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)

With the aid of a specific rabbit antibody preparation to purified monoclonal murine IgE, two plaque-forming cell (PFC) assays have been developed for the detection and enumeration of mouse IgE-secreting cells. The first assay, utilizing protein A-coated sheep red cells (protein A-SRC), detected antibody-secreting cells on the basis of the class of the secreted Ig irrespective of antigen specificity. With this assay, 30% of the class of the viable cells of two distinct IgE-secreting hybridoma cell lines were scored as PFC. Under these conditions, plaques were not obtained with IgG1 or IgG2a-secreting hybridoma cells. The second PFC assay, which utilized SRC coated with ovalbumin (OA-SRC), enumerated cells secreting anti-OA IgE antibodies. Similar kinetic patterns were observed for the cellular (IgE PFC/spleen) and humoral (IgE serum levels) responses of (C57BL/6 x DBA/2)F1 mice following immunization with 10 micrograms of OA adsorbed to 1 mg of A1(OH)3. Thus, it is concluded that the reverse plaque assay detecting all IgE-secreting cells, as well as the antigen-specific IgE PFC assay, can be used for the quantitation of IgE responses at the cellular level.
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PMID:The enumeration of mouse IgE-secreting cells using plaque-forming cell assays. 616 50

A panel of monoclonal rat antibodies binding to mouse mu heavy chain were tested for their ability to inhibit the formation of antigen-specific plaques in the hemolytic plaque assay. Nine antibodies inhibited SRC-specific direct IgM plaques at high concentrations (greater than 20 micrograms/ml). In contrast to all others, however, one antibody inhibited these plaques at much lower concentrations (down to 0.4 microgram/ml) when added to the assay. This antibody also inhibited plaques formed by cells secreting antibodies against trinitrophenyl or phosphorylcholine determinants. IgG plaques with any of the above specificities were not inhibited. IgM secretion was unaffected by the monoclonal anti-mu antibody. Its inhibitory effect on plaque formation rather appears to be a consequence of its ability to inhibit complement dependent, IgM mediated lysis of erythrocytes. This monoclonal anti-IgM antibody therefore provides a convenient reagent to distinguish specific direct IgM plaques from indirect IgG plaques.
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PMID:A monoclonal antibody with specificity for murine mu heavy chain which inhibits the formation of antigen-specific direct IgM plaques. 618 65

Absorption of 14C-labelled poliovirus-2 to sedimentable solids of primary sludge samples collected from a secondary treatment facility during a 6-month period averaged 94%; for anaerobically digested sludge, 99%. The extent of virus adsorption was influenced by the amount of solids. Maximal adsorption occurred at or above 0.5% solids with sludge diluted with deionized water and above 1.5% solids when diluted with the respective particle-free sludge supernatants. A Tris-HCl buffer containing NaCl, glycerol, and serum was found to efficiently elute poliovirus-2 from primary sludge solids. By means of re-extraction and concentration by centrifugation (the TEC procedure), the average recoveries of poliovirus-2 were 92-94% based upon either infectivity or radioactivity analyses. Similarly, recoveries were 90-92% for poliovirus-2 in digested sludge. Maximum elution was dependent upon all four TEC buffer components and the restriction of solids to less than or equal to 1.0%. The procedure was found to be more efficient than glycine-NaOH and Freon procedures or elution with beef embryo extract. As adapted for effluents the procedure increased the yield and improved the consistency of virus recovery. The arithmetic mean titers and obtained during a monitoring study for primary and digested sludge were 4.2 X 10(5) and 5.1 X 10(3) plaque-forming units (pfu)/L; for primary, secondary, and final effluents 2.3 X 10(5), 4.7 X 10(3), and 4.7 X 10(2) pfu/L, respectively.
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PMID:A multiple extraction--centrifugation method for the recovery of viruses from waste water treatment plant effluents and sludges. 632 80

Fluorescein (FITC)-haptenated mouse spleen cells are capable of inducing a B cell immune response characterized by the production of antibodies directed against hapten-altered self structures. The induction of this response is thymus-independent and strictly dependent on the hapten concentration used for labeling the cells. Pretreatment of mice with immunogenic, labeled spleen cells strongly suppressed the plaque-forming cell response to a subsequent challenge with FITC-labeled spleen cells, sheep (SRC) or horse (HRC) red cells labeled with the same hapten and native FITC-dextran. Mice primed with lightly haptenated (nonimmunogenic) cells 7 days before challenge were completely unresponsive to the immunogenic dose of labeled cells and displayed a significantly reduced response to FITC-SRC or FITC-HRC. However, the response to FITC-dextran was enhanced, as compared to unprimed animals. The concept of immunogenic vs. nonimmunogenic requirements of an antigen to induce unresponsiveness, and the specificity of the B cell clones affected by suppression is discussed.
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PMID:Suppression of the immune response to altered self induced by immunogenic and nonimmunogenic altered self structures. 698 16

This article reviews many of the applications of intravascular ultrasonic imaging for coronary and peripheral arterial disease. In vitro studies demonstrate an excellent correlation between ultrasound measurements of lumen and plaque cross-sectional area compared with histologic sections. In vivo clinical studies reveal the enhanced diagnostic capabilities of this technology compared with angiography. Ultrasonic imaging also permits visualization of the atherosclerotic plaque itself for the first time in vivo. In addition to accurately describing the plaque morphology, ultrasonography can identify some of the tissue characteristics of the plaque. During interventional procedures, ultrasonic imaging has been shown to be beneficial for enhanced diagnosis as well as improvement of our understanding of the mechanism of newer interventional devices such as directed atherectomy, rotational or TEC atherectomy, or excimer laser. Initial studies suggest that ultrasound guidance of intravascular stent deployment may be critical for optimizing stent placement. Randomized studies are currently in progress to determine whether the guidance provided by intravascular ultrasonic imaging will alter the results of interventional procedures so that the restenosis rate can be improved.
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PMID:Lessons from intravascular ultrasonography: observations during interventional angioplasty procedures. 822 89

Alzheimer's disease (AD) is a devastating neurological disorder characterized by loss of cognitive skills and progressive dementia. The pathological hallmark of AD is the presence of numerous senile plaques throughout the hippocampus and cerebral cortex associated with degenerating axons, neurofibrillary tangles, and gliosis. The core of the senile plaque primarily is composed of the 39-43 amino acid beta-amyloid peptide (Abeta), which forms fibrils of beta-pleated sheets. Although considerable genetic evidence implicates Abeta in the pathogenesis of AD, a direct causal link remains to be established. Senile plaques are foci of local inflammatory processes, as evidenced by the presence of numerous activated microglia and acute phase proteins. Abeta has been shown to elicit inflammatory responses in microglia; however, the intracellular events mediating these effects are largely unknown. We report that exposure of microglia and THP1 monocytes to fibrillar Abeta led to time- and dose-dependent increases in protein tyrosine phosphorylation of a population of proteins similar to that elicited by classical immune stimuli such as immune complexes. The tyrosine kinases Lyn, Syk, and FAK were activated on exposure of microglia and THP1 monocytes to Abeta, resulting in the tyrosine kinase-dependent generation of superoxide radicals. The present data support a role for oxidative damage in the pathogenesis of AD, provide an important mechanistic link between Abeta and the generation of reactive oxygen intermediates, and identify molecular targets for therapeutic intervention in AD.
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PMID:Amyloid fibrils activate tyrosine kinase-dependent signaling and superoxide production in microglia. 906 90

Endothelial cell (EC) gap formation and barrier function are subject to dual regulation by (1) axial contractile forces, regulated by myosin light chain kinase activity, and (2) tethering forces, represented by cell-cell and cell-substratum adhesions. We examined whether focal adhesion plaque proteins (vinculin and talin) and focal adhesion kinase, p125FAK (FAK), represent target regulatory sites involved in thrombin-mediated EC barrier dysfunction. Histologically, thrombin produced dramatic rearrangement of EC actin, vinculin, and FAK in parallel with the evolution of gap formation and barrier dysfunction. Vinculin and talin were in vitro substrates for phosphorylation by EC PKC, a key effector enzyme involved in thrombin-induced EC barrier dysfunction. Although vinculin and talin were phosphorylated in situ under basal conditions in 32P-labeled EC, thrombin failed to alter the basal level of phosphorylation of these proteins. Phosphotyrosine immunoblotting showed that neither vinculin nor talin was significantly phosphorylated in situ on tyrosine residues in unstimulated ECs, and this was not further increased after thrombin. In contrast, both thrombin and the thrombin receptor-activating peptide (TRAP) produced an increase in FAK phosphotyrosine levels (corrected for immunoreactive FAK content) present in EC immunoprecipitates. Ionomycin, which produces EC barrier dysfunction in a myosin light chain kinase-independent manner, was used to increase intracellular Ca2+ and evaluate the Ca2+ sensitivity of this observation. In contrast to thrombin, ionomycin effected a dramatic decrease in the phosphotyrosine-to-immunoreactive FAK ratios, suggesting distinct effects of the two agents on FAK phosphorylation and function. These data indicate that modulation of cell tethering via phosphorylation of focal adhesion proteins is complex, agonist-specific, and may be a relevant mechanism of EC barrier dysfunction in permeability models that do not depend on an increase in myosin 20-kD regulatory light chain phosphorylation.
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PMID:Thrombin-mediated focal adhesion plaque reorganization in endothelium: role of protein phosphorylation. 937 19

Angiostatin, a fragment of plasminogen, has been identified and characterized as an endogenous inhibitor of neovascularization. We show that angiostatin treatment of endothelial cells in the absence of growth factors results in an increased apoptotic index whereas the proliferation index is unchanged. Angiostatin also inhibits migration and tube formation of endothelial cells. Angiostatin treatment has no effect on growth factor-induced signal transduction but leads to an RGD-independent induction of the kinase activity of focal adhesion kinase, suggesting that the biological effects of angiostatin relate to subversion of adhesion plaque formation in endothelial cells.
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PMID:Angiostatin induces endothelial cell apoptosis and activation of focal adhesion kinase independently of the integrin-binding motif RGD. 957 25

Several lines of evidence have demonstrated that IFNs could be relevant in the treatment of certain neoplastic diseases such as carcinomas. In particular, IFN-alpha, in addition to the anti-proliferative and cytostatic effects, was demonstrated to be capable of inducing cell death by apoptosis both in vivo and in vitro. Numerous protocols have also been proposed which consider the association of IFN-alpha with other drugs. Among these are retinoids, a class of compounds capable of inducing inhibition of cell growth and differentiation. We address the question here by analyzing the role of cell adhesion in susceptibility to IFN-alpha, RA and their combination of a human cell line derived from a squamous carcinoma of the cervix, the Bcl-2-negative SiHa cell line. In this context, cytoskeleton components and several surface molecules playing a role in cell substrate and cell-to-cell relationships have been evaluated. We found that RA treatment is capable of improving stress fiber formation, decreasing cell detachment and increasing cell-adhesion capability. However, no variations in the ability to adhere to specific extracellular-matrix molecules were found in RA-treated cells. No quantitative changes were detected in integrins involved as receptors for extracellular matrix molecules (VLAI-VLA5) or in other cell-adhesion-associated molecules (e.g., CD44). By contrast, 2 important molecules involved in cell-adhesion processes appeared to be up-regulated by RA exposure: focal adhesion kinase and E-cadherin, involved in adhesion plaque formation and cell-to-cell contacts, respectively. Keeping in mind the importance of adhesion properties in the cell-growth pathway, our findings could be of interest in the study of carcinoma-cell proliferation and metastatic potential.
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PMID:Antiproliferative activity of interferon alpha and retinoic acid in SiHa carcinoma cells: the role of cell adhesion. 959 Jan 30

Cellular interactions with the extracellular matrix determine to a large extent cell behavior, including cell migration. These interactions take place at specialized cellular structures, the focal adhesions, which have a substrate-specific morphology. To determine the molecular and functional relevance of this observation, the composition of isolated focal adhesions developed by fibroblasts adhering to fibronectin or laminin-1 was analyzed by indirect immunofluorescence and immunoblotting with or without stabilization of the structures by cross-linking. In the absence of cross-linking, integrins, talin, vinculin and, to a lower extent, paxillin remained associated with the focal adhesions formed on both substrates, indicating a tight association of these proteins with the extracellular matrix support. By contrast, alpha-actinin, FAK, and actin were apparently loosely maintained within focal adhesions and were found associated to these structures only after stabilization by cross-linking. Interestingly, although both substrates induced clustering and aggregation of all these proteins, their relative concentration, with the exception of alpha-actinin, was lower within the focal adhesions formed on laminin-1 than in those formed on fibronectin. Moreover, as assessed in migration assays, the locomotory speed of fibroblasts was higher on laminin-1 than on fibronectin. Altogether these results indicate that integrins involved in cellular interactions with fibronectin or laminin-1 trigger the formation of focal adhesion structures which differ by molecular organization, concentration in several adhesion plaque components, and function.
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PMID:Targeting of cytoskeletal linker proteins to focal adhesion complexes is reduced in fibroblasts adhering to laminin-1 when compared to fibronectin. 1022 34


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