Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.10.1 (ERK)
 95,504 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The biological effects of flt3-L, and the expression of its tyrosine kinase receptor (flt3, CD135) were investigated on the immature subsets of human circulating peripheral blood progenitors obtained from cancer patients or normal volunteer donors, after mobilization with rhG-CSF or chemotherapy. flt3 was expressed at low levels, and its expression increased concomitantly with expression of CD38 within the CD34+ cell population. Despite this low-level expression, flt3-L exerted synergistic effects with a combination of c-kit ligand, IL-3, IL-6, GM-CSF and G-CSF, mainly to induce proliferation of CD34+/CD38- cells. In addition, flt3-L increased the detection of HPP-CFC, both immediately after cell selection, and after 7 and 14 d of cultures. We conclude that flt3-L is active on circulating early mobilized haemopoietic progenitors, despite the low- level expression of its receptor.
 ...
PMID:Early progenitor cells from human mobilized peripheral blood express low levels of the flt3 receptor, but exhibit various biological responses to flt3-L. 1046 May 91

The functional significance of CD95/Fas expressed by candidate hematopoietic stem cells (HSCs) from human fetal liver was studied by testing the effect of agonistic anti-CD95 monoclonal antibody (mAb) CH-11 and soluble CD95 ligand (sCD95L) on the growth of CD34(++)CD38(-)lineage cells in vitro. Candidate fetal HSCs exhibited a dose-dependent proliferative response to CH-11 as well as to sCD95L when combined with kit ligand (KL) + interleukin 3 (IL-3) under serum-deprived culture conditions. CH-11 mAb increased, in a synergistic fashion, the number of myeloid colony-forming unit culture (CFU-C) generated by candidate HSCs in liquid cultures with the cytokine combinations KL + IL-3, KL + granulocytemacrophage colony-stimulating factor, and KL + IL-6. CH-11 mAb and sCD95L also enhanced erythropoiesis supported by KL + IL-3 + erythropoietin (Epo). Furthermore, sCD95L was able to increase the number of megakaryocytes, granulocytes, and CD34- cells generated in the presence of KL + IL-3 + Epo + thrombopoietin. An analysis performed using Western blotting revealed that the membrane-bound CD95L (mCD95L) was expressed by both immature (total CD34+/++) and mature (CD34-) hematopoietic lin(-) FL cells. Among the CD34(++)lin(-)cells, both the freshly isolated CD38+ and CD38 subsets as well as CD95+ and CD95- cells constitutively expressed mCD95L, demonstrating that the CD95/CD95L system represents a paracrine and potentially autocrine regulator of early hematopoiesis. To study the role of the endogenously produced CD95L, we determined the effects of a neutralizing anti-CD95L NOK-1 on the growth of candidate HSCs. By blocking the endogenous CD95L with NOK-1 mAb, we observed an increase in CFU-C generated by candidate HSCs. We conclude that the endogenous CD95L has an inhibitory effect on fetal candidate HSCs, which can be blocked by sCD95L and CH-11 mAb.
 ...
PMID:Role of CD95/Fas and its ligand in the regulation of the growth of human CD34(++)CD38(-) fetal liver cells. 1048 Apr 34

Fas (CD95, APO-1) is a member of the TNF receptor family, and engagement of Fas by its ligand, Fas ligand (FasL), can induce apoptotic death of Fas expressing cells. Signaling through Fas has previously been shown to induce apoptosis of CD34+ human hematopoietic progenitor cells after exposure to IFN-gamma or TFN-alpha. In contrast, we found that FasL promoted a significantly increased viability of primitive CD34+CD38- cells. Thus, incubation with FasL for 48 hours reduced cell death from 46 to 29% compared to cells cultured in medium alone as measured by propidium iodide (PI) incorporation (n = 8, p < 0.02). Inhibition of apoptosis was confirmed by morphological analysis and by the Nicoletti technique. Furthermore, by using a delayed addition assay at the single cell level we found that sFasL treatment had a direct viability-promoting effect on CD34(+)CD38(-) cells. The effect of sFasL was completely blocked by NOK-1, a neutralizing mAb against FasL. In agreement with previous reports, FasL alone slightly increased cell death of more mature CD34(-)CD38+ cells, indicating an interesting shift in the responsiveness to FasL during early hematopoiesis.
 ...
PMID:Fas ligand promotes cell survival of immature human bone marrow CD34+CD38- hematopoietic progenitor cells by suppressing apoptosis. 1048 Apr 36

Primary plasma cell leukaemia (P-PCL) is a variant of multiple myeloma (MM) first diagnosed in the leukemic phase, with >2000/mm(3) circulating plasma cells (PCs) and plasmacytosis >20% of the white cell count. We investigated the clinical characteristics, therapy, immunophenotype and prognosis factors of 18 patients. Common features at diagnosis were asthenia (seven patients), renal insufficiency (ten patients), bone pain (seven patients), splenomegaly or hepatomegaly (five patients). Hypercalcemia was present at diagnosis in seven patients and was the most potent poor prognosis factor (P<0.05). Most patients (16 out of 18) were treated with an anthracyclin containing regiment; complete remission was attained in one patient and partial remission in 11 patients while six patients had no response. The median survival time from diagnosis was 7 months (2--12, 95% confidence interval), but response to treatment had favorable predictive value (P<0.05). The PCs were usually positive for mature B-cell markers (PCA-1, CD38). They expressed integrins which may increase their binding to endothelial cells and thus participate in PCL physiopathology by favoring plasmocyte extramedullary spread.
 ...
PMID:Primary plasma cell leukaemia: a report of 18 cases. 1116 24

EphB4 (HTK) and its ligand, ephrinB2, are critical for angiogenesis and result in fatal abnormalities of capillary formation in null mice. EphB4 was originally identified in human bone marrow CD34(+) cells by us and has since been reported to be expressed in erythroid progenitors, whereas the ligand ephrinB2 is expressed in bone marrow stromal cells. Reasoning that the developmental relationship between angiogenesis and hematopoiesis implies common regulatory molecules, we assessed whether EphB4 signaling influences the function and phenotype of primitive human hematopoietic cells. Ectopically expressed EphB4 in cell lines of restricted differentiation potential promoted megakaryocytic differentiation, but not granulocytic or monocytic differentiation. Primary cord blood CD34(+) cells transduced with EphB4 resulted in the elevated expression of megakaryocytic and erythroid specific markers, consistent with EphB4 selectively enhancing some lineage-committed progenitors. In less mature cells, EphB4 depleted primitive cells, as measured by long-term culture-initiating cells or CD34(+)CD38(-) cell numbers, and increased progenitor cells of multiple cell types. Effects of ectopic EphB4 expression could be abrogated by either targeted mutations of select tyrosine residues or by the tyrosine kinase inhibitor, genistein. These data indicate that EphB4 accelerates the differentiation of primitive cells in a nonlineage-restricted manner but alters only select progenitor populations, influencing lineages linked by common ancestry with endothelial cells. EphB4 enforces preferential megakaryocytic and erythroid differentiation and may be a molecular bridge between angiogenesis and hematopoiesis.
 ...
PMID:Receptor tyrosine kinase, EphB4 (HTK), accelerates differentiation of select human hematopoietic cells. 1192 61

Pathological features and genomic basis of a rare case of ALK(+), CD30(-), CD20(-) large B-cell lymphoma were analyzed. A 36-year-old Japanese female was admitted because of lumbago and constitutional symptoms. Physical examination and laboratory tests showed anemia (hemoglobin, 7.5 g/dL), mild hepatosplenomegaly, and immunoglobin G (IgG) lambda-type monoclonal gammopathy (IgG, 2782 mg/dL). The lymphoma spread exclusively in extranodal sites such as bone marrow, liver, spleen, ovary, and muscle. Biopsy specimens obtained from the ovary showed monomorphic proliferation of large immunoblastic cells with basophilic cytoplasm, round-shaped nuclei with a high nuclear to cytoplasmic ratio, and prominent single nucleolus. Immunostaining with anti-anaplastic lymphoma kinase (ALK) antibody, ALK1, showed finely granular cytoplasmic staining pattern. These cells were also positive for epithelial membrane antigen, CD4, CD19, CD38, CD138, cytoplasmic IgG, and lambda chain, but negative for CD30 (Ber-H2), CD56, CD57, and other T- and B-cell markers. Southern blot analyses revealed that Ig heavy and lambda light chain genes, but not T-cell receptor (TCR) beta gene, were clonally rearranged. Chromosomal analyses by conventional G-banding, spectral karyotyping, and fluorescence in situ hybridization showed complex abnormality involving 2p23, and chromosome 2 was translocated to chromosome 17. As 2;17 translocation resulting in the fusion of clathrin heavy chain (CLTC) gene with ALK was previously reported in inflammatory myofibroblastic tumor, we performed reverse transcriptase-polymerase chain reaction and demonstrated that the lymphoma cells contained CLTC-ALK fusion transcript. Under the diagnosis of ALK(+), CD30(-), CD20(-) large B-cell lymphoma, she was treated with conventional combination chemotherapies. However, the lymphoma was primarily chemotherapy resistant, and the patient died 11 months after admission. We consider that this case confirms the existence of ALK(+), CD30(-), CD20(-) large B-cell lymphomas proposed by Delsol et al. (16) and further provides relevant information regarding their clinicopathological features and cytogenetics.
 ...
PMID:ALK+, CD30-, CD20- large B-cell lymphoma containing anaplastic lymphoma kinase (ALK) fused to clathrin heavy chain gene (CLTC). 1292 Feb 29

In this study we compared the activation of monocytes by different bacterial products via Toll-like receptors (TLR), and by different proinflammatory mediators. In response to TLR-2, -4 and -5 engagement, approximately 50% of monocytes produced TNF-alpha, compared to only 5% after induction with IFN-gamma or GM-CSF. Furthermore, a small proportion of monocytes produced IL-10 after stimulation via TLR, but not after stimulation with cytokines. Both TLR-ligands and inflammatory cytokines induced the expression of CD25, CD69, CD80 and, surprisingly, also of CD83, commonly regarded as an activation marker for mature dendritic cells (DC). Conversely, TLR-ligands downregulated CD38, CD86 and ICOS-L. Importantly, signaling lymphocytic activation molecule (SLAM; CD150) was identified as a monocyte activation marker that could be induced ex novo via TLR-2, -4 and -5, but not by single stimulation with monocyte activators like IL-1, TNF-alpha, IFN-beta, IFN-gamma, GM-CSF or CD40-L. SLAM expression was transient and required mitogen activated protein kinase (MAPK) p38, but not ERK or JNK, and was surprisingly independent of NF-kappaB. SLAM+ monocytes, which are absent in blood, were detected in spleen and tonsils, where they could be localized to T-cell areas and germinal centers. Together, by comparing the response of monocytes to TLR-ligands and inflammatory cytokines, we have identified a monocyte activation marker, SLAM, which differs in its inducibility from other monocyte activation markers. SLAM+ monocytes and macrophages were identified for the first time in vivo. Their presence might be a sign of innate immune activation.
 ...
PMID:Distinct responses of monocytes to Toll-like receptor ligands and inflammatory cytokines. 1509 75

In this study, we examined the mechanism by which CD38 cleavage is regulated through the mitogen-activated protein (MAP) kinases after stimulation by fMLP and interleukin-8 (IL-8) in neutrophils. Both fMLP and IL-8 increased chemotaxis and decreased CD38 protein in neutrophils, but did not change CD38 mRNA levels. Both fMLP and IL-8 increased CD38 in supernatants, which was inhibitable with PMSF. fMLP stimulation resulted in phosphorylation of p38 MAP kinase and p42/44 MAP kinase (ERK). SB20358, a p38 MAP kinase inhibitor, down-regulated neutrophil chemotaxis. Conversely, PD98059, an ERK inhibitor, did not influence chemotaxis to either agonist. The addition of SB20358 blocked the decrease of CD38 on neutrophils and the increase in supernatants induced by fMLP or IL-8, whereas PD98059 did not. These findings suggest that CD38-mediated chemotaxis to fMLP or IL-8 is characterized by proteolytic cleavage of CD38 and signaling through p38 MAP kinase. Activation of the protease for cleavage appears to be a postreceptor event that is dependent on p38 MAP kinase signaling.
 ...
PMID:CD38 cleavage in fMLP- and IL-8-induced chemotaxis is dependent on p38 MAP kinase but independent of p44/42 MAP kinase. 1549 8

To explore the difference of biological characteristics between two subpopulations of adult bone marrow mesenchymal stem cells (MSC), this study was designed to observe the morphological feature and immunophenotype of the adult MSC in the ex vivo culture, the mononuclear cells isolated from normal adult bone marrow were cultured in DMEM with 10% fetal bovine serum. Cell morphology, immunophenotype and cell cycle of two different subgroups were investigated. Cells from 80% confluence were passed through a 10 microm filter, then the fillered cells were cultured in the semisolid methylcellulose medium. The results showed that (1) two different subpopulations were observed in the ex vivo culture. The fibro-like cell was called mature MSC (mMSC) and the smaller round cell was defined rapidly as MSC self-renewing cells (RS cells); (2) the average proportion of cells in G(0)/G(1) of RS cells was approximately 99%, but that of mMSCs was 90%; (3) both of the two populations were negative on the lineage-committed antigen (such as CD34, CD45, CD3, CD19, CD33, HLA-DR, CD38), while positive on the expression of CD90, CD105, C166, CD29, CD44, CD49e, CD54, CD13. However, the expression of these antigens on RS cells was weaker than that on mMSC, but CD117 and KDR were higher expressed when compared with the mMSC; (4) after 4 to 5 week semisolid culture, no hematopoietic progenitor cell colonies were observed. It is concluded that adult MSCs are heterogeneous in that distinct morphological populations exist. The RS cells appear to be the more primitive with greater potential for self-renewal and multilineage differentiation.
 ...
PMID:[Comparative study on various subpopulations in mesenchymal stem cells of adult bone marrow]. 1574 36

On the basis of responses to surface IgM (sIgM) cross-linking, B cells from 41 patients with B-chronic lymphocytic leukemia were categorized as 15 nonresponders (group I) and 26 responders (group II). The latter cases were subclassified as those seven where proliferation was induced (subgroup IIa) and the remaining 19 in whom apoptosis occurred (subgroup IIa). Signal disruption in group I was confirmed by the absence of Ca2+ mobilization. Activation of PI3K was constitutive in subgroup IIa, but not in subgroup IIb, and that of Akt induced by anti-mu in subgroup IIa, but not in subgroup IIb. Among the MAPK, ERK was more highly activated relative to p38 in subgroup IIa, whereas activation of p38 predominated over that of ERK in subgroup IIb. For subgroup IIb cells, based on tyrosine phosphorylation and translocation into lipid rafts, sIgM signaling was shown to be enhanced by Zap70. The different consequences of signaling through sIgM were associated with biological prognosis indicators. These included high levels of CD38, lack of mutations in the IgVH chain genes, preferential usage of full-length CD79b, and severe clinical stage. Thus, modification of sIgM-induced signaling could be a therapeutic approach.
 ...
PMID:B cell response to surface IgM cross-linking identifies different prognostic groups of B-chronic lymphocytic leukemia patients. 1574 15


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>