeficiency)
 71,517 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The Epstein-Barr virus (EBV) has been classically associated with nasopharyngeal carcinoma and Burkitt's lymphoma, a monoclonal B-cell non-Hodgkin's lymphoma. Since the EBV genome has also been found in post-transplant lymphomas and lymphomas arising in individuals infected with the human immunodeficiency virus, evidence has now accumulated that EBV might be the initiator of a multi-step process leading from polyclonal B-cell hyperplasias to monoclonal lymphoma. In a retrospective study of 60 T-cell lymphomas of various types, we found EBV DNA in 21 (35%) using Southern- and/or dot-blot techniques. Eight of 14 nodal samples of angio-immunoblastic lymphadenopathy (57%) were shown to harbour detectable EBV DNA. The tumour with the next highest frequency, 47% (7/15 cases analyzed) was pleomorphic T-cell lymphoma, medium- and large-cell type; EBV was found both in nodal and in extranodal lymphomas of this type. Lymphoepitheloid (Lennert's) lymphoma and large-cell anaplastic lymphoma were positive in 2/5 and 3/8, respectively, of the cases analyzed. No viral DNA could be demonstrated in 3 T-immunoblastic and 5 T-lymphoblastic lymphomas. Clonotypic analysis revealed monoclonal as well as oligoclonal virus populations. Our data suggest that, at least in some of these entities, the presence of the EBV genome might be due to secondary mechanisms such as escape from immune surveillance.
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PMID:Prevalence of Epstein-Barr virus DNA in different T-cell lymphoma entities in a European population. 131 68

This study analyzes the association of Epstein-Barr virus (EBV) with non-Hodgkin's lymphoma (NHL) arising in patients without pre-existing overt immunodeficiency. The authors examined 201 lymphomas (105 high-grade B-cell, 82 peripheral T-cell, 7 high-grade non-B-cell, non-T-cell, and 7 hairy-cell leukemia) for EBV gene expression by immunohistologic procedures using monoclonal antibodies to EBV latent, immediate early, and replicative infection antigens. Transformation-associated EBV latent membrane protein 1 (LMP 1) was detected in 13 (6%) NHL, comprising 4 (4%) high-grade B-cell, 8 (10%) peripheral T-cell, and 1 non-B-cell, non-T-cell lymphomas. Anaplastic large-cell lymphoma of T-cell type was consistently LMP 1-negative. EBV nuclear antigen 2 was demonstrated in only three (1%) cases. Induction of replication as defined by expression of the immediate early BamHI Z leftward reading frame 1 (BZLF1) protein was detected in five cases, but early (EA) and late (VCA and MA) lytic cycle antigens were only found in two cases and in one case, respectively. The presence of EBV was confirmed by in situ DNA hybridization in 9 of 11 EBV antigen-positive lymphomas. This study shows the surprisingly frequent presence of EBV in peripheral T-cell NHL in European patients without pre-existing overt immunodeficiency. Interestingly, most sporadic B-cell NHL are not associated with the virus. Furthermore, the usefulness of selected monoclonal antibodies for the routine immunohistological diagnosis of EBV infection was confirmed.
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PMID:A survey of Epstein-Barr virus gene expression in sporadic non-Hodgkin's lymphomas. Detection of Epstein-Barr virus in a subset of peripheral T-cell lymphomas. 131 39

Although the subject is now seldom formally addressed, much of the pathologic research into malignant lymphoma is still tacitly directed at developing a rational and reproducible classification. Pure morphology, while remaining of critical importance in the diagnosis of malignant lymphomas, has been exhausted as a means of understanding the biology of these tumors, which must be the eventual basis of a firm, enduring and clinically relevant classification. Thus, histopathologists have turned first to immunohistochemistry and now to molecular genetics to make sense of their morphologic observations. Correlation of various genetic (including oncogenetic) rearrangements with morphology has preoccupied pathologists this past year and has led to important advances in the understanding of B- and T-cell lymphomas. Lymphomas occurring in a setting of immunodeficiency, whether therapeutically induced or acquired, have received special attention, and the possible role of the Epstein-Barr virus in their pathogenesis has induced pathologists to develop exciting in situ molecular hybridization techniques for its identification in tissues. The certainties underlying the diagnosis and classification of Hodgkin's disease (in which Epstein-Barr virus also appears to play a role), formally the only truly secure area for pathologists, have been disturbed, and the borderline between Hodgkin's disease and non-Hodgkin's lymphoma is now seriously blurred. The lymphoma pot has been well and truly stirred; we must now wait to see what the new sediment offers.
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PMID:Pathology of malignant lymphomas. 145 95

Using a monoclonal antibody specific to the Lewis X antigen (anti-Lex), the authors studied 103 cases of Hodgkin's disease (HD) in comparison with 57 cases of non-Hodgkin's lymphoma (NHL); three cases of granulocytic sarcoma (GS); two cases of malignant histiocytosis (MH); one case of monoblastic leukemia (ML); one case of interdigitating reticulum cell sarcoma (IRCS); six cases of histiocytosis X (HX); one case of reticulohistiocytoma (RH); 44 various reactive conditions of the lymph node (LN). Reed-Sternberg and related (R-S) cells stained selectively in 80 of 92 cases of HD (87.0%), excluding 11 cases of lymphocyte predominance type. The stain was better in B-5-fixed specimens than in formalin-fixed specimens, showing a dense deposit of reaction products at a paranuclear site and on the cell surface. The staining results were compared with those of Leu-M1 and found to be superior both qualitatively and quantitatively (detection rate of R-S cells: 87.0% versus 68.5% of Leu-M1). Granulocytes, rare epithelioid histiocytes, and some endothelial and/or erythrocytes also stained with anti-Lex. The stain had positive results in three cases of GS showing a diffuse cytoplasmic staining pattern. Of NHL, two of 29 peripheral T-cell lymphomas stained to show rare paranuclear deposits without cell surface staining. The stain had negative results in MH, ML, IRCS, HX, and RH. Of 45 reactive LN, minute subcapsular collections of Lewis X+, altered-appearing Langerhans'-like cells, were observed in all ten LN from human immunodeficiency virus (HIV)-associated persistent generalized lymphadenopathy (PGL). The stain had negative results in all other various reactive conditions of LN. In conclusion, Lewis X staining is useful as a marker for R-S cells in paraffin sections with staining results superior to those of Leu-M1. Lewis X staining also detects subcapsular clustering of altered-appearing Langerhans'-like cells in PGL, which has not been described previously and warrants additional study.
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PMID:The Lewis X antigen. A new paraffin section marker for Reed-Sternberg cells. 170 18

Since the recognition of Kaposi's sarcoma as a manifestation of the acquired immunodeficiency syndrome, subsequent malignancies such as non-Hodgkin's B-cell lymphoma and primary central nervous system lymphoma have been found to be associated with individuals infected with the human immunodeficiency virus (HIV). The epidemiology, clinical manifestations, and current concepts of pathogenesis are reviewed in this article. In addition, the relation between HIV and other malignancies, including Hodgkin's lymphoma, T-cell lymphomas, and anorectal carcinoma, is discussed. In general, HIV-related malignancies are more aggressive, respond poorly to treatment, and are associated with an extremely high rate of mortality.
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PMID:HIV-related malignancies. 187 28

A rapidly proliferating T-cell line, HCD8, was derived from the peripheral blood lymphocytes of an apparently healthy individual during the course of a T-cell cloning experiment. This T-cell line expressed a very unusual phenotype: CD1+, CD2-, CD3+ (cytoplasmic), CD4-, CD5+, CD7+, CD8-, interleukin-2 receptor (IL-2 R) (p55)-, and T-cell antigen receptor (TCAR) alpha beta-. Assays for reverse transcriptase activity and for human T-lymphotropic retroviral sequences in the cellular DNA were negative, indicating that the cells were not transformed by human T-lymphotropic virus (HTLV)-I, HTLV-II, or human immunodeficiency virus (HIV)-I. Culturing the cells in the differentiation inducing agent 12-O-tetradecanoyl phorbol 13-acetate induced an increased expression of CD3 but no other significant changes in T-cell markers. A small population of CD4-negative and CD8-negative T-lymphocytes exist in human peripheral blood and they exhibit natural killer (NK) and antibody-dependent cell-mediated cytotoxic (ADCC) activity. However, the authors' cell line failed to demonstrate such cytotoxic function. The TCAR gene rearrangement studies showed that both T gamma genes were rearranged while the T beta genes were in the germ line configuration and the T delta genes were deleted. HCD8 strongly expressed the antigens Leu M1 and Ki-1, markers detected only rarely on normal unstimulated human T-cells, but quite consistently found on Reed-Sternberg cells and cells of some large pleomorphic T-cell lymphomas. HCD8 may be used to study the control of Leu M1 and Ki-1 expression in T-cells and it may provide some insight into the cellular origin of the above-mentioned lymphomas.
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PMID:A T-cell line with an unusual phenotype. 255 76

BHRF1, one of many Epstein-Barr virus (EBV)-encoded proteins, shows strong functional homology to the human bcl-2 proto-oncogene product, a protein involved in the pathogenesis of a subset of B-cell lymphomas, ie, follicle center cell lymphomas (FCCL). We have investigated the presence of possible latent and lytic transcripts of BHRF1 using a reverse transcriptase-polymerase chain reaction (RT-PCR)-based assay in a group of EBV-associated B-cell lymphomas in patients with (N = 5) or without overt immunodeficiency (N = 4), in T-cell lymphomas (N = 9), and in cases of Hodgkin's disease (N = 6). BHRF1 transcription was found consistently in EBV-associated (ie, diffuse EBER 1/2-positive) B-cell lymphomas in patients with or without immune deficiency, whereas in EBV-associated T-cell lymphomas or in EBV-associated Hodgkin's disease, BHRF1 transcription was only detected in two T-cell lymphomas and one case of Hodgkin's disease, which also harbored EBER 1/2-positive reactive cells. Moreover, weak BHRF1 signals were found in two T-cell lymphomas where EBER 1/2 expression was detected mainly in sporadic reactive lymphocytes and in one reactive tonsil with sporadic EBER 1/2-positive lymphocytes. BHRF1 transcripts were found to be generated by the C or W promoter (associated with viral latency) and/or by the H promoter (associated with the virus lytic cycle). In all cases with H promoter-derived BHRF1 transcripts, transcripts encoding ZEBRA were also detected, suggesting a reactivation of the virus lytic cycle. Analysis of other EBV genes revealed transcription of BARFO in all tested EBV-harboring tissues. Transcription of EBNA1 and LMP1 was usually detected, whereas EBNA2 transcription was found exclusively in B-cell lymphomas in immunocompromised patients. These data demonstrate that BHRF1 transcripts are exclusively found in EBV-associated B-cell lymphomas. When BHRF1 transcripts are detected in T-cell lymphomas or in Hodgkin's disease, it is probably due to the presence of reactive EBER 1/2-positive lymphocytes. The consistent transcription of BHRF1 in EBV-associated B-cell lymphomas suggests a possible pathogenic role for this gene product in EBV-positive B-cell lymphomas analogous to bcl-2.
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PMID:BHRF1, the Epstein-Barr virus (EBV) homologue of the BCL-2 protooncogene, is transcribed in EBV-associated B-cell lymphomas and in reactive lymphocytes. 765 18

The Epstein-Barr virus (EBV) is associated with an increasing range of reactive and neoplastic lesions. There is a need for a sensitive and specific method for detecting latent EBV in routine histological sections. We report the use of a highly sensitive paraffin section RNA/RNA in situ hybridization (ISH) technique using digoxigenin-labelled antisense riboprobes for demonstrating EBV encoded small RNAs (EBERs), EBV gene products that are transcribed in abundance during latent EBV infection. We applied EBER-ISH to 846 paraffin embedded specimens, including cases of reactive lymphoid hyperplasia (n = 28), infectious mononucleosis (16), Burkitt's lymphoma (44), immunodeficiency-associated lymphomas in transplant recipients (9) and AIDS patients (128), Hodgkin's disease (130), CD30 antigen positive lymphomas (106), peripheral T-cell lymphomas (104), sporadic B-cell non-Hodgkin's lymphomas (162), undifferentiated nasopharyngeal carcinoma (86), salivary gland lymphoepithelioma (11), and oral hairy leukoplakia (5). Strong, reproducible EBER staining was seen in EBV latently infected cells in archival surgical biopsy and autopsy specimens. EBER-ISH is specific, has a sensitivity comparable to that of the polymerase chain reaction, and is now the method of choice for the in situ detection of latent EBV infection.
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PMID:Detection of Epstein-Barr virus small RNAs in routine paraffin sections using non-isotopic RNA/RNA in situ hybridization. 798 72

A 31-year-old renal transplant recipient developed an unusual T-cell lymphoproliferative disorder 3 years after transplantation. The neoplasm involved the spleen, without concomitant hepatomegaly, lymphadenopathy, or obvious bone marrow involvement. Peripheral blood involvement developed after splenectomy. Immunophenotypically, the neoplastic cells expressed CD2, CD3, CD7, CD16, CD45, CD56, and the gamma/delta T-cell receptor on the surface membrane. The neoplastic cells were negative for surface membrane CD4, CD5, and CD8. Serologic and/or DNA analyses for viruses, including Epstein-Barr virus, human T-cell lymphotropic virus-1, human immunodeficiency virus, and human herpesvirus-6, were negative. Cytogenetic findings included a translocation breakpoint at chromosome 7p15, consistent with involvement of the T-cell receptor gamma-chain locus. Although gamma/delta T-cell lymphomas have been reported to have a predilection for hepatosplenic localization, this is the first well-documented case to be described in the setting of posttransplantation immunosuppression.
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PMID:Gamma/delta T-cell posttransplantation lymphoproliferative disorder primarily in the spleen. 808 54

LMP-1, an Epstein-Barr viral (EBV) latency protein, is considered a viral oncogene because of its ability to transform rodent fibroblasts in vivo and render them tumorigenic in nude mice. In human B cells, EBV LMP-1 induces DNA synthesis and abrogates apoptosis. LMP-1 is expressed in EBV-transformed lymphoblastoid cell lines, nasopharyngeal carcinoma (NPC), a subset of Hodgkin's disease (HD), and in EBV-associated lymphoproliferative disorders (EBV-LPDs). Recently, focused deletions near the 3' end of the LMP-1 gene (del-LMP-1, amino acids 346-355), in a region functionally related to the half-life to the LMP-1 protein, have been reported frequently in human immunodeficiency virus (HIV)-associated HD (100%) and EBV+ Malaysian and Danish peripheral T-cell lymphomas (100%, 61% respectively), but less frequently in cases of HD not associated with HIV (28%, 33%) and infectious mononucleosis (33%). To further investigate the potential relationship of del-LMP-1 to EBV-LPDs associated with immunosuppression or immunodeficiency, we studied 39 EBV-associated lymphoproliferations (10 benign, 29 malignant) from four distinct clinical settings: posttransplant (4 malignant, 1 reactive); HIV+ (18 malignant, 2 reactive); nonimmunodeficiency malignant lymphoma (ML) (7 cases); and sporadic EBV infection with lymphoid hyperplasia (7 cases). The presence of EBV within lymphoid cells was confirmed by EBV EBER1 RNA in situ hybridization or by polymerase chain reaction (PCR) analysis. EBV strain type and LMP-1 deletion status were determined by PCR. EBV strain types segregated into two distinct distributions: HIV+ (9 A; 11 B) and non-HIV (19 A, 0 B), consistent with previous reports. Overall, del-LMP-1 were found in 1 of 5 (20%) Burkitt lymphomas (BL); 17 of 24 (71%) aggressive non-Hodgkin's lymphoma (agg-NHL), and 2 of 10 (20%) reactive lymphoid proliferations. Of the agg-NHLs, del-LMP-1 were present in 4 of 4 PT-ML (100%); 10 of 15 HIV+ ML (67%); and 3 of 5 nonimmunodeficiency malignant lymphoma (ML, 60%). A total of 2 of 7 (28%) sporadic EBV-associated lymphoid hyperplasias contained a del-LMP-1. All del-LMP-1 were identical by DNA sequence analysis. No correlation was identified between the presence of del-LMP-1 and the EBV strain type observed. The high incidence of del-LMP-1 observed in agg-NHLs (71%), in contrast to the relatively low incidence observed in reactive lymphoid proliferations (28%), suggests that the deleted form may be preferentially selected in lymphomatous processes. All posttransplant agg-NHLs contained a del-LMP-1, and a similar frequency of del-LMP-1 was observed in both HIV-associated ML (66%) and nonimmunodeficiency ML (60%), suggesting that impairment of immune function alone is not a requirement for the expansion of malignant cells infected by EBV stains containing the deleted LMP-1 gene.
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PMID:Epstein-Barr virus latent membrane protein-1 oncogene deletions: correlations with malignancy in Epstein-Barr virus--associated lymphoproliferative disorders and malignant lymphomas. 870 80


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