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 Ki-1 antibody not only detects a Hodgkin-associated membrane molecule of 120 kd (Ki-1/120 = CD30), but also reacts with an independently synthesized molecule of 57 kd (Ki-1/57) that only occurs intracellularly. Hodgkin's disease-derived cell lines L428 and L540 contain both Ki-1-reactive antigens, whereas others, e.g., U266/Bl myeloma cells, only express the intracellular Ki-1/57. The present immunoelectronmicroscopic analysis detected the Ki-1/57 antigen of U266/Bl cells not only in the cytoplasm, but also in association with the nuclear envelope, chromatin structures, and nucleoli. This Ki-1/57-specific type of labeling also was observed in L428 and L540 cells that, in contrast to U266/Bl cells, showed an additional staining of cell membranes and cytoplasmic vesicles. These results were confirmed by two independent methods: 1) cytocentrifuge preparations of isolated nuclei of L540 cells showed a spotted Ki-1-specific labeling, 2) immunoprecipitations demonstrated that the Ki-1/57, but not the Ki-1/120 antigen, was transferred into the nuclei of L540 and U266/Bl cells, whereas the Ki-1/120 antigen with its 90-kd precursor remained in the non-nuclei fraction of L540 cells.
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PMID:Cellular localizations and processing of the two molecular forms of the Hodgkin-associated Ki-1 (CD30) antigen. The protein kinase Ki-1/57 occurs in the nucleus. 131 Aug 32

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

Murine monoclonal antibody HRS-4 (Ab1), which defines the cell-bound and soluble CD30 antigen associated with Hodgkin's lymphoma, was used to generate monoclonal anti-idiotypic antibodies (Ab2) in syngeneic BALB/c mice. Murine monoclonal Ab2 14G9 and Ab2 9G10 directed against HRS-4 were shown to be anti-idiotypic Ab2 beta carrying the internal image of the CD30 antigen. These antibodies bound specifically to HRS-4 and effectively inhibited binding of HRS-4 to a CD30 antigen preparation at concentrations as low as 50 ng/ml. KLH-coupled Ab2 beta 14G9 and 9G10 induced in BALB/c mice and New Zealand white rabbits a specific polyclonal humoral response against the 120 kDa band of the CD30 antigen. Moreover, BALB/c mice immunized i.p. with KLH-coupled 14G9 and 9G10 exhibited a statistically significant (p less than 0.01) delayed-type hypersensitivity reaction against CD30 expressing Hodgkin-derived L540-cells. We conclude from these data that Ab2 beta 14G9 and 9G10, mimicking structures of the nominal CD30 antigen, are capable of inducing a CD30-specific T-cell- and B-cell-mediated immune response in mice and even across species barriers in rabbits. These CD30 anti-id antibodies may hold promise for use as vaccines against CD30-antigen-expressing lymphomas.
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PMID:Anti-idiotype vaccine against Hodgkin's lymphoma: induction of B- and T-cell immunity across species barriers against CD30 antigen by murine monoclonal internal image antibodies. 131

We describe the clinical course of a 20-year-old man who suffered generalized convulsive seizures with postictal aphasia and hemiparesis of the right side. Computed tomography (CT) displayed a left postcentral lesion with prominent perifocal edema and only a little contrast medium enhancement. The completely removed tumor proved to be a primary cerebral non-Hodgkin lymphoma consisting of T-cells. Only ten days after the operation the patient once more presented a clinical deterioration. A nuclear magnetic resonance imaging (MRI) displayed an annular structure in the area previously operated upon, suspected to be an abscess. The second operation disclosed a large recurrence of the primary T-cell lymphoma extending diffusely into the white matter. On account of the rapid recurrence, a whole brain irradiation was started twelve days after the second operation. Four cycles of chemotherapy followed. Immunohistochemical studies of the anaplastic large lymphoma cells showed staining with the pan T-cell markers (UCHL1, CD3) and with the CD30 (Ki-1) antibody. The B-cell markers (L26, LN1) were negative. The EMA (epithelial membrane antigen) was only partially expressed. Further investigation excluded the presence of systemic lymphoma manifestation. 24 months after the last operation the patient remained free of symptoms. The last MRI displayed no evidence for the recurrence of a lymphoma. In reference to this unusual clinical course the few previously reported cases of the extremely rare primary cerebral T-cell lymphoma are reviewed.
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PMID:Primary cerebral anaplastic T-cell-lymphoma (type Ki-1): review and case report. 131 14

Distribution and phenotype of Epstein-Barr virus (EBV)-harboring cells were determined in Hodgkin's disease (HD) biopsies by in situ hybridization with [35S]-labeled RNA probes specific for the small EBV-encoded nuclear RNAs, EBER1 and EBER2, in some instances preceded by immunohistology for CD20, CD30, CD45RO, and CD68 antigens, the T-cell receptor beta-chain, and latent membrane antigen (LMP) of EBV. Twenty-three of 46 HD cases displayed EBER transcripts in all Hodgkin and Reed-Sternberg (H-RS) cells, and 18 of these cases showed LMP expression exclusively in neoplastic cells. EBER+ small reactive cells were present in 39 cases in low numbers, and in three cases in abundance. Thus, presence of H-RS cells with or without LMP expression was not accompanied by an unrestricted proliferation of reactive EBER+/LMP- lymphoid cells in the majority of HD patients. Simultaneous in situ hybridization with [35S]-labeled immunoglobulin light chain (IgLC) gene probes and nonisotopically labeled EBER probe showed a phenotype of mature B lymphocytes and a polyclonal composition for a large proportion of the EBER+ small cells. However, in contrast to noninfected cells, CD20 expression was not detectable in many of these cells, which may indicate downregulation of certain differentiation antigens in latently EBV-infected small lymphoid cells in vivo.
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PMID:Distribution and phenotype of Epstein-Barr virus-harboring cells in Hodgkin's disease. 132 Sep 54

An immunotoxin containing an anti-CD30 monoclonal antibody (Ber-H2) and saporin, a ribosome-inactivating protein type 1, is described. It specifically inhibits protein synthesis by Hodgkin derived target cell lines with a very high efficiency (IC50 ranging from 5 x 10(-12) M to 5 x 10(-14) M, as saporin), while irrelevant immunotoxins do not. Present results suggest that this immunotoxin could be used for in vivo therapy as well as for ex vivo bone marrow purging in Hodgkin's disease and CD30+ lymphomas.
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PMID:Ber-H2 (anti-CD30)-saporin immunotoxin: a new tool for the treatment of Hodgkin's disease and CD30+ lymphoma: in vitro evaluation. 132 90

Ki-1 (CD30)-positive, large-cell anaplastic lymphoma (LCAL) is a distinctive subset of non-Hodgkin's lymphoma; morphologically, the neoplastic cells of LCAL may closely resemble Reed-Sternberg cell variants of Hodgkin's disease. The neoplastic cells in Hodgkin's disease are often CD30-positive, as are some of the transformed lymphocytes in infectious mononucleosis. Recent evidence suggests an etiologic role for the Epstein-Barr virus (EBV) in Hodgkin's disease. Because of the phenotypic similarities between Hodgkin's disease and LCAL, we used the polymerase chain reaction (PCR) to analyze eight specimens of LCAL for EBV genome. Diagnoses were established by paraffin section morphology and immunohistochemistry. For comparison, we also analyzed nine non-Hodgkin's lymphomas other than the LCAL type, three Hodgkin's disease specimens, and nine non-neoplastic lymph nodes. PCR was performed using DNA extracted from frozen tissue; DNA was amplified using two sets of oligonucleotide primers corresponding to the BamH1 W-fragment of the EBV genome. Amplified EBV genome was obtained from all specimens except for one mantle zone lymphoma, one diffuse mixed-cell lymphoma, and six non-neoplastic lymph nodes. EBV terminus region probing and in situ hybridization techniques, each less sensitive than PCR, were performed in selected cases in an attempt to corroborate our PCR results. Only 2 of 13 specimens contained EBV detectable by these other techniques, and neither specimen was a LCAL. In view of the high incidence of latent EBV infections in humans, the biologic significance of our PCR results is uncertain. Despite the detection of EBV genome by PCR in a high percentage of lymphomas, we were unable to substantiate an etiologic role for EBV in LCAL. The PCR technique may be too sensitive to provide meaningful data on the possible role of EBV in lymphomagenesis.
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PMID:Detection of Epstein-Barr virus genome in Ki-1 (CD30)-positive, large-cell anaplastic lymphomas using the polymerase chain reaction. 132 22

A 59-year-old man was initially diagnosed as having Hodgkin's disease, nodular sclerosis type, and complete remission was achieved after combination chemotherapy. One year later, he developed a high fever and recurrence of the Hodgkin's disease was diagnosed. Salvage chemotherapy was ineffective, and the patient died. Autopsy specimens showed infiltration of lymphoma cells into multiple organs. Lymph nodes showed characteristics of non-Hodgkin's lymphoma, with expansion of anaplastic large cells; this differed from the histological features at initial diagnosis. Immunohistochemical staining was positive for CD30/Ki-1, but negative for CD15 (LeuM1). These findings were compatible with Ki-1 lymphoma, suggesting that this may be a case of CD30/Ki-1 lymphoma preceded by Hodgkin's disease and that a certain proportion of Ki-1 lymphomas and Hodgkin's disease may share the same cellular origin.
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PMID:CD30/Ki-1-positive anaplastic large cell lymphoma preceded by Hodgkin's disease. 132 72

The ability of the Ber-H2 (CD30) monoclonal antibody (mAb) to target in vivo Hodgkin (H) and Reed-Sternberg (R-S) cells was investigated in six patients with advanced Hodgkin's disease (HD). The patients were injected with scaled-up quantities of 'cold' Ber-H2 mixed-up to a small dose of 131I-labelled Ber-H2, and in vivo binding of the antibody to H and R-S cells was assessed by immunohistological analysis of tumour biopsies and immunoscintigraphy. Only 50% of tumour sites were imaged at scintigraphy by the 131I-labelled Ber-H2. In contrast, immunohistological studies on tissue biopsies, taken 24-72 h following the mAb injection, showed that H and R-S cells in all tumour sites, including those that were not imaged by immunoscintigraphy, were specifically and strongly labelled in vivo by the injected Ber-H2, at a dose as low as 30-50 mg of antibody. In vivo binding of a single dose of Ber-H2 mAb to H and R-S cells did not result in any anti-tumour effect. The excellent in vivo targeting of H and R-S cells with the Ber-H2 mAb may have been the result of multiple favourable factors, including: (a) the restricted expression of the CD30 antigen in normal human tissues; (b) the low level of soluble CD30 in the serum of our patients; and (c) the high affinity of the Ber-H2 mAb for the CD30 molecule. The immunohistological results presented in this study provide a strong argument for using the Ber-H2 mAb as a carrier for delivering cytotoxic agents (isotopes or toxins) to neoplastic cells of HD refractory to conventional therapy.
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PMID:In vivo targeting of Hodgkin and Reed-Sternberg cells of Hodgkin's disease with monoclonal antibody Ber-H2 (CD30): immunohistological evidence. 132 18

Two hundred Hodgkin's and non-Hodgkin's lymphomas were immunohistochemically studied for the presence of the CD30 (Ki-1) activation antigen using a monoclonal antibody BerH2 on paraffin-embedded, formaldehyde-fixed tissue. Immunohistochemistry was performed by using the avidin-biotin complex technique and was preceded by enzymatic digestion with pepsin (0.05% for 20 minutes). Ninety percent (56/64) of cases of Hodgkin's disease, other than lymphocyte predominance type, showed positive tumor cells, although the positivity was often focal. In contrast, lymphocyte predominance type showed CD30 in only two of nine cases. CD30 was commonly seen in non-Hodgkin's lymphomas. Five of 37 large-cell lymphomas showed extensive CD30 positivity and morphologically represented large-cell anaplastic lymphomas ("Ki-1 lymphomas"). Apart from this, occasional CD30-positive cells were seen in nine of 32 large-cell non-Hodgkin's lymphomas. About half of the nodular small cleaved-cell lymphomas contained CD30-positive cells, two of them showing large numbers of positive cells both within and outside the nodules. Lymphocytic lymphoma sometimes (6/17) showed a few CD30-positive cells. Peripheral T-cell lymphomas showed positive cells in three of eight cases. The positive cases were one lymphoma with small groups of epithelioid cells (Lennert's lymphoma) and two immunoblastic lymphadenopathylike peripheral T-cell lymphomas. The results show that CD30 is more widespread than originally thought in non-Hodgkin's lymphomas and that especially nodular small cleaved-cell lymphomas often contain positive cells. These findings have to be considered in the immunohistochemical differential diagnosis of lymphomas. Obviously, CD30 alone cannot be used to differentiate between Hodgkin's and non-Hodgkin's lymphomas. The CD30-positive cells in non-Hodgkin's lymphoma may represent a link between Hodgkin's and non-Hodgkin's lymphomas.
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PMID:CD30 distribution. Immunohistochemical study on formaldehyde-fixed, paraffin-embedded Hodgkin's and non-Hodgkin's lymphomas. 133 42


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