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)

A bispecific antibody directed to T and B cells (CD3 x CD19 bsAb) was daily infused intravenously in escalating doses from 10 micrograms up to 5 mg in three patients with chemotherapy-resistant non-Hodgkin lymphoma; in this way we aimed to activate T cells to kill the malignant B cells. Only limited toxicity was observed, consisting of moderate fever preceded by chills or shivers and mild thrombocytopenia. No human anti-(mouse Ig) antibodies were found. Pharmacokinetics showed a t1/2 of 10.5 h with peak levels of 200-300 ng/ml after infusion of 2.5 mg bsAb. bsAb in serum was functionally active in vitro. After bsAb infusion a rise in serum tumour necrosis factor alpha was observed, accompanied by an increase in soluble CD8 and to some extent in soluble interleukin-2 receptor (IL-2R), but not in interferon gamma. IL-4 or soluble CD4. No evidence was found for monocyte activation (no increases in IL-6, IL-8 or IL-1 beta in serum). No gross changes in histology or number of IL-2R+, CD4+ or CD8+ cells were found in the lymph nodes after therapy, but one patient showed activated CD8+ T cells within the tumour nodules. In conclusion, after intravenously administered CD3 x CD19 bsAb only moderate toxicity was found, probably due to CD8+ T cell activation and cytokine release, without CD4+ T cell activation.
 ...
PMID:CD8 T cell activation after intravenous administration of CD3 x CD19 bispecific antibody in patients with non-Hodgkin lymphoma. 754 21

Establishing reference ranges by multiparametric immunophenotyping of mature B cells in bone marrow of healthy adults is of interest because the detection of bone marrow infiltration and persistence of light chain restriction, as well as discrimination between reactive and malignant lymphocytes are important applications of B-cell immunophenotyping. To determine the pattern of antigens as expressed by malignant mature B lymphocytes in the present study, bone marrow aspirates of healthy adults were investigated for the presence and percentage frequency of those antigens as defined for immunophenotyping of B cells by the REAL Classification. For this purpose, analysis of CD19-positive B lymphocytes by 'live gate' analysis was performed. The established two-color as well as three-color stainings will serve as a basis for future investigations designed to test multiparametric analysis of B lymphocytes in bone marrow aspirates. All investigated antibodies stained with varying percentage frequency on B-cell subtypes, and no statistical significant difference was found between bone marrow aspirates of women and those of men. On the basis of this analysis, all the reported lineage antigen combinations are present both in malignant B lymphocytes and in normal B cells in considerable percentage frequency. These findings are of importance for follow-up investigations of patients with non-Hodgkin's lymphomas by multiparametric immunophenotyping.
 ...
PMID:Immunophenotyping of B lymphocytes by multiparametric flow cytometry in bone marrow aspirates of healthy adults. 754 30

Based on observations of 66 cases, in which tissues were specially processed to optimize the simultaneous preservation of cell membrane antigens and morphology, we provide evidence in favor of a relationship between follicular dendritic reticulum cells (FDRC) and Reed-Sternberg (RS) cells of Hodgkin's disease (HD) other than the lymphocyte predominance subtype. RS cells were intimately related to the FDRC network (75% of cases), and the expression of CD21 antigen was frequent (41% of cases). Exclusive expression of CD21 antigen was found in 11 cases of HD, while the expression of other B-cell-associated markers (CD19, CD20, CD22) was both variable and inconsistent. The expression of T-cell antigens (CD3, CD4, CD8) was rare. Null phenotype of RS cells was observed in 27 of 66 cases (41%). Epstein-Barr virus (EBV) nucleic acids were found in 34 of 66 (51.5%) cases. Double labeling techniques showed the presence of EBV-positive RS cells within the FDRC network. A non-B-cell origin of RS cells was supported by the differential expression of EBV latent antigens in HD (latent membrane protein+, EB nuclear antigen 2-), which is unusual in EBV-driven lymphoblastoid cell lines and EBV-positive B-cell lymphomas. FDRC and RS cells are known to share morphological traits (binucleated cells), and both cell types possess Fc receptor for IgG. The hypothesis is further backed by the findings of CD15 antigen expression by occasional RS-like dysplastic FDRC in Castleman's disease (five cases), which is characterized by hyperplasia of FDRC. Whether FDRC might be the only cells involved in the conversion to RS cells by the loss or gain of antigens remains to be determined.
 ...
PMID:Relation of follicular dendritic reticulum cells to Reed-Sternberg cells of Hodgkin's disease with emphasis on the expression of CD21 antigen. 768 51

Cross-linking of specific tumor antigens with the T-cell-associated CD3 and CD28 antigens can increase IL-2 secretion, proliferation and antigen-specific cytotoxicity in resting T cells. This cross-linking can be achieved effectively by bispecific monoclonal antibodies (BiMAb) with specificity for both the tumor antigen and CD3 or CD28 antigen, respectively. To take advantage of the enhanced activation of CD3 pre-activated T cells by additional activation via the CD28 antigen, BiMAb OKT3/HRS-3 with reactivity to both CD3 and the Hodgkin's-lymphoma-associated CD30 antigen and the BiMAb 15E8/HRS-3 with reactivity to both CD28 and CD30 antigen were generated by hybridoma fusion. Resting T cells, represented by Jurkat cells (CD3+/CD28+) were specifically activated to produce IL-2 by co-cultivation with an EBV-transformed B-cell line (LAZ509, CD30+/CD19+) only in the presence of the CD30/CD28 cross-linking BiMAb and an additional cross-linking anti-CD3/CD19 BiMAb (OKT3/6A4). Neither the cross-linking BiMAbs alone nor any combination of the monospecific parental MAbs induced a comparable IL-2 production by Jurkat cells in the presence of LAZ509. In addition, using a combination of these BiMAbs, an antigen-dependent cytotoxicity was induced by targeting APC-depleted peripheral blood lymphocytes to CD30+ L540 cells. T cells, previously specifically activated by CD3/CD30 in the presence of CD30 antigen, were cytotoxic to CD30+ cell lines only after incubation with BiMAb anti-CD28/CD30. Neither of the BiMAbs nor any of the parental antibodies induced a comparable effect. Our results indicate that such BiMAbs may offer a new approach for specific immunotherapy of Hodgkin's lymphoma, which takes advantage of cytokine secretion and cytotoxicity of activated T cells.
 ...
PMID:CD30-antigen-specific targeting and activation of T cells via murine bispecific monoclonal antibodies against CD3 and CD28: potential use for the treatment of Hodgkin's lymphoma. 768 89

A 70-year-old woman with a 2-year history of B-cell chronic lymphocytic leukemia (CLL) developed headache, fever, chills, and weakness. Bone marrow examination revealed both CLL and large cell immunoblastic lymphoma (Richter's syndrome). As expected, the CLL was of B-cell lineage. The neoplasm expressed low-density monotypic IgM lambda, the pan-B-cell antigens CD19, CD20, and CDw75, and the CD5 and CD43 antigens. The large cell immunoblastic lymphoma was of T-cell lineage, positive for the CD45RB, CD3, CD45RO, and CD43 antigens, and negative for the CD20 and CDw75 antigens. Both neoplastic components were negative for Epstein-Barr virus RNA and latent membrane protein. Although 3% to 5% of patients with B-cell CLL may develop higher-grade lymphoma, usually the lymphoma is of B-cell lineage and often represents a histologic manifestation of clonal evolution. Less commonly, B-CLL patients may develop transformation to a higher grade tumor that resembles Hodgkin's disease. Both the usual form of Richter's syndrome and particularly the Hodgkin's variant of Richter's syndrome may be associated with Epstein-Barr virus. Patients with B-cell CLL rarely develop a higher grade lymphoma of T-cell lineage. To our knowledge, only one other example has been reported in the literature. Epstein-Barr virus was not associated with either neoplasm in this case.
 ...
PMID:B-cell chronic lymphocytic leukemia followed by high grade T-cell lymphoma. An unusual variant of Richter's syndrome. 787 59

The experiments have been undertaken whether DNA contents could be measured using whole blood lysis method by FACScan. Cell population in the phases of G1, S and G2 + M were well analyzed, when we used 3 x 10(6) cells lysed with 0.1% Triton X-100 in 1 ml of phosphate buffered saline, staining with 30 micrograms/ml of propidium iodide (PI) within 30 min after staining with PI. We have further developed cell cycle analysis for cells bearing lineage specific antigens recognized with FITC-conjugated monoclonal antibodies using two color analysis. When we fixed cells with 50% ice-cold ethanol after staining cells with FITC-conjugated antibodies, positive population ratio in these cells have been unchanged before and after fixing for CD3, CD4, CD5, CD8. CD10, CD19, CD14, CD33, and HLA-DR, but CD7 positive cells were markedly decreased after fixing. Using this method, CD41 positive leukemia cells have 3.4% in S phase and 6.8% in G2 + M phase, while CD41 negative cells have 1.8% in S phase and 2.0% in G2 + M phase in a patient with AML: M7, resulting leukemia cells were rich in S phase and G2 + M phase. The similar results were obtained in patients with AML:M2 using CD33 antibodies. During the clinical course, the changes of the blast numbers were well-correlated with changes of S-phase proportion in the patient with AML:M2. Among 47 patients with hematological malignancies in our hospital tested here, only 2 cases with 4.3% of total patients showed to have aneuploidy in malignant cells. One is a patient with non-Hodgkin lymphoma, the other is myelodysplastic syndrome.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:[Analysis of DNA contents in hematological malignant cells using whole blood lysis method]. 799 13

Disease relapse after autologous bone marrow transplantation (ABMT) may arise from residual tumor in the recipient and/or from cancer cells that are reinfused. The aim of purging by negative selection is to remove tumor cells from the marrow without adversely affecting the engraftment potential of the normal cell. We report the results of a study on fifty-six patients (pts) with non Hodgkin's lymphoma or acute leukemia submitted to ABMT after immunomagnetobead (IMB) purging (11 pts), Maphosphamide purging (31 pts) and no purging (14 pts). The IBM procedure involved one incubation of 3 monoclonal antibodies (CD10, CD19 and CD22) and two incubations with magnetic beads (Dynabeads M-450). The median recovery of mononuclear cells and CFU-GM was 40% and 45% after IMB purging and 84% and 5% after Maphosphamide purging respectively. The rate of leukocyte, neutrophils and platelets recovery following ABMT was similar in the three groups of pts, although platelet recovery was slow in patients received graft purged with Maphosphamide. Our study confirms the clinical feasibility of the IMB procedure, but only randomized studies will be able to definitely address the question of the clinical utility of purging.
 ...
PMID:Progenitor cells purging: negative selection. 801 65

Immunosuppressed individuals are at high risk for the development of hematologic malignancies. The typical lymphomas arising in organ transplant recipients are B-cell non-Hodgkin's lymphomas that contain Epstein-Barr virus (EBV) DNA sequences. We investigated the characteristics of posttransplant lymphomas that lacked expression of the usual markers associated with EBV transformation. We describe four large-cell lymphomas seen recently at our institution. Two of these four cases were CD4+, one was CD8+, and in one staining for CD4 and CD8 expression was not performed. One CD4+ lymphoma was a CD30+, EBV- large-cell lymphoma from a 65-year-old kidney transplant recipient, the second was an EBV+ large-cell lymphoma from a 25-year-old heart transplant patient. Two T-cell lymphomas were EBV+ and had clonal T-cell receptor beta gene rearrangements. The other two lymphomas expressed T-cell markers CD4 and CD43, and lacked expression of B-cell markers CD19, CD20, CD21, CD22, CD23, and surface Ig. Both CD4+ lymphomas were tumorigenic after their heterotransplantation into severe combined immunodeficient (SCID) mice. Cytogenetics, immunophenotyping, and genotyping of the secondary tumors from SCID mice showed their clonality and identity with the patients' primary tumors. Novel CD4+ lymphoma cell lines, LH521/4 and LK418/4, were established from tumors that had been passaged in SCID mice. An immunodeficient environment may facilitate the growth of these T-cell or biphenotypic lymphomas; the etiology of their genesis can include transformation with EBV and other, as yet unidentified mechanisms.
 ...
PMID:Characterization of posttransplant lymphomas that express T-cell-associated markers: immunophenotypes, molecular genetics, cytogenetics, and heterotransplantation in severe combined immunodeficient mice. 810 Jul 21

The rates of endocytosis, intracellular degradation, and cell-surface shedding of 125I-labeled monoclonal antibodies (MoAbs) HD-37 (anti-CD19), B1 (anti-CD20), MB-1 (anti-CD37), BC8 (anti-CD45), and DA4-4 (anti-mu) by B-lymphoma cells were compared by cellular radioimmunoassay, ultrastructural autoradiography, sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and thin layer chromatography using biopsy specimens from 12 patients with non-Hodgkin's lymphomas. 125I-BC8 was stably retained on the surface of lymphoma cells without appreciable internalization or shedding, whereas 125I-DA4-4 underwent rapid endocytosis and degradation. 125I-B1 was not internalized or degraded by tumor cells, but rapidly dissociated from the cell surface in intact form. Moderate rates of endocytosis, intracellular metabolism, and cell-surface shedding were shown by 125I-HD37 and 125I-MB-1. The 3 patients with diffuse, small cleaved-cell lymphomas internalized and degraded antibodies more slowly than did patients with other histologic subtypes. These kinetic differences may be important in the selection of MoAbs for immunotoxin and radioimmunoconjugate therapy of B-cell malignancies.
 ...
PMID:Retention of B-cell-specific monoclonal antibodies by human lymphoma cells. 811 40

High-grade B-cell-type non-Hodgkin's lymphomas are observed in 5% to 8% of patients positive for the human immunodeficiency virus. Nearly all cases belong to one of the three major histologic types: centroblastic or large noncleaved cell, immunoblastic and Burkitt's lymphoma, or small noncleaved cell. Some cases that are polymorphic are termed high-grade B-cell, not otherwise specified (NOS). The authors determined the immunophenotype of each histologic category of acquired immunodeficiency syndrome (AIDS)-related non-Hodgkins' lymphoma and sought a relationship with the presence of the Epstein-Barr virus (EBV). B-cell differentiation antigens, activation marker expression (human leukocyte antigen-DR, CD10, CD19, CD20, CD21, CD22, CD23, CD25, CD30, CD38), and epithelial membrane antigen were analyzed. The clonality was determined by the detection of cytoplasmic immunoglobulin, surface immunoglobulin, and the analysis of joining region (JH) immunoglobulin gene configuration by Southern blot. Epstein-Barr virus was detected either by Southern blot analysis using BamHI W probe fragment or by in situ hybridization with EBV-encoded RNA transcripts-1 specific probe. The immunophenotypic and genotypic results were compared with the morphology results and with the presence or absence of EBV. Burkitt's lymphomas were associated with EBV in 50% of cases, were monoclonal, and expressed mostly immunoglobulin (Ig) MK, CD10, CD19, CD20, CD22, and CD38. This immunophenotypic profile closely resembled those of the centroblastic cases (large noncleaved cell), in which EBV was absent. Epstein-Barr virus was associated with 90% of immunoblastic cases, and only CD10, CD20, and CD38 were expressed. CD71 was expressed in all categories of non-Hodgkin's lymphoma, and CD21 and CD23 were rarely expressed. Two cases of immunoblastic lymphoma and one case of high-grade B-NOS were polyclonal regarding JH rearrangement, but EBV tested with 1.9-Kb Xhol fragment was clonal. No significant immunophenotypic changes were noted in relation to the presence of EBV. Such studies comparing morphology, immunophenotype, and genotype could help classify and better understand the pathogenesis of AIDS-related non-Hodgkin's lymphoma.
 ...
PMID:Immunophenotypic and genotypic analysis of acquired immunodeficiency syndrome-related non-Hodgkin's lymphomas. Correlation with histologic features in 36 cases. French Study Group of Pathology for HIV-Associated Tumors. 820 68


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>