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

In this communication we show that T cell locomotion is affected by direct interaction with neurohormones. Opioid peptides, including beta-END, MET-ENK, LEU-ENK, and related enkephalin analogues enhanced migration of human peripheral blood T lymphocytes. Activity was dependent on the peptide NH2-terminal sequence, stimulated by enkephalin analogues with specificity for classical delta or mu types of opiate receptor, and inhibited by the opiate receptor antagonist naloxone. Our studies suggest that such neuropeptides stimulate T cell chemotaxis by interaction with sites analogues to classical opiate receptors. We propose that the endogenous opioids beta-END, MET-ENK, and LEU-ENK are potent immunomodulating signals that regulate the trafficking of immune response cells.
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PMID:Neurohormones regulate T cell function. 233 33

The in vitro and in vivo effects of naloxone (NAL) and endogenous opioids namely methionine and leucine enkephalins (MET-ENK, LEU-ENK) and beta-endorphin (BETA-END) on the brain and lung angiotensin converting enzyme (ACE) activities were investigated. All three peptides dose -dependently inhibited ACE activity in vitro except 10(-5) M concentration of BETA-END which increased the lung ACE activity. NAL which intensified the in vitro inhibitory effect of the used opioids showed an antagonistic effect on the in vivo suppressive effect of BETA-END on both brain and lung ACE activities whereas it had neither antagonistic nor synergistic effect on the in vivo inhibiting effect of MET-ENK and LEU-ENK on the lung ACE activity. The results were consistent with those obtained by using morphine and NAL. As a result the possible contributory action of the excessively released endogenous opioids to overcome shock via their inhibiting effect on ACE was discussed.
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PMID:The in vitro and in vivo effects of enkephalins and beta-endorphin on ACE activity in mice. 301 70

We established three sister cell lines, NALM-30, NALM-31 and NALM-32, with biphenotypic features carrying myeloperoxidase mRNA and protein with complex Philadelphia (Ph) chromosome, t(9;22;10)(q34;q11;q22), from a patient with Ph-positive acute leukemia in relapse. Epstein-Barr virus nuclear antigen was negative. The morphological appearance of the cell lines is that of immature lymphoid cells. Expression of myeloid- and lymphoid-associated surface membrane antigens on these cells was detected allowing for the classification of "biphenotypic" leukemia. Immunophenotypically, the established cell lines reported here fulfill the European Group for the Immunological Characterization of Leukemias (EGIL) criteria for B-lineage derivation, however, surface and cytoplasmic immunoglobulin chains were negative. Whereas TGF-beta R (CD105), MCSFR (CD115), SCFR (CD117), IL-4R/IL-13R (CD124) and IL-6R (CD126) were not expressed, the cell lines were mostly positive for IFN-gamma R (CD119), IL-7R (CD127) and FLT-3R (CD135). The NALM-30, NALM-31 and NALM-32 cell lines together with their serial sister cell lines NALM-27 and NALM-28 which were established from the same patient at diagnosis provide unprecedented opportunities for studying a multitude of biological aspects related to normal and neoplastic immature B-lymphocytes.
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PMID:Myeloperoxidase positive acute lymphoblastic leukemia cell lines, NALM-30, NALM-31 and NALM-32, carrying Philadelphia chromosome with biphenotypic characteristics. 1036 60

In the present study, we show that endothelial-like cells (ELCs) can develop from human CD14-positive mononuclear cells (CD14 cells) in the presence of angiogenic growth factors. The CD14 cells became loosely adherent within 24 h of culture and subsequently underwent a distinct process of morphological transformation to caudated or oval cells with eccentric nuclei. After 1 week in culture the cells showed a clear expression of endothelial cell markers, including von Willebrand factor (vWF), CD144 (VE-cadherin), CD105 (endoglin), acetylated low-density lipoprotein (AC-LDL)-receptor, CD36 (thrombospondin receptor), FLT-1, which is vascular endothelial cell growth factor (VEGF) receptor-1, and, to a weaker extent, KDR (VEGF receptor-2). Furthermore, in these cells structures resembling Weibel-Palade bodies at different storage stages were identified by electron microscopy, and upon culturing on three-dimensional fibrin gels the cells build network-like structures. In addition, cell proliferation and vWF expression was stimulated by VEGF, and the endothelial cell adhesion molecules CD54 (ICAM-1), and CD106 (VCAM-1) became transiently inducible by tumor necrosis factor-alpha (TNF-alpha). In contrast, the dendritic markers CD1a, and CD83 were not expressed to any significant extent. The expression of CD68, CD80 (B7-1), CD86 (B7-2), HLA-DR and CD36 may also suggest that ELCs might be related to macrophages, sinus lining or microvascular endothelial cells. Taken together, our observations indicate that ELCs can differentiate from cells of the monocytic lineage, suggesting a closer relationship between the monocyte/macrophage- and the endothelial cell systems than previously supposed.
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PMID:Endothelial-like cells derived from human CD14 positive monocytes. 1092 8

Microvessel density (MVD) was estimated in a series of 202 vertical growth phase (VPG) melanomas and 68 corresponding metastases, using a marker for angiogenic endothelial cells (CD105) and Factor-VIII. The expression pattern of vascular endothelial growth factor (VEGF), FLT-1, KDR and thrombospondin-1 (TSP-1) was studied by immunohistochemistry, in situ hybridization and reverse-transcriptase polymerase chain reaction. CD105 stained significantly less vessels, but gave only limited additional prognostic information compared with Factor-VIII, and MVD was an independent prognostic factor for both markers. Ninety-eight percent of all cases showed expression of VEGF, and higher expression was found significantly more frequent in thinner and less vascularized tumors. Possible autocrine loops were suggested by co-expression of VEGF and its two receptors in tumor cells, and by a significant correlation between KDR and tumor cell proliferation (Ki-67) in the subgroup of thicker tumors. Staining of VEGF receptors in endothelium was not correlated with MVD. Strong expression of TSP-1 in tumor stroma was found in 43% of the primary tumors, and was significantly correlated with increased thickness, proliferation and MVD, as well as decreased survival. These data suggest that MVD is associated with prognosis in cutaneous melanomas, and that the VEGF system and particularly TSP-1 seem to be involved in the regulation of angiogenesis and progression of these tumors.
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PMID:Expresson of vascular endothelial growth factor, its receptors (FLT-1, KDR) and TSP-1 related to microvessel density and patient outcome in vertical growth phase melanomas. 1143 69

We report a method of purifying, characterizing and expanding endothelial cells (ECs) derived from CD133(+) bone marrow cells, a subset of CD34(+) haematopoietic progenitors. Isolated using immunomagnetic sorting (mean purity 90 +/- 5%), the CD133(+) bone marrow cells were grown on fibronectin-coated flasks in M199 medium supplemented with fetal bovine serum (FBS), vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF) and insulin growth factor (IGF-1). The CD133(+) fraction contained 95 +/- 4% CD34(+) cells, 3 +/- 2% cells expressing VEGF receptor (VEGFR-2/KDR), but did not express von Willebrand factor (VWF), VE-cadherin, P1H12 or TE-7. After 3 weeks of culture, the cells formed a monolayer with a typical EC morphology and expanded 11 +/- 5 times. The cells were further purified using Ulex europaeus agglutinin-1 (UEA-1)-fluorescein isothiocyanate (FITC) and anti-FITC microbeads, and expanded with VEGF for a further 3 weeks. All of the cells were CD45(-) and CD14(-), and expressed several endothelial markers (UEA-1, VWF, P1H12, CD105, E-selectin, VCAM-1 and VE-cadherin) and typical Weibel-Palade bodies. They had a high proliferative potential (up to a 2400-fold increase in cell number after 3 weeks of culture) and the capacity to modulate cell surface antigens upon stimulation with inflammatory cytokines. Purified ECs were also co-cultivated with CD34(+) cells, in parallel with a purified fibroblastic cell monolayer. CD34(+) cells (10 x 10(5)) gave rise to 17,951 +/- 2422 CFU-GM colonies when grown on endothelial cells, and to 12,928 +/- 4415 CFU-GM colonies on fibroblast monolayers. The ECs also supported erythroid blast-forming unit (BFU-E) colonies better. These results suggest that bone marrow CD133(+) progenitor cells can give rise to highly purified ECs, which have a high proliferative capacity, can be activated by inflammatory cytokines and are superior to fibroblasts in supporting haematopoiesis. Our data support the hypothesis that endothelial cell progenitors are present in adult bone marrow and may contribute to neo-angiogenesis.
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PMID:Differentiation and expansion of endothelial cells from human bone marrow CD133(+) cells. 1172 32

Primary intraosseous vascular anomaly, previously called intraosseous hemangioma, is a very rare malformation that is usually seen in the vertebral column and in the skull. It is exclusively described in sporadic cases and no hereditary component has yet been reported. The most commonly affected bones in the skull are the mandible and the maxilla, and life-threatening bleeding after a simple tooth extraction is frequently observed. Here, we report two consanguineous families containing a total of four affected patients manifesting primary intraosseous vascular malformation (VMOS (vascular malformation osseous)) of the craniofacial region. The phenotypic expression is remarkably similar in both families. The characteristic findings include severe blood vessel expansions within the craniofacial bones and midline abnormalities such as diastasis recti, supraumbilical raphe, and hiatus hernia. Malformation is restricted to the mandibular and maxillary area in the prepubertal age, and rapid expansion starts after age 12 or 13. A 15-year follow-up of one of the patients demonstrated that the vascular malformation did not extend beyond the craniofacial region despite severe involvement of almost all bones in the skull. Detailed clinical and radiological evaluation provided neither evidence of soft-tissue involvement nor any sign of gross arterial, venous, or combined malformations, indicating that bone changes are a primary rather than a secondary effect due to any other vascular anomaly in the craniofacial region. An antibody against a universal proliferation marker, Ki-67, detected nonproliferative, single-layered endothelial cells, suggesting that this abnormality is a vascular malformation rather than a hemangioma. alpha-actin staining (antibody against perivascular tissue such as smooth muscle cells (SMCs) and/or pericytes) demonstrated that pathologic vessels lost their surrounding supportive tissues, as was previously seen in other types of vascular anomaly. Homozygosity mapping excluded the following loci and/or genes: multiple cutaneous venous malformation (VMCM1; gene, TIE2) on chromosome 9p21; venous malformation with glomus cells (VMGLOM) on chromosome 1p22-p21; hereditary hemorrhagic telangiectasia type 1 (HHT1; gene, endoglin) and type 2 (HHT2; gene, activin) on chromosomes 9q34.1 and 12q11-q14, respectively; and cerebral cavernous malformation type 1 (CCM1; gene, KRIT1), type 2 (CCM2), and type 3 (CCM3) on chromosomes 7q11.2-q21, 7p15-p13, and 3q35.2-q27, respectively. To the best of our knowledge, this is a new disorder, which we call hereditary intraosseous vascular malformation of the craniofacial region.
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PMID:Hereditary intraosseous vascular malformation of the craniofacial region: an apparently novel disorder. 1193 89

The effects of angiogenic growth factors on the growth, vascular architecture and the downstream cytokine signaling of sarcomas are unknown. These are of potential great importance since sarcoma, like endothelium, is of mesodermal origin and therefore could grow in response to these factors. Three human sarcomas (leiomyosarcoma SK-LMS-1, liposarcoma SW872 and fibrosarcoma SW684) and one murine fibrosarcoma (KHT) were grown in nude and C3H/He mice, respectively. Tumor structural vessels, perfused vessels and hypoxia were quantified immunohistochemically. Fast-growing murine KHT tumors had a markedly higher number of structural vessels compared with the human sarcomas. In both murine and human sarcomas, approximately half of the total structural vessels were perfused, and the numbers of perfused vessels decreased with increasing tumor volume. In vitro, basal mRNA expression of several angiogenic growth factors and their receptors differed between two of the human sarcoma cell lines, SK-LMS-1 and SW872. Compared with SK-LMS-1, untreated SW872 cells had higher levels of mRNA expression for FGF11, FGF14, angiopoietin, CD105 and VEGFR1. Two sarcoma cell lines were also treated with 10 ng/ml of six angiogenic growth factors (FGF1, FGF2, FGF7, FGF10, VEGF and SCF) for 24 h, and mRNA expression of endogenous FGF family members (FGF1, FGF2, FGF10, FGF11, FGF13 and FGF14) were quantitatively measured using RNase protection at various times following treatments. Again, SW872 cells were more responsive to exogenous growth factor treatment compared with SK-LMS-1 cells in terms of the elevation of endogenous FGF mRNA expression. In the SW872 cells, all of the exogenous angiogenic growth factor treatments, except for VEGF, upregulated endogenous FGF1, FGF2 and FGF14 mRNA expression. The SK-LMS-1 cells, in contrast, only responded to exogenous FGF1, FGF7 and FGF10, but did not respond to VEGF.
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PMID:Comparison and modulation of angiogenic responses by FGFs, VEGF and SCF in murine and human fibrosarcomas. 1206 86

A novel human endothelial cell line, AS-M, has been established from a cutaneous angiosarcoma on the scalp. The cells expressing platelet endothelial cell adhesion molecule-1 (CD31) were isolated using magnetic beads and subsequently cultured for a year. To date, the cells have undergone more than 100 population doublings (PDs). The AS-M cells manifested endothelial characteristics, such as active uptake of acetylated low-density lipoprotein labeled with 1,1'-dioctadecyl 3,3,3',3'-tetramethylindocarbocyanine perchlorate (Dil-Ac-LDL), capacity to bind the Ulex europeaus agglutin-I (UEA-I), and expression of von Willebrand factor (vWF) and CD31. The single cell-derived clone, AS-M.5, showed a constitutive expression of CD31, vWF, angiotensin-converting enzyme (ACE), endoglin (CD105), and the endothelial cell receptor tyrosine kinases KDR and Tie-1. Similarly to freshly isolated endothelial cells, the AS-M.5 responded to induction by bacterial lipopolysaccharide (LPS) by increased transcription of cell adhesion molecules and cytokines. The AS-M.5 cultures required endothelial growth supplements for optimal growth and long-term propagation in vitro. However, in contrast to normal endothelial cells, p53 gene products were detected in nuclei of AS-M.5 cells. Cytogenetic analyses consistently revealed a hypodiploid karyotype with complete loss of one homologue of several chromosomes and a homogeneous pattern of distinct karyotypic changes. Although the AS-M.5 presented characteristics suggestive of tumor cells, they did not develop into tumors when inoculated subcutaneously into nude mice. The cell line AS-M.5 could be a useful model system to study endothelial pathobiology in vitro.
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PMID:Establishment and characterization of an angiosarcoma-derived cell line, AS-M. 1474 47

Human bone marrow-derived mesenchymal stem cells (MSCs) have the potential to differentiate into mesenchymal tissues like osteocytes, chondrocytes, and adipocytes in vivo and in vitro. The aim of this study was to investigate the in vitro differentiation of MSCs into cells of the endothelial lineage. MSCs were generated out of mononuclear bone marrow cells from healthy donors separated by density gradient centrifugation. Cells were characterized by flow cytometry using a panel of monoclonal antibodies and were tested for their potential to differentiate along different mesenchymal lineages. Isolated MSCs were positive for the markers CD105, CD73, CD166, CD90, and CD44 and negative for typical hematopoietic and endothelial markers. They were able to differentiate into adipocytes and osteocytes after cultivation in respective media. Differentiation into endothelial-like cells was induced by cultivation of confluent cells in the presence of 2% fetal calf serum and 50 ng/ml vascular endothelial growth factor. Laser scanning cytometry analysis of the confluent cells in situ showed a strong increase of expression of endothelial-specific markers like KDR and FLT-1, and immunofluorescence analysis showed typical expression of the von Willebrand factor. The functional behavior of the differentiated cells was tested with an in vitro angiogenesis test kit where cells formed characteristic capillary-like structures. We could show the differentiation of expanded adult human MSCs into cells with phenotypic and functional features of endothelial cells. These predifferentiated cells provide new options for engineering of artificial tissues based on autologous MSCs and vascularized engineered tissues.
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PMID:Mesenchymal stem cells can be differentiated into endothelial cells in vitro. 1515 14


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