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)

In man, Hodgkin's disease (HD) represents the most frequent lymphoma entity whose pathogenesis is still unknown. In order to contribute to the characterization of the molecular mechanisms of this disease, cDNAs coding for the HD characteristic antigen CD30 were cloned from expression libraries of the human HUT-102 cell line using the monoclonal antibodies Ki-1 and Ber-H2. The open reading frame of the cDNA that can be translated from two mRNA species of 2.6 kb, and 3.8 kb, respectively, predicts a 595 amino acid protein with leader, extracellular, single transmembrane, and intracellular domains. When expressed in COS-1 cells, the cDNA presented properties comparable to native CD30 antigen. The CD30 extracellular domain proved to be homologous to members of the nerve growth factor receptor superfamily. Six cysteine-rich motifs could be recognized within the putative ligand-binding domain.
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PMID:Molecular cloning and expression of a new member of the nerve growth factor receptor family that is characteristic for Hodgkin's disease. 131 Aug 94

In 160 non-Hodgkin lymphomas (NHL) of B and T cell origin the expression of leucocyte function-associated antigen-1 (LFA-1) and one of its counter-structures named 7F7-antigen was studied. Functional and structural similarities and the 7F7-reactivity of pICAM-1 transfected COS-cells prove that 7F7-antigen is identical with ICAM-1. The expression of both adhesion structures occurred variably and clearly depended on the maturation stage and on the B and T cell origin of lymphomas but was not associated with the proliferative status of tumour cells. The concomitant expression of both adhesion molecules was a characteristic feature of germinal centre derived NHL, particularly of those with neoplastic follicular structures (corr. contingency coeff. = 0.506; P less than 0.02), whereas both adhesion structures were less often expressed on lymphomas with a more diffuse pattern of tumour infiltration. Most B-NHL of low-grade malignancy expressed LFA-1 while their counterparts of high-grade malignancy often tended to be LFA-1 negative. In B cell neoplasias of low-grade malignancy the lack of ICAM-1 and a leukaemic course of the disease were significantly correlated (P less than 0.0005). The results indicate that the differential expression of both adhesion molecules may account for distinct patterns of growth and spread in subtypes of lymphoid malignancies.
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PMID:Expression of leucocyte function-associated antigen-1 and 7F7-antigen, an adhesion molecule related to intercellular adhesion molecule-1 (ICAM-1) in non-Hodgkin lymphomas and leukaemias: possible influence on growth pattern and leukaemic behaviour. 267 91

The human B cell restricted activation antigen B7 identifies an in vivo primed subpopulation of B cells that demonstrate an accelerated response to triggers of B cell activation and proliferation. The cDNA encoding B7 was molecularly cloned by cDNA expression. The identity of the B7 cDNA was confirmed by indirect immunofluorescence and immunoprecipitation of a 44/54-kDa protein from B7 transfected COS cells. The sequence of the B7 polypeptide predicts a type I membrane protein of 262 amino acids with eight potential N-linked glycosylation sites in the extracellular region and a short, highly positively charged cytoplasmic tail. The extracellular region is homologous to the Ig gene superfamily and consists of two contiguous Ig-like domains. The first Ig domain has the characteristics of a variable domain and the second that of a constant region domain. B7 mRNA was detected only on anti-Ig activated B lymphocytes and not in other hematopoietic cells. After in vitro activation of B cells with anti-Ig, B7 mRNA was maximally expressed between 4 and 12 h with four RNA transcripts of 1.7, 2.9, 4.2, and 10 kb. The 2.9-kb mRNA predominated in in vitro-activated B cells whereas the 1.7-kb mRNA was most abundant in tumor cells of B cell origin. B7 expression was confined to several histologically defined subgroups of B cell malignancies. The majority of non-Hodgkin's lymphomas were B7+ whereas the B cell leukemias and circulating non-Hodgkin's lymphomas were generally negative. These results demonstrate that the B7 gene encodes a unique molecule belonging to the Ig superfamily and that B7 expression is limited to normal activated B cells and noncirculating B cell malignancies.
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PMID:B7, a new member of the Ig superfamily with unique expression on activated and neoplastic B cells. 279 10

A new anti-macrophage monoclonal antibody (PG-M1) was produced by immunizing BALB/c mice with fresh spleen cells from a patient with Gaucher's disease. PG-M1 reacts strongly with a fixative-resistant epitope of an intracytoplasmic molecule, selectively expressed by virtually all macrophages of the human body. Although attempts to immunoprecipitate the molecule recognized by PG-M1 have failed so far, the reactivity of the antibody with COS-1 and WOP cells transfected with a human complementary DNA clone encoding for the CD68 antigen suggests that PG-M1 is a new member of the CD68 cluster. However, unlike other CD68 antibodies (KP1, EBM11, etc.), which react with both macrophages and myeloid cells, PG-M1 detects a fixative-resistant epitope on the macrophage-restricted form of the CD68 antigen. In 957 routinely fixed, paraffin-embedded samples, PG-M1 showed a more restricted reactivity with elements of the monocyte/macrophage lineage than the previously described monoclonal antibodies MAC-387 (anti-calgranulins), KP1 (CD68) and Ki-M1P. Among hematological malignancies, PG-M1 only labels acute leukemias of M4 and M5 type and rare examples of malignant histiocytosis/true histiocytic sarcoma. In contrast, acute leukemias of the M1, M2, M3, M6, M7, and L1-L3 types, non-Hodgkin's lymphomas, and Hodgkin and Reed-Sternberg cells of Hodgkin's disease are consistently PG-M1-negative. In the daily diagnostic practice, PG-M1 seems to be particularly valuable for the diagnosis of myelomonocytic or monocytic leukemia and neoplasms of true histiocytic origin in routine paraffin sections.
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PMID:PG-M1: a new monoclonal antibody directed against a fixative-resistant epitope on the macrophage-restricted form of the CD68 molecule. 768 94

TASK is a new member of the recently recognized TWIK K+ channel family. This 395 amino acid polypeptide has four transmembrane segments and two P domains. In adult human, TASK transcripts are found in pancreas<placenta<brain<lung, prostate<heart, kidney<uterus, small intestine and colon. Electrophysiological properties of TASK were determined after expression in Xenopus oocytes and COS cells. TASK currents are K+-selective, instantaneous and non-inactivating. They show an outward rectification when external [K+] is low ([K+]out = 2 mM) which is not observed for high [K+]out (98 mM). The rectification can be approximated by the Goldman-Hodgkin-Katz current equation that predicts a curvature of the current-voltage plot in asymmetric K+ conditions. This strongly suggests that TASK lacks intrinsic voltage sensitivity. The absence of activation and inactivation kinetics as well as voltage independence are characteristic of conductances referred to as leak or background conductances. For this reason, TASK is designated as a background K+ channel. TASK is very sensitive to variations of extracellular pH in a narrow physiological range; as much as 90% of the maximum current is recorded at pH 7.7 and only 10% at pH 6.7. This property is probably essential for its physiological function, and suggests that small pH variations may serve a communication role in the nervous system.
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PMID:TASK, a human background K+ channel to sense external pH variations near physiological pH. 931 5

Interleukin (IL)-18 was identified as a molecule that induces IFN-gamma production and enhances NK cell cytotoxicity. In this paper, we report upon the purification and characterization of human IL-18 receptor (hIL-18R). We selected the Hodgkin's disease cell line, L428, as the most strongly hIL-18R-expressing cell line based on the results of binding assays. This binding was inhibited by IL-18 but not by IL-1beta. The dissociation constant (Kd) of 125I-IL-18 binding to L428 cells was about 18.5 nM, with 18,000 binding sites/cell. After immunizing mice with L428 cells and cloning, a single monoclonal antibody (mAb) against hIL-18R was obtained (mAb 117-10C). Sequentially, hIL-18R was purified from 3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonic acid (CHAPS)-extracted L428 cells by wheat germ lectin-Sepharose 4B chromatography and mAb 117-10C-Sepharose chromatography. The internal amino acid sequences of hIL-18R all matched those of human IL-1 receptor-related protein (IL-1Rrp), the ligand of which was unknown to date. When expressed in COS-1 cells, the cDNA of IL-1Rrp conferred IL-18 binding properties on the cells and the capacity for signal transduction. From these results, we conclude that a functional IL-18 receptor component is IL-1Rrp.
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PMID:Purification and characterization of the human interleukin-18 receptor. 932

Recent studies have demonstrated that the malignant Reed-Sternberg cells of Hodgkin's lymphoma (HL) secrete and are responsive to interleukin (IL)-13. We hypothesized that overexpression of a soluble IL-13 decoy receptor (sIL-13Ralpha2) via adenoviral-mediated gene transfer would inhibit IL-13-induced Reed-Sternberg cell proliferation. Western blot and ELISA analysis verified expression of sIL-13Ralpha2 in cell lysates and supernatants of AdsIL-13Ralpha2-transduced COS-7 cells. Treatment of two IL-13-responsive HL-derived cell lines, HDLM-2 and L-1236, with AdsIL-13Ralpha2-conditioned medium, resulted in the inhibition of cell proliferation, and down-regulated the phosphorylation of signal transducer and activator of transcription 6 (STAT6), an important mediator of IL-13 signaling. i.v. delivery of AdsIL-13Ralpha2 in NOD/SCID mice with s.c. implanted HDLM-2 cells delayed tumor onset and growth while enhancing survival compared with control mice. Intratumoral administration of AdsIL-13Ralpha2 led to the regression or stabilization of established tumors and was associated with diminished STAT6 phosphorylation. Our data demonstrate that AdsIL-13Ralpha2 can suppress HL growth in vitro and in vivo.
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PMID:Soluble interleukin-13Ralpha2 decoy receptor inhibits Hodgkin's lymphoma growth in vitro and in vivo. 1512 69

A 48-year-old woman with a follicular, grade III, B-cell non-Hodgkin lymphoma developed clinical, immunopathological and histological features of paraneoplastic pemphigus. The skin symptoms flared after repeated cyclophosphamide infusions, and were preceded and accompanied by a progressive dyspnoea. Although the skin and oral mucosal disease went into remission with high-dose steroid and intravenous immunoglobulin therapy, the severe alveolitis led to death. Immunoblotting of human epidermal extracts showed that the patient's serum IgG reacted with the 210-kDa envoplakin, 190-kDa periplakin, as well as the recombinant protein of BP180 NC16a domain. IgG and IgA enzyme-linked immunosorbent assays for desmoglein 3 were positive, too. Indirect immunofluorescence studies on COS-7 cells transiently transfected with desmocollin 1-3 cDNAs showed that the patient's serum contained IgG and IgA antibodies to desmocollin 3 as well as IgG antibodies to desmocollin 2. Serum IgG and IgA strongly stained rat bronchial epithelium, corresponding to autoantibodies possibly involved in the pathomechanism of the severe lung disease. In this case, which was characterized by a mixed IgA/IgG antibody panel displaying known and unique antigenicity, the serious episodes of paraneoplastic pemphigus flared after cyclophosphamide treatment.
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PMID:Exacerbation of paraneoplastic pemphigus by cyclophosphamide treatment: detection of novel autoantigens and bronchial autoantibodies. 1514 20