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

Biologically relevant assays were used to compare the potency of kelatorphan (N-[3(R)-[(hydroxyamino)carbonyl]-2-benzyl-1-oxopropyl]-L-alanine) as inhibitor of the peptidase-induced metabolism of enkephalins to that of bestatin, a non-specific inhibitor of aminopeptidase and thiorphan, a highly potent blocker of the neutral endopeptidase (EC 3.4.24.11) designated as enkephalinase. Kelatorphan almost completely inhibited the formation of the three metabolites [3H]Tyr, [3H]Tyr-Gly and [3H]Tyr-Gly-Gly produced by incubation of [3H][Tyr1,Met5]enkephalin with rat striatal slices. Co-administered with [Met5]enkephalin in mouse brain, kelatorphan was able to prevent by 80% the degradation of the exogenous peptide. Moreover, a mixture of thiorphan (1 microM) and bestatin (20 microM) or kelatorphan alone (20 microM) induced a 2.2 to 2.5-fold increase in endogenous [Met5]enkephalin overflow after evoked depolarization of superfused rat striatal slices. In this assay, kelatorphan was the only compound to increase by 63% the basal level of released [Met5]enkephalin. Kelatorphan was about 100 times less potent than bestatin to inhibit the total rat striatal aminopeptidases, but as efficient (IC50 = 4 X 10(-7) M) as bestatin to inhibit a minor aminopeptidase activity resembling aminopeptidase M. Therefore the reported enhanced analgesic potency of kelatorphan with regard to the association of bestatin and thiorphan is very likely related to its ability to almost completely inhibit enkephalin-degrading enzymes (including the Tyr-Gly releasing peptidase) and to its better selectivity for the biologically relevant aminopeptidase M. Kelatorphan would be a valuable probe, preferable to the association of bestatin and thiorphan, to investigate the physiological functions regulated by a phasic enkephalinergic activity.
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PMID:In vitro and in vivo effects of kelatorphan on enkephalin metabolism in rodent brain. 386 79

Recent developments on neutral endopeptidase (NEP, EC 3.4.24.11) are described. These include (1) the development of a novel colorimetric assay with a chromogenic substrate (Glutaryl-Gly-Gly-Phe-2-naphthylamide) coupled with aminopeptidase M (EC 3.4.11.2). (2) A detergent form of the pig kidney enzyme has been purified by immuno-adsorbent chromatography and its molecular properties compared with other forms of the enzyme from rabbit kidney and pig intestine. (3) Rat kidney microvilli contain two endopeptidases of about equal activity when assayed with [125I]iodo-insulin B chain as substrate. One is similar to the rabbit and pig endopeptidases in being sensitive to inhibition by phosphoamidon. The other is insensitive to the inhibitor, though susceptible to chelating agents. The two enzymes are resolvable and have been partially characterized. (4) Endopeptidases of the phosphoramidon-sensitive type are present in various tissues in addition to the principal locations in brush borders of kidney and intestine.
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PMID:Microvillar membrane neutral endopeptidases. 612 11

Preparations of microvilli from kidneys of BALB/c mice contain an alkaline metallo-endopeptidase, meprin (metallo-endopeptidase from renal tissue). Certain genealogically related inbred mice are markedly deficient in meprin activity. The meprin-deficient strains (CBA/J and C3H/HeJ) exhibit normal levels of other brush-border enzymes: alkaline phosphatase, aminopeptidase M and another proteinase, a phosphoramidon-sensitive neutral endopeptidase. Meprin deficiency cannot be attributed to a shift in pH optimum and is unlikely to be due to the presence of endogenous inhibitors.
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PMID:Certain mouse strains are deficient in a kidney brush-border metallo-endopeptidase activity. 634 6

A thermolysin-like metalloendopeptidase, optimally active at a neutral pH, was identified in human serum. The enzyme cleaves the synthetic substrate glutaryl-Ala-Ala-Phe-2-naphthylamide at the Ala-Phe bond. Activity was determined by measuring the rate of formation of Phe-2-naphthylamide in a coupled enzyme assay in the presence of excess aminopeptidase M. 2-Naphthylamine released during the reaction was determined by a diazotization procedure. Enzyme activity is not affected by inhibitors of serine, thiol, or carboxyl proteases, but is sensitive to inhibition by metal chelators such as EDTA and o-phenanthroline. Dialysis against EDTA leads to loss of activity, which can be fully restored by zinc and cobalt ions. The serum enzyme closely resembles a membrane-bound metalloendopeptidase (EC 3.4.24.11) abundant in lung, spleen, and kidney in that both enzymes are inhibited by the same active-site-directed inhibitors. In addition, an antiserum obtained against the metalloendopeptidase from rabbit kidney shows strong cross-reactivity with the serum enzyme. Metalloendopeptidase activity was measured in 150 controls and in 95 patients with sarcoidosis; the two groups had significantly different enzyme activities (p less than 0.001). The mean enzyme activity in the sarcoidosis group was more than threefold higher than that of the control group. The mean enzyme activity for patients with active disease was more than double that of patients with inactive disease and more than four times that of controls (p less than 0.001). This is noteworthy because angiotensin converting enzyme, a zinc-dipeptidyl carboxypeptidase with a mechanism of action similar to that of the metalloendopeptidase, has also been reported to be increased in the serum of patients with active sarcoidosis. Enzyme activity in patients with active tuberculosis, primary pulmonary neoplasms, and idiopathic interstitial pulmonary fibrosis did not differ significantly from that of controls.
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PMID:Identification of a thermolysin-like metalloendopeptidase in serum: activity in normal subjects and in patients with sarcoidosis. 636 93

The usefulness of optimized and newly elaborated histochemical methods for proteinases is illustrated on two selected substances. DAP IV (Gly-Pro-MNA,FBB,pH 7.2) was discovered in 39% and DAP II (Lys-Ala-MNA,FBB,pH 5.5) in 60% of the lymphocytes of human peripheral blood (ly). The reaction product of such ly differs in quality and quantity. On the ultrastructural level, the reaction product of DAP IV (Gly-Pro-MNA,HNF) was found in cell membranes and lysosomes. Enzyme activity in other areas was probably suppressed during the preparation procedure. Although the number of ly revealed with Lys-Pro-MNA and Phe-Pro-MNA at pH 5.5 and with Lys-Pro-MNA at pH 7.2 is high, these substrates do not distinctly discriminate DAP IV and DAP II. DAP IV occurs exclusively in T lymphocytes. The number of DAP IV-positive ly was not decreased in patients with myelofibrosis, plasmacytoma, chronic granulocytic leukemia, or tricholeukemia. It was, however, greatly reduced in chronic lymphatic leukemia (CLL). In patients with malignant lymphomas other than CLL, ly presence is related to the stage of the disease. Decreased values indicate a more severe stage or a relapse. In the majority of patients with gastric cancer DAP IV-positive ly were decreased. They were normal or increased in patients with peptic ulcer. The assessment of the number of DAP IV-positive ly is a simple method that provides information regarding the condition of patients with malignant lymphomas and gastric carcinoma. Neutrophilic leukocytes and their precursors, and to a lesser extent monocytes, are revealed when N-acetyl-Met-I-naphthyl ester (Ac-Met-N) is used as substrate. Membrane-bound lysosomal and cytosol proteinases were investigated together with disaccharidases in jejunal biopsies of patients with malabsorption syndrome. Activities of all enzymes were affected in patients with celiac disease. According to their impairment enzymes could be arranged: Lactase(L). trehalase (T), brush border endopeptidase (BBEP), gamma-glutamyl transferase (GGT), DAP IV, enzyme(s) cleaving Ac-Mer-N, aminopeptidase A, cytosol peptidases and aminopeptidase M. In the propria, DAP IV is decreased or absent, while GGT and, particularly, DAP II are increased. After a gluten-free diet, activities are restored in a reverse order. BBEP and GGT are useful as auxiliary parameters in the assessment of the damage or differentiation degree of enterocytes. DAP IV is a sensitive indicator of the involvement of the propria.
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PMID:Proteinases in pathology. Usefulness of histochemical methods. 701 84

In the past, studies on CD34+ cells have been based on the use of monoclonal antibodies conjugated with different fluorochromes that show different fluorescence intensity and yield variable results. Moreover, most of these studies have neither specifically focused on adult human BM samples nor have they used combinations to explore specifically the phenotype of myeloid committed CD34+ cells. The aim of the present study has been to characterize the normal human CD34+ precursor cells from adult BM in order to identify missing or extremely rare phenotypes that can be used for detecting minimal residual disease (MRD) in patients with AML. For this purpose we have utilized the fluorochrome conjugates that provide the most sensitive signals for identifying low antigenic expression, and the technique has been adapted to the characterization of cells present at very low frequencies. Normal human BM samples from 13 adult healthy volunteers have been analyzed using triple stainings at flow cytometry. The mean percentage of CD34+ cells detected was 0.72 +/- 0.33%; these cells displayed an heterogeneous light-scatter distribution. Most CD34+ cells coexpressed CD38 (96.7 +/- 5.7%), HLADR (81.6 +/- 14.0%), CD33 (84.7 +/- 18.3%), CD13 (84.6 +/- 16.2%) and CD71 antigens (65.5 +/- 9.1%). In addition, almost half of CD34+ cells were CD117+ (60 +/- 26.8%). Only a small proportion of CD34+ cells coexpressed CD4 (15.5 +/- 11.7%, CD36 (31.7 +/- 6.2%), CD61 (16.3 +/- 12.9%), CD41 (6.5 +/- 5.5%) or the lymphoid associated markers CD10 (18.6 +/- 11.8%) and CD19 (12.3 +/- 13.2%). Reactivity for the CD15 antigen was observed in a small population of CD34+HLADR+ cells (11.6 +/- 11.2%) although its intensity of expression was lower than that of the more mature granulocytic cells. No CD34+ cells displayed CD14, CD65, CD20, strong CD22, CD3 and CD56 antigens. Accordingly, most adult bone marrow CD34+ cells appeared to be committed to the myeloid lineage (CD13+/CD33+) and displayed an intermediate-to-large FSC/SSC while the lymphoid-committed CD34+ cells (CD19+, CD10+) were in a minority with low FSC/SSC values. By triple marker stainings several phenotypes of CD34+ precursor cells were found to be either undetectable or present at very low frequencies (< 1 x 10(-3)) in the normal human adult bone marrow. These data may be of great value for defining leukemia 'associated' phenotypes used to detect minimal residual disease in adult acute leukemia patients.
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PMID:Phenotypic analysis of CD34 subpopulations in normal human bone marrow and its application for the detection of minimal residual disease. 747 81

Single- and multicolor flow cytometry were used to define progenitor subsets in normal human bone marrow and peripheral blood, cord blood, and blood following mobilization of CD34+ progenitor cells by cyclophosphamide or cyclophosphamide/etoposide/G-CSF treatment. CD34 cells were quantitated and subsets of CD34+ cells were defined by coexpression of CD33, CD13, CD10, CD19, CD45RA, and CD71. Myeloid and erythroid progenitors were quantitated by sorting single CD34+ cells into individual wells of 96-well plates containing methylcellulose, IL-3, GM-CSF, G-CSF, IL-6, and erythropoietin. Comparative studies of CD34 cells showed that the percentage of CD34+ mononuclear cells was greatest in blood samples from patients following mobilization treatment with cyclophosphamide/etoposide/G-CSF averaging 2%. By comparison, the remaining sample groups ranged from 1.68 to 0.15% CD34 cells in this order, bone marrow > cord blood > cyclophosphamide mobilized blood > peripheral blood. Comparison of CD34 cells per milliliter of bone marrow or blood showed a range of 22.4 x 10(4) to 0.65 x 10(4)/ml in the following order, bone marrow > chemotherapy/etoposide/G-CSF > cord blood > cyclophosphamide-mobilized blood. Comparative analysis of CD34 subsets from different sources showed significant differences, particularly bone marrow and blood samples. A distinct population of CD34+ CD19+ (Leu 12) CD10+ (CALLA) pre-B lymphocyte cells was defined in bone marrow with lower side and forward light scatter characteristics and was variable between donors (29.8 +/- 16.9%, mean +/- 1 SD; range, 3-54%; n = 8). This population was not found to a significant degree in blood and also expressed CD45RA (Leu 18). Coexpression studies of CD45RA and CD71 (transferrin receptor) expression on CD34+ cells defined a CD45RA- CD71+ population containing 89 +/- 6.3% (n = 4) BFU-E and a CD45RA+ CD71+ population that contained all CFU-GM (n = 4). LeuM7 (CD13) stained a larger percentage to a greater intensity than MY7 (CD13). Coexpression of CD45RA (Leu 18) and CD13 (LeuM7) defined a subset of CD13+ CD45RA+ cells enriched for CFU-GM and CFU-M with a cloning efficiency of 31%. Coexpression of CD33 (MY9) and CD13 (MY7) defined a population that was predominantly CFU-GM with a cloning efficiency of 38%. These studies define CD34+ phenotypes containing pure populations of B lymphocyte, granulocyte-macrophage, or erythroid progenitors and demonstrate the utility of multiparameter flow cytometry to define lineage-committed CD34+ cells.
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PMID:Phenotypic analysis and characterization of CD34+ cells from normal human bone marrow, cord blood, peripheral blood, and mobilized peripheral blood from patients undergoing autologous stem cell transplantation. 750 11

A 75-year-old man developed a cluster of differentiation (CD)4-positive but human T-cell lymphotropic virus type I (HTLV-I)-negative T lymphoid neoplasm with overwhelming cutaneous involvement and mild thrombocytosis. Twelve courses tetrahydropyranyl adriamycin, cyclophosphamide, vincristine and prednisone (THP-COP) combination chemotherapy led him to complete remission. After four months of complete remission, however, atypical immature cells (blasts) appeared in peripheral blood and bone marrow. Surface marker analysis revealed the blasts to be CD2-, CD3-, CD4-, CD5-, CD7+, CD8-, CD10, CD13 +/-, CD19-, CD20-, CD25-, CD33+ and human leukocyte antigen-DR (HLA-DR+). Staining for myeloperoxidase, esterases, PAS and platelet peroxidase were all negative. The patient was diagnosed as having both CD7 and CD33 positive acute myeloid leukemia (AML). The relation between the T cell lymphoid neoplasm and AML was not clear. Thrombocytosis became more marked after acute leukemia occurred and the platelet count varied in parallel with the blast cell count in peripheral blood. When the leukemic cell count was high, thrombopoietic activity could be detected in the serum. In addition, conditioned medium obtained from primarily-cultured blasts had detectable thrombopoietic activity, which implied the blasts directly to produce a thrombopoietic factor(s). Analysis of the serum concentration for cytokines with associated thrombopoietic activity indicated that the blasts possibly produced a thrombopoietic factor(s) distinct from interleukin (IL)6, IL3, leukemia inhibitory factor (LIF), erythropoietin and granulocyte macrophage-colony stimulating factor. To our knowledge, this is the first reported case of an acute myeloid leukemia with marked thrombopoiesis (more than 2000 x 10(3)/microliter of maximum platelet count in peripheral blood.
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PMID:Acute myeloid leukemia possibly producing thrombopoietic factor(s). 750 2

A method for automatic lineage assignment of acute leukemias was developed. Input are eight list mode data files acquired with a FACScan flow cytometer. For each cell, four parameters are measured: forward light scatter, orthogonal light scatter, fluorescein fluorescence, and phycoerythrin fluorescence. Eight data files are acquired in the following sequence: unstained, isotype controls, CD10/CD19, CD20/CD5, CD3/CD22, CD7/CD33, HLADR/CD13, and CD34/CD38. First, each of the data files 3 to 8 are clustered independently employing an algorithm based on nearest neighbors. Next, the clusters are associated across the data files to form cell populations, using the assumption of light scatter invariance across tubes for each population. The mean positions of each cell population are fed into a decision tree. The decision tree first identifies normal cell populations, i.e., monocytes, neutrophils, eosinophils, basophils, NK cells, T-lymphocytes, and B-lymphocytes. After elimination of the normal cell populations from the data space, the residual cell populations are classified as B-lineage ALL, T-lineage ALL, AML, AUL, B-CLL, or unknown. The effectiveness of this novel approach is shown with case studies of B-lymphoid, T-lymphoid, and Myeloid acute leukemias.
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PMID:Automatic lineage assignment of acute leukemias by flow cytometry. 750 22

We present a patient with acute lymphatic leukemia, eosinophilia, and a 5;14-translocation, a rare but well-documented condition. In order to clarify whether granulocytes were involved in the disease, we applied the MAC (Morphology-Antibody-Chromosomes) technique to samples of the bone marrow and, during a central nervous system relapse, to those of the cerebrospinal fluid. The karyotype of the blast cells was 47,XY, + X,t(5;14)(q31;q32),i(7)(q10). Interphase cytogenetic study by in situ hybridization with an X-specific alphoid probe revealed the abnormality in CD10, CD19, and TdT (terminal deoxynucleotidyl transferase) positive lymphoid cells, whereas CD13 positive, Sudan black B positive, eosinophilic, and basophilic granulocytes as well as monocytes and small lymphocytes did not have the abnormality. Our results show that the eosinophilic and basophilic granulocytes in this subtype of acute leukemia do not belong to the malignant clone but are reactive. This study also confirmed the usefulness of the MAC technique in distinguishing neoplastic and reactive cells in malignancy.
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PMID:Power of the MAC (morphology-antibody-chromosomes) method in distinguishing reactive and clonal cells: report of a patient with acute lymphatic leukemia, eosinophilia, and t(5;14). 751 64


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