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)

We describe a family in which two sisters with the autosomal dominant skeletal dysplasia, Leri-Weill dyschondrosteosis (LWD), developed Hodgkin's disease (HD) in late adolescence. In a preliminary attempt to identify HD susceptibility gene(s), HLA-typing and linkage analysis were carried out in the family. Using HLA molecular typing, both sisters were found to have inherited a variant of the HD-susceptibility allele, DPB1*0301, known as DPB1*2001. Following a previous report of a constitutional chromosome translocation (t(2q;8p)) in a family with LWD, preliminary linkage studies were carried out using chromosome 2q and 8p molecular markers. Regions covered by 7/10 chromosome 2 markers and 4/8 chromosome 8 markers were excluded as the location of a candidate LWD gene. Given the rarity of LWD and HD, their simultaneous occurrence is unlikely to have been due to chance. We suggest that a mutation in the LWD gene itself, or a gene closely linked to it, perhaps acting with increased susceptibility to infection conferred by DPB1*2001, resulted in HD in the two sisters.
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PMID:Molecular genetic analysis of a family with a history of Hodgkin's disease and dyschondrosteosis. 776 45

We conclude that the most common secondary cancers which develop after marrow transplantation are lympho-proliferative disorders and solid tumors. The consequences of the secondary malignancies are serious, with more than 90% of the patients with non-Hodgkin lymphomas associated with EBV infection and more than 75% of the patients with solid tumors dying despite treatment. Secondary leukemia developing in donor T-s is rare, but was fatal in all cases. EBV infection plays a major role in leading to the non-Hodgkin lymphomas in a setting of immune dysregulation from ATG or anti-T-cell monoclonal antibody treatment of acute GVHD. Other factors are also important for development of non-Hodgkin lymphoma and include T-cell depletion of donor marrow and HLA-mismatching between donor and recipient, known to lead to dysregulation of T-lymphocyte function. These factors set up an environment of proliferative stimuli which cannot be controlled by the recovering immune system, setting the stage for a secondary cancer. The role of irradiation is becoming more prominent in association with solid tumors, particularly in aplastic anemia patients conditioned with irradiation. The final event of tumor expression is most likely the result of a cascade of events, perhaps initiated with the conditioning regimen or with stimuli to proliferation, which, after later signals, leads to malignant transformation. For lymphoproliferative disorders, the time of latency is shorter than for solid tumors, suggesting a different molecular mechanism. The incidence of oncogene expression or mutation in tumor suppressor genes in these solid tumor patients has not been investigated.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Secondary malignancies after marrow transplantation for leukemia or aplastic anemia. 780 95

T helper cell (TH) function, as assessed by interleukin-2 (IL-2) production and [3H]thymidine incorporation, was studied in 47 newly diagnosed untreated patients with Hodgkin's disease (HD) and 34 healthy controls. Three different stimuli were used to stimulate in vitro peripheral blood mononuclear cells (PBMC): influenza A vaccine (FLU), HLA alloantigens (ALLO) and phytohaemagglutinin (PHA). Four different patterns of TH function were observed in HD patients: (1) IL-2 production in response to all of the stimuli (40%); (2) IL-2 production in response to ALLO and PHA but not to FLU (26%); (3) IL-2 production in response to PHA alone (19%); and (4) failure to respond by IL-2 production to any of the three of the stimuli (15%). Thus, defective in vitro TH function was detected in the majority of these patients (60%). Defective TH function was observed in none of the 34 controls. Severely compromised TH function (patterns 3 and 4) tended to be associated with more advanced clinical presentation and more compromised haematological parameters (P < 0.05). The IL-2 production assay was more sensitive than the proliferative assay as only 30% of the HD patients failed to proliferate in response to FLU, and none failed to proliferate in response to either ALLO or PHA; this assay can detect subtle, multiple patterns of immune dysregulation in untreated HD patients. Our results suggest that HD is associated with a fundamental dysregulation in TH function, illustrate the complexity of such dysregulation, and raise the possibility that HD progression will be associated with a type-1-type-2 switch in immunoregulatory cytokine production.
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PMID:Multiple defects of T helper cell function in newly diagnosed patients with Hodgkin's disease. 783 3

The most recent sophisticated investigations have provided new and revealing but also contradictory and controversial informaiton on the biological nature and the cellular origin of Hodgkin and Reed-Sternberg (H-RS) cells. Immunophenotypic analyses have shown consistent expression of CD15, CD30, CD74, and HLA-Dr antigens, but generally lack of T- or B cell-associated markers in H-RS cells. The H-RS cells are also devoid of many monocyte/macrophage-associated antigens. Molecular genetic studies have demonstrated heterogeneous findings with respect to rearrangements of T-cell receptor and immunoglobulin genes. Only a small percentage of the cases have rearrangements; this cannot always be attributed to the threshold of sensitivity of the method and/or the scarcity of the malignant cells in tissues examined. The H-RS cells do not express transcription factors such as BSAP, TCF-1, and GATA-3, known to be associated with lymphoid cells. It appears that evidence to support a lymphoid origin for H-RS cells is still lacking. On the contrary, the mechanism responsible for the unique clinical and histopathologic alterations associated with this disease has become clear. The H-RS cells have been shown to secrete IL-1, IL-5, IL-6, IL-9, TNF-a, M-CSF, and TGF-b, and, less frequently, IL-4 and G-CSF. These cytokines are likely to be responsible for the increased cellular reaction and fibrosis observed in tissues involved by HD and for the immunosuppression in patients with HD. Like most lymphomas, the etiology or pathogenesis of HD remains unknown. The 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.
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PMID:The nature of Reed-Sternberg cells: phenotype, genotype, and other properties. 784 86

A patient with refractory relapsed Hodgkin's disease underwent an autologous bone marrow transplant in July 1987 and achieved remission of Hodgkin's disease. He had complete hematological recovery but developed pancytopenia 3 years post bone marrow transplantation with morphological evidence of myelodysplasia. High-dose cyclophosphamide, 200 mg/kg, chemotherapy followed by an allogeneic bone marrow transplant from a HLA-matched sibling was performed in April 1991 with complete hematological recovery. Allogeneic bone marrow transplantation was thus used successfully to treat a potential complication of autologous bone marrow transplantation.
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PMID:Allogeneic marrow transplantation for myelodysplastic syndrome complicating autologous bone marrow transplantation. 792 4

Current problems relating pathology of malignant lymphomas were reviewed. Unique geopathologic features of malignant lymphomas have been increasingly made clear. Japanese lymphomas, previously reported as having relative excess of T cell lymphomas, are now proved similar to Euro-American lymphomas with regard to T/B ratio, i.e. 75% and 20% respectively, except ATLL related with HTLV-I. Instead, characteristics of Japanese lymphomas are 1) low incidence rate of overall lymphomas and 2) scarcity of Hodgkin's disease (HD) and follicular lymphomas. These differences seems to be related to the difference in HLA composition among susceptible individuals. Since HLA haplotypes regulate host's immunoreactivity through their unique molecular structures, it is possible that "narrow" cognitive molecules could trigger the autoimmune reaction and "broad" one could accept altered cell as "self", thus leading to the late-onset lymphomagenesis. Viewing the evidences that no consistent immuno-gene rearrangements were detected in significant cases of ALCL (anaplastic large cell lymphoma) and HD, it was suggested that these lymphomas derive from the precursor cell before the rearrangement of immunogenes. Thus, lymphomas could be divided into two categories, i.e. 1) pre-rearrangement lymphomas (HD and ALCL) and 2) post-rearrangement lymphomas (common NHL).
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PMID:[Pathology of malignant lymphomas]. 802 89

Molecular typing of HLA class II loci has been performed on a sample of 196 patients with Hodgkin lymphoma. Division of patients into two histological categories--nodular sclerosing Hodgkin disease versus all other types--shows significant overall association of the nodular sclerosing group with the HLA class II region. Haplotypes and alleles defined for the four loci typed--DRB1, DQA1, DQB1, and DPB1--were present in both excess and deficit in the nodular sclerosing sample. Some of the effects are attributable to particular DRB1 and DQB1 alleles, while other effects are best explained by haplotypes marking the entire class II region. The latter effects might be due to variation in additional, as-yet-unexamined loci in the class II region or to particular combinations of alleles from two or more loci. These data also explain why earlier studies showed HLA linkage but not association, and they substantiate the specific involvement of the immune system in certain neoplastic diseases.
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PMID:Localization of predisposition to Hodgkin disease in the HLA class II region. 811 19

87 patients underwent bone marrow transplantation (BMT) in Innsbruck between 1983 and 1992. 81 patients were suffering from hematologic malignancies and severe aplastic anemia and six patients had advanced solid tumours/sarcoma. 56% of the patients undergoing HLA-identical sibling BMT were in an advanced or refractory stage of disease at the time of BMT. 19 patients underwent autologous BMT and 5 patients received a graft from an HLA-matched unrelated donor. Patients were treated with standard conditioning regimens according to the underlying disease. Cyclosporine A (CsA) was given prophylactically against graft-versus-host disease (GVHD) either alone or in combination with methotrexate. Probability of survival for patients transplanted in the first chronic phase of chronic myelogenous leukemia (CML) was 85%, whereas the disease free survival (DFS) for patients transplanted in accelerated phase or blast crisis was only 40%. DFS for acute myelogenous leukemia (AML) in first complete remission and acute lymphoblastic leukemia (ALL) standard-risk (i.e., first or second complete remission) was 71% and 60%, respectively. All patients transplanted for non-Hodgkin's lymphoma (NHL) or Hodgkin's disease had refractory or advanced disease. Probability of survival for lymphoma patients was 60%. Acute GVHD > grade II developed in 35% of patients undergoing HLA-identical sibling BMT (46% in the high-risk group vs. 21% in the standard-risk group). Main causes of death in the high-risk group were relapse (31%), severe bacterial or fungal infections (17%), interstitial pneumonia (11%) and acute GVHD (6%).
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PMID:[Innsbruck results of bone marrow transplantation in treatment of hematologic neoplasms and solid tumors]. 819 54

HLA-class II molecules can be induced in low-grade non-Hodgkin B lymphoma cells by either membrane IgM cross-linking or phorbolester stimulation. The ability of phorbolesters to substitute for anti-IgM antibodies in the activation of normal and malignant human B cells has been taken as evidence for the involvement of protein kinase C (PKC) in signals transduced through membrane IgM receptors (mIgR). Here we report on freshly isolated lymphoma B cells from different patients; the cells show a distinct regulation of HLA-class II expression. In certain lymphoma cases phorbol-myristate-acetate (PMA) not only fails to up-regulate HLA-class II molecules but also inhibits anti-IgM or interleukin-4 induced class II expression. This negative signal induced by PMA seems to operate specifically in HLA-class II regulation because PMA can induce other anti-IgM mediated events like blast transformation and induction of IL-4 responsiveness at the same time. Therefore these cells support the concept of functional heterogeneity in low-grade non-Hodgkin lymphoma and may represent a differentiation stage where anti-IgM antibodies and phorbolesters influence the regulation of HLA-class II expression in a contrary direction.
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PMID:Differential signal requirement for upregulation of HLA-class II molecules in human lymphoma B cells. 834 Feb 86

Epstein-Barr virus (EBV) as a member of the herpesvirus family persists lifelong in the human body and causes diseases associated with virus replication (infectious mononucleosis, oral hairy leukoplakia) as well as neoplastic conditions such as nasopharyngeal carcinoma, B-cell lymphoma, Hodgkin's disease associated with viral latency. This complex biology relates to a highly regulated control of the persisting virus. Still, EBV is lytically produced in certain compartments of the human body. Epithelial cells were found to be of key importance for this. Various routes (cell fusion, IgA receptor-mediated uptake) were described for EBV to enter epithelial cells in the absence of CR2 receptor. Viral entry into cells, however, via CR2 receptor fusion or IgA mediated was not found to be sufficient for viral production. The molecular mechanisms for the lack of viral production in most target cells are primarily the presence of silencer activities and the early elimination of cells entering the lytic cycle. Only terminally differentiated epithelial cells are capable of supporting an efficient lytic cycle of EBV replication. EBV-mediated suppression of apoptosis as well as down-regulation of cellular and viral gene products, such as HLA molecules, which mediate recognition by the immune system, are important contributing factors to the development of these neoplasias where viral genes, possibly via interaction with anti-oncogenes, such as p53, in context with genetic and environmental factors play a key role. Novel diagnostic tools and a vaccine have been developed which could help to control EBV-related diseases.
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PMID:Epstein-Barr virus and its interaction with the host. 840 48


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