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)

Multiparameter flow cytometry was applied on normal human bone marrow (BM) cells to study the lineage commitment of progenitor cells ie, CD34+ cells. Lineage commitment of the CD34+ cells into the erythroid lineage was assessed by the coexpression of high levels of the CD71 antigen, the myeloid lineage by coexpression of the CD33 antigen and the B-lymphoid lineage by the CD10 antigen. Three color immunofluorescence experiments showed that all CD34+ BM cells that expressed the CD71, CD33, and CD10 antigens, concurrently stained brightly with anti-CD38 monoclonal antibodies (MoAbs). In addition, the CD38 antigen was brightly expressed on early T lymphocytes in human thymus, characterized by CD34, CD5, and CD7 expression. Only 1% of the CD34+ cells, 0.01% of nucleated cells in normal BM, did not express the CD38 antigen. The CD34+, CD38- cell population lacked differentiation markers and were homogeneous primitive blast cells by morphology. In contrast the CD34+, CD38 bright cell populations were heterogeneous in morphology and contained myeloblasts and erythroblasts, as well as lymphoblasts. These features are in agreement with properties expected from putative pluripotent hematopoietic stem cells; indeed, the CD34 antigen density decreased concurrently with increasing CD38 antigen density suggesting an upregulation of the CD38 antigen on differentiation of the CD34+ cells. Further evidence for a strong enrichment of early hematopoietic precursors in the CD34+, CD38- cell fraction was obtained from culture experiments in which CD34+ cell fractions with increasing density of the CD38 antigen were sorted singularly and assayed for blast colony formation. On day 14 of incubation, interleukin-3 (IL-3), IL-6, and GM-CSF, G-CSF, and erythropoietin (Epo) were added in each well. Twenty-five percent of the single sorted cells that expressed CD34 but lacked CD38 antigen gave rise to primitive colonies 28 to 34 days after cell sorting. The ability to form primitive colonies decreased rapidly with increasing density of the CD38 antigen. During 120 days of culture, up to five sequential generations of colonies were obtained after replating of the first-generation primitive colonies. This study provides direct evidence for the existence of a single class of progenitors with extensive proliferative capacity in human BM and provides an experimental approach for their purification, manipulation, and further characterization.
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PMID:Sequential generations of hematopoietic colonies derived from single nonlineage-committed CD34+CD38- progenitor cells. 170 33

In halothane-anesthetized and -ventilated cynomologus macaque monkeys, the effects of administering vehicle (n = 3) or the neutral endopeptidase inhibitor N-[L-(1-carboxy-2-phenyl)ethyl]-L-phenylalanyl-beta-alanine (16 mg/kg, n = 5; or 100 mg/kg, n = 3, intravenously) was examined. Cisternal CSF aliquots were examined by radioimmunoassay: 1) for Met enkephalin; 2) after trypsin and carboxypeptidase B treatment for encrypted enkephalin (X-ENK); 3) for substance P; and 4) for unmetabolized drug. Similar measures were carried out in femoral artery and femoral venous plasma, except that substance P was not assayed. In CSF, prior to drug, low, but measurable levels of enkephalin (61 pg/ml), X-ENK (285 pg/ml) and substance P (16 pg/ml) were observed. Vehicle-injected animals showed no change from baseline levels over a 4-hr sampling period in either plasma or CSF levels. In contrast, following 16 mg/kg, in CSF, there was a significant 9-fold increase in MET and 11-fold increase in X-ENK at 30 min. CSF-substance P levels rose also by a factor of 2, with the peak effect observed at 60 min. All levels displayed a significant reduction by 4 hr. There was no statistical difference between the maximum effects observed with either the 16- or 100-mg/kg dose. Plasma peptide levels of enkephalin and X-ENK were not altered by drug. CSF displayed significant drug levels by 30 min, which were between 0.1 and 1% of levels observed concurrently in plasma.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of [N-(L-(1-carboxy-2-phenyl)ethyl]-L-phenylalanyl-beta-alanine (SCH32615), a neutral endopeptidase (enkephalinase) inhibitor, on levels of enkephalin, encrypted enkephalins and substance P in cerebrospinal fluid and plasma of primates. 170 28

Ubenimex (Bestatin) significantly enhanced the G- and GM-CSF-induced colony formation of human bone marrow cells at concentrations of 0.001, 0.01, 0.1 and 1.0 microgram/ml (21-61% enhancement), but not at 10 micrograms/ml. Ubenimex did not influence the EPO-induced erythroid colony and burst formation between 0.0001-100 micrograms/ml. Against human and mouse leukemic cell lines, the growth-inhibitory activities of ubenimex were dose-dependently observed. Aminopeptidase activities on U937 and TF-1 cells were almost inhibited with 10 and 100 micrograms/ml of ubenimex, respectively. Cross-linking studies of 125I-GM-CSF binding to TF-1 cells demonstrated that the 150-kDa band of 2 major bands was enhanced after incubation with 0.01 microgram/ml ubenimex but decreased after that with 100 micrograms/ml, and that the 95-kDa band was not changed at any concentration of ubenimex. Change in density of the 150-kDa band on ubenimex-treated TF-1 cells was correlated with that in expression of CD10 (neutral endopeptidase) on them, whereas that in expression of CD13 (aminopeptidase N) was not changed at any concentration. These results suggest that one possible mechanism of ubenimex action in hematopoietic progenitor cells is the up-regulation of the high affinity receptor for GM-CSF and that in leukemic cell lines is suppression of amino acid incorporation via peptidase regulation.
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PMID:Enhancing effect of ubenimex (bestatin) on proliferation and differentiation of hematopoietic progenitor cells, and the suppressive effect on proliferation of leukemic cell lines via peptidase regulation. 191 72

Conversion of the octapeptide dynorphin (Dyn) A-(1-8) to Leu5-enkephalin (LE) by endopeptidase EC 3.4.24.15 (EP-24.15) in vivo was examined using the technique of ventriculocisternal perfusion. Peptides were administered intracerebroventricularly in the presence or absence of the EP-24.15 inhibitor N-[1-(R,S)-carboxy-3-phenylpropyl]-Ala-Ala-Phe-p-aminobenzoate (cFPAAF-pAB) via cannulae placed into the lateral ventricle of urethane-anesthetized rats. The concentration of Dyn-like peptides and LE within the CSF was monitored by radioimmunoassay in samples of CSF taken from a second cannula placed in the cisterna magna. In the absence of inhibitor, less than 5% of the Dyn A-(1-8) administered was recovered in CSF. Immunoreactive LE, which is normally not found in CSF, increased rapidly in content following Dyn A-(1-8) infusion, an observation suggesting that the larger peptide is converted to LE. When the inhibitor cFPAAF-pAB was coadministered with Dyn A-(1-8), the concentration of immunoreactive Dyn A-(1-8) after 5 min was 40 times higher than that found in the absence of inhibitor. The angiotensin converting enzyme inhibitor captopril reduced the degradation of Dyn A-(1-8) to a much lesser degree. The inhibitor of EP-24.15 also afforded some protection of other Dyn-like peptides. No EP-24.15 activity was found in rat CSF, whereas high activity was found in the choroid plexus. Taken together, these data clearly indicate that an ectoenzyme form of EP-24.15 rapidly converts intracerebroventricularly administered Dyn-like peptides to LE.
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PMID:An inhibitor of endopeptidase-24.15 blocks the degradation of intraventricularly administered dynorphins. 197 55

A pilot study was performed to investigate the toxicity, pharmacokinetics and therapeutic effect of intrathecally administered radiolabelled monoclonal antibody (MAb) in patients with meningeal acute lymphoblastic leukaemia (ALL). Six children aged 3-16, in second or subsequent central nervous system (CNS) relapse of ALL, received between 629 and 1480 MBq of 131Iodine conjugated to either MAb HD37 (CD19, n = 2) or WCMH15.14 (CD10, n = 4). Conjugate was administered as a single injection either via an Ommaya reservoir (n = 4) or by lumbar puncture (n = 2). Acute toxicity was manifest by headache (n = 4), nausea and vomiting (n = 4) and pyrexia (n = 2). All acute symptoms resolved within 72 h. Transient myelosuppression occurred in three patients. Pharmacokinetic studies included investigation of whole body, blood and CSF clearance of isotope. 131I was seen to clear from the CSF by biexponential kinetics. Five patients responded to therapy. In four, the CSF became clear of blast cells at both 2 and 4 weeks following antibody injection, but evidence of relapse was seen at 6 weeks. The fifth patient, with blast cells present on a cytospin preparation, responded to therapy over an 8-week period but relapsed at 12 weeks. This study demonstrates the potential of targeted radiotherapy in CNS ALL, but further studies are necessary to increase the length of remission.
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PMID:A pilot study of monoclonal antibody targeted radiotherapy in the treatment of central nervous system leukaemia in children. 202 71

A new human myeloid cell line has been established recently from the bone marrow cells of a patient with chronic myelogenous leukemia in blast crisis. The active proliferation and survival of the cells in RPMI 1640 medium containing fetal calf serum are clearly dependent on the presence of either natural or recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF). Despite permanent culturing in rhGM-CSF (100 U/mL), the cells do not differentiate and bear the myelomonocytic surface markers CD34, CD13, CD36, as well as HLA-DR, but not CD3, CD7, CD10, CD11b, CD14, CD20, or CD42b. The predominant karyotype, apart from tetraploidy in several cells, is 45, XX, -9, -17, -19, -22, 7p-, 9q+ (der t[9;22]), der (13q), with three additional marker chromosomes, from which one was observed in the patient's leukemic cells. On BglII-digested DNA, Southern blot analysis with bcr 5' as the probe detected two additional hybridizing restriction fragments of 8.6 and 11.0 kilobase pairs.
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PMID:Establishment and characterization of a granulocyte-macrophage colony-stimulating factor-dependent human myeloid cell line. 219 61

Calcitonin gene-related peptide (CGRP) was found to potently inhibit a substance P endopeptidase isolated from human CSF. CGRP potentiated substance P irritant actions; a possible mechanism is interaction for a common metabolic step. Somatostatin is another peptide capable of competing with substance P endopeptidase.
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PMID:Calcitonin gene-related peptide is a potent inhibitor of substance P degradation. 241 71

A case of primary cerebral malignant lymphoma associated with hydrocephalus is reported. The patient was a 54 year-old male who enjoyed good health until the onset of headache and vomiting 4 weeks before admission. His consciousness was alert and neurological examination revealed severe papilloedema with retinal hemorrhage. No lymph node or abdominal tumor enlargement were noted. CT scan and MR images revealed no abnormal lesion except mild ventriculomegaly. CSF study revealed mild elevation of protein and sugar and cell count was 66/3. CSF cytology revealed atypical lymphoid cell with irregular nuclear contour and large nucleolus. Immunological marker studies of the tumor cell revealed increasing of anti J-5 (CD10), anti B-4 (CD19) and OKT-IA1. The patient was treated by a whole brain irradiation and chemotherapy after V-P shunt. It is 12 months since the operation, and the patient's condition is still good.
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PMID:[A case of primary malignant lymphoma of the brain associated with acute hydrocephalus]. 281 71

An endopeptidase hydrolyzing dynorphins A and B and alpha-neo-endorphin at the Arg6-Arg7 or Arg6-Lys7 bonds, was partially purified from human cerebrospinal fluid and further characterized by various biochemical techniques including HPLC gel permeation (UltroPac TSK G3000SW) and ion exchange (TSK DEAE-3SW) chromatography. A procedure for quantitative analysis of the enzyme in individual CSF samples is also described. The activity in lumbar CSF of women in late pregnancy was significantly lower than that in control samples.
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PMID:Assay and biochemical characterization of a dynorphin converting enzyme in human cerebrospinal fluid. 289 68

The effect of rIL-4 on the expression of low affinity receptor for the Fc part of IgE (Fc epsilon R2/CD23) and class II MHC antigens on Burkitt's lymphoma (BL) cell lines was investigated. Some of the BL lines contained low percentages of CD23 and HLA-DQ-positive cells, but virtually all cells expressed HLA-DR. IL-4 induced CD23 and class II MHC Ag expression on 7 of 9 BL. Optimal CD23 and class II MHC expression was observed after 48-72 h of incubation. Induction of CD23 and class II MHC Ag in the BL cell line BL2 by IL-4 was confirmed at the specific mRNA level. Significant activation of HLA-DQ mRNA was obtained after 6 h of incubation with IL-4 and gradually increased during prolonged incubation. Maximal induction of mRNA transcription occurred after 48 to 72 h. Optimal induction of HLA-DR and CD23 transcription in BL2 was also observed after 48 to 72 h. The induction of CD23 and class II MHC Ag seems to be specific for IL-4, because rIL-1, rIL-2, rIFN-gamma, recombinant granulocyte-macrophage-CSF, and a commercial source of low m.w. B cell growth factor were ineffective. In addition, the expression of class I MHC Ag, the transferrin receptor, CD38, CD25, CD10, CD20, and CD21 were not affected by IL-4. Interestingly, IFN-gamma and PGE2 suppressed the IL-4-induced membrane expression of CD23 and class II MHC Ag in a dose-dependent way. IFN-gamma also blocked IL-4-induced CD23 mRNA transcription in BL2 completely, whereas PGE2 (10(-7) M) was partially inhibitory. The induction of CD23 and class II MHC Ag by IL-4 required intact protein synthesis as shown by its inhibition by cycloheximide. These results indicate that the induction of CD23 and class II MHC Ag by IL-4 is regulated in a coordinated way.
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PMID:Regulation of Fc receptor for IgE (CD23) and class II MHC antigen expression on Burkitt's lymphoma cell lines by human IL-4 and IFN-gamma. 296 26


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