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)

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

Acute lymphoblastic leukemia (ALL) cells of precursor-B type were assessed for expression of the cell surface peptidase CD13 (aminopeptidase-N) after 72 hours' culture in 10% B cell growth factor (BCGF), TPA, or medium alone. CD13 was analyzed phenotypically using a specific monoclonal antibody (mAb) by flow cytometry, and also with a spectrophotometric enzyme assay to measure the cleavage of specific peptide substrates. CD13 antigen was induced in all 10 cases of precursor-B ALL after culture with BCGF, with weaker expression seen in cells incubated with TPA or in medium alone. Aminopeptidase-N-like enzymatic activity was also demonstrated in cultured cells, particularly after BCGF exposure. Using the mAb WM-15, which specifically inhibits aminopeptidase-N function, we demonstrated that induction of true aminopeptidase-N activity was largely restricted to BCGF-treated cells, in which approximately 20% of total aminopeptidase activity was due to aminopeptidase-N. Phenotypic expression of the peptidase CD10 (neutral endopeptidase) was not altered on cultured cells. These findings indicate that CD13 expression can be selectively upregulated on ALL cells in response to proliferative stimuli. This peptidase, in cooperation with CD10 and perhaps other surface enzymes, may act to regulate the concentration of molecules at the cell surface which influence the growth of precursor-B ALL cells.
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PMID:Functional and phenotypic upregulation of CD13/aminopeptidase-N on precursor-B acute lymphoblastic leukemia after in vitro stimulation. 755 27

The diagnosis of primitive hematologic malignancies in extramedullary sites (lymphoblastic lymphoma of T- or B-cell type and myeloid sarcoma) on paraffin-embedded tissue sections is difficult and often impossible because of the primitive morphology of the neoplastic cells. The authors studied 21 extramedullary tumors of lymphoid or myeloid blasts. They used a panel of 22 antibodies on frozen sections and 9 antibodies on paraffin sections to determine the spectrum of immunophenotypes and to develop a practical panel for diagnosis. All but two of the cases could be classified as lymphoid or myeloid using immunohistologic analysis. Thirteen cases were classified as lymphoblastic lymphoma/acute lymphoblastic leukemia (LBL/ALL); 10 were classified as precursor T (CD7+, CD3+/-, CD45+) and 3 as precursor B-cell (CD19+/-CD10+CD45-) type. Five cases were classified as myeloid sarcoma (CD13+ myeloperoxidase+, lysozyme+). Two LBL/ALL coexpressed either CD33 (1 case) or CD15 (1 case), and one myeloid sarcoma coexpressed TdT and CD7. One case appeared to be truly mixed lineage, coexpressing CD3 with myeloperoxidase and lysozyme, and two cases expressed no lineage-specific antigens. There were clinical differences between the three major tumor types, and within the category of T-precursor LBL/ALL, classification according to stage of thymocyte differentiation was associated with distinctive clinical features. In conclusion, the spectrum of immunophenotypes detected on frozen section was similar to that reported by flow cytometry on peripheral blood and bone marrow specimens. The most useful antigens on frozen sections were CD7 and CD3 (T cell), CD10 and CD19 (B cell), and CD13 (myeloid). TdT was coexpressed by one myeloid sarcoma and was undetectable in 40% of LBL/ALL. On paraffin sections, myeloperoxidase and lysozyme were reliable markers of myeloid lineage, but none of the markers used on paraffin sections distinguished between LBL/ALL of T- and B-precursor types. Both B-LBL/ALL and myeloid sarcomas were often CD45- on paraffin sections, which may be a obstacle in determining the diagnosis. These distinctions appear to have clinical relevance.
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PMID:Extramedullary tumors of lymphoid or myeloid blasts. The role of immunohistology in diagnosis and classification. 757 94

1. We have examined several phosphorus-containing peptides as potential mixed inhibitors of two neurotensin-degrading zinc metallopeptidases, endopeptidase 3.4.24.15 and endopeptidase 3.4.24.16. 2. Among a series of 13 phosphonamide peptides, N-(2-(2-naphtyl)ethylphosphonyl-glycyl-prolyl-norleucine (phosphodiepryl 08) was found to inhibit potently the hydrolysis of neurotensin by purified endopeptidase 3.4.24.15 and 3.4.24.16 with an identical Ki value of 0.4 nM. 3. Phosphodiepryl 08 displayed a strong selectivity towards the two peptidases since it failed to inhibit several other zinc-containing peptidases such as endopeptidase 3.4.24.11, angiotensin-converting enzyme, aminopeptidase M, leucine aminopeptidase and carboxypeptidases A and B. 4. The protective effect of phosphodiepryl 08 on neurotensin degradation was examined in vitro and in vivo in central and peripheral bioassays. 5. Phosphodiepryl 08 virtually abolished neurotensin degradation by 4-day-old plated pure cultured neurones from mouse embryos and greatly potentiated neurotensin-induced antinociception in the mouse hot plate test. 6. In the periphery, phosphodiepryl 08 inhibited neurotensin degradation by membranes prepared from isolated longitudinal smooth muscle of guinea-pig ileum and greatly potentiated the neurotensin-induced contraction of the same longitudinal smooth muscle preparation. 7. Our study indicates that phosphodiepryl 08 behaves as a potent and selective mixed inhibitor of endopeptidase 3.4.24.15 and 3.4.24.16 and can be used as a powerful agent to prevent neurotensin degradation, in vitro and in vivo, in central and peripheral assays.
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PMID:Phosphorus-containing peptides as mixed inhibitors of endopeptidase 3.4.24.15 and 3.4.24.16: effect on neurotensin degradation in vitro and in vivo. 758 3

Peripheral blood or bone marrow of 24 patients with chronic myeloid leukemia (CML) were characterized for their surface membrane marker profiles using flow cytometry and fluorescence microscopy. Purine metabolism enzyme activities were compared with membrane immunophenotype and cytochemical stains. CML subtypes were correlated with the expression of surface membrane antigens detected by the monoclonal antibodies. On the basis of immunophenotyping we found the following characteristic marker profiles: In stable phase of CML (CML-SP)-CD15, CD11b, CDw65, CD13, in accelerated phase of CML (CML-AP)-CD15, CDw65, CD11b, CD13 and CD33, in myeloid blastic phase of CML(CML-BP-M)-CD13, CD33, HLA-DR, CD11b, CD15, CDw65, in myeloid and lymphoid (mixed) blastic phase of CML (CML-BP-M+L)-CD13, CD33, CD34, HLA-DR, CD11b, CD10 and in chronic myelomonocytic leukemia (CMML)-CD14, CDw65, CD11b, CD33 and HLA-DR. Analysis of purine metabolism enzyme activities showed that there was a correlation between the values of adenosine deaminase (ADA) and purine nucleoside phosphorylase (PNP) and various types of CML. ADA levels in CML-SP, CML-AP and CMML were comparable with those in normal cells. In CML-BP-M, which represents proliferation of less mature myeloid cells (similar to less mature AML subtypes), ADA activity increased and PNP activity decreased. ADA activity was significantly different between control group and CML-BP-M (p < 0.01), between CML-SP and CML-BP-M (p < 0.05). The values of PNP activity were the highest in stable phase of CML (125 pkat. 10(-6) cells) and the lowest (23 pkat.10(-6) cells) in CML-BP-M+L. PNP activity in the other groups corresponded to control values. High ADA/PNP ratio was found in CML-BP-M and CML-BP-M+L (0.7 and 2.0, respectively) in comparison to CML-SP (0.2). It follows from our results that ADA/PNP ratio enables to discriminate between stable and blast phases of CML (p < 0.01). The level of the cytochemical enzymes (CHAE, MPO, SBB, ANAE and 5' NT) varied and reflected the degree of cell differentiation and maturation. CHAE and MPO were characteristic enzymes for CML, ANBE for CMML and 5' NT for CML-BP-lymphoid.
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PMID:Chronic myeloid leukemia: correlation between purine metabolism enzyme activities and membrane immunophenotype. 761 76

Monoclonal antibody (MoAb) M27 was generated after immunization of mice with the human B-lineage acute lymphoblastic leukemia cell line Pre-ALP. Under reducing conditions, MoAb M27 precipitated a 60-kD surface-membrane molecule from Pre-ALP cells. Expression cloning of Pre-ALP cDNA showed that M27 recognizes carboxypeptidase M (CPM), a cell-surface, zinc-dependent protease known to cleave off basic C-terminal amino acids from peptide hormones. Using M27 antibody, CPM was detected only at discrete B lymphocyte developmental stages, namely on committed precursors and on germinal center cells. CPM was also expressed on mature T cells, mainly after activation. These results provide the first description of a carboxy-peptidase on lymphoid cells. In addition, CPM was found on granulocytes and monocytes, but not on their progenitors. Strikingly, CPM was present only on CD38+ cells, irrespective of lineage affiliation. Of interest, CPM displayed a largely overlapping distribution with the CD10 and CD13 peptidases, with which it shares common substrates (enkephalins, bradykinin). Collectively, the present data show a previously unrecognized distribution pattern of CPM on lymphoid and myeloid cells and suggest that CPM may cooperate with CD10 and CD13 to regulate biologic activity of peptide hormones on leukocytes.
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PMID:Distribution of carboxypeptidase M on lymphoid and myeloid cells parallels the other zinc-dependent proteases CD10 and CD13. 762 Jan 64

Several hundred phosphinic peptides having the general formula Z-(L,D)Phe psi (PO2CH2)(L,D)Xaa'-Yaa'-Zaa', where Xaa' = Gly or Ala and Yaa' and Zaa' represent 20 different amino acids, have been synthesized by the combinatorial chemistry approach. Peptide mixtures or individual peptides were evaluated for their ability to inhibit the rat brain zinc endopeptidases 24-15 and 24-16. Numerous phosphinic peptides of this series act as potent (Ki in the nanomolar range) mixed inhibitors of these two peptidases. However, our systematic and comparative strategy led us to delineate the residues located in P2' and P3' positions of the inhibitors that are preferred by these two peptidases. Thus, endopeptidase 24-15 exhibits a marked preference for inhibitors containing a basic residue (Arg or Lys) in the P2' position, while 24-16 prefers a proline in this position. The P3' position has less influence on the inhibitory potency and selectivity, both peptidases preferring a hydrophobic residue at this position. On the basis of these observations, we have prepared highly potent and selective inhibitors of endopeptidase 24-15. The Z-(L,D)Phe psi-(PO2CH2)(L,D)Ala-Arg-Met compound (mixture of the four diastereoisomers) displays a Ki value of 70 pM for endopeptidase 24-15. The most selective inhibitor of endopeptidase 24-15 in this series, Z-(L,D)Phe psi (PO2-CH2)(L,D)Ala-Arg-Phe, exhibits a Ki value of 0.160 nM and is more than 3 orders of magnitude less potent toward endopeptidase 24-16 (Ki = 530 nM). Furthermore, at 1 microM this selective inhibitor is unable to affect the activity of several other zinc peptidases, namely endopeptidase 24-11, angiotensin-converting enzyme, aminopeptidase M, leucine aminopeptidase, and carboxypeptidases A and B. Therefore, Z-(L,D)Phe psi (PO2CH2)(L,D)Ala-Arg-Phe can be considered as the most potent and specific inhibitor of endopeptidase 24-15 developed to date. This new inhibitor should be useful in assessing the contribution of this proteolytic activity in the physiological inactivation of neuropeptides known to be hydrolyzed, at least in vitro, by endopeptidase 24-15. Our study also demonstrates that the combinatorial chemistry approach leading to the development of phosphinic peptide libraries is a powerful strategy for discovering highly potent and selective inhibitors of zinc metalloproteases and should find a broader application in studies of this important class of enzymes.
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PMID:Development of highly potent and selective phosphinic peptide inhibitors of zinc endopeptidase 24-15 using combinatorial chemistry. 766 87

Agnogenic myeloid metaplasia (AMM) is a chronic myeloproliferative disorder arising from a single hematopoietic cell. Approximately 5% of reported cases of AMM have terminated in leukemic crisis; however, the precise characteristics of the leukemic cells have rarely been reported. We report a case of AMM that occurred in a 42-year-old man and was complicated by leukemic transformation. The leukemic cells were morphologically lymphoblastoid cells with a negative reaction to peroxidase staining, and phenotypically characterized as CD7+, CD34+, HLA-DR+, CD4-, CD8-, CD10-, CD13-, and CD33-. Southern blot analysis revealed that T cell receptor-beta, gamma, and immunoglobulin heavy chain genes in leukemic cells were retained in germ-line configuration. These observations suggest that leukemic cells in our case involved early hematopoietic stem cells rather than those strictly committed to myeloid or lymphoid precursors. To our knowledge, this is the first report of stem cell leukemia arising in a patient with AMM.
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PMID:CD7, CD34-positive stem cell leukemia arising in agnogenic myeloid metaplasia. 768 80

We investigated the phenotypes of blast cells of 53 patients with acute leukemia by a modified streptavidin-biotin alkaline phosphatase (SAB-AP) labeling technique, using a panel of monoclonal antibodies [MoAb; anti-CD11b, CD13, CD14, CD33, CD34, CD41, CD3, CD7, CD10, CD19, anti-HLA-DR, and anti-myeloperoxidase (MPO)]. The selection of an optimal fixative solution for each antigen from five options of various combinations of formalin, acetone, methanol, and/or ethanol, successfully conserved cell morphology and improved specific reaction compared with the conventional methods which used a single fixative for multiple antigens. We compared the SAB-AP results with those obtained by flow cytometry (FCM) for surface markers in each case. High concordance rates for both positive and negative results were observed for each marker. However, positive reaction for some markers (anti-CD13, CD14, CD33, and CD34) were often noted only in the cytoplasm by the SAB-AP method, indicating that combination of these two methods is essential for the precise immunophenotyping of poorly differentiated leukemia cells.
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PMID:Usefulness of immunocytochemistry for phenotypical analysis of acute leukemia; improved fixation procedure and comparative study with flow cytometry. 771 39

We examined the expression of CD10 and G-CSF receptor (G-CSFR) on the lymphoid population of mononuclear cells obtained from bone marrow (BM) using two-colour analysis. In the BM of children with ALL in remission, the CD10+ population was significantly increased (20.6 +/- 5.1% compared with that of controls (2.5 +/- 0.5%). More than half (61.3 +/- 2.9%) of the CD10+ cells co-expressed G-CSFR, but not CD13. These results indicate G-CSFR+ B-cell precursors are markedly increased in BM of ALL in remission, suggesting the probable involvement of G-CSF in the human early B-cell ontogeny.
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PMID:Expression of granulocyte colony-stimulating factor receptor on CD10-positive human B-cell precursors. 773 63


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