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 MLR-3 monoclonal antibody reacts with activated but not with resting lymphocytes. We report that MLR-3 identifies an early activation molecule since its binding is detectable on T cells 1.5-2 hr after in vitro activation. Its expression, therefore, does not require DNA synthesis and precedes, by many hours, that of the receptors for interleukin-2 (IL-2R) and transferrin (TF-R). The MLR-3 antigen is also found on activated thymocytes (including the large early thymic CD3- subset) and B cells. The majority of T- and B-lymphoblastoid cell lines, as well as the myeloid and erythroid cell lines HL60, GM1 and K562, are MLR-3+; conversely, non-haemopoietic cell lines are MLR-3 negative. Seventy percent of B-cell chronic lymphocytic leukaemia and 15% of B non-Hodgkin's lymphomas (B-NHL) are MLR-3+. On tissue sections MLR-3 is reactive with epithelia, sweat glands, hair follicles and Henle's loop but not with vessels, connective, endothelium and many other tissues. In vitro studies show that MLR-3 (1-100 micrograms/ml) significantly alters the thymidine uptake of mitogen-treated lymphocytes:augmentation is found when T and B cells are induced with TPA-Ionomycin and reduction when induced with phytohaemoagglutinin (PHA) or Staphylococcus aureus Cowan strain 1 (SAC), respectively. On SDS-PAGE, MLR-3 immunoprecipitates a disulphide-linked heterodimer of MW 29,000-35,000: both subunits are glycosylated, phosphorylated and exhibit a pI of 4.1 and 5.0, respectively. Our data, particularly the in vitro results, suggest that the MRL-3 molecule could have an important role in the early hours of activation for the progression of resting lymphocytes into mitosis.
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PMID:Early lymphocyte activation molecule defined by the monoclonal antibody MLR-3: biochemical and functional studies. 326 71

A monoclonal antibody, designated BM-1, which is reactive in B5 formalin-fixed, paraffin-embedded tissues, has been generated against a cytoplasmic and nuclear antigen expressed in human myeloid precursor cells and derived leukemias. Using the avidin-biotin-complex immunoperoxidase procedure, BM-1 was found to stain selectively myeloid precursor cells in normal bone marrow and mature granulocytes in the blood. In a screen of 26 normal adult and fetal human organs fixed in B5 formalin, BM-1 was negative in all nonhematopoietic tissues with the exception of tissue granulocytes and scattered cells in the peripheral cortex of the thymus. Likewise a screen of 30 solid tumor cell lines including a spectrum of carcinomas, sarcomas, and neural-derived tumors was negative. BM-1 was also negative with 21 T and B cell lymphomas and 11 Hodgkin's disease tumors. A preliminary study of tumors of the hematopoietic system revealed that BM-1 was reactive with M2 and M3 acute myelogenous leukemias (AML), chronic myelogenous leukemias (CML) and myelomonocytic leukemias, and granulocytic sarcomas. M1, M4, M5, and M6 AML clot preparations were negative in this study, indicating that BM-1 may have a role in the histopathologic diagnosis of myelogenous leukemia. Myeloid leukemic cell lines HL-60, ML-2, KG1, and TPH-1-O showed BM-1 nuclear and/or cytoplasmic reactivity in a subpopulation of cells, but erythroid and lymphoid leukemias and all lymphoma cell lines were negative. Immunoperoxidase studies of a panel of fetal tissues showed BM-1 positive cells in the peripheral cortex of the thymus and portal myelopoietic regions of the liver at 18 weeks gestation. Finally, DNA-cellulose and solid phase radioimmunoassay (RIA) techniques developed in our laboratory demonstrate that the BM-1 antigenic domain is reactive only after binding to eukaryotic but not prokaryotic single- or double-stranded DNA. Immunoblot techniques using a DNA-cellulose purified protein sample revealed that BM-1 recognizes a 183 kD protein. These studies indicate that BM-1 is recognizing a myeloid-specific antigen that, because of its DNA binding characteristics, may have an important role in the differentiation of myeloid cells at the molecular level.
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PMID:Immunohistochemical characterization of a 183 KD myeloid-specific-DNA-binding protein in B5 fixed, paraffin-embedded tissues, and bone marrow aspirates by monoclonal antibody BM-1. 330 47

The expression of a particular alpha-naphthyl acetate esterase isoenzyme which is specific for monocytes was examined in a panel of cultured leukemia-lymphoma cell lines (n = 88), freshly obtained leukemia-lymphoma cells (n = 527), and in fresh (n = 10) and cultured (n = 22) leukemia cells treated with the phorbol ester 12-O-tetradecanoylphorbol 13-acetate (TPA). The sodium fluoride-sensitive isoenzyme was separated by isoelectric focusing on horizontal thin-layer polyacrylamide gels. The esterase isoenzyme was not detected in untreated or TPA-treated lymphoid, erythroid, or Hodgkin's disease-derived cell lines, but was seen in leukemia cell lines of monocytic origin. TPA induced the new expression of this marker isoenzyme in two leukemia cell lines of promyelocytic and erythroid origin that are known to differentiate along the monocytic-macrophage cell lineage; TPA stimulation increased the staining intensity of the band in monocytoid cell lines. This esterase isoenzyme was found in 92% of the cases classified morphologically as acute myelomonocytic or monocytic leukemia, but only in 3% of the non-monocytic acute myeloid leukemias. All lymphoid or erythroid leukemias or lymphomas were negative. Treatment with TPA of AML and CML cells, which commonly differentiate to monocyte/macrophage-like cells, showed de novo the monocyte-specific isoenzyme. It is concluded that this isoenzyme is a characteristic marker for monocytic leukemia cells and will be a useful tool for the discriminatory identification of the monocytic element in normal and leukemic cells.
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PMID:Occurrence of particular isoenzymes in fresh and cultured leukemia-lymphoma cells. III. Esterase isoenzyme in monocytes. 349 69

Two new monoclonal antibodies (Lym-1 and Lym-2), reactive with the cell surface of B-lymphocytes and derived tumors, have been produced using tumor cell nuclei preparations as immunogens. Specificity screens using live cell radioimmunoassay techniques with 52 well-characterized human lymphoma and leukemia cell lines showed that both Lym-1 and Lym-2 bound to cell lines of B-cell lineage but were unreactive with those of T-cell, myeloid, or erythroid derivation. The B-cell specificity of these reagents was confirmed on 36 lymphoma and 15 leukemia biopsy specimens by using immunoperoxidase or immunofluorescence techniques. Additionally, flow cytometric analysis of 22 lymphoma biopsies showed that the majority of B-cell tumors were Lym-1 and/or Lym-2 positive and that within a given biopsy, a high percentage of the malignant cell population was stained. In both the immunoperoxidase and flow cytometric studies, reactive T-cells or T-cell lymphomas were consistently negative with the exception of Hodgkin's disease tissues which, in some instances, showed a higher than expected positivity with Lym-1 and Lym-2. Approximately 40% of B-cell chronic lymphocytic leukemias were found to be positive with Lym-1 while 80% were positive with Lym-2. Immunoperoxidase staining of frozen sections of human lymphoid tissues showed that both Lym-1 and Lym-2 stained germinal center and mantle zone B-lymphocytes as well as interfollicular histiocytes. Flow cytometric analysis of normal peripheral blood demonstrated specific staining of B-cells which comprised approximately 8% of circulating lymphocytes. Immunoperoxidase staining of nonlymphoid human organs and tissues revealed weak reactivity of Lym-1 with surface colonic epithelium only. Consistent with these findings, 35 solid tumor cell lines of diverse nature were found unreactive with both Lym-1 and Lym-2. Although standard techniques have thus far failed to identify the antigen recognized by Lym-2, the membrane antigen which binds Lym-1 has been shown by immunoprecipitation and competitive radioimmunoassay studies to be a polymorphic variant of the HLA-Dr antigen. Solid-phase radioimmunoassay techniques have shown that the antigens recognized by Lym-1 and Lym-2 are not significantly modulated after antibody exposure nor shed into the circulation of lymphoma patients. Finally, using iodine-125 labeled preparations of purified Lym-1 and Lym-2, we have determined that both reagents have a relatively large number of antibody binding sites per tumor cell and increased avidity for lymphoma cells when compared to normal and reactive lymph node B-cells.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Two new monoclonal antibodies, Lym-1 and Lym-2, reactive with human B-lymphocytes and derived tumors, with immunodiagnostic and immunotherapeutic potential. 354 94

A study was made of the bone marrow status in unirradiated zones of 33 patients with stage I-II Hodgkin's disease in complete 9-12 year remission after therapeutic irradiation of the lymphatic collectors of the upper part of the trunk in combination with irradiation of the spleen (16 patients) or splenectomy (17 patients). The total count of myelokaryocytes, myelogram, a relative and absolute content of lymphoid cells, immature granulocytes and elements of the erythroid series were defined in the punctates of the upper portion of the ilium. T- and B-lymphocyte count, the number of granulocytomacrophage (CFU-C) and stromal (CFU-F) precursor cells were defined using morphocytochemical and immunological methods. At that time an increase in the relative and absolute content of C- and B-lymphocytes was noted. The T-cell count and the total number of myelokaryocytes, on the one hand, and the content of immature granulocytes and erythronormoblasts, on the other hand, showed correlation of various degree which was particularly noticeable in the group of unoperated patients. The total number of myelokaryocytes in 1 microliter of the bone marrow of the patients after splenectomy, on an average, significantly exceeded that in the group of patients with the irradiated spleen. These changes were considered to be a result of the rearrangement of T-differentiating lymphocytes with their raised accumulation in the bone marrow after irradiation of a considerable volume of the lymphoid tissue and spleen or after splenectomy.
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PMID:[The bone marrow in Hodgkin's disease following radiotherapy and splenectomy]. 358 20

Bone marrow biopsies of patients with a myelodysplastic syndrome (MDS) may, in the absence of an increased number of blasts in the bone marrow smears, contain small clusters of immature precursors. The presence of these cell nests, previously described as "abnormal localized immature precursors" or ALIP, bears a strong prognostic value predisposing patients to early death with an increased risk to develop myeloid leukaemia. In order to describe and delineate this histological characteristic more precisely, we compared bone biopsies of patients with MDS, used in these previous studies, with bone marrow biopsies performed for staging procedures in patients with Hodgkin's disease, non-Hodgkin's lymphoma and carcinoma. From this comparison we conclude that immature precursors are readily differentiated from proerythroblasts, myeloblasts and small-sized megakaryocytes, and that they most probably represent precursors of the myelo-monocytic-erythroid series. A clearcut increase in their number, mostly resulting in the formation of small clusters, is only found in biopsies from patients with MDS.
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PMID:The histological characterization of ALIP in the myelodysplastic syndromes. 376 79

Monolayer cultivation of the radiated bone marrow was performed in 39 lymphogranulomatosis patients with a long-term remission attained after radiotherapy according to the radical program. In 41 patients, the non-radiated bone marrow was also subjected to monolayer cultivation. Counts were made of the total number of myelokaryocytes and myelogram. Analysis of the punctates from the radiated areas has shown that the growth of fibroblast colonies occurred where complete or partial recovery of the cellularity was detected and the total focal dose per bone marrow was less than 35 Gy. With the use of large doses the growth of the colonies was detected in none of the cases. In the radiated areas, the patients commonly manifested bone marrow aplasia. Investigation of the punctates from intact areas pointed to the growth of the colonies in the majority of cases whereas the myelogram count to the increased percentage of the reticular cells, lymphoid and erythroid elements.
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PMID:[Function of the bone marrow stroma in patients with lymphogranulomatosis undergoing radiation therapy]. 378 91

14 patients developed acute nonlymphocytic leukemia and 1 patient developed Burkitt's leukemia following longterm chemotherapy and/or radiotherapy for other disorders. The main primary disorders included multiple myeloma, Hodgkin's disease, non-Hodgkin's lymphoma and breast carcinoma. Acute leukemia developed earlier in patients treated by chemotherapy with or without radiotherapy than in patients treated by radiotherapy alone (63 months, range 24-132 months; 201 months, range 48 months to 30 years, respectively). 13 patients presented without organomegaly and 8 were pancytopenic. Abnormalities of myeloid and erythroid cell lines were observed in the majority of the patients. A high rate of acute erythroleukemia (5 out of 14) was found. Increased reticulin fibers were found in 3 patients. The leukemia was invariably refractory to treatment with a median survival of 4 months. The possible role of preexisting abnormal marrow structure in the development of therapy-related leukemia is discussed.
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PMID:Acute leukemia following chemotherapy and radiation therapy--a report of 15 cases. 658 10

The influence of splenectomy on erythroid burst colony formation by peripheral blood mononuclear cells from 10 patients (four with hereditary spherocytosis, two with beta-thalassaemia major, two with Hodgkin's disease and two with idiopathic thrombocytopenic purpura) was studied. In every instance splenectomy was followed by a lowering of blood BFU-E. The post-splenectomy levels ranged from 0 to 30% of the preoperative levels. Mononuclear cells from the spleens of eight patients were cultured and found to contain numerous BFU-E. The total quantity of BFU-E in the whole blood and in the spleen of the patients was generally of the same order of magnitude. The number of splenic BFU-E did not correlate with spleen size. Splenic BFU-E differed from peripheral blood BFU-E in that they were more sensitive to erythropoietin (Ep) and in that they failed to respond to burst promoting activity (BPA) produced by preincubating the spleen mononuclear cells with phytohaemagglutinin M (PHA). In contrast, media conditioned by PHA-treated spleen cells contained BPA active on peripheral blood BFU-E from normal individuals. These data suggest that the spleen may have an influence on the numbers and functional properties of BFU-E.
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PMID:The relationship between human spleen and blood erythroid burstforming units (BFU-E). 668 75

The expression of the proto-oncogene bcl-2 was examined in a panel of 75 continuous human leukemia-lymphoma cell lines originated from different hematopoietic cell types. The presence of the bcl-2 protein, as evidenced by Western blotting, and its mRNA, as determined by Northern blotting, were not restricted to cells with the chromosomal translocation t(14;18)(q32;q21), but were also detected in a large number of cell lines without t(14;18). The amount of the bcl-2 protein and mRNA in the cell lines with t(14;18) was in the same order of magnitude as in other bcl-2 expressing cell lines of the same lineage, but without the translocation. Bcl-2 was found in all types of hematopoietic cell lines which were assigned to the following lineages based on their phenotypical characteristics: pre-B, B, plasma, T, myeloid, monocytic, erythroid-megakaryocytic and Hodgkin's lymphoma derived cell lines. The levels of accumulated mRNA and protein corresponded fairly well in most of the cell lines examined. Our results suggest the notion that bcl-2 expression is widely present in hematopoietic cell lines without restriction to single lineages and, in fact, clearly independent of the chromosomal aberration t(14;18). It is conceivable that bcl-2 expression is a common feature in established hematopoietic cell lines and may contribute to their unlimited growth in vitro.
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PMID:Expression of bcl-2 mRNA and protein in leukemia-lymphoma cell lines. 747 72


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