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)

The nature of the Reed Sternberg (RS) cell, the malignant cell of Hodgkin's disease (HD), remains unknown. Cytogenetic studies have yielded ambiguous results regarding the chromosomal profile of this cell. In an attempt to further clarify the ploidy status of the RS cell, we analyzed the DNA content of CD30-positive RS cells and RS cell variants in HD lesions from 32 patients using an image analysis system. A diploid and/or near-diploid (DNA index [DI], 1.0 +/- 0.2) and a tetraploid (2.0 +/- 0.2) RS cell population were identified in 9 and in 11 of the 32 cases examined, respectively. An aneuploid RS cell population was identified in 8 of the 32 cases examined. The remaining four cases contained two RS cell subpopulations with different DNA content, each one representing more than 15% of the total RS cell population. There was no significant correlation between the DNA content of the RS cells and the category of HD. Furthermore, analysis of multiple biopsies of an individual patient taken from different lymphoid organs at the same or different time periods showed a constant DNA profile. Our data indicate that RS cells can express variable DNA content and suggests that multiple subpopulations of RS cells with different DNA content may simultaneously coexist within the same HD lesion in some patients. In addition, the RS cell population within each patient appears to express a specific DNA content profile, possibly representing unique clones. These highly individualized profiles potentially may be useful as markers to follow the clinical course of patients with HD.
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PMID:Determination of the DNA content of the Reed-Sternberg cell of Hodgkin's disease by image analysis. 133 3

In Hodgkin's disease, Epstein-Barr virus (EBV) is found in CD30-positive Reed-Sternberg cells. We therefore studied 60 CD30-positive non-Hodgkin's lymphomas (NHLs) for the presence of EBV by the polymerase chain reaction (PCR) and DNA in situ hybridization (DISH), and by immunohistochemistry for the latent EBV proteins LMP and EBNA-2. CD30-negative NHLs and reactive lymph nodes served as controls. The CD30-positive cases comprised 17 anaplastic large cell lymphomas (ALCLs) (> 75 per cent CD30-positive cells) and 43 non-ALCLs (with 5-35 per cent CD30-positive cells). By PCR, 40 of 60 CD30-positive NHLs (67 per cent) were EBV-positive; in CD30-negative cases, 6/29 (21 per cent) were EBV-positive, as were 12/50 (24 per cent) reactive lymph nodes. The DISH procedure demonstrated the EBV genome exclusively in the nuclei of tumour cells in 23 of the 37 PCR EBV-positive cases that were tested. PCR-negative cases were always DISH-negative, as were the PCR-positive reactive lymph nodes and CD30-negative NHLs. Immunohistochemistry demonstrated LMP in neoplastic cells of 7/47 (15 per cent) CD30-positive NHLs, both ALCL and non-ALCL always in PCR EBV-positive cases, but never in the two control groups. EBNA-2 staining could not be detected. It is concluded that EBV is present (and transcriptionally active) in a sizeable number of NHLs and an association between the presence of the EBV genome and CD30 expression seems likely.
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PMID:High incidence of EBV genome in CD30-positive non-Hodgkin's lymphomas. 133 46

The present study was performed to clarify the reported inconsistencies regarding the frequency of the association of Epstein-Barr virus (EBV) and Hodgkin's disease (HD). Biopsies from 102 patients with HD were screened for the presence of EBV-encoded small nuclear RNA (EBER) and latent membrane protein (LMP) by using a non-isotopic in situ hybridization (ISH) and immunohistology (IH), respectively. The results were additionally compared with those obtained by polymerase chain reaction (PCR) for EBV-DNA detection. EBV was detected by EBER-ISH in 67% of the HD cases and in 25% of the control group cases consisting of normal lymph nodes. The results of PCR performed on cases with amplifiable DNA were overall congruent with those obtained by EBER-ISH. With respect to the cellular localization of EBV, four categories of HD could be established: (a) cases with EBV-infected tumour cells (42/102), (b) cases with additional infection of bystander cells (4/102); (c) cases with EBV infection restricted to non-malignant bystander cells (23/102); and (d) cases with neither EBV-infected tumour cells nor bystander cells (33/102). LMP expression was detectable only in the neoplastic cell population of those cases with EBER-positive tumour cells, suggesting a frequent involvement of EBV in the pathogenesis of HD.
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PMID:EBV infection patterns in Hodgkin's disease and normal lymphoid tissue: expression and cellular localization of EBV gene products. 133 92

Previous studies have detected EBV DNA by Southern blotting or in situ hybridization in biopsy material from up to 30 per cent of adult cases of Hodgkin's disease. Here we have used monoclonal antibodies specific for the EBV latent membrane protein LMP1 to examine archival material from children with Hodgkin's disease. Material from 74 cases (54 males and 20 females) was examined and 37 (30 males and 7 females) were classified as LMP1-positive in the malignant cells. LMP1 positivity was present in 4/13 (31 per cent) of lymphocyte predominant, 14/36 (39 per cent) of nodular sclerosis, 17/20 (85 per cent) of mixed cellularity, 1/2 (50 per cent) of lymphocyte depletion, and 1/3 (33 per cent) of unclassified subtypes. The positive cases by clinical stage were I 9/22 (41 per cent), II 9/20 (45 per cent), III 11/24 (46 per cent), and IV 8/8 (100 per cent). LMP1 positivity was present in 2/5 (40 per cent) children aged less than 5 years, 12/27 (44 per cent) aged 5-10 years, and 23/42 (48 per cent) aged between 10 and 15 years. The association between EBV and Hodgkin's disease in children thus appeared to be more frequent in patients with mixed cellularity and advanced disease, but examples of EBV-positive tumours were found in all histological subtypes, stages, and ages. Stepwise discriminant function analysis showed that clinical stage IV and mixed cellularity histology are independently associated with LMP1 positivity. These observations indicate that Hodgkin's disease in children is at least as strongly linked to EBV as is the disease in adults.
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PMID:Epstein-Barr virus (EBV) and Hodgkin's disease in children: incidence of EBV latent membrane protein in malignant cells. 133 43

The most recent sophisticated investigations have provided new and revealing, but also contradictory and controversial information on the biological nature and the cellular origin of Hodgkin and Reed-Sternberg cells (H-RS). Immunophenotypic analyses have shown variable phenotypic antigen expression; but, on balance the data suggest a lymphoid cell expressing T- and/or B-cell-associated markers and certain activation antigens while lacking immunological features of monocytes-macrophages or other lineages. Molecular genetic studies have demonstrated heterogenous findings with respect to rearrangements of T-cell receptor and immunoglobulin genes. Only a small percentage of the cases has rearrangements; this might be due to the threshold of sensitivity of the method combined with the scarcity of the malignant cells. Epstein-Barr virus (EBV) genomes are clonally integrated in the H-RS cells of about half the cases. The significance of these findings--whether EBV is a causative agent or an epiphenomenon--remains to be elucidated. H-RS cells express mRNA and proteins of various cytokines and cytokine receptors implying a predominant role for cytokines in the pathophysiology of HD. The mononuclear and polynuclear H-RS cells are capable of DNA synthesis and nuclear division; the lack of cellular division leads to multinuclearity through the process of endomitosis. Mutations and expression of only a limited number of oncogenes have been tested thus far. Whether the bcl-2 oncogene is involved in HD remains a matter of debate. Aneuploidy and non-random chromosomal abnormalities are the results of cytogenetic analyses of H-RS cells. However, no chromosomal marker specific for HD has yet been found. Thus, while studies of EBV involvement, growth factor production, oncogene expression and chromosomal abnormalities contributed a fair amount of new data on the nature of H-RS cells, only immunophenotyping and genotyping provided some indication of the cellular derivation: an activated lymphoid cell that possibly expresses oncogenes, that probably is infected with EBV, that most likely produces cytokines, that certainly has multiple karyotypic abnormalities.
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PMID:Recent results on the biology of Hodgkin and Reed-Sternberg cells. I. Biopsy material. 133 48

Epstein-Barr virus (EBV) DNA is frequently identified in benign and malignant lymphoproliferative conditions. As shown by in situ hybridization studies viral DNA is localized within malignant cells as well as benign lymphocytes. Clonal and nonclonal EBV genomes are present in Hodgkin's disease (HD), lymphomas of the immunocompromised host and reactive lymph node hyperplasia. Lytic infection with formation of linear genomes is observed in the same conditions but appears to be infrequent in HD as shown by quantitation of mRNA coding for viral capsid antigen. Expression of the oncogene LMP (latent membrane protein) is seen in Sternberg-Reed (SR) cells and immunoblasts of AIDS-related lymphoma and infectious mononucleosis (IM). In HD, the region of the BNLF1 oncogene coding for the amino terminal and transmembrane domains (associated with oncogenic function) of LMP appears to be homogeneous whereas the region coding for the intracytoplasmic (carboxy terminal) domain of LMP is heterogeneous. Cytological similarities between SR cells and immunoblasts of IM and AIDS-related lymphomas are consistent with the hypothesis that the BNLF1 oncogene is one possible inducer of morphological features of SR cells. Whether chromosomal integration of EBV DNA is an important factor in activation of such a transforming activity remains to be elucidated. EBV DNA positive and negative HD cases with numerous SR cells lack significant mRNA expression of the two recombinase activating genes (RAG-1 and RAG-2). Therefore the SR cells appear to be derived from lymphocytes beyond the pre-B-cell or common thymocyte stage which may or may not subsequently become infected by EBV.
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PMID:Significance of the detection of Epstein-Barr virus DNA in lymph nodes in patients with Hodgkin's disease. 133 49

The majority of non-Hodgkin's B-cell lymphomas contain a t(14;18) translocation that places the bc12 gene into juxtaposition with the transcriptically active Ig heavy-chain locus, thus deregulating the expression of this proto-oncogene. The bc12 gene product is a membrane-associated mitochondrial protein that regulates cell survival through unknown mechanisms. Although overproduction of the normal protein appears sufficient for conferring a selective growth or survival advantage to B cells, point mutations that alter the coding region of translocated bc12 genes have been described previously by others in a lymphoma cell line. However, it is not known whether somatic mutations that alter BCL2 proteins occur in vivo or whether they result from chemotherapy or arise through other mechanisms. For these reasons, we obtained DNA from the t(14;18)-containing tumors of five patients who had not undergone treatment for their disease, and used a polymerase chain reaction (PCR)-mismatch technique for rapid identification of point mutations in a portion of the bc12 open reading frame (ORF) corresponding to the first 131 aminoacids (aa) of the 239 aa p26 BCL2 protein. DNAs from two t(14;18)-containing cell lines were also analyzed. Point mutations in this region of the bc12 gene ORF were detected in three of five patients' tumors and in both cell lines. PCR-mismatch analysis of bc12 in cell lines and non-Hodgkin's lymphoma cases that lacked the t(14;18) translocation was negative, thus establishing the specificity of these results. DNA sequencing determined that these mutations are predicted to produce aa substitutions in the BCL2 proteins of two of the primary tumors and one of the cell lines. Interestingly, two of the patients contained an identical C----T transition that resulted in a nonconservative aa substitution (proline----serine) at position 59 of the BCL2 protein. Further analysis excluded the possibility that these mutations represented hereditary polymorphisms or PCR artifacts. A cluster of four point mutations within the translocation + bc12 allele of one patient had hallmarks of the somatic hypermutation mechanism that is associated with Ig genes and that contributes to antibody diversity. Because of the region of the bcl2 gene analyzed in these t(14;18) translocations is located nearly 300 kbp from the Ig heavy-chain locus, our data suggest that the Ig gene somatic hypermutation mechanism can act over extreme distances of DNA. It remains to be established whether these somatic mutations that alter BCL2 proteins influence the pathobiology of nonHodgkin's lymphomas.
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PMID:Frequent incidence of somatic mutations in translocated BCL2 oncogenes of non-Hodgkin's lymphomas. 133 99

The association between AIDS and a spectrum of malignancies relates to chronic, profound defects in both cellular and humoral mechanisms of immune surveillance. Ironically, as AIDS patients live longer in response to increasingly effective antiretroviral therapies, the incidence of AIDS-related malignancies will continue to rise. The emergence of non-Hodgkin's lymphomas (NHL) as a major sequela of HIV infection bears a striking relationship to depletion of CD4 lymphocytes, particularly below 50/mm3. The ability to interfere early in the course of active HIV infection with additional mechanisms that may promulgate transformed cell hyperproliferation and clonal expansion--growth factors, HIV itself or other viruses (Epstein-Barr, in particular), aberrant oncogene or tumor suppressor genes expression, factors that induce genetic instability or DNA damage or alter host or viral genome repair--might decrease the occurrence or prolong the time to development of AIDS-related malignancies. The development of antiretroviral strategies that confer long-term suppression of HIV activity and relative preservation of immune function are essential to the ultimate prevention of malignancies that arise as a consequence of HIV-induced immunosuppression.
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PMID:The pathogenesis of AIDS lymphomas: a foundation for addressing the challenges of therapy and prevention. 136 82

Many nonrandom chromosome abnormalities have been associated with non-Hodgkin's lymphomas (NHL). Some of these are nonspecific changes seen in many different histologic subtypes. We describe a series of abnormalities of chromosome bands 10q23-25 seen in 159 consecutive NHL patients with abnormal cytogenetic findings. The proportion of karyotypes with abnormalities of 10q varied from 3% among the immunoblastic lymphomas to 67% in the diffuse large cleaved cell lymphomas. Seventeen (10.7%) had abnormalities of 10q23-25. All but one of these were B-cell tumors. The abnormalities consisted of six deletions and 11 translocations. Sixteen of the 17 patients had the 10q abnormality when cells were first karyotyped. The remaining patient acquired the 10q abnormality in the third of a series of biopsies. In the follicular histologic subtypes [follicular small cleaved cell (FSC), follicular mixed small cleaved and large cell (FM), and follicular large cell noncleaved (FL-NC)], abnormalities of 10q were found in nine patients, all in association with abnormalities of 14q32. Seven of these were associated with the t(14;18)(q32;q21). Overall, 10q23-25 abnormalities were observed in 11.9% (8/67) of low-grade [small lymphocytic (SL), FSC, and FM] lymphoma cases. DNA was available from five patients with abnormalities of 10q and was probed for rearrangements with the HOXII (TCL3) oncogene probe. As expected, we did not find such rearrangements in these five patients with B-cell tumors. Abnormalities of 10q23-25 have been reported previously in NHL but not at this frequency.
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PMID:Recurrent abnormalities of chromosome bands 10q23-25 in non-Hodgkin's lymphoma. 138 77

The Epstein-Barr virus (EBV) has been increasingly detected in Hodgkin's disease (HD), but its role in pathogenesis remains uncertain. We analyzed 20 specimens of HD known to contain EBV DNA by a sensitive reverse transcriptase polymerase chain reaction (RT-PCR). The cases were assessed for the presence of RNA transcripts of the BNLF1 gene (coding for the viral latent membrane protein [LMP]) and the late replicative gene BLLF1 (coding for the principle envelope glycoprotein [gp220/350]). LMP RNA transcripts were found in 9 of 20 (45%) cases, mostly those containing many copies of viral DNA and of mixed cellularity (MC) histological subtype. Only one LMP RNA-positive case was also positive for RNA transcripts of the active replication gene BLLF1. Our results show that viral burden in HD is not primarily related to active viral replication, but is associated with LMP gene expression.
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PMID:Epstein-Barr virus burden in Hodgkin's disease is related to latent membrane protein gene expression but not to active viral replication. 138 93


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