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)

Hodgkin's disease (HD) has seldom been reported after transplantation. Epstein-Barr virus (EBV) is present in about 50% of Reed-Sternberg cells in HD developing in immunocompetent individuals, but is more frequently found in HD of acquired immune deficiency syndrome patients. We report 7 cases of HD that occurred in transplant recipients. Clinical and pathological data and studies of EBV reveal specific features of HD after transplantation. Six patients received kidney transplants and 1 patient received combined kidney and pancreas transplantation. Immunosuppressive therapy consisted of cyclosporine, steroids, azathioprine, and antilymphocyte globulins. One patient received, in addition, anti-CD3 mAb therapy and an EBV+ B cell lymphoma developed. Retrospective EBV serological data from patients were collected. Tumors were classified according to pathology. EBV studies were conducted by immunohistochemical methods with monoclonal antibodies to EBV-latent membrane protein (LMP) or EBV-nuclear antigen 2 (EBNA2), and by in situ hybridization for latent nuclear EBV-early RNAs (EBERs). The mean lapse of time between transplantation and HD was 49 months. Six patients presented with enlarged lymph nodes and 1 patient presented with liver involvement. HD was classified as IA in 2 patients, IIA in 3 patients, IIIB in 1 patient, and IVB in 1 patient. Four patients had primary EBV infection after graft, before HD, and the others reactivated latent EBV infection. Histological subtypes were mixed cellularity in 6 cases and lymphocytic depletion in 1 case. Latent EBV infection was detected with EBERs in all tumors. Reed-Sternberg cells expressed LMP, and were negative for EBNA2 expression. Six patients were treated: 2 patients at stage I received radiotherapy, and relapsed within 1 year with a more advanced stage of HD; chemotherapy was indicated as primary therapy in 5 patients, and as salvage therapy in 2 patients; it was associated with radiotherapy in 4 patients. Immunosuppressive therapy was reduced in all patients. Four patients were alive and in complete remission 18, 25, 31, and 67 months after chemotherapy, with a functioning graft in 3 patients. Two patients died of infection. Mixed cellularity is the most frequent histological subtype observed in HD occurring in transplant patients. EBV is present in all Reed-Sternberg cells. Posttransplant HD shows similarities with human immunodeficiency virus-associated HD. These facts argue for a role of EBV infection and immunosuppression in the progression of HD after transplantation.
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PMID:Hodgkin's disease after transplantation. 856 May 77

Two-hundred and four cases of peripheral T cell lymphoma (PTCL) occurring in Europeans without any sign of HIV-infection were investigated for their association with an Epstein-Barr virus (EBV) infection. Polymerase chain reaction (PCR) was applied for EBV-DNA detection, in situ hybridisation (ISH) for the cellular localization of EBV-encoded small nuclear RNA (EBER) and immediate early gene expression (BHLF) and immunohistology (IH) for the detection of EBV-encoded latent membrane protein 1 (LMP1) and EBV nuclear antigen 2 (EBNA2) expression. PCR and EBER-ISH produced congruent results in almost all cases with amplifiable DNA, leading to the finding of an overall frequency of EBV presence in 87/204 (42.6%) of the PTCL cases. Through EBER-ISH, the virus was identified to be exclusively present in small and blastic bystander lymphocytes in 29 cases, whilst an additional infection of neoplastic T cells was observed in the remaining 58 EBV-positive cases. The entity presenting with the most frequent EBV infection of tumour cells was that of angioimmunoblastic type PTCL, whilst the primary cutaneous PTCLs only seldom harbored the virus. Forty-eight of the EBV-positive TCLs showed an infection of a small proportion (1-20%) of the tumour cell population, whilst another ten cases, belonging to the pleomorphic TCL (PMTCL) group, displayed an infection of several to almost all neoplastic T cells (20-100%). Additional lytic EBV-infected cells could be detected in four cases by BHLF-ISH. LMP1 expression was present in a small proportion of the neoplastic T cells in 24 of the 58 cases with tumour cell infection, whilst an EBNA2 expression was detectable only in one case. Some non-malignant EBV-infected B-immunoblasts and Hodgkin/Reed Sternberg-like cells also expressed LMP1 in several cases. Our data imply a role of EBV in the pathogenesis of only a few PMTCL cases with predominant tumour cell infection, whilst the pathogenic significance of an EBV infection in the other PTCLs remains unclear due to the usually partial infection of the neoplastic cell component.
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PMID:Frequent presence of latent Epstein-Barr virus infection in peripheral T cell lymphomas. A review. 857 54

Recent studies have suggested that Epstein-Barr virus (EBV) may play a role in the etiology of Hodgkin's disease (HD). In a previous study, we used a latent membrane protein 1 (LMP1)-specific antibodies to examine archival material from 74 British children with HD and found 50% of cases to be positive. It is known that there are geographic and ethnic variations in the incidence of HD. We have investigated LMP1 status in formalin-fixed, paraffin wax-embedded lymph nodes with HD involvement from 53 children and 48 adults from Kenya using immunohistochemical staining. We also developed sensitive and specific in vitro gene amplification protocols for examining the EBV strain type in such material using several combinations of primers derived from the EBNA 2 and EBNA 3 coding regions. LMP1 positivity was present in 100% of the pediatric cases (two lymphocyte-predominant, 25 nodular sclerosis, 16 mixed cellularity, 5 lymphocyte depletion, and 5 unclassified) and in 66% of the adult cases (two of three lymphocyte-predominant, 26 of 39 nodular, sclerosis, two of two mixed cellularity, and two of four lymphocyte depletion). Tests to type the EBV strain were undertaken in 25 EBV-positive pediatric cases. A combination of type-specific polymerase chain reactions for EBNA 2 and EBNA 3C genes indicated that seven patients had type 1, eight had type 2, and 10 had dual infections with both types. Five cases with dual infections were further investigated using a sensitive in situ hybridization for the EBV-encoded, small nuclear nonpolyadenylated RNAs (EBERs). EBER transcripts were detected in Reed-Sternberg and Hodgkin cells and in occasional infiltrating lymphocytes. These observations indicate that in Kenya EBV is consistently associated with pediatric cases of HD, and that biopsies from a number of such cases appear to carry both type 1 and type 2 viral sequences.
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PMID:The consistent association between Epstein-Barr virus and Hodgkin's disease in children in Kenya. 861 9

To get insight into the failure of the immune system to eradicate Epstein-Barr virus (EBV) harboring Hodgkin and Reed-Sternberg cells (H-RS cells), expressing the latent membrane protein 1 (LMP1), we analyzed major histocompatibility complex (MHC) class I expression on H-RS cells in relation to the presence of activated cytotoxic cells, i.e., granzyme-B-expressing lymphocytes. H-RS cells in EBV+ cases of Hodgkin's disease (HD) were found to express significantly higher levels of MCH class I heavy- and light-chain molecules compared with EBV- HD cases. When low levels of MHc class I expression were found (mainly in EBV- cases), these were not associated with low levels of the transporter protein associated with antigen presentation 1 (TAP-1). The relatively high levels of MHC class I expression in H-RS cells in EBV+ HD cases were accompanied by significantly higher numbers of activated cytotoxic T lymphocytes (CTLs) as shown by the presence of increased numbers of CD8 and granzyme B+ lymphocytes. However, these cells were only sporadically detected in the close vicinity of the H-RS cells. These data suggest that mechanisms other than downregulation of MHC class I or TAP-1 expression on H-RS cells are involved in the failure of the immune system to eradicate EBV harboring H-RS cells. Probably, the function of activated CTLs is locally inhibited by the H-RS cells or by reactive cells in the vicinity of the H-RS cells.
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PMID:Analysis of major histocompatibility complex class I expression on Reed-Sternberg cells in relation to the cytotoxic T-cell response in Epstein-Barr virus-positive and -negative Hodgkin's disease. 861 11

Limited information is current available on the molecular and immunophenogenotypic characteristics of CD30-positive anaplastic large cell (ALC) lymphomas occurring in human immunodeficiency virus (HIV)-infected individuals. To address this issue, the authors have undertaken a combined analysis of these lymphomas in a comparison with other Epstein-Barr virus (EBV)-associated tumors in the setting of HIV infection. Twenty-one AIDS-related lymphomas, including five CD30-positive ALC and 11 small noncleaved cell (SNCC) lymphomas, and five Hodgkin's disease (HD) specimens were characterized regarding the immunophenogenotypic features, the frequency and subtype distribution of EBV (as defined by in situ hybridization [ISH], Southern blot, and a polymerase chain reaction [PCR] amplification of the EBV nuclear antigen-2 [EBNA-2] region) antigen expression (latent membrane protein-1 [LMP-1], EBNA-2, and for alterations of the tumor suppressor gene p53. Combined immunophenotypic and immunogenotypic analyses showed a derivation from anomalously matured B cells in four of five CD30-positive ALC lymphomas, whereas SNCC showed features of mature B cells; no evidence of immunoglobulin or TCR gene rearrangement could be obtained in HD cases. Combined ISH and Southern blot analyses revealed that EBV was more strictly associated with HD (five of five) and CD30-positive ALC lymphomas (four of five) than with SNCC lymphomas (four of 11). EBV-positive samples from CD30-positive ALC lymphomas carried type 1 EBV (two of two specimens tested), whereas both EBV subtypes were observed in SNCC lymphomas and HD samples. All three forms of viral latent gene expression were found in the EBV positive CD30-positive ALC lymphomas. SNCC specimens did not express LMP-1 or EBNA-2, whereas HD specimens expressed LMP-1 (four of five tested) but no EBNA-2. Immunostaining for ZEBRA was consistently negative. HHV-6 DNA sequences were detected by PCR in one SNCC of the 19 specimens analyzed. Three out of five CD30-positive ALC lymphoma specimens and six of 10 SNCC showed nuclear staining for p53. No mutation was detected in any of the three CD30-positive Alc lymphoma analyzed, whereas an aberrant SSCP pattern was found in all the four SNCC samples tested. At variance with SNCC lymphomas, AIDS-related B-cell CD30- positive ALC lymphomas are strictly associated with EBV infection and may also express the broad lymphoblastoid cell line-like (LMP-1-positive, EBNA-2-positive) pattern, and lack p53 genetic lesions. Unlike EBV, HHV-6 probably does not represent a relevant factor involved in the pathogenesis of CD30-positive ALC and other HIV related lymphomas.
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PMID:Immunophenotypic and molecular analyses of acquired immune deficiency syndrome-related and Epstein-Barr virus-associated lymphomas: a comparative study. 861 54

Sixty cases of B-cell nodal non-Hodgkin's malignant lymphoma (B-ML), and 46 cases of T-cell nodal lymphoma (T-ML) were surveyed for Epstein-Barr virus (EBV) genomes, RNA, and associated proteins. We used a Southern blot analysis, polymerase chain reaction (PCR), and EBV-encoded small RNA-1 (EBER-1) in situ hybridization to investigate the presence of EBV. We performed an immunohistochemical study on EBV-related oncoproteins, such as EBV-determined nuclear antigen-2 (EBNA-2), latent membrane protein (LMP), and viral interleukin-10 (vIL-10). In addition, we also analyzed the terminal repetitive sequence of EBV (EBV-TR) to investigate the EBV-infected cell clonality. Non-Hodgkin's lymphomas were grouped into three types by number of EBV-infected cells: I) almost all lymphoma cells showed an EBV presence; II) some scattered lymphoma cells showed an EBV presence; and III) only a few cells showed such a presence, which was probably due to a latent EBV infection. In 25 of 60 B-MLs, EBV-infected cells were found; 7 were type I, 1 was type II, and 17 were type III. In 27 of 46 T-MLs, EBV-infected cells were found; no cases were type I, 5 cases were type II, and 22 cases were type III. Seven B-MLs and 3 T cell lymphomas showed clonal TR bands. Expression of EBNA-2 was found in only three B-MLs, whereas LMP was seen in four B-MLs and six T-MLs. All EBNA-2/LMP-positive cases showed an EBV presence. In B-MLs, expression of EBNA-2 and LMP was detected in almost all lymphoma cells; in T-MLs, however, LMP was found in only a small portion of the lymphoma cells. Expression of IL-10 was closely associated with LMP. In summary, it was thus speculated that EBV infection was associated with the various states of lymphomagenesis.
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PMID:Epstein-Barr virus infection and associated products (LMP, EBNA2, vIL-10) in nodal non-Hodgkin's lymphoma of human immunodeficiency virus-negative Japanese. 903 1

Tumor cells of Epstein-Barr virus (EBV)-associated Hodgkin's disease (HD) express the viral protein, latent infection membrane protein-1 (LMP1), but evade cytotoxic responses normally directed at this antigen. We tested whether local production of the immunoregulatory interleukins (IL)-4 and -10 may have a role in this process. IL-4 RNA was not detectable in any of the HD cases. By contrast, isotopic in situ hybridization and correlation with the presence of EBV gene products showed significantly higher proportions of cases with IL-10 expressing tumor cells in LMP1-positive (17 of 26, 66%) as compared with LMP1-negative HD cases (six of 37, 16%). Absence of EBV BCRF1 RNA indicated that the transcripts originated from the cellular IL-10 gene. Similarly, an association between IL-10 expression and EBV-infection of tumor cells was found in AIDS-related malignant non-Hodgkin lymphomas (ARL). Very small proportions of EBV-infected cells, mainly blasts, expressed IL-10 in infectious mononucleosis tonsils. Thus, although not entirely exclusive to EBV-positive cases, IL-10 expression is frequently associated with EBV-infection in HD and ARL and appears to be upregulated by EBV, most likely through LMP1. In view of the established inhibitory effects of IL-10 on cell mediated immunity, it is suggested that IL-10 expression may contribute to evasion of LMP1-positive cells from cytotoxicity directed at viral antigens.
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PMID:Frequent expression of interleukin-10 by Epstein-Barr virus-harboring tumor cells of Hodgkin's disease. 863 12

Hodgkin's disease rarely involves the skin and when it does is an indication of advanced stage disease. Primary cutaneous Hodgkin's disease is exceedingly rare, and only a few cases are reported. We describe a patient who developed multiple cutaneous lesions of Hodgkin's disease 2 years before manifesting nodal disease of mixed cellularity subtype. Reed-Sternberg cells in the skin as well as lymph nodes and bone marrow were positive for Epstein-Barr viral transcripts and expressed viral latent membrane protein. Epstein-Barr virus has not previously been demonstrated in primary cutaneous Hodgkin's disease, and its presence in lesions in all sites in this case supports a diagnosis of primary cutaneous disease with subsequent evolution into systemic disease.
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PMID:Primary cutaneous Hodgkin's disease with evolution to systemic disease. Association with the Epstein-Barr virus. 865 56

Hodgkin's disease (HD) varies in prevalence, morphologic findings, and association with Epstein-Barr virus (EBV) in different parts of the world. HD in the Philippines and its relationship to EBV has not been studied. We reviewed all cases of HD in the Philippines for the years 1989 to 1994, diagnosed at three large hospitals in Manila and Cavite. During this study period, 68,121 surgical specimens were accessioned, of which there were 21 cases (0.03%) of HD. There were 11 males and nine females; sex was unknown in one case. The median age was 22 yr (range, 11 to 64 yr). Thirteen cases occurred in patients less than 30 yr old, including six of 11 males and seven of nine females. The remaining cases were distributed among other age groups, with five cases in males occurring after the age of 50 yr. There were 10 cases of nodular sclerosis, nine cases of mixed cellularity, and two cases of nodular lymphocytic predominance. Nine cases were positive for EBV latent membrane protein: six of nine mixed cellularity and three of 10 nodular sclerosis. In situ hybridization confirmed the immunohistochemical results, and revealed EBV RNA predominantly in Reed-Sternberg and Hodgkin cells. A few small lymphocytes were also positive in many cases. These results suggest that HD is uncommon in the Philippines, similar to other Asian countries such as Japan. However, the age distribution and histologic subtypes of HD in the Philippines seem to be more similar to that of Western industrialized countries such as the United States. EBV was present in a subset of cases, most frequently in mixed cellularity.
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PMID:Hodgkin's disease in the Philippines. 865 16

Recent studies have suggested that Epstein-Barr virus (EBV) may play a role in the aetiology of Hodgkin's disease. To determine the role of EBV in childhood Hodgkin's disease in different geographical areas, immunohistochemical staining and in situ hybridisation were used to analyse latent membrane protein 1 (LMP 1) and small nuclear non-transcribed RNAs (EBER-1) respectively. Testing for EBV within the Reed-Sternberg and Hodgkin's cells was carried out in childhood Hodgkin's disease from 10 different countries. The proportion of LMP 1 positive cases varied significantly, being 50% of cases from the United Kingdom (38/75), South Africa (9/18), Egypt (7/14), and Jordan (8/16), 60% from the United Arab Emirates (6/10), 70% from Australia (11/16), 81% from Costa Rica (34/42), 88% from Iran (7/8), 90% from Greece (20/22), and 100% of the 56 cases from Kenya. A sensitive polymerase chain reaction based EBV strain typing technique was established using archival tissues. EBV strain type 1 was shown to be predominant in childhood Hodgkin's disease from the United Kingdom, South Africa, Australia, and Greece. Type 2 was predominant in Egypt. EBV strain types 1 and 2 were both detected in some cases of childhood Hodgkin's disease in the United Kingdom, Costa Rica, and Kenya. The high incidence of EBV and the presence especially in developing countries of dual infection with both strain types 1 and 2 may reflect socioeconomic conditions leading to malnutrition induced immunological impairment. The possibility of HIV infection also needs to be explored.
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PMID:The role of Epstein-Barr virus in Hodgkin's disease from different geographical areas. 866 41


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