Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.24.11 (CD10)
9,792 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The non-Hodgkin's lymphomas (NHL) are a heterogeneous group of lymphoid neoplasms displaying a wide variation in cell morphology, histological patterns, immunological phenotype and prognosis. In this paper we compare the results of phenotypic investigation of 322 tissue biopsies with the histology based on the Kiel classification. Immunological analysis revealed that 81 per cent of these tumours were of B cell origin, 12 per cent of T cell origin and the remaining 7 per cent could not be characterized as representing either cell lineage. This last group included a number of cases which had received a histological diagnosis of true histiocytic lymphoma. The original morphological diagnosis, based on routine haematoxylin and eosion sections correlated with the immunologically determined phenotype in 86 and 93 per cent of the T- and B-cell cases respectively. The B cell tumours were phenotypically heterogenous with respect to immunoglobulin (Ig) heavy chain and B lymphocyte subset marker expression. IgG was most often found associated with NHL of cb/cc histology and a small subgroup of lymphocytic NHL. IgA expression was uncommon and occurred in combination with IgD and G in three cases and alone in two cases of NHL. The most common immunoglobulin isotype expressed was IgM this isotype occurred with IgD most often in lymphocytic and centrocytic NHL and less often in tumours of cb/cc histology. Whilst greater than 90 per cent of the lymphocytic NHLs expressed the CD5 antigen, between 20 and 75 per cent of B-cell tumours of other histologies also expressed this epitope. The CD10 antigen and the epitope recognized by the monoclonal reagent FMC7 were widely distributed on tumour cells from all histologies. TdT expression commonly regarded as a marker for immature cells was found in one case of follicle centre cell lymphoma. All cases of T cell NHL displayed marked heterogeneity for both pan T and T subset antigens which is significant in terms of the routine diagnosis of T NHL and with regard to the rational classification of node based T NHL. Unlike resting peripheral blood T cells, MHC class II, OKT 10 and CD25 epitopes were expressed reflecting activation of tumour populations.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Correlation between histology and immunophenotype in a series of 322 cases of non-Hodgkin's lymphoma. 264 57

The interaction of different polypeptide growth factors with their cell surface receptors, which are typically rich in cysteine, is modulated by sulfhydryl (SH) reagents. Because the extracellular domain of both human TNFRs are likewise rich in cysteine residues, we examined the effect of SH reagents on these receptors in human histiocytic lymphoma U937 cells, which express both p60 and p80 forms. Iodoacetamide induced down-regulation of cell surface TNFRs in a dose- and time-dependent manner. Down-regulation was complete at 10 mM IAA for 1 h at 37 degrees C. The decrease was minimal at 4 degrees C. The down-modulation was also observed with other cell-permeable and -impermeable thiol reagents. The expression of other cell surface molecules such as CD3, CD11b, CD23, and CD25 were not affected. IAA induced the down-regulation of TNFR on cells of both epithelial and myeloid origin. With the use of receptor-specific Abs, we found that the kinetics of down-modulation of the p60 and p80 receptors by IAA were very similar. We also found that down-modulation was not a result of internalization but rather of the shedding of the receptors, as ascertained by receptor-ligand cross-linking analysis, immunoassay, Western blot analysis, and ligand-blot analysis. When TNFRs with a molecular mass of 80 kDa disappeared from the cell surface, a 42-kDa polypeptide appeared in the medium. Thus, we demonstrate that SH reagents down-regulate TNFRs by inducing shedding of both receptors from the cell surface, most likely by activating an endopeptidase that cleaves the receptor.
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PMID:Role of sulfhydryl groups in induction of cell surface down-modulation and shedding of extracellular domain of human TNF receptors in human histiocytic lymphoma U937 cells. 793 May 91

ESPL1/Separase, an endopeptidase, is required for centrosome duplication and separation of sister-chromatides in anaphase of mitosis. Overexpression and deregulated proteolytic activity of Separase as frequently observed in human cancers is associated with the occurrence of supernumerary centrosomes, chromosomal missegregation and aneuploidy. Recently, we have hypothesized that increased Separase proteolytic activity in a small subpopulation of tumor cells may serve as driver of tumor heterogeneity and clonal evolution in chronic myeloid leukemia (CML). Currently, there is no quantitative assay to measure Separase activity levels in single cells. Therefore, we have designed a flow cytometry-based assay that utilizes a Cy5- and rhodamine 110 (Rh110)-biconjugated Rad21 cleavage site peptide ([Cy5-D-R-E-I-M-R]2-Rh110) as smart probe and intracellular substrate for detection of Separase enzyme activity in living cells. As measured by Cy5 fluorescence the cellular uptake of the fluorogenic peptide was fast and reached saturation after 210 min of incubation in human histiocytic lymphoma U937 cells. Separase activity was recorded as the intensity of Rh110 fluorescence released after intracellular peptide cleavage providing a linear signal gain within a 90-180 min time slot. Compared to conventional cell extract-based methods the flow cytometric assay delivers equivalent results but is more reliable, bypasses the problem of vague loading controls and unspecific proteolysis associated with whole cell extracts. Especially suited for the investigaton of blood- and bone marrow-derived hematopoietic cells the flow cytometric Separase assay allows generation of Separase activity profiles that tell about the number of Separase positive cells within a sample i.e. cells that currently progress through mitosis and about the range of intercellular variation in Separase activity levels within a cell population. The assay was used to quantify Separase proteolytic activity in leukemic cell lines and peripheral blood samples from leukemia patients.
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PMID:Measurement of separase proteolytic activity in single living cells by a fluorogenic flow cytometry assay. 2626 33