Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019829 (Hodgkin's disease)
 30,247 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

There is good evidence for an association between Epstein-Barr virus (EBV) and Hodgkin's disease (HD). In approximately one-third of cases, the EBV genome is detectable in Reed-Sternberg (RS) cells and there is expression of the viral nuclear antigen EBNA-1 and the latent membrane protein LMP-1. Expression of LMP-2 has been demonstrated at the mRNA level, and it is presumed that the protein is expressed alongside LMP-1. The LMP-2 protein is known to contain an epitope presented to cytotoxic T-cells which is restricted through the HLA class I antigen A*0201 in healthy seropositive individuals. Since most HLA-A*02-positive Caucasians are HLA-A*0201-positive, it was hypothesized that HLA-A*02-positive individuals would be under-represented among Caucasians with EBV-associated HD. HLA-A*02 status was determined, using flow cytometry and/or the polymerase chain reaction, for 276 individuals including 176 cases of HD. There was no significant difference between the frequency of HLA-A*02 positivity in HD cases and controls, and between EBV-associated and non-associated cases of HD. The A*02 alleles of 14 cases of EBV-associated HD were further subtyped using nested PCR; all except one case were found to be A*0201-positive. We therefore investigated whether there was any evidence for mutation of the epitope representing amino acids 426-434 of LMP-2a which is restricted through HLA-A*0201. In 10/11 cases the nucleotide sequence encoding this epitope was identical to the published sequence; in the remaining case there was a mutation which would not be expected to alter the conformation of the epitope. Overall, our data suggest that other mechanisms of immune escape must be operative in EBV-associated HD.
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PMID:Determination of HLA-A*02 antigen status in Hodgkin's disease and analysis of an HLA-A*02-restricted epitope of the Epstein-Barr virus LMP-2 protein. 925

In order to clarify the effects of Epstein-Barr virus (EBV) infection on apoptosis and proliferative activity of non-Hodgkin's lymphoma, 135 Japanese lymphoma cases were investigated for the presence of viral RNA and its correlation with bcl-2 protein (Bcl-2) expression. In addition, the role of EBV in lymphoma-genesis was also studied in terms of EBV genotyping and specific deletion in the gene for the latent membrane protein 1 (LMP-1). EBER-1 RNA in situ hybridization revealed EBV in 18 cases (13.3%), comprising 12 of 44 T cell (27.3%) and 6 of 91 B cell (6.6%) lymphomas. Type A EBV was found in all 18 cases (100%), and 17 of the 17 (100%) evaluable cases showed a 30-bp deletion within the 3' end of LMP-1. Comparison of apoptotic indices (AI), assessed by DNA nick-end labelling, and proliferative activity, estimated in terms of Ki-67 labelling and mitotic indices (KI and MI), demonstrated an overall correlation among AI, KI and MI increases in association with Bcl-2 negativity, indicating a close relation between apoptosis and proliferation. EBV-positive cases showed significantly elevated AI values, independent of Bcl-2 positivity, with no change in KI and MI. These results indicate that EBV in Japanese non-Hodgkin's lymphomas is exclusively of type A with a specific deletion in LMP-1 and that it tends to be present in T cell lymphomas. Moreover, EBV up-regulates apoptosis without any relation to Bcl-2 expression and exerts only minor effects on proliferation.
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PMID:Apoptosis, proliferative activity and Bcl-2 expression in Epstein-Barr-virus-positive non-Hodgkin's lymphomas. 926 May 92

Epstein Barr-Virus (EBV) is a lymphotropic herpes virus, well recognised for its oncogenic properties. In recent years substantial evidence has accumulated supporting a role for EBV in the pathogenesis of Hodgkin's disease. The epidemiologic and histologic features of Hodgkin's disease (HD) have long indicated a possible infective cause. Our study involves the detection of the EBV encoded latent membrane protein 1 (LMP-1) in 45 cases of Hodgkin's disease using immunohistochemical methods. In this study we detected LMP-1 positivity in the Reed-Sternberg and Hodgkin's cells in 31% of cases of HD. In mixed cellularity the positivity was 21.7% while nodular sclerosis exhibited positivity of 50% of the cases. The lymphocyte depletion subtype showed 100% positivity. All cases of lymphocyte predominance and the single unclassified case were negative for LMP. The demonstration of LMP-1 in Hodgkin's disease has important implications since it is one of the latent gene products which produces B Lymphocyte transformation.
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PMID:Study of association of Epstein Barr-virus with Hodgkin's disease. 935 6

Burkitt's lymphoma (BL) cell lines are heterogenous with regard to phenotype, growth characteristics, Epstein-Barr virus (EBV) latent gene and BCL-2 expression. Previously we have demonstrated that transfection with the EBV genes LMP or EBNA-2 upregulates BCL-2 in B-cell lines. In order to test the functional relevance of these findings, cell lines were examined with regard to their sensitivity towards different apoptosis-inducing agents. BL cell lines transfected with LMP expressed high levels of BCL-2, and were compared with the parental cell line expressing little or no BCL-2. We also studied EBV immortalized lymphoblastoid cell lines (LCL) with high BCL-2 expression and strong resistance towards low serum concentrations. Hydrocortisone (HC) and 2-chlorodeoxyadenosine (2-CDA) were used alone or in different combinations. Cell growth and apoptosis were studied morphologically and by determination of viability and DNA fragmentation. BL cell lines showed different sensitivity towards HC-induced apoptosis, and sensitive cell lines became more resistant towards HC after infection with EBV or transfection with LMP and subsequent upregulation of BCL-2 expression. BL cell lines and LCL were relatively insensitive towards 2-CDA-induced apoptosis, and high concentrations of 2-CDA were necessary, independently of the levels of BCL-2 expression. In contrast to low-grade non-Hodgkin's lymphomas, 2-CDA does not appear to be a valuable drug for the treatment of Burkitt's lymphoma. LMP expression provides resistance towards hydrocortisone-induced apoptosis in vitro, possible through upregulation of BCL-2.
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PMID:Influence of Epstein-Barr virus latent gene expression on the apoptosis-inducing effects of cortisone and 2-chlorodeoxyadenosine (2-CDA) in B-cell lines. 938 86

Fludarabine is a highly effective chemotherapeutic agent for chronic lymphocytic leukemia/small lymphocytic lymphoma and is also active in other B-cell lymphoproliferative disorders. Although highly efficacious in destroying the malignant B-cells, fludarabine also causes T-cell lymphopenia and immunosuppression. We present five patients given fludarabine for low-grade B-cell lymphoproliferative disorders who showed transformation of the primary neoplasm to a higher grade tumor. Immunohistologic antibody studies were performed on paraffin-embedded tissue sections of the initial tissue (when available) and on the follow-up biopsy specimens for CD20, CD3, CD45RO, CD43, CD30, CD15, and latent membrane protein (LMP-1) for Epstein-Barr virus (EBV). The initial diagnoses in these five patients included chronic lymphocytic leukemia/small lymphocytic lymphoma (three cases), follicle center lymphoma (one case), and Waldenstrom's macroglobulinemia (one case). All of the follow-up biopsy specimens showed scattered Hodgkin's-like cells, and two of the five also showed foci of large-cell transformation. The Hodgkin's-like cells showed CD30 immunoreactivity in four of the five cases and CD15 immunoreactivity in three of the five. Strong immunoreactivity of the large, atypical, Hodgkin's-like cells for LMP-1 of EBV was noted in four cases; in the remaining case, this finding was equivocal. In situ hybridization for EBV-encoded RNA was positive in four of the five cases. Molecular studies by polymerase chain reaction (PCR) showed the presence of EBV in three of the five cases. PCR for detection of immunoglobulin heavy chain demonstrated identical monoclonal rearrangements in the original lymphoma and transformation in one case with available material. The CD4 lymphocyte count in each patient was less than 550/microL, indicating cellular dysfunction. Transformation of low-grade non-Hodgkin's lymphomas after fludarabine therapy might be associated with EBV and severe immunosuppression.
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PMID:Detection of Epstein-Barr virus in transformations of low-grade B-cell lymphomas after fludarabine treatment. 938 67

This study was aimed at defining the histogenesis of the pathologic spectrum of acquired immunodeficiency syndrome-related non-Hodgkin's lymphomas (AIDS-NHL), including AIDS-related small noncleaved cell lymphoma (AIDS-SNCCL), AIDS-related large noncleaved cell lymphoma (AIDS-LNCCL), AIDS-related large cell immunoblastic lymphoma plasmacytoid (AIDS-IBLP), and AIDS-related primary effusion lymphoma (AIDS-PEL). Forty-six cases of AIDS-NHL were investigated for the expression pattern of BCL-6, a protein specifically expressed by germinal center (GC) B-cells, and CD138/syndecan-1 (syn-1), a marker of post-GC B-cell differentiation. Expression of BCL-6 and syn-1 segregated two major phenotypic patterns among AIDS-NHL: (1) the BCL-6+/syn-1- pattern associated with AIDS-SNCCL and AIDS-LNCCL; (2) the BCL-6-/syn-1+ pattern associated with AIDS-IBLP and AIDS-PEL. Among systemic AIDS-NHL infected by Epstein-Barr virus (EBV), expression of the EBV-encoded latent membrane protein-1 (LMP-1) preferentially associated with the BCL-6-/syn-1+ profile. Analysis of nonneoplastic lymph nodes showed that the two phenotypic patterns detected in AIDS-NHL correspond to physiologic stages of B-cell development, i.e., GC B-cells (BCL-6+/syn-1-) and preterminally differentiated post-GC B-cells (BCL-6-/syn-1+). Thus, BCL-6+/syn-1- AIDS-NHL reflects a GC stage of differentiation, whereas AIDS-NHL which are BCL-6-/syn-1+, and LMP-1+ when infected by EBV, derive from B cells that have entered post-GC plasmacell differentiation. These findings are relevant for the pathogenesis and differential diagnosis of AIDS-NHL.
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PMID:Differential expression of BCL-6, CD138/syndecan-1, and Epstein-Barr virus-encoded latent membrane protein-1 identifies distinct histogenetic subsets of acquired immunodeficiency syndrome-related non-Hodgkin's lymphomas. 944 32

The EBV plays a major role in the development of lymphoproliferative disorders in immunosuppressed patients. After organ transplantation most of lymphoproliferative disorders associated with EBV are polymorphic, with various expression of clonality. The pattern of EBV latency genes expression is rather the same as in lymphoblastoid cells lines and the EBV infected cells strongly expressed activation and adhesion molecules in most cases. In AIDS-related lymphomas the frequency of EBV as well as the expression of latency genes are related to the localization and to the histological subtypes. While EBV is observed in 30 to 50% of cases of Burkitt's lymphomas occurring the early stage of AIDS, its association in primary brain lymphomas and immunoblastic lymphomas developed in the late stage is observed in nearly all cases as well as in Hodgkin's disease. In primary brain lymphomas, the high expression of LMP-1 protein is correlated to the expression of BCL2 oncoprotein suggesting a transactivation of bcl2 by LMP-1 as it was reported in vitro. In non overt immunosuppressed patients the role of EBV is less clearly established, particularly in Burkitt's lymphoma where EBV is now considered as a cofactor. In B-cell lymphoma EBV is detected in about 5% of cases except in peculiar situations such as in lymphoma occurring in pleural cavity after longstanding pleural chronic inflammation and in Richter's syndrome with Reed-Sternberg-like cells. In peripheral T-cell lymphomas, EBV is observed in about 25% of cases, but its frequency varies with the histology and the localisation. EBV is present in nearly all cases of angio-immunoblastic type and in the nasal lymphoid proliferations developed from the NK cells. Detected in 30 to 80% in the Reed-Sternberg cells of Hodgkin's disease cases, the pathogenic significance of EBV remains to be determined in this disease.
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PMID:[Role of Epstein-Barr Virus in lymphoproliferative disorders]. 945 45

A new category of oncogenes regulating apoptosis, p53 and bcl-2, and the Epstein Barr virus (EBV) latent membrane protein-1 (LMP-1) have been related to Hodgkin's disease (HD) pathogenesis. We attempt to determine p53, mdm2, p21waf-1, bcl-2 and LMP-1 immunohistochemical expression in tissue sections from formalin-fixed, paraffin-embedded lymph node biopsies of pediatric HD. P53 was detected in the nucleus of Reed Sternberg cells and their variants (H-RS) in 68% of the HD cases. However, there was no statistically significant association with either clinical stages or with histological subtypes. P21waf-1, an indirect marker of p53 functional status, showed nuclear labelling of H-RS in all the studied cases. MDM2 co-expressed with p53 in 62% of the cases, suggesting that both proteins regulate one another, in HD by a self regulatory loop. Bcl-2 cytoplasmatic expression in H-RS was demonstrated in 65% of the cases. There was co-expression of bcl-2 and p53 in 51%, but it failed to correlate with a poor prognosis. LMP-1 labelling was shown in 51% of the cases, disclosing a statistically significant association with the under 6-year group (p = 0.005, Fisher's exact test). Since LMP-1 induces the expression of bcl-2 in vitro, the relation of both proteins was analysed and found to co-express in 15/37 cases, with a statistically significant association only in the under 6-year group (p = 0.001, Fisher's exact test). Abnormal accumulation of these oncoproteins in tumour cells could play a role in the pathogenesis of a subset of pediatric HD.
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PMID:Oncogene expression in tumour cells of pediatric Hodgkin's disease in Argentina--correlation with Epstein Barr virus presence. 954 44

To analyze the association of Epstein-Barr virus (EBV) with gastrointestinal non-Hodgkin's lymphomas arising in immunocompetent patients, 56 consecutive cases of gastrointestinal lymphomas (B-cell: 52-cases, T-cell: 3 cases, T/NK-cell: 1 case) occurring in the stomach (33 cases), intestine (22 cases) and esophagus (1 case) were investigated for the presence of EBV using polymerase chain reaction analysis as a screening method followed by EBER-1 RNA and DNA in situ hybridization (ISH) and immunohistochemistry for the expression of latent membrane protein 1 (LMP-1). Forty-seven cases demonstrated extractable DNA and EBV DNA was detected only in 4 cases. Among the, RNA (EBER-1) and DNA ISH analysis confirmed the presence of the EBV genome in tumor cells in 3 cases (T/NK-cell lymphoma of ileum, gastric high-grade B-cell lymphoma of mucosa-associated lymphoid tissue, gastric diffuse large B-cell lymphoma). Only the T/NK cell lymphoma showed diffuse positivity of tumor cells while 2 gastric B-cell lymphomas demonstrated a scattered positive reaction and no cases expressed LMP-1. Nine cases without extractable DNA by the PCR method showed no nuclear signal by EBER-1 ISH. These findings suggest that most sporadic primary gastrointestinal lymphomas in Korea are not associated with EBV.
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PMID:Epstein-Barr virus and gastrointestinal lymphomas in Korea. 966 33

The aim of this study was to explore the expression of retinoblastoma protein and EBV status in a cohort of cases of Hodgkin's disease from South Africa. Seventy one cases of Hodgkin's disease were accessed over a 6-year period and were classified according to the Rye Classification. Relevant sections were stained with commercially available antibodies to retinoblastoma protein (pRb) and EBV-LMP-1. In addition, in situ hybridization for EBERs was also performed. The results of this study show that 43 of 71 cases expressed EBV by both immunohistochemistry and in situ hybridization. These included 18 mixed cellularity, 19 nodular sclerosis and six lymphocyte depleted subtypes. pRb expression was seen in lymphocytes, mononuclear Hodgkin's and Reed-Sternberg cells in 67 of the cases. From this study it appears that pRb expression is seen in the majority of cases of Hodgkin's disease: 67/71 (94.4 per cent). Thirty-nine of 43 cases (90.7 per cent) of EBV positive cases were also positive for pRb. The results of this study indicate that pRb immunoexpression is detected in the vast majority of cases of Hodgkin's disease, and that this expression is independent of the EBV status of the case.
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PMID:Retinoblastoma protein and Epstein-Barr virus (EBV) expression in South African Hodgkin's disease. 972 90


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