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)

We examined the configuration of the immunoglobulin genes in the leukemic blast cell DNA of 20 adults with precursor B-cell acute lymphoblastic leukemia (ALL), treated according to the BMFT protocol. Sixteen of 20 (80%) patients expressed HLA-DR antigens and lacked detectable T-cell antigens. Eleven of the 20 patients (55%) were positive for the CD10 antigen and therefore classified as common ALL. Six patients were classified by immunological phenotyping as null-ALL (30%). Three patients (15%) expressed both immature B-cell markers CD19, CD22, or CD24 and myelomonocytic markers CDw65 or CD15, suggesting precursor B-ALL with cross-lineage expression of myeloid markers. In 18 of the 20 patients (90%), rearrangements and/or deletions of the immunoglobulin heavy-chain (IgH) gene locus were found. In none of the patients was a light-chain gene rearrangement observed. Two patients (10%) had a rearrangement of one allele for the J beta 1 gene region of the TCR-beta gene. In four patients (20%) more than two hybridizing bands for the IgH genes were detected. Two of these four patients with multiple hybridizing bands for the IgH genes had a t (4;11) translocation. Two of five patients with the t (4;11) translocation co-expressed both B-cell antigens and the myeloid antigens CD15 or CDw65. No correlation was found between the immunophenotype of the ALL and the arrangement pattern of their IgH genes. Kaplan-Meier plot analysis revealed no significant difference between adult precursor B-ALL patients with monoclonal or oligoclonal IgH gene rearrangements and their disease-free survival rates.
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PMID:Presence of more than two rearranged immunoglobulin heavy-chain genes in adult precursor B-cell acute lymphoblastic leukemia. 155 98

The expression of interleukin-2 receptors (IL-2R) was examined in 328 adult patients with non-T-cell (non-T) acute leukaemia and blast crisis of chronic myelocytic leukaemia (CML.BC) using two monoclonal antibodies, anti-Tac for IL-2R alpha chain (IL-2R alpha) and Mik beta 1 for IL-2R beta chain (IL-2R beta). Leukaemic cells in the following cases were positive for anti-Tac; 28/192 of acute myelocytic leukaemia (AML), 24/44 CML-BC, 4/28 CD19(+)CD10(-) acute lymphoblastic leukaemia (ALL), and 20/64 common ALL (c-ALL). IL-2R beta was not detected on leukaemic cells of any case examined. Eleven of IL-2R alpha(+) AML were derived from myelodysplastic syndrome. None of the IL-2R alpha positive leukaemic cells responded to exogenous recombinant human IL-2 (rhIL-2) in culture. In addition, IL-2R alpha expression on non-T leukaemic cells was closely correlated with coexpressing different lineage markers and the presence of the Philadelphia abnormality. Marked increase of serum soluble IL-2R alpha was demonstrated in the IL-2R alpha(+) patients examined. Clinically, the IL-2R alpha(+) patients showed significantly lower response to chemotherapy and poorer prognosis than IL-2R alpha(-) patients. Our results clearly indicate the diagnostic importance of IL-2R alpha expression in non-T acute leukaemia with a close relation to the particular cellular characteristics and the prognosis.
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PMID:Diagnostic and clinical importance of interleukin-2 receptor alpha chain expression on non-T-cell acute leukaemia cells. 158 Dec 11

In this study an amphotropic retrovirus has been used to efficiently transduce normal human (NF) and scleroderma (systemic sclerosis; SSc) dermal fibroblasts (SScF) with a sequence encoding a temperature-sensitive mutant of the SV40 large T antigen (tsA58-U19). From the primary outgrowths of skin explants, cultures were generated whose growth was stringently temperature-dependent. When grown at a low, permissive temperature (35 degrees C), both normal and SSc-transduced cells continuously divided with similar doubling times, whereas at a high, nonpermissive temperature (39.5 degrees C), division of both the NF and SScF cells was rapidly arrested. These cells have been passaged more than 50 times, have the typical morphological appearance of fibroblasts, and have retained an anchorage-dependent phenotype. The transduced normal cells (tsT-NF) synthesized the matrix molecules collagen and fibronectin and expressed phenotypic antigens characteristic of their nontransduced counterparts, including MHC Class I, VLA beta 1 (CD29), Hermes 1 (CD44), VLA-4 alpha (CD49d), ICAM-1 (CD54) and LFA-3 (CD58) and the cell surface ectoenzymes neutral endopeptidase (CD10), aminopeptidase N (CD13), and dipeptidyl peptidase IV (CD26). Analysis of the transduced SSc fibroblasts (tsT-SScF) showed that these cells exhibited certain major features of the SSc pathology, notably the abnormally high synthesis of type I collagen, increased expression of ICAM-1, and depressed levels of CD26. Moreover, these phenotypic characteristics were retained even after prolonged culture in vitro. The tsT-SScF cells also retained their responsiveness to cytokines, since interferon-gamma (IFN-gamma) and tumor necrosis factor-alpha (TNF-alpha) both produced a marked increase in ICAM-1 expression. Our findings show that infection of SScF with the SV40 tsT antigen extends the life span of these cells and does not ablate their abnormal phenotypic and functional characteristics.
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PMID:Scleroderma-derived human fibroblasts retain abnormal phenotypic and functional characteristics following retroviral transduction with the SV40 tsT antigen. 755 50

We have previously demonstrated that IL-7 can sustain the growth of normal human B cell precursors (BCP) for several weeks on bone marrow-derived stromal cells. Flow cytometric analysis of BCP recovered from IL-7 supplemented cultures revealed two- to threefold higher levels of cell surface CD19, compared with BCP maintained without IL-7. Short term culture of BCP showed that IL-7 enhancement of CD19 was dose-dependent, with increases detected by day 1 and plateauing by days 3 to 4. IL-7 increased cell-surface CD19 on small lymphoid cells, and to a greater degree on lymphoblasts, whereas cell-surface CD10 was unchanged. The CD34+/CD19+ pro-B cell population showed a greater increase in cell-surface CD19 compared with pre-B and immature B cells. IL-1, IL-3, IL-4, IL-6, and stem-cell factor had no effect on CD19. The potential functional significance of IL-7-enhanced cell-surface CD19 was examined using a F(ab')2 fragment of anti-CD19. This reagent had no effect on [3H]TdR incorporation in BCP cultured in the absence or presence of IL-7 for 5 days, but homotypic adhesion of BCP was induced at a concentration as low as 1.0 ng/ml F(ab')2 anti-CD19. IL-7 enhanced the F(ab')2 anti-CD19 induced homotypic adhesion of BCP in a dose-dependent manner. Blocking antibody studies indicated that members of the beta 1 or beta 2 integrin families did not mediate anti-CD19-induced homotypic adhesion, even though the adhesion was completely ablated by 10 mM EDTA. The pre-B and immature leukemic B cell lines NALM-6 and 1E8 expressed comparable levels of cell-surface CD19, and exhibited comparable increases after IL-7 stimulation. However, their homotypic adhesion responses to anti-CD19 were different. NALM-6 cells exhibited a strong homotypic adhesion response to anti-CD19 that was EDTA-resistant, and beta 1/beta 2 integrin independent. 1E8 cells only responded to anti-CD19 after IL-7 stimulation; this response was EDTA-sensitive and beta 1/beta 2 integrin independent. These collective results indicate that IL-7 not only acts as a growth factor for human BCP, but also regulates signal transduction through cell-surface CD19.
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PMID:Functional effect of IL-7-enhanced CD19 expression on human B cell precursors. 768 30

Studies assessing mechanisms of proximal tubular cell (PTC) physiology and pathophysiology increasingly utilize cell culture systems to avoid the complexity of whole organ/whole animal experiments. However, no well-differentiated PTC line derived from adult human kidney currently exists. Therefore, the goal of this research was to establish such a line by transduction with human papilloma virus (HPV 16) E6/E7 genes. A primary PTC culture from normal adult human renal cortex was exposed to a recombinant retrovirus containing the HPV 16 E6/E7 genes, resulting in a cell line designated HK-2 (human kidney-2) which has grown continuously in serum free media for more than one year. HK-2 cell growth is epidermal growth factor dependent and the cells retain a phenotype indicative of well-differentiated PTCs (positive for alkaline phosphatase, gamma glutamyltranspeptidase, leucine aminopeptidase, acid phosphatase, cytokeratin, alpha 3 beta 1 integrin, fibronectin; negative for factor VIII-related antigen, 6.19 antigen and CALLA endopeptidase). Furthermore, HK-2 cells retain functional characteristics of proximal tubular epithelium (Na+ dependent/phlorizin sensitive sugar transport; adenylate cyclase responsiveness to parathyroid, but not to antidiuretic, hormone). The E6/E7 genes are present in the HK-2 genome, as determined by PCR. To assess its potential usefulness as a tool for studying injury and repair, HK-2 cells were exposed to a toxic concentration of H2O2 +/- iron chelation (deferoxamine) or hydroxyl radical scavenger (Na benzoate) therapy. Only the former blocked H2O2 cytotoxicity, reproducing results previously obtained with freshly isolated rat proximal tubular segments. In conclusion, an immortalized adult human PTC line has been established by transduction with HPV 16 E6/E7 genes. It appears to be well-differentiated on the basis of its histochemical, immune cytochemical, and functional characteristics, and it can reproduce experimental results obtained with freshly isolated PTCs. Thus, this new PTC line could have substantial research application.
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PMID:HK-2: an immortalized proximal tubule epithelial cell line from normal adult human kidney. 812 21

This study was conducted to evaluate the negative regulation of enkephalinase by an endogenously produced peptide, namely transforming growth factor-beta 1 (TGF beta 1). We found that TGF beta 1 acts in human endometrial stromal cells and sex skin fibroblasts in culture to cause a striking decrease (60% to > 90% in 3-7 days) in the specific activity of enkephalinase (membrane metalloendopeptidase; EC 3.4.24.11) by reducing the levels of enkephalinase mRNA and protein. Platelet-derived growth factor caused a slight reduction in enkephalinase specific activity in endometrial stromal cells; epidermal growth factor caused a slight decrease in enkephalinase specific activity in sex skin fibroblasts. In studies in which TGF beta 1 treatment and [35S]methionine labeling were conducted simultaneously, radiolabeling of enkephalinase was decreased. When proteins were radiolabeled with [35S] methionine before treatment with TGF beta 1, the extent of enkephalinase radiolabeling was similar to that in nontreated cells. These findings are indicative that TGF beta 1 acts to decrease enkephalinase activity by a reduction in gene transcription or mRNA stability and not by accelerated degradation of enkephalinase protein.
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PMID:Transforming growth factor-beta 1 inhibits enkephalinase (EC 3.4.24.11) gene expression in human endometrial stromal cells and sex skin fibroblasts in culture. 832 37

The present study was undertaken to characterize the direct chronotropic effect of bradykinin in isolated spontaneously beating atria of the guinea pig. Bradykinin caused concentration-dependent increases in the beating rate of atria. In contrast, the active metabolite of bradykinin and the typical bradykinin B1 receptor agonist, Des-Arg9-bradykinin, had no effect on the beating rate of atria. Inhibition of converting enzyme or neutral endopeptidase by captopril or SQ-28603, respectively, did not affect beating rate but potentiated bradykinin-induced increase in beating rate. The potent bradykinin B2 receptor antagonist, HOE 140, antagonized bradykinin-induced chronotropic effect. In contrast, the bradykinin B1 receptor antagonist, Lys-[Leu8]Des-Arg9-bradykinin, had no effect. The increase in beating rate caused by bradykinin was not affected by blockade of beta 1-adrenoceptors, cyclooxygenase, or nitric oxide synthesis using atenolol, indomethacin and N omega-nitro-L-arginine, respectively. Unlike bradykinin, angiotensin I and angiotensin II caused very small or no change in beating rate in the presence or absence of captopril and SQ-28603. These results indicate that bradykinin causes a direct positive chronotropic effect which is mediated by activation of bradykinin B2 receptors independently of prostaglandins and beta 1-adrenoceptors.
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PMID:Bradykinin B2 receptor-mediated chronotropic effect of bradykinin in isolated guinea pig atria. 856 11

The marrow microenvironment is a complex, three-dimensional structure composed of many cell types and abundant extracellular matrix. Much of the data are derived from analysis of the adherent layer of murine and, especially, human long-term marrow cultures. An essential feature of this in vitro counterpart to the marrow microenvironment is the presence of flat angulated cells functionally defined as marrow stromal cells with the following phenotype: type IV collagen(+), laminin(+), vimentin(+), CD10(+), muscle actin(+), Stro-1(+), and negative for CD45, Mac-1, and HLA-DR. Stromal precursors are Stro-1(+) and CD34(+). Regulation of hematopoietic precursors by the microenvironment occurs by elaboration of regulatory molecules such as hematopoietic cytokines, by cell-cell contact via adhesion molecules such as alpha 4 beta 1 integrin, and by interactions with components of the extracellular matrix as in the case of the glycosaminoglycan hyaluronic acid with cell-associated CD44. Although little about the regulation of stromal cell development itself is known, several studies indicate the transplantability of marrow stromal cells under specific conditions. These developments suggest a potential role of stromal cells in cell therapy. Transfected stromal cells may serve as suitable vehicles for gene delivery to correct single gene disorders in which the product of the target gene does not require stringent regulation as, for example, in the correction of Factor VIII and Factor IX deficiency. Further studies are warranted to investigate marrow stromal cell physiology and regulation to better understand hematopoiesis and to explore the possible use of stroma in therapy.
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PMID:Biology of bone marrow stroma. 859 83

A 16-year-old boy was operated upon for synovial sarcoma of the right thigh and underwent chemotherapy consisted of adriamycin (320 mg), cisplatin (780 mg), etoposide (4,200 mg) and ifosfamide (30,000 mg). He developed secondary leukemia 18 months after the chemotherapy. Acute lymphoblastic leukemia (L3) was initially diagnosed because of poor staining of alpha-naphtyl butylate esterase and induction chemotherapy with the LVP regimen (L-asparaginase 5,000 U/m2 day 8-21, vincristine 1.5 mg/ m2 day 1, 6, 11, 16, 21, 26, prednisolone 40 mg/m2 day 1-28) was performed. After the therapy was initiated, the leukemia was finally diagnosed as acute momocytic leukemia (M5a) because of the following data; blasts were positive for CD33 and HLA-DR and negative for CD10, CD19 and CD20; serum lysozyme was 104.0 micrograms/ml; re-evaluation revealed that blasts were strongly positive for alpha naphtyl butyrate esterase in a small part of the slides; 95% of the bone marrow cells showed t (9; 11) chromosomal aberration; gene rearrangement was positive for MLL and negative for JH, JK and TCR C beta 1. Nevertheless, complete remission was obtained after 1 course of LVP therapy. He received bone marrow transplantation from an unrelated volunteer donor after 3 courses of consolidation therapy. He has remained in complete remission for 16 months.
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PMID:[Complete remission achieved by L-asparaginase, vincristine and prednisolone (LVP) therapy in secondary leukemia (M5a type) with an MLL gene rearrangement]. 905 68