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)

Lymphoproliferative disorders involving Epstein-Barr virus (EBV) infected natural killer (NK) cells are reported with increasing frequency, but the nature and role of EBV infection in these cells remains undefined. In this study, we have investigated virus-cell interactions in the EBV-positive YTN10 cell line, an NK-like cell line established from a patient with lymphoblastic lymphoma. Low level expression of the EBV receptor CD21 molecule was detected by FACS and reverse transcriptase polymerase chain reaction (RT-PCR) analysis. Immunoblotting and RT-PCR analysis identified a latency II pattern of EBV gene expression, consisting of EBNA-1 transcription from the Qp promoter, in the absence of other EBNA gene expression, and accompanied by LMP-1 and LMP-2A expression. The EBV genome was present in episomal form and there was evidence for lytic viral replication. This latency pattern is typical of EBV gene expression in nasopharyngeal carcinoma and Hodgkin's disease, and differs from the full spectrum of EBV latent gene expression in most posttransplant lymphoproliferative disorders and from the restricted EBNA-1 expression in Burkitt's lymphoma tissues. The interaction between EBV and NK cells described here has important implications for the pathogenesis and treatment of EBV-infected NK malignancies.
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PMID:Virus-cell interactions in a natural killer-like cell line from a patient with lymphoblastic lymphoma. 897 60

Six Epstein-Barr virus (EBV)-related lymphoproliferative disorders were investigated to verify whether the EBV strain harbored by neoplastic cells had the same EBNA-2 and latent membrane protein-1 (LMP-1) DNA sequences of the virus carried by normal lymphocytes of the same patients. Within each case, the analysis of neoplastic lymph nodes, reactive lymphadenopathies, and/or EBV+ spontaneous lymphoblastoid cell lines gave concordant results with respect to type-specific EBNA-2 region and LMP-1 gene. In particular, five cases showed the same deletion in the 3' end of the LMP-1 gene in both normal and neoplastic cells. We also determined the prevalence of LMP-1 deletions in a large series of normal peripheral blood mononucleated cells (PBMCs) from Italian individuals. The analysis showed that 50% (9 of 18) of PBMCs from human immunodeficiency virus (HIV)-seronegative donors carried a 30-bp deletion in the C-terminal portion of the LMP-1 gene, whereas a nondeleted fragment was amplified in about 44% (8 of 18) of the cases. Only one sample (5.6%) showed the amplification of a full-length LMP-1 band together with a deleted fragment. Similarly, PBMCs from HIV-infected patients showed an almost equivalent prevalence of full-length (17 of 37, 46%) and deleted (16 of 37, 43.2%) LMP-1 fragments, whereas about 11% of samples (4 of 37) showed evidence of double infections. Of note, deletions in the LMP-1 gene were detected with similar prevalence values in EBV+ Hodgkin's disease (HD) (13 of 30, 43.3%) and non-Hodgkin's lymphoma (NHL) (2 of 5, 40%) cases from HIV-seronegative patients and in HIV-related, EBV+ NHLs (4 of 7, 57.1%). Conversely, a 30-bp LMP-1 deletion was found in 10 of 12 HIV-associated HD cases (83%), a prevalence significantly higher than that detected in HIV-unrelated HD (P = .01). These findings indicate that: (1) the same EBV strain carrying LMP-1 deletions is harbored by normal and neoplastic cells of patients with EBV+ disorders, ruling out that these mutations might result from immunoselection phenomena; (2) in the Italian population, the prevalence of LMP-1 deletion mutants is comparable to that of EBV strains with full-length LMP-1; (3) HIV-induced immunosuppression is not associated with an increased prevalence of LMP-1 deletions in PBMCs; and (4) HIV-related HD cases, but not those of HIV-seronegative Italian patients, are closely correlated with the presence of LMP-1 deletions, suggesting that infection with these strains may increase the risk of developing HD in the HIV setting.
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PMID:Epstein-Barr virus strains with latent membrane protein-1 deletions: prevalence in the Italian population and high association with human immunodeficiency virus-related Hodgkin's disease. 905 56

A subset of Hodgkin's disease (HD) patients have detectable Epstein-Barr virus (EBV) genomes in the malignant Reed-Sternberg (R-S) cells. R-S cells express only a limited set of latent EBV proteins, but only LMP1 and LMP2 can potentially elicit a CD8+ cytotoxic T-lymphocyte (CTL) response. We have evaluated if either of these proteins could be used as targets for specific adoptive T-cell therapy for EBV-positive (EBV+) HD. The success of this strategy requires that R-S cells are susceptible to lysis by CD8+ CTL, and that CTL specific for LMP1 and LMP2 can be detected and potentially amplified in HD patients. Antigen presentation and CTL sensitivity was evaluated with an in vitro maintained, phenotypically representative R-S cell line, HDLM-2. The R-S cells were able to process and present viral proteins, and to be efficiently lysed by specific CTL in a Class I-restricted manner. Since CTL responses to LMP1 and LMP2 do not represent the dominant responses to EBV, we examined if CTL clones specific for these proteins could be isolated despite the presence of weak or nondetectable responses in polyclonal T-cell lines. LMP-specific clones were generated from individuals either by cloning from the polyclonal EBV-reactive T-cell lines or by direct stimulation of peripheral blood mononuclear cells (PBMC) with cells expressing LMP1 or LMP2 as the only EBV protein. Our ability to isolate CTL specific for LMP proteins from individuals with HD and the sensitivity of R-S cells for CTL-mediated lysis suggest that the pursuit of specific adoptive immunotherapy represents a viable strategy for the subset of HD patients with EBV+ tumors.
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PMID:Isolation of Epstein-Barr virus (EBV)-specific cytotoxic T lymphocytes that lyse Reed-Sternberg cells: implications for immune-mediated therapy of EBV+ Hodgkin's disease. 905 19

Non-Hodgkin's lymphomas occurring in AIDS patients (AIDS-NHL) are known to be highly associated with Epstein-Barr virus (EBV). However, there have been no previous detailed studies of the distribution of EBV-infected non-neoplastic lymphoblasts, which may act as precursors of AIDS-NHL. In the present study, an attempt was made to detect such EBV-infected cells in patients' lymphoid organs. Fifteen non-neoplastic lymph nodes obtained from HIV-positive individuals were processed for in situ demonstration of EBV-encoded small RNA (EBER-1) and EBV-encoded latent membrane protein 1 (LMP-1). An increased number of EBER-1-expressing cells were observed (9/15). EBER-1-positive cells were present much more frequently in advanced cases, as evaluated using the histopathologic criteria of Grundmann (1/6 cases showing irregular follicular hyperplasia; 3/4 showing the beginning follicular destruction; 2/2 showing progressive follicular destruction; 3/3 showing follicular involution). LMP-1 was detected in 3/9 EBER-1-positive cases, and all three of these cases were at the most advanced stage. Furthermore, cells expressing LMP-1 were larger (62.83 +/- 6 microm2) than EBER-1+ LMP-1- cells (29.05 +/- 7 microm2). These results indicate that cells with latent expression of the EBV gene increase in number in lymphoid organs of HIV-infected individuals at an advanced stage and that some of the cells are in a transformed state. It is possible to speculate that these cells are precursors of AIDS-NHL.
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PMID:Epstein-Barr virus-infected lymphocytes in non-neoplastic lymph nodes of patients infected with human immunodeficiency virus. 910 12

The aim of this study was to assess the incidence and immunophenotype of Reed-Sternberg-like (R-S-like) cells in the setting of posttransplantation lymphoproliferative disorders (PTLD). Twenty-eight formalin-fixed, paraffin-embedded cases (17 renal and 11 heart/heart-lung PTLDS) were analyzed for the presence of typical binucleate cells with inclusionlike nucleoli--the Reed-Sternberg phenotype. An immunohistochemical evaluation for the following markers was performed: CD3, CD20, CD79a, CD15, CD30, CD45, EBV-LMP-1, and vimentin. Monoclonality was assessed by staining for light chain restriction. Eleven cases contained R-S-like cells (9 renal and 2 heart/heart-lung PTLD). All 11 cases were positive for CD45 (LCA), EBV-LMP-1, and vimentin. Ten of 11 cases were CD20/CD79a positive, one case being of a null immunophenotype. Nine cases expressed CD30, whereas 0 of 11 were positive for CD15. In nine cases, expression of both kappa and lambda light chains was present; the remaining two cases failed to express either light chain. This study shows that the R-S-like cells encountered in PTLD have an activated B cell immunophenotype, are invariably EBV-LMP-1 positive, are often CD30 positive, and are CD15 negative. This latter immunophenotypic feature separates R-S-like cells from the R-S cells seen in Hodgkin's disease. The strong staining for EBV-LMP-1 in R-S-like cells also indicates a strong association between EBV-LMP and the R-S morphological phenotype in the context of PTLDs.
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PMID:An immunohistochemical analysis of Reed-Sternberg-like cells in posttransplantation lymphoproliferative disorders: the possible pathogenetic relationship to Reed-Sternberg cells in Hodgkin's disease and Reed-Sternberg-like cells in non-Hodgkin's lymphomas and reactive conditions. 910 51

Hodgkin's disease (HD) typically has a bimodal age distribution and is less common than non-Hodgkin's lymphoma in the pediatric age group, especially in very young children. Recent reports described a high prevalence of Epstein-Barr virus (EBV) in HD from developing countries in both adult and pediatric populations. In this series, we studied with immunohistochemical analysis 44 cases of pediatric HD from the United States to investigate the association with EBV in developed countries and to determine which subtypes occur in this group. The 44 cases (40 boys, 4 girls; male-to-female ratio, 10:1) were categorized as nodular lymphocyte predominance in 16 (36.4%) of 44; nodular sclerosis in 13 (29.5%); and mixed cellularity in 4 (9.1%). Eleven of the cases were difficult to subclassify by the usual morphologic and immunophenotypic criteria. Of these, eight (18.1%) were designated interfollicular HD, and three were classified as HD "not otherwise specified." EBV LMP was positive in 38.6% of cases: 5 (38.5%) of the 13 with nodular sclerosis; 3 (75%) of the 4 with mixed cellularity; 1 (6.0%) of the 16 with nodular lymphocyte predominance; 7 (87.5%) of the 8 with interfollicular HD; and 1 (33.3%) of the 3 with HD "not otherwise specified." There was a strong association between the age of the patient and EBV expression. In children 4 years or younger, all of the 3 cases were LMP positive; in the 5- to 9-year-old age group, 8 (61.5%) of 13 were LMP positive; and in the 10- to 15-year-old group, only 21.4% were positive. Our results confirm the male predominance in pediatric HD and show an association with EBV, especially in the youngest patients and with the mixed cellularity and interfollicular subtypes. Most, but not all, cases of pediatric HD can be subclassified by traditional criteria.
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PMID:Childhood Hodgkin's disease in the United States: an analysis of histologic subtypes and association with Epstein-Barr virus. 911 Mar

Epstein-Barr virus (EBV) infections are common in Japanese children, with infectious by EBV type 1. The relationships between EBV infection and lymphadenopathies in Hodgkin's disease (HD), non-Hodgkin's lymphomas (NHL), reactive follicular hyperplasia (RFH), and infectious mononucleosis (IM) in 37 Japanese children were evaluated. Formalin-fixed, paraffin-embedded lymph node specimens that were obtained at surgical resection or biopsy were evaluated for the presence of EBV DNA and the latent membrane protein-1 (LMP-1) using polymerase chain reaction (PCR) and immunohistochemical staining. The PCR detected EBV DNA in nine of 13 (69.2%) patients with RFH, including a case of IM, all three (100%) patients with HD, and one of 21 (4.8%) patients with NHL. All EBV-positive samples contained EBV type 1. Reed-Sternberg's cells in HD were immunohistochemically positive for LMP-1, whereas all cases of RFH and NHL were negative for LMP-1. Results suggest that EBV infection may be related to HD. Although no proof exists that EBV infection contributes to the transformation of cells, thus causing RFH or NHL, the present authors suggest that the EBV-positive cases in Japanese children demonstrate a relationship between the clinical and histopathological features of the lymphadenopathy and EBV-type 1 infection.
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PMID:Epstein-Barr virus infection, Hodgkin's disease, non-Hodgkin's lymphoma, and reactive follicular hyperplasia in Japanese children: evaluation of paraffin-embedded specimens using polymerase chain reaction and immunohistochemistry. 914 Dec 47

The occurrence of Hodgkin's disease (HD) and non-Hodgkin's lymphoma (NHL) appearing in the same individual indicates a closer relationship between the 2 diseases than previously believed. The purpose of our study was to analyze cases of HD and NHL in a defined population clinically, histopathologically and immunohistochemically to look for similarities indicating a common cellular origin. Between 1974 and 1994, 77 individuals were identified from the Swedish Cancer Registry and the National Health Care Programme for HD as potentially having both diagnoses. Thirty-two patients who had both HD and NHL were available for histo-pathological re-examination and immunohistochemical staining with CD30, CD15, LMP, p53, CD45 (LCA), CD3, CD45R0 (UCHL-1), L26, MB2 and CD45R (4KB5). The most common relation was HD preceding a high-grade malignant NHL (16 of 32 patients), unexpectedly often of T-cell phenotype (7 of 16 patients). The next common association was NHL of B-CLL type followed by HD (7 of 32 patients). At clinical presentation, the first lymphoma did not differ from lymphomas not associated with a second lymphoma, whereas the second one often appeared with a disseminated and aggressive clinical form. There was a significant correlation between the expression of p53 and LMP in first and second lymphomas. CD3 antibody was frequently expressed both in HD and NHL, whereas positivity for B-cell-related antibodies, CD30, CD15 and CD45R0, was less frequent and generally lower than previously described. The occurrence of HD and NHL in an individual is unusual. Tumour biological features common to both HD and NHL may indicate a similar cellular origin, regardless of the time interval between the diagnoses, and may contribute to the understanding of the pathogenesis of lymphoma.
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PMID:Patients suffering from both Hodgkin's disease and non-Hodgkin's lymphoma: a clinico-pathological and immuno-histochemical population-based study of 32 patients. 917 1

The presence of Epstein-Barr virus (EBV) was studied in specimens of 50 primary non-Hodgkin's lymphomas (NHL) of the salivary gland and the oral cavity and 11 solitary adenolymphomas of the parotid gland, using EBER-1/2 in situ hybridisation and by immunohistochemistry for the detection of latent membrane-protein-1 (LMP-1). None of the patients were tested for HIV-infection, nor were there any clinical signs to suspect HIV-infection. In one adenolymphoma, few reactive EBER-1/2 positive cells were detected. In this case staining for LMP-1 was negative. In one oral B-cell NHL, EBER-1/2 positive lymphoma cells were identified; these cells also expressed LMP-1. None of the 31 oral (30 B-cell and one T-cell) and 18 salivary gland (all B-cell) NHLs and none of the 10 adenolymphomas were EBER-1/2 positive or expressed LMP-1. These results indicate that EBV is not involved in the pathogenesis of oral and salivary gland primary NHL and adenolymphoma in immunocompetent patients.
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PMID:Adenolymphoma and non-Hodgkin's lymphoma of the salivary glands and oral cavity in immunocompetent patients are not associated with latent Epstein-Barr virus. 923 Nov 69

Epstein-Barr virus (EBV) is detected in Hodgkin and Reed-Sternberg (HRS) cells in up to 50% of patients with Hodgkin's disease (HD). HD patients have been reported to express high serum titers against EBV antigens, even prior to the diagnosis of HD. Patients with high serum titers have a poorer prognosis. The aim of this study was to examine the relationship between the presence of EBV in HRS cells and the antibody titers reactive with different EBV antigens. Frozen serum and histopathological tissues were available from 107 untreated HD patients diagnosed between 1979 and 1991. The presence of EBV in the HRS cells was evaluated with immunohistochemistry directed against the LMP-1 antigen and/or with in situ hybridization of EBER-1. Analyses were performed of serum titers against early antigen (EA), diffuse (IgA and IgG) and restricted (IgG), virus-capsid antigen (VCA) (IgA and IgG), and EBV-encoded nuclear antigens (EBNA, EBNA 1, EBNA 2A, EBNA 2B, EBNA 6). EBV was detected in 27/107 (25%) tumor specimens, with a higher proportion in the MC group 8/13 (62%) (p < 0.01). IgG VCA and EBNA were detected in 99/107 (93%), evidence of a previous EBV infection. There were no significant relationships between antibody titers reactive with different EBV antigens and detectable EBV in HRS cells. Furthermore, there did not appear to be any relationship between EBV serology or the presence of EBV in HRS cells and clinical outcome. The role of EBV in the development of HD, especially its relationship to the immunological response, remains unclear.
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PMID:Lack of correlation between EBV serology and presence of EBV in the Hodgkin and Reed-Sternberg cells of patients with Hodgkin's disease. 924 79


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