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)

Twenty-two cases of Hodgkin's disease (HD), representing the 4 different subclasses, were studied by immunophenotypic and immunogenotypic analysis. Quantitative immunophenotypic analysis of HD infiltrates showed a predominance of CD3-positive T cells in all subtypes except the lymphocytic depletion (HDLD) subtype. Only 5 samples of HD [2 of lymphocytic predominance (HDLP), 2 of mixed cellularity (HDMC), and one of nodular sclerosis type (HDNS)] were found to have both their Ig and T-cell antigen receptor (TcR) genes in the germ-line configuration. The remaining patients with HDLP (3 cases), HDNS (5 cases), and HDMC (4 cases), all exhibited rearrangements of either TcR gamma or TCR gamma and TcR beta genes, while all 5 cases of HDLD had either TCR gamma or immunoglobulin heavy-chain gene rearrangement. These results substantiate the view that Hodgkin's lymphomas contain clonal lymphocyte populations and that different rearrangement patterns may be associated with different subclasses of HD.
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PMID:Clonal rearrangements of T-cell receptor and immunoglobulin genes and immunophenotypic antigen expression in different subclasses of Hodgkin's disease. 311 31

We examined 91 specimens (from 87 patients) for the expression of B-cell- and T-cell-associated differentiation antigens and rearrangements of the Ig and beta-chain of the T-cell (beta-TCR) genes. Of these, 74 were representative of various histologic subtypes of non-Hodgkin's lymphoma and related disorders, 11 of Hodgkin's disease, and 6 of reactive lymphoid hyperplasia. An Ig gene clonal rearrangement correlated to a monotypic (kappa/lambda) phenotype in 32 of 33 histologically defined lymphoma samples. The genotypic analysis also confirmed clonality in six of seven malignant diffuse lymphomas that were nonmonotypic but expressed pan-B antigens; in four, more than one clone was detected within individual tumors. A beta-TCR clonal rearrangement was found in 19 of 19 tumor samples considered as malignant T-cell lymphoma on the basis of histopathology and of the CD3-positive phenotype of tumoral cells, and in two cases of CD3-positive lymphomatoid disorders. A loss of pan-T antigens (CD7, CD5, CD2, CD4/CD8) was observed in all but three of these CD3-positive samples. Such an incomplete T-cell phenotype always correlated to the presence of a monoclonal process as revealed by genotypic analysis. DNA analysis was the only way to demonstrate clonality in other samples with either a polymorphous (partial involvement, pseudolymphoma, angioimmunoblastic lymphodenopathy [AILD]) or an undifferentiated (large cell anaplastic) phenotype. It is concluded that although in the majority of cases immunophenotyping alone provides criteria adequate for the diagnosis of lymphoid malignancy, in some, particularly polymorphous or large cell anaplastic processes, genetic probe analysis was additionally discriminative.
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PMID:Comparison of genetic probe with immunophenotype analysis in lymphoproliferative disorders: a study of 87 cases. 319 72

Hodgkin's disease (HD) is an aggressive human lymphoproliferative disease that displays a curious pleomorphic histopathologic appearance unlike that of any of the common non-Hodgkin's lymphomas (NHL). Although the bizarre giant cells of the HD lesion, the Reed-Sternberg cells (RSC) and mononuclear variant Hodgkin's cells (HC), have been considered to be malignant cells, little objective evidence supports this conclusion. We have studied the proliferative characteristics of T cell as well as RSC and HC-enriched populations from HD lesions, and found the majority of the proliferative activity in the T cell populations. RSC-enriched populations not only showed little spontaneous proliferation, but also did not respond to a variety of cytokine growth factors in vitro, suggesting that these cell populations are not actively growing cells. Further molecular studies to identify possible monoclonal T or B cell populations in HD lesions, using a TCR beta chain probe and IgH probes respectively on Southern blot analysis, revealed no evidence of monoclonal lymphoid cell populations. Additional studies on the characteristic T cell immunodeficiency in HD were also undertaken. Our previous studies had associated a decrement in IL-2 production with this defect. Our studies now show that an intrinsic T cell abnormality exists when HD patients' T cells are stimulated with agonistic MAb that can optimally activate and stimulate IL-2 production in normal control T cells.
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PMID:In vitro analysis of cell populations involved in Hodgkin's disease lesions and in the characteristic T cell immunodeficiency. 326 Dec 71

CD30L, the ligand for the activation antigen CD30, is a member of the tumor necrosis factor family of cytokines. Binding of CD30L to CD30, which is a member of the nerve growth factor/tumor necrosis factor receptor family, induces proliferation in peripheral blood lymphocytes and Hodgkin's derived cell lines with a T-cell phenotype such as HDLM-2 and L540, while cell lines derived from anaplastic large cell lymphomas, such as Karpas 299, undergo cell death. In order to investigate whether mutations of the CD30 antigen are responsible for these opposite effects, we cloned the open reading frame of CD30 cDNAs from the cell lines L540 and Karpas 299 and from peripheral blood lymphocytes by reverse transcriptase polymerase chain reaction. Sequencing of independent plasmid clones revealed that these cells have a silent transition (A-->G) at position 771 of the open reading frame compared to the published sequence derived from the HTLV-1+ cell line HUT-102. As published data have shown that crosslinking of CD30 induces an elevation of cytosolic free calcium ([Ca2+]i) in TCR positive Jurkat cells, we have analysed the effect of crosslinking of CD30 on L540 and Karpas 299 cells. No elevations of [Ca2+]i have been observed in these cell lines after crosslinking of CD30 with HRS-4. We conclude (i) that the different functional effects of CD30 in PBL, L540 and Karpas 299 are not due to differences in the primary structure of the receptor; and (ii) that the different responses observed upon engagement with CD30L for the cell lines L540 and Karpas 299 do not correlate with differences in mobilization of [Ca2+]i after crosslinking of CD30.
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PMID:Opposite effects of the CD30 ligand are not due to CD30 mutations: results from cDNA cloning and sequence comparison of the CD30 antigen from different sources. 752 1

T cells infiltrating (T-TIL) B cell non-Hodgkin's lymphomas (NHL) are thought to represent a local host response to the tumor. However, tumor progression in the presence of this T cell infiltrate suggests that the T-TIL may be functionally impaired. To address this issue we determined whether response to stimulation of T-TIL from 25 patients with NHL through the T cell receptor (TCR/CD3) and the interleukin-2 (IL-2) receptor (IL-2R) was intact, since activation of these receptors is important for proliferation and cytokine production. Our results demonstrate defects in response to stimulation via TCR/CD3 and the IL-2R in T-TIL cells from patients with NHL that were not observed with T cells from the peripheral blood. T-TIL showed minimal proliferation to anti-CD3 and only modest proliferation to IL-2 alone or when combined with anti-CD3. Moreover, cytokine production in T-TIL was impaired since stimulation through the TCR/CD3 complex did not induce mRNA for interferon gamma (IFN gamma), IL-2, IL-4 or IL-10. The functional unresponsiveness of these cells may be linked to altered signalling through the TCR/CD3 since an abnormal tyrosine phosphorylation pattern was detected in T-TIL after stimulation with anti-CD3.
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PMID:Responses to T cell receptor/CD3 and interleukin-2 receptor stimulation are altered in T cells from B cell non-Hodgkin's lymphomas. 755 87

Non-Hodgkin large cell lymphomas occurs more commonly in organ-transplanted patients than in the general population. They are usually of B-cell origin whereas T-cell lymphomas are rare. We report a new case of peripheral T-cell lymphoma in an immunosuppressed renal transplanted patient. The patient presented a hepatosplenic mass with a widespread extension causing serious pancytopenia. It was classified as a pleomorphic medium and large cell type and corresponded to the "common" alpha beta-TCR type lymphoma. Lymphomatous cells exhibited an incomplete mature T-cell phenotype. T-cell receptor gene clonal rearrangement associated with a germline configuration of the immunoglobulin heavy chain gene confirmed a clonal T-cell genotype. By using both Southern blot analysis and polymerase chain reaction, we failed to demonstrate any association with Epstein-Barr virus or human T-cell lymphotropic virus type I or type II.
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PMID:Peripheral T-cell lymphoma in a chronically immunosuppressed renal transplant patient. 756 30

Although tumor infiltrating lymphocytes (T-TIL) from B cell non-Hodgkins lymphoma patients contain tumor-reactive T cells, they display poor proliferation and IFN-gamma production when stimulated through the TCR-CD3. To determine if there was altered signaling linked to TCR-CD3 ligation, tyrosine phosphorylation was examined in T-TIL because it represents an early and critical event in T cell activation. After stimulation with anti-CD3 Ab, Western blotting with anti-phosphotyrosine showed reduced phosphorylation in T-TIL when compared with peripheral blood-derived T cells from normal individuals. The altered phosphorylation was not due to the reduced expression of signaling elements linked to the TCR-CD3 complex. T-TIL expressed normal levels of CD3 epsilon, TCR zeta chain, and the three tyrosine kinases, p56lck (Lck), p59fyn, and ZAP-70. However, in T-TIL, anti-Lck Ab reacted with a 60-kDa protein, which appears to be the phosphorylated form of Lck. Binding of anti-Lck Ab to the 60-kDa protein was blocked by Lck peptide. In addition, anti-Lck Ab immunoprecipitated a phosphorylated 60-kDa protein from gamma-32P-labeled T-TIL that was not seen in normal resting T cells. In vitro kinase assay studies also demonstrated that TCR-CD3 engagement increased the kinase activity of Lck in normal T cells but not in T-TIL. These results suggest that although T-TIL from B cell non-Hodgkins lymphoma patients contain the signal transduction molecules associated with TCR-CD3 activation pathway, they are impaired in tyrosine phosphorylation and Lck activity, which may contribute to the functional defects of these cells.
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PMID:T cells infiltrating non-Hodgkin's B cell lymphomas show altered tyrosine phosphorylation pattern even though T cell receptor/CD3-associated kinases are present. 763 3

We describe a modified denaturing gradient gel electrophoresis (DGGE) procedure with a 40-nucleotide GC clamp in the polymerase chain reaction to improve resolution in amplifying T cell receptor-gamma (TCR-gamma) rearrangements. DNA from 46 cases of lymphoblastic leukemia/lymphoma, 5T cell lines, 2 B cell lines, 7 normal lymphocytes, and 3 cases of Hodgkin's disease was amplified by polymerase chain reaction. In addition, 20 cases of paraffin-embedded T cell lymphomas and 5 cases of reactive hyperplasia were also studied. Clonal TCR-gamma rearrangements were identified on DGGE by the presence of a predominant band. Results obtained from 5 T cell lines and 12 lymphoblastic leukemia/lymphomas containing known TCR-gamma gene rearrangements revealed 100% concordance in detecting clonal rearrangements between DGGE and traditional Southern blot analysis. Of the remaining 34 lymphoblastic leukemia/lymphoma cases studied by DGGE alone, 30 were positive. DGGE analysis of 10 lymphoblastic leukemia/lymphoma cases with known group IV gamma to J gamma 1 or J gamma 2 rearrangement sequences confirmed that the electrophoretic migration was dependent on the tumor-specific rearranged TCR-gamma sequence. In addition, 17 of 20 cases of paraffin-embedded T cell lymphomas were positive by DGGE, 6 of which had the clonal population also identified in fresh tissue DNA. DGGE analysis of GC-clamped polymerase chain reaction products can provide a way to more accurately detect TCR-gamma clonality of lymphoid tumors and can be applied to archival tissues.
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PMID:Analysis of T cell receptor-gamma gene rearrangements by denaturing gradient gel electrophoresis of GC-clamped polymerase chain reaction products. Correlation with tumor-specific sequences. 785 38

Two recently discovered genes, the recombination activating genes 1 and 2 (RAG-1 and RAG-2), are necessary to perform variable (V), diversity (D), and joining (J) recombination. They synergistically activate VDJ recombination to generate immunocompetent lymphocytes. Disruption of either gene results in a maturation arrest at a very early B and T cell progenitor stage. Expression and downregulation of RAG's are closely associated with interleukin 7, sIgM and TCR-CD3 complex, respectively. Assessment of RAG mRNA expression is a valuable marker in identifying the genotypic maturation status of leukemias and lymphomas. Persistent RAG expression in otherwise mature lymphoid proliferations may explain puzzling biological and clinical observations such as multiple rearrangements in lymphomas with a mature phenotype. Lack of RAG expression in Hodgkin's disease with abundant Reed-Sternberg cells is consistent with a mature phenotype of the latter. Availability of a anti-RAG-1 monoclonal antibody in the near future will facilitate RAG analysis of lymphomas.
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PMID:Expression of human recombination activating genes (RAG-1 and RAG-2) in lymphoma. 787 97

Hodgkin and Reed-Sternberg (H&RS) cells are generally accepted to be the neoplastic cells of Hodgkin's disease (HD), even though they represent only a minority of the cellular infiltrate in affected tissues. Recent immunologic studies and Southern blot analyses of DNA extracted from whole lymph node tissue favored, but did not convincingly prove a lymphoid origin of H&RS cells. To detect rearrangements of the T-cell receptor gamma chain (TCR gamma) genes at the single-cell level as an indication of early T-cell lymphoid differentiation, we isolated H&RS cells by micromanipulation from cytospin preparations of fresh biopsy material. TCR gamma chain rearrangement was detected by polymerase chain reaction using four "forward primers" that were constructed corresponding to all four V families and two "reverse primers" corresponding to consensus sequences of J segments. Rearrangements of all V families in combination with the different J segments were detected in human peripheral blood and tonsillar T cells. Although rearrangements of TCR gamma chain genes were shown in single cells of 10 of 10 T-cell leukemias, no rearrangement of these genes was found in single H&RS cells from 13 consecutive patients with HD. Our results indicate that H&RS cells from the vast majority of cases are not derived from T cells. This finding may have implications for the pathogenesis of HD and the development of more effective treatment regimens.
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PMID:Hodgkin and Reed-Sternberg cells do not carry T-cell receptor gamma gene rearrangements: evidence from single-cell polymerase chain reaction examination. 788 76


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