Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:2.7.10.2 (focal adhesion kinase)
44,029 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Phagocyte-derived interleukin-12 (IL-12) is a key cytokine that induces the development of an effective Th1 type immune response in various inflammatory and infectious disorders. To determine the importance of IL-12 in the pathogenesis of autoimmune renal injury we examined the renal production of this heterodimeric cytokine in the MRL-Fas(lpr) lupus nephritis model. Compared with normal mice RT-PCR products encoding both the p35 and p40 subunits of IL-12 were markedly increased in the kidney of MRL-Fas(lpr). Immunofluorescence staining demonstrated expression of the IL-12 p75 heterodimer on isolated infiltrating mononuclear cells and also on proximal tubular epithelial cells in MRL-Fas(lpr) but less in normal mice kidneys. The enhanced expression of IL-12 correlated with an increased intrarenal transcription of IFN-gamma. The p35 and p40 transcripts and soluble IL-12 p75 protein were also produced by cultured TEC. In addition, membrane bound IL-12 was detected on Tec. We conclude that IL-12 production is significantly up-regulated in MRL-Fas(lpr) lupus nephritis. In addition to mononuclear cells, TEC are an important source of IL-12 and could thereby participate in the development of a Th1 type immune response in autoimmune renal injury.
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PMID:Up-regulation of tubular epithelial interleukin-12 in autoimmune MRL-Fas(lpr) mice with renal injury. 899 20

Several peptide growth factors, including members of the fibroblast growth factor (FGF) superfamily, are potential inducers of mesoderm in vertebrates. Receptor binding of basic FGF (FGF-2) is promoted by cell surface or extracellular matrix proteoglycans. The substantial biosynthesis of proteoglycans by embryonic cells (called embryoglycans) and their potential role as ligands for growth factor receptors led us to examine the role of embryoglycans that carry the developmentally regulated oligosaccharide epitope TEC 1, in the binding of FGF-2 to cultured rabbit inner cell masses (ICMs). Culture of isolated ICMs in the presence of FGF-2 gave rise to well delimited colonies with migrating cells at the periphery. In these cells, TEC 1 staining shifts from a punctate pattern over the entire membrane, to an apical, finely granular distribution with some internalization. This shift occurs after 96 hours in culture. Here we show that: (1) migrating cells are mesoderm-like in phenotype; (2) antibodies against TEC 1 blocked FGF-2 mediated differentiation in vitro; (3) antibodies against TEC 1 selectively blocked binding of FGF-2 to ectodermal receptors and, vice versa, the binding of TEC 1-specific antibodies to ectodermal cells can be competed by excess FGF-2; (4) the same switch in TEC 1 staining patterns was observed in vivo, between the day 7 and the day 9 rabbit embryo. These data suggest the involvement of defined species of embryonic cell surface epitopes in the regulation of FGF-2 receptor binding. Moreover, this proposed binding activity is temporally restricted to ectodermal cells and disappears early during differentiation. Thus, the apical TEC 1 redistribution can be considered as the earliest indicator of mesoderm formation.
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PMID:Embryoglycans regulate FGF-2-mediated mesoderm induction in the rabbit embryo. 901 Jul 79

The TEC gene encodes for a novel orphan nuclear receptor. Recently, it has been shown to be involved in the recurrent t(9;22) translocation observed in extraskeletal myxoid chondrosarcoma, in a fusion gene with the EWS gene. We report her on its precise localization on chromosome 9 by fluorescence in situ hybridization.
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PMID:Localization of TEC to 9q22.3-q31 by fluorescence in situ hybridization. 903 50

The pathogenesis of myxoid chondrosarcoma (CS) is poorly understood. A recurrent translocation, t(9;22) (q22;q12), has been recognized in CS, specifically in extraskeletal myxoid CS. Recently, this translocation has been shown to represent a rearrangement of the EWS gene at 22q12 with a novel gene at 9q22 designated CHN (or TEC). Sequence analysis suggests that CHN encodes a novel orphan nuclear receptor with a zinc finger DNA-binding domain. The structure of this gene fusion has been characterized in only a limited number of extraskeletal myxoid CSs and its presence in other types of CS has not been extensively examined. We studied 46 cases of CS (8 extraskeletal myxoid, 4 skeletal myxoid, 4 mesenchymal, and 30 other) for the EWS/CHN gene fusion by reverse transcriptase polymerase chain reaction, Southern blotting, and long-range DNA polymerase chain reaction. The EWS/CHN gene fusion was present in 6 of 8 extraskeletal myxoid CSs and was not detected in any of the remaining cases, including the 4 skeletal myxoid CSs. The negative findings in the latter cases suggest that skeletal myxoid CS is pathogenetically distinct from its extraskeletal counterpart. Notably, 2 cases of extraskeletal myxoid CS showed neither an EWS/CHN fusion transcript nor EWS/CHN genomic fusion nor EWS or CHN genomic rearrangement, suggesting genetic heterogeneity within extraskeletal myxoid CS. Finally, we also provide evidence for alternative splicing of the 3' end of the fusion transcript. Extraskeletal myxoid CS thus represents yet another sarcoma type containing a gene fusion involving EWS.
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PMID:Molecular analysis of the fusion of EWS to an orphan nuclear receptor gene in extraskeletal myxoid chondrosarcoma. 906 Aug 41

The selective induction of effector functions of a T-cell clone (DB14), specific to pigeon cytochrome c 43-58 (p 43-58) and restricted to I-Ab, was analyzed using a professional antigen-presenting cell, B hybridoma (Th 2.58), and various non-professional antigen-presenting cells (APC), L cells transfected with I-Ab (I-Ab L cells), a medullary thymic epithelial cell line (m-TEC) and a cortical thymic epithelial cell line (c-TEC). The m-TEC, and c-TEC expressed I-Ab upon induction with interferon gamma (IFN-gamma). When stimulated with p 43-58 in the presence of I-Ab L cells as well as Th 2.58 cells, the DB14 cells showed marked proliferation and, after 18 hr of culturing, exhibited significant cytotoxicity against the APC. By contrast, in the presence of m, c-TEC, the DB14 cells showed neither proliferation nor cytotoxicity against these TEC but exhibited considerable detachment activity towards them. Furthermore, DB14 cells became expressed activation markers CD69 or CD44) following stimulation with p 43-58 plus m-TEC or c-TEC. The addition of rIL-2 to the culture of DC14 cells, p 43-58 and m-TEC or c-TEC, restored the proliferative responses. However, it was shown that anergy was not involved in the negligible proliferative responses of DB14 cells after stimulation with p 43-58 plus m, c-TEC. The present findings indicate that differences in APC functions are present among the non-professional APC and suggest that the selective induction of T-cell functions can be achieved using the appropriate non-professional APC. The characteristic activation of T cells by TEC may be related to their functional roles in situ.
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PMID:Detachment activity but not cytotoxicity induced in a T-cell clone following antigen presentation in the presence of thymic epithelial cells. 908 68

Angiogenesis plays a key role in tumor growth, progression and metastasis. The modulation of angiogenesis represents a potentially useful target for novel forms of anticancer therapy. Two such modulators are AGM-1470 (TNP-470, angioinhibin), which is a synthetic analog of the antibiotic fumagallin, and the monoclonal antibody TEC-11 to endoglin. We investigated the mechanisms of action of these modulators on human microvascular and macrovascular endothelial cells and on the transformed endothelial cell line ECV-304 in vitro. The administration of AGM-1470 or TEC-11 resulted in a significant inhibition of cell proliferation in all cell types used; this effect was reversible upon removal of these compounds from the culture medium. Furthermore, biochemical and morphological analyses showed that neither AGM-1470 or TEC-11 induce apoptosis. Both AGM-1470 and TEC-11 inhibited the production of urokinase-type plasminogen activator (u-PA), an enzyme involved in the early steps of neovascularization. Finally, the incubation of endothelial cells with both AGM-1470 and TEC-11 did not produce an additive effect on growth cell inhibition, apoptosis or u-PA production. Since both AGM 1470 and TEC-11 inhibit crucial events such as endothelial cell growth and protease production, our results provide a basis for their therapeutic use as angiostatic molecules in cancer.
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PMID:In vitro inhibition of endothelial cell growth by the antiangiogenic drug AGM-1470 (TNP-470) and the anti-endoglin antibody TEC-11. 909 28

The fate of orally administered total 14C-labelled Escherichia coli extract (TEC, OM-89) was compared to that of its major 14C-labeled high molecular weight fractions (HEC, > 30 kD) in mice. High molecular weight substances (> 30 kD) were observed in blood 1 h after oral administration of the products, TEC and HEC. This suggests absorption from the digestive tract of the total E. coli extract. Blood clearance after 24 h indicates that the product was rapidly eliminated or taken up by the tissues. Its highest organ distribution among the measured organs was found in the liver, followed by the spleen and the Peyer's patches. Low molecular weight fractions (LEC, < 30 kD) were also used as control. This pilot study provides a rationale for in vivo pharmacological investigations with oral administration of the E. coli immunomodulating extract OM-89.
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PMID:Absorption kinetics of a 14C-labelled Escherichia coli extract after oral administration in mice. 910 54

Selective induction of effector functions in a T cell clone, DB14, specific for pigeon cytochrome c 43-58 (p43-58) and restricted to I Ab was analyzed using professional antigen presenting cells (APC), B hybridoma (Th2.58), and various non professional APC, L cells transfected with I Ab (I-Ab L cells), a medullary thymic epithelial cell line (m-TEC) and a cortical thymic epithelial cell line (c-TEC). The m-TEC and c-TEC (m, c-TEC) expressed I-Ab after culturing with interferon-gamma (IFN-gamma). When stimulated with p43-58 in the presence of I-Ab L cells as well as Th2.58 cells, the DB14 cells showed marked proliferation and exhibited significant cytotoxicity against these APC after 18 hr of culture. By contrast, in the presence of m, c-TEC the DB14 cells showed neither proliferation nor cytotoxicity against these TEC but exhibited considerable detachment activity against them. Furthermore DB14 cells became expressed activation markers (CD69 and CD44) after antigen (p43-58) stimulation with m-TEC or c-TEC. Addition of rIL-2 to the culture of DB14 cells, p43-58 and m, c-TEC restored the proliferative responses. However, it was shown that anergy was not involved in the lack of proliferative response of DB14 cells after antigen stimulation with m, c-TEC. The present findings indicate that differences in APC function are present among non-professional APC and suggest that the selective induction of T cell functions can be achieved using appropriate non-professional APC. The characteristic activation of T cells by TEC may be related to their functional roles in situ.
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PMID:[Selective induction of effector functions in a T cell clone following antigen presentation in the presence of thymic epithelial cells]. 914 12

Germ cells were isolated from rabbit fetal gonads between 18 and 22 days post coitum and examined morphologically, ultrastructurally and for immunocytochemical and cytochemical characteristics. Observations were compared with the information available from the corresponding cells of other mammalian species. The general morphology and ultrastructure of healthy isolated rabbit fetal germ cells were found to be very similar to those of the rabbit and mouse diploid germ cells in situ. Moreover, rabbit fetal germ cells shared common immunocytochemical characteristics with mouse undifferentiated embryonic stem cells or embryonic carcinoma cells, such as the presence of TEC-1 (SSEA-1) antigens, a peripheral network of F-actin, the absence of cytokeratins 8/18 and lamins A/C and an alkaline phosphatase activity. No difference between the sexes was observed. Morphological and physiological similarities with the migrating and cultured primordial germ cells of the mouse also suggest that diploid rabbit germ cells would be good candidates for deriving pluripotential embryonic germ cells (EG cells) if favourable culture conditions could be found. In conclusion, the rabbit may be a suitable model for investigations on EG cells in domestic mammals with delayed meiosis.
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PMID:Ultrastructural and immunocytochemical analysis of diploid germ cells isolated from fetal rabbit gonads. 922 45

Angiography in a 37 year old female with a three week history of typical crescendo angina found an 80% stenosis of the proximal left anterior descending (LAD) artery. The patient underwent percutaneous transluminal coronary angioplasty involving TEC artherectomy of the LAD artery. The specimen removed by atherectomy was found to have the appearance of papillary endothelial hyperplasia. This is an unusual histological diagnosis that occurs in association with thrombus. It is rarely found within arterial vessels and has not been reported in a coronary artery. Papillary endothelial hyperplasia is now thought to be a form of organising thrombus, probably dependent on the production of basic fibroblast growth factor by the endothelium.
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PMID:Papillary endothelial hyperplasia in a TEC coronary atherectomy specimen. 922 5


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