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

The presence of Epstein-Barr virus (EBV) genome in Hodgkin's and Reed-Sternberg (HRS) cells, as detected using in situ hybridization (ISH) with biotinylated BamHI "V" probes, along with the expression of EBV-encoded latent membrane protein (LMP) and vimentin was examined in paraffin-embedded sections of 39 immunomorphologically characterized cases of Hodgkin's disease (HD). ISH demonstrated EBV in HRS cells in 15 of 39 cases, whereas LMP expression was detected in 11 of 39 cases, only in the presence of EBV genome detection. With the exception of 1 case, in which HRS cells expressed B-cell-associated antigens, the LMP-positive cases included specimens in which HRS cells were of non-B, non-T phenotype. LMP expression showed a stronger association with lymphocyte depletion (LD) (3/3) and mixed cellularity (MC) (6/11) than with lymphocyte predominance (0/5) or nodular sclerosis (2/20) subtypes. Vimentin expression on HRS cells was found in all the LMP-expressing cases and only in a fraction (13/28) of LMP-negative cases. This study supports the view that HD represents a heterogeneous group of diseases also in terms of EBV association, LMP expression being strongly related to the "aggressive" LD and MC histological subtypes. In light of the supposed interactions between vimentin and LMP, their co-expression on HRS cells, as detected in this study, provides further evidence for a significant role of EBV in the development of a proportion of HD cases.
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PMID:Co-expression of Epstein-Barr virus latent membrane protein and vimentin in "aggressive" histological subtypes of Hodgkin's disease. 767 48

Epstein-Barr virus (EBV) latent membrane protein 1 (LMP 1) is expressed in Hodgkin and Reed-Sternberg (HRS) cells in about one half of Hodgkin's disease (HD) cases. In vitro, LMP 1 induces B-cell expression of CD23 antigen, ICAM-1 and LFA-3. To evaluate the influence of LMP 1 on the expression of these molecules in HRS cells in vivo, we performed a quantitative frozen section immunohistological study comparing the numerical density (cells per unit area) of HRS cells expressing the CD23 antigen, ICAM-1 and LFA-3 in 14 LMP 1-positive and 13 LMP 1-negative HD cases. CD23 antigen was demonstrated in HRS cells in five LMP 1-positive and three LMP 1-negative cases (not significant). The relative density of HRS cells tended to be lower in the LMP 1-positive than in the LMP 1-negative cases, but this did not reach significance (0.2 > 2p > 0.1). All recognizable HRS cells expressed ICAM-1 and LFA-3 irrespective of LMP 1 status. We conclude that expression of CD23 antigen and LMP 1 are not coordinated in HD. Although LMP 1 may have some influence on CD23 antigen expression, it is unlikely that the latter is of importance in the putative EBV induced growth transformation of HRS cells in vivo.
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PMID:Influence of Epstein-Barr virus encoded latent membrane protein 1 on the expression of CD23 antigen, ICAM-1 and LFA-3 in Hodgkin and Reed-Sternberg cells. A morphometric analysis. 768 82

The presence of Epstein-Barr virus (EBV) correlates with some cases of Hodgkin's disease (HD), and its latent membrane protein (LMP) has oncogenic potential by inducing expression of bcl-2 protein. Bcl-2 confers a longer half-life to the cell, which overexpresses it. As the translocation t(14,18), which is most often found in follicular lymphomas, and leads to overexpression of bcl-2, has also been reported in HD, it is possible that there is a correlation between these events in this entity. We stained immunohistochemically 40 cases of HD for the presence of bcl-2 and EBV-LMP. Bcl-2 positivity within reactive lymphocytes was revealed in 29 cases. In five of these cases a week, positive reaction in cytoplasm of Reed-Sternberg cells was observed (one mixed cellularity and four nodular sclerosis cases). The EBV-LMP immunopositivity was observed in 16 of these 29 cases (ten MC and six NS cases). The simultaneous presence of bcl-2 protein and EBV-LMP was found in two cases, the remaining three bcl-2-positive cases did not have EBV-LMP. These results do not support the hypothesis of the correlation between the expression of bcl-2 protein and the presence of EBV-LMP in the pathogenesis of HD as the LMP-dependent stimulation of bcl-2 oncogene.
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PMID:Expression of bcl-2 protein and Epstein-Barr virus latent membrane protein in Hodgkin's disease. 769 30

Interleukin-12 (IL-12), a cytokine with in vitro and in vivo immunomodulatory effects, is produced by lymphocytes and stimulated monocytes. Little is known about the production and possible role of IL-12 in human lymphoproliferative disorders. We examined IL-12 expression by immunohistochemistry using antibodies recognizing the p40, p35 subunits, and the p70 heterodimeric IL-12 protein, and by Northern blot in lymph nodes from patients with Hodgkin's disease (HD), non-Hodgkin's lymphomas (NHL), and nonneoplastic lymphoid lesions. In the majority of the HD cases (28 of 34), IL-12 immunoreaction was found in small lymphoid cells cultured around Hodgkin and Reed-Sternberg (H&RS) cells. No IL-12 signal was seen in H&RS cells. Transcripts for IL-12 were found by Northern and dot blot analysis in 13 of 19 (IL-12 p40) and 11 of 19 (IL-12 p35) cases. The HD cases were further examined for the presence of Epstein-Barr virus (EBV) latent membrane protein (LMP-1). All cases with EBV-LMP-1 positivity (22 of 34 cases) also expressed IL-12. No IL-12 immunoreaction was found in neoplastic cells of 33 cases of various NHLs, which were all LMP-1 negative and showed no EBV-genome sequence, as assessed by polymerase chain reaction (PCR). In 24 nonneoplastic lymphoid lesions, few dispersed IL-12 positive cells were seen in the parafollicular area and in the sinus of the lymph node. The marked presence of IL-12 in the majority of HD cases indicates that IL-12 might play a role in the pathobiology of HD, suggesting that this cytokine is involved in EBV-positive HD.
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PMID:Interleukin-12 expression in human lymphomas and nonneoplastic lymphoid disorders. 771 89

The link between Hodgkin's disease (HD) and Epstein-Barr virus (EBV) is well documented in childhood and here the same hypothesis has been examined in adults, by comparing cases from an industrialized and a developing country. In this study the prevalence of EBV markers in nodal lesions of adult HD were compared in 21 patients from France (Fr) and 25 from Algeria (Al), all clinically staged during 1990-1992. Median age was 29 years. Histologic subtypes included lymphocytic predominance (LP) Fr 1; nodular sclerosis (NS) Fr 16, Al 16; mixed cellularity (MC) Fr 4, Al 9. EBV markers examined included expression of latent membrane protein (LMP) in Reed-Sternberg and Hodgkin cells (RSC) by immunochemistry; EBV-DNA and -RNA in situ hybridization (ISH); EBV-DNA by polymerase chain reaction (PCR). Results showed that RSC were LMP-positive in 4 (2 NS, 2 MC) French and 7 (3 NS, 4 MC) Algerian. All LMP+ cases were also positive for EBV DNA-RNA ISH. ISH was positive in RSC of 33% of the French and 72% of Algerian patients (p < 0.02). The positivity was more frequent in MC (77%) than in other histologic types (45%). The EBV genome was detected by PCR on DNA extracted from frozen samples in 84% of Fr and 95% of Al patients (100% of MC and 86% of other histologic types). Conclusion. The discrepancy between PCR and ISH results may be due to the lesser sensitivity of the ISH technique, or, alternatively, to the presence of EBV in the lymphoid cells surrounding RSC.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Comparison of Epstein-Barr virus markers in Reed-Sternberg cells in adult Hodgkin's disease tissues from an industrialized and a developing country. 777 54

To assess the role of the Epstein-Barr virus (EBV) latent membrane protein 1 (LMP1) gene in the development of Hodgkin's lymphoma (HL), the polymorphism of this gene in EBV isolates from different geographic locations was analyzed. A 497 bp fragment spanning LMP1 gene exons 1 and 2 was amplified by polymerase chain reaction (PCR), using a primer pair bracketing a Xhol restriction site. PCR products were subjected to Xhol digestion and to DNA sequencing analysis. Twenty-five HL biopsy specimens from the United States and five HL and four non-Hodgkin's lymphoma (NHL) biopsy specimens from Italy were examined. Eighty percent of LMP1-positive samples (12 of 15) from the United States maintained the Xhol restriction site and the remaining 20% partially lost the Xhol site. One of four EBV-positive HL and one of the three EBV-positive NHL specimens from Italy lost the restriction site. The other three EBV-positive HL DNAs were partially cut by Xhol. Direct DNA sequencing analysis revealed that those Italian samples not digested by Xhol were due to a G to C transversion at the first base of codon 18, resulting in the change of glycine to arginine. Those DNA samples partially cut by Xhol were due to a mixture of G/C at the same location. In contrast, those partially digested American HL DNAs had a mixture of G/T at the second base of codon 17.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Geographic sequence variation of latent membrane protein 1 gene of Epstein-Barr virus in Hodgkin's lymphomas. 777 37

CD30 (Ki-1)-positive anaplastic large cell lymphoma (CD30+ ALCL) is a morphologically and immunophenotypically distinct subset of non-Hodgkin's lymphoma. Although the presence of Epstein-Barr virus (EBV) has been well documented in a significant proportion of cases of Hodgkin's disease, another CD30+ malignancy, few studies have examined the association of EBV with CD30+ ALCL. These latter studies have produced conflicting findings. To further investigate the existence of a putative association of EBV with CD30+ ALCL, and whether this association, if present, shows geographic variation, we examined 34 formalin-fixed, paraffin-embedded specimens from cases of CD30+ ALCL from the United States and Hong Kong. Immunophenotypically, 15 cases were of B lineage, 15 cases were of T lineage, one case expressed both B- and T-cell markers, and three were of null lineage. A highly sensitive in situ hybridization method was performed with use of an antisense oligonucleotide probe to the EBV-encoded RNA (EBER-1). EBV-RNA was identified in 3 of 14 CD30+ ALCL specimens from Hong Kong patients and in 1 of 20 from the American patients. The EBER-1 signal was present in all or virtually all of the tumor cell nuclei in the three EBV-RNA-positive CD30+ ALCL Hong Kong cases, but was only focally present in the single EBV-positive American case. The latent membrane protein-1 (LMP1) of EBV was identified in only one of the four positive cases, a Hong Kong case. Our results suggest that in contrast to Hodgkin's disease, EBV has no significant association with CD30+ ALCL.
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PMID:Infrequent association of Epstein-Barr virus with CD30-positive anaplastic large cell lymphomas from American and Asian patients. 780 37

Specimens from 82 children with Hodgkin's lymphoma were studied by immunohistochemical technique for Epstein-Barr virus encoded latent membrane protein (LMP). LMP was demonstrated in 67 cases 81.7%, the positive rate for the mixed cellular subtype was 90.9%. The positive rate for the 3-5 year old group of patients was 100%, 75% for the 6-10 year old group and only 62.5% for the 11-14 year old group. These findings suggest that Epstein-Barr virus is strongly associated with Hodgkin's lymphoma, the younger the age, the stronger the association. Mixed cellular subtype of Hodgkin's lymphoma had the strongest association with Epstein-Barr virus among all subtypes.
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PMID:[The association of Epstein-Barr virus with Hodgkin's lymphoma in childhood]. 780 52

The Epstein-Barr virus (EBV) has been demonstrated in association with cases of Hodgkin's disease (HD) indicating that, in at least in some cases, EBV may play a pathogenic role in the development of HD. To determine the prevalence of EBV in HD in a Mexican adult population, we studied 39 formalin-fixed and/or B-5, paraffin embedded samples of patients with HD, by immunoperoxidase; in situ hybridization was done in 32 of the 39 cases. We analyzed the presence of the latent membrane protein (LMP) and EBV-specific DNA sequences. Reed-Sternberg cells and mononuclear variants were positive for LMP in 28 cases (72%). LMP staining was found both on the cell surface and/or within the cytoplasm with enhancement in the Golgi area. The LMP was found in the single case of diffuse lymphocyte predominant HD, in 6/12 cases of nodular sclerosis (50%), in 10/15 cases of mixed cellularity (67%) and in all eleven cases of lymphocyte depleted HD (100%). No EBV-specific DNA sequences were found by in situ hybridization. Our results show: 1) a higher association of EBV in our population compared to the approximately 48% reported in developed countries; 2) all histologic subtypes of HD in Mexico appear to be strongly associated with EBV in contrast to the strong association with only mixed cellularity seen in Western populations; 3) the high prevalence of EBV in HD in Mexico may be a function of histology, ethnic groups, socioeconomic factors and/or geography.
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PMID:[High prevalence of the Epstein-Barr virus in a Mexican population with Hodgkin's disease]. 783 15

We have recently identified in Epstein-Barr virus (EBV) positive Hodgkin's disease (HD) a variant of the latent membrane protein 1 (LMP1) oncogene characterized by four point mutations and a 30 base pair deletion. These findings led us to test whether such mutants were also present in other lymphoproliferative disorders (LPD). We analysed 98 EBV DNA positive cases (67 LPD, 15 benign conditions, 16 lymphoblastoid cell lines) by PCR for deletions within the LMP1 gene. DNA sequencing of the region coding for the carboxy terminal protein domain was performed on 24 cases. In 13 cases the same combination of 4 point mutations at positions 168,320, 168,308, 168,295 and 168,225 was identified. Of these cases, 12 had an additional point mutation at position 168,357 and eight at position 168,355, and nine had a 30 base pair deletion including nucleotides 168,285 to 168,256. These deletion mutants were identified in HD, angioimmunoblastic lymphadenopathy, B-immunoblastic lymphoma, peripheral T-cell lymphoma, and two lymphoblastoid cell lines. Our findings reveal a high frequency of non-random point mutations at preferential sites within the 3' (carboxy terminal) region of the LMP1 oncogene. The association of these mutational hot spots with LPD suggests that they are involved in EBV related lymphomagenesis and that they define a clinically relevant EBV strain.
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PMID:Mutational hot spots within the carboxy terminal region of the LMP1 oncogene of Epstein-Barr virus are frequent in lymphoproliferative disorders. 784 77


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