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)

For differentiating between inflammatory and neoplastic intrathecal lymphopleocytosis, analysis of CSF cell surface markers was employed in two patients. In one case, diagnosis of intrathecal spreading of a previously not diagnosed lymphoma was established by identifying a uniform population of CALLA-negative (CALLA = common acute lymphoblastic leukaemia antigen) lymphocytes carrying kappa light chains, which reacted with an anti-B monoclonal antibody. In the second case, cytological examination of CSF showed atypical lymphoid cells as well as lymphoblasts and numerous mitoses. On the other hand, analysis of the CSF cell surface markers revealed a typical inflammatory reaction pattern in which antibody-positive inducer (helper) T-lymphocytes predominated. This pointed to inflammatory lymphopleocytosis as likely diagnosis.
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PMID:[Analysis of surface markers on cerebrospinal fluid-producing cells. Contribution to the differential diagnosis of intrathecal lymphomas]. 643 84

Using two-color flow cytometry, we analyzed the subpopulations of CD34+ stem and progenitor cells in the blood and bone marrow from 10 patients with hematological malignancies. Peripheral blood mononuclear cells (PBMNC) harvested after chemotherapy (high-dose Ara C and VP-16) and rhG-CSF, and BM mononuclear cells, which were obtained before chemotherapy (BMMNCbefore) and after the stem cell collection (BMMNCafter) were isolated by Ficoll-Hypaque centrifugation. The purified cells were stained with FITC-conjugated anti-CD34 antibody and one of the following PE-conjugated antibodies: anti-CD7, CD10, CD11b, CD11c, CD13, CD19, CD33, CD38, CD45RO, CD56, and HLA-DR. CD34+ PBMNC harvested and the CD34+ BMMNCafter expressed CD13 and CD33 more frequently than CD34+ BMMNCbefore but expressed CD10 and CD19 less frequently than CD34+ BMMNCbefore. These data suggested that harvested PBMNC contain more myeloid lineage committed progenitors than BMMNCbefore, which might contribute to the rapid recovery of neutrophils after peripheral blood stem cell transplantation. No significant phenotypic differences of CD34+ cells between harvested PBMNC and BMMNCafter were observed except for the expression of CD11c. CD34+ PBMNC harvested coexpressed CD11c more frequently than both CD34+ BMMNCbefore and CD34+ BMMNCafter, which expression might be associated with commitment to the monocyte lineage.
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PMID:Phenotypic differences of CD34-positive stem cells harvested from peripheral blood and bone marrow obtained before and after peripheral blood stem cell collection. 751 35

Human macrophage colony-stimulating factor (hM-CSF) cDNA joined to the leader region of the precursor of the yeast mating pheromone alpha-factor (MF alpha L) was expressed at high levels in BmN cells and in silkworm (Bombyx mori) larvae, using recombinant Bombyx mori nuclear polyhedrosis virus, as a vector. The biological activity of rhM-CSF detected in the haemolymph was 1 x 10(6) colony-formation units/ml, approximately half of the expression level directed by the native signal peptide of hM-CSF in silkworm larvae. The secreted rhM-CSF was purified to homogeneity. N-terminal analysis showed that the signal peptide had been removed, indicating that insect cells possess the enzymic activity necessary to cleave the pro-alpha-factor leader region from the fusion protein at the carboxy side of Lys-Arg dibasic residues, which is the cleavage site recognized by KEX2 endopeptidase in yeast cells.
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PMID:Yeast-prepro-alpha-factor-leader-region-directed synthesis and secretion of truncated human macrophage colony-stimulating factor in the silkworm Bombyx mori. 771 Jul 3

The presence and regulated expression of peptidase activity is a powerful mechanism with the potential to terminate or alter receptor recognition, cell membrane signal transduction, and physiological responses of immune cells to exogenous opioid peptides. In this study, the expression of an endopeptidase that hydrolyzes beta-endorphin to gamma-endorphin and other peptide products was investigated during in vitro differentiation and maturation of recombinant granulocyte-macrophage colony-stimulating factor (rGM-CSF) -derived, bone marrow-derived macrophages. In freshly isolated intact isolated mouse bone marrow cells the rate of beta-endorphin hydrolysis is undetectable (<0.1 nmol beta-endorphin hydrolyzed/h/10[6] cells). However, total intracellular beta-endorphin hydrolytic activity was increased significantly to 20.0 +/- 1.7 nmol/h/10(6) cells in the mature mouse macrophages derived in vitro by culture with rGM-CSF. rGM-CSF-derived macrophages expressed significantly higher levels of both protein and mRNA for the major beta-endorphin endopeptidase, gamma-endorphin-generating enzyme/insulin-degrading enzyme (gamma-EGE/IDE). Moreover, this enzymatic activity appears to be responsible for cleavage of exogenous beta-endorphin by intact rGM-CSF-derived macrophages or peritoneal macrophages to generate gamma-endorphin and other peptide products.
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PMID:Increased expression of an endopeptidase (gamma-EGE/IDE) hydrolyzing beta-endorphin during differentiation and maturation of bone marrow macrophages. 940 Aug 16

We recently established an acute promyelocytic leukemia (APL) cell line (HT93) that has the capacity to differentiate into neutrophils and eosinophils in response to all-trans retinoic acid (ATRA) and human hematopoietic cytokines. The cells had a myeloblastic morphology, were positive for surface CD33, CD34, and CD56, and showed the following karyotypes: 46, XY, t(1;12)(q25;p13), 2q+, t(4;6)(q12;q13), and t(15;17)(q22;q11). When the cells were cultured with ATRA, they showed nuclear segmentation and developed secondary granules consisting in part of neutrophils and eosinophils. In the presence of ATRA and granulocyte colony-stimulating factor (G-CSF), the cells showed polymorphonuclear neutrophil differentiation accompanied by expression of surface CD11b, CD15, CD10, positive activity for neutrophil alkaline phosphatase (NAP), and NAP mRNA expression. In cultures with ATRA and granulocyte-macrophage colony-stimulating factor (GM-CSF), IL (interleukin)-3, or IL-5, HT93 showed remarkable eosinophil maturation at day 8 as determined by luxol fast blue staining, in addition to expression of eosinophil peroxidase and major basic protein. These results indicate that HT93 is an APL cell line with the ability to differentiate into neutrophils and eosinophils, and that these lineages are dependent on the CSF added. HT 93 should prove to be a useful model in analyzing the effects of hematopoietic cytokines on proliferation, differentiation, and maturation of hematopoietic progenitors.
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PMID:Hematopoietic cytokine-dependent differentiation to eosinophils and neutrophils in a newly established acute promyelocytic leukemia cell line with t(15;17). 947 3

An N-terminus sequence of human interleukin 1beta (hIL-1beta) was used as a fusion expression partner for the production of two recombinant therapeutic proteins, human granulocyte-colony stimulating factor (hG-CSF) and human growth hormone (hGH), using Saccharomyces cerevisiae as a host. The expression cassette comprised the leader sequence of killer toxin of Kluyveromyces lactis, the N-terminus 24 amino acids (Ser5-Ala28) of mature hIL-1beta, the KEX2 dibasic endopeptidase cleavage site, and the target protein (hG-CSF or hGH). The gene expression was controlled by the inducible UAS(gal)/MF-alpha1 promoter. With the expression vector above, both recombinant proteins were well secreted into culture medium with high secretion efficiencies, and especially, the recombinant hGH was accumulated up to around 1.3 g/L in the culture broth. This is due presumably to the significant role of fused hIL-1beta as secretion enhancer in the yeast secretory pathway. In our recent report, various immunoblotting analyses have shown that the presence of a core N-glycosylation resident in the hIL-1beta fragment is likely to be of crucial importance in the high-level secretion of hG-CSF from the recombinant S. cerevisiae. When the N-glycosylation was completely blocked with the addition of tunicamycin to the culture, the secretion of hG-CSF and hGH was decreased to a negligible level although the other host-derived proteins were well secreted to the culture broth regardless of the presence of tunicamycin. The N-terminal sequencing of the purified hG-CSF verified that the hIL-1beta fusion peptide was correctly removed by in vivo KEX2 protease upon the exit of fusion protein from Golgi complex. From the results presented in this article, it is strongly suggested that the N-terminus fusion of the hIL-1beta peptide could be utilized as a potent secretion enhancer in the expression systems designed for the secretory production of other heterologous proteins from S. cerevisiae.
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PMID:Novel secretion system of recombinant Saccharomyces cerevisiae using an N-terminus residue of human IL-1 beta as secretion enhancer. 1051 58

The regulatory roles of a number of early-acting growth factors on the generation of natural killer (NK) cells and B cells from primitive progenitors were studied. Experiments focused on the contributions of granulocyte-macrophage colony-stimulates factor (GM-CSF) and interleukin-3 (IL-3) to the regulation of the early events of lymphopoiesis.Two progenitor populations isolated from human fetal liver were studied, CD38(-)CD34(++)lineage(-) (Lin(-)) cells (candidate hematopoietic stem cells [HSCs]) and the more mature CD38(+)CD34(++)Lin(-) cells. The effects of different cytokines on the generation of CD56(+)CD3(-) NK cells and CD19(+) B cells were studied in serum-deprived cultures in the absence of stroma.NK cells generated in vitro were able to kill NK-sensitive target cells, expressed NK-associated marker CD161 (NKR-P1A), but exhibited little or no expression of CD2, CD8, CD16, CD94/NKG2A, or killer cell inhibitory receptors (KIRs). Among the cytokine combinations tested, kit ligand (KL) and IL-15 provided the best conditions for generating CD56(+) NK cells from CD38(+)CD34(++)Lin(-) cells. However, either flk-2/flt3 ligand (FL), GM-CSF, IL-3, or IL-7 could partially substitute KL. All of these cytokines also supported the growth of NK-cell progenitors from candidate HSC, with the combination of IL-15, KL, GM-CSF, and FL generating the greatest number of CD56(+) cells. B cells were generated from both progenitor populations in response to the combined effects of KL, FL, and IL-7. Both B and NK cells were generated with the further addition of IL-15 to these cultures. The in vitro generated B cells were CD10(+), CD19(+), HLA-DR(+), HLA-DQ(+), and some were CD20(+), but no cytoplasmic or surface immunoglobulin M expression was observed. In contrast with NK lymphopoiesis, GM-CSF, IL-3, and IL-15 had no effect on the generation of B cells from CD38(-)CD34(++)Lin(-) cells, and GM-CSF inhibited B-cell generation from CD38(+)CD34(++)Lin(-) progenitors. These findings indicate a differential regulation of NK and B lymphopoiesis beginning in the early stages of hematopoiesis as exemplified by the distinctive roles of IL-7, IL-15, GM-CSF, and IL-3.
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PMID:Differential effects of interleukin-3, interleukin-7, interleukin 15, and granulocyte-macrophage colony-stimulating factor in the generation of natural killer and B cells from primitive human fetal liver progenitors. 1098 97

We investigated the levels of 6 different cytokines in the sera of 10 newly diagnosed patients with B cell lineage acute lymphoblastic leukemia (ALL) and detected a significant increase in IL-6 and IFN-alpha serum levels in comparison to that of healthy controls. Whole blood cell cultures of 10 ALL patients and 20 control individuals were induced with classical cytokine inducers, such as virus, PHA and LPS, and their ability to produce 9 different cytokines was compared. Blood cells of ALL patients produced significantly less IL-1alpha, IL-1beta, IL-10 and TNF-alpha than control cells and not significanly lower levels of IL-6, but comparable with control levels of IL-2, IL-4. rHuGM-CSF added to cell cultures 24 h before induction significantly enhanced the production of IL-1alpha, IL-1beta and TNF-alpha in controls, but only IL-1alpha and IL-1beta in the blood cell cultures of patients with ALL. GM-CSF did not significantly influence the production of IFN-alpha, IFN-gamma, IL-2, IL-4 and IL-10 in the control cells and the cells of ALL patients. The patients examined differed not only in the expression of CD10 and CD34 antigens on blast cells, but also in the reaction to GM-CSF treatment, which was found as very high standard deviation values. We suppose that these differences can partially explain the different effects of GM-CSF when used to ameliorate neutropenia of ALL patients after chemotherapy and to reduce the incidence of microbial infections.
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PMID:Cytokine production in whole blood cell cultures of patients with B-lineage acute lymphoblastic leukemia. The influence of granulocyte-macrophage colony-stimulating factor. 1126 94

A novel cell line, designated OHK, was established from ascites of a 59-year-old Japanese woman with diffuse large B-cell lymphoma showing a peculiar serosal tropism, as seen in primary effusion lymphomas (PEL). OHK exhibited a large pleomorphic morphology with irregular nuclei and distinct nucleoli, and included immunoblastic and Reed-Sternberg-like giant cells. On ultrastructural examination, rich intermediate filaments, and well-developed Golgi apparati and rough endoplasmic reticulum, were seen. Immunophenotypically, OHK lacked T and B cell-associated antigens, and had CD10, CD30, CD33 and CD138 antigens. Although OHK cells did not express immunoglobulin (Ig) protein, Southern blot analysis demonstrated clonal rearrangements of Ig heavy and light chain genes. These observations suggest that OHK cells are derived from preterminally differentiated B cells, and that they have features of PEL. Kaposi's sarcoma-associated herpesvirus and Epstein-Barr virus were not detected. OHK displayed hyperploid karyotypes with multiple structural abnormalities, and produced some cytokines such as macrophage-colony-stimulating factor (M-CSF), granulocyte-CSF, interleukin 6 and transforming growth factor beta 1. In particular, vascular endothelial growth factor (VEGF), whose stimulation of vascular permeability is thought to be critical to the pathogenesis of PEL, was also produced in large quantities. These results indicate that OHK may be a useful tool for the investigation of PEL.
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PMID:Establishment and characterization of a Kaposi's sarcoma-associated herpesvirus- and Epstein-Barr virus-negative malignant lymphoma cell line (OHK) with primary effusion lymphoma immunophenotype. 1184 5

Insulin-like growth factor-I is a neurotrophic factor and can prevent neurons from ischemic brain injury. However, the large molecular weight and metabolic effects can be problematic in its central delivery. Glycine-proline-glutamate (GPE) is the N-terminal tripeptide of insulin-like growth factor-I, which is naturally cleaved in the plasma and brain tissues. GPE reduces neuronal loss from hypoxic-ischemic brain injury following central administration. Central penetration and the stability of GPE in the plasma and central nervous system were examined in rats using radioimmunoassay and HPLC. GPE was rapidly metabolised in the plasma (8 min) after intraperitoneal administration. Despite having a short half-life in plasma, GPE was detected in the cerebrospinal fluid up to 40 min after intraperitoneal administration. With present of peptidase inhibitors, GPE existed in the brain tissue up to 3 h after intracerebroventricular administration, suggesting a role for peptolysis in its stability. The endopeptidase inhibitors 4- (2-aminoethyl) benzenesulfonyl fluoride hydrochloride (AEBSF) reduced GPE metabolism in the brain tissue while acid peptidase inhibitor pepstatin-A decreased GPE metabolism in the plasma. GPE reduced neuronal loss in the CA1-2 sub-region of the hippocampus given (intraperitoneally) after 30 min of hypoxic-ischemic injury in adult rats, further suggested the effectiveness of GPE central uptake. These results indicated that GPE crosses the blood-CSF and the functional CSF-brain barriers. The longer half-life of GPE in the CNS may be due to its unique enzymatic stability.
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PMID:Central penetration and stability of N-terminal tripeptide of insulin-like growth factor-I, glycine-proline-glutamate in adult rat. 1575 41


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