Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.10.2 (focal adhesion kinase)
 44,029 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Lymphocyte subpopulations analysis by an 11-monoclonal antibody (MoAb) panel was carried out in pleural fluid and in peripheral blood in 30 patients affected by newly diagnosed, untreated pleural effusion of different etiology determinated with bacteriological, cytological or histological criteria. Lymphocytes were the predominant cell type, in pleural fluid, in neoplastic pleural effusions as well as in congestive heart failure pleural effusions and, especially, in tuberculous pleural effusions. Lymphocyte analysis in pleural fluid and in peripheral blood suggests the involvement of different mechanisms for the lymphocyte accumulation in the pleural space according to different etiologies. Tuberculous pleural effusions showed an evident CD4+ and TEC T5.9+ lymphocyte accumulation from peripheral blood. In these patients, cutaneous skin test response to purified protein derivative was strongly related to this situation. In neoplastic pleural effusions there was a lower percentage of CD4+ lymphocytes, reflecting circulating lymphocyte pool; however, in neoplastic pleural effusions, various lymphocyte patterns may be sometimes observed depending on different histologies. Passive lymphocyte accumulation seems to be the most important mechanism in congestive-heart-failure pleural effusions.
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PMID:Lymphocyte subpopulations analysis in pleural fluid and peripheral blood in patients with lymphocytic pleural effusions. 167 76

The interaction between felodipine and digoxin was studied after a single oral dose and at steady state in 14 patients with congestive heart failure. Felodipine (10 mg) was randomly given as an extended release (FER) tablet in a double-blind, placebo-controlled, cross-over fashion. In addition, felodipine (10 mg) was given openly as a plain tablet, following the double-blind period. Each period lasted for 7 d. Felodipine ER did not alter the pharmacokinetics of digoxin when given as a single dose or at steady state compared with placebo. At steady state the felodipine plain tablet resulted in an 11% increase (P less than 0.05) in peak plasma concentrations of digoxin. Systolic time intervals as noninvasively measured haemodynamic parameters were not significantly altered following the felodipine ER period, while the felodipine plain tablet significantly decreased the pre-ejection/left ventricular ejection time ratio compared to placebo.
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PMID:Effects of felodipine on plasma digoxin levels and haemodynamics in patients with heart failure. 265 2

In this review, the role of tyrosine kinases in angiotensin II-mediated signal transduction pathways in vascular smooth muscle is discussed. Angiotensin II was isolated by virtue of its vasoconstrictor abilities and has long been thought to play a critical role in hypertension. However, recent studies indicate important roles for angiotensin II in inflammation, atherosclerosis, and congestive heart failure. The expanding role of angiotensin II indicates that multiple signal transduction pathways are likely to be activated in a tissue-specific manner. Exciting recent data show that angiotensin II directly stimulates tyrosine kinases, including pp60(c-src) kinase (c-Src), focal adhesion kinase (FAK), and Janus kinases (JAK2 and TYK2). Angiotensin II may activate receptor tyrosine kinases, such as Axl and platelet-derived growth factor, by as-yet-undefined autocrine mechanisms. Finally, unknown tyrosine kinases may mediate tyrosine phosphorylation of Shc, Raf, and phospholipase C-gamma after angiotensin II stimulation. These angiotensin II-regulated tyrosine kinases appear to be required for angiotensin II effects, such as vasoconstriction, proto-oncogene expression, and protein synthesis, on the basis of studies with tyrosine kinase inhibitors. Thus, understanding angiotensin II-stimulated signaling events, especially those related to tyrosine kinase activity, may form the basis for the development of new therapies for cardiovascular diseases.
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PMID:Angiotensin II signal transduction in vascular smooth muscle: role of tyrosine kinases. 913 Apr 41

Originally known to be a vasoconstrictor and thought to play a critical role in hypertension, angiotensin II has recently emerged to be important in inflammation, atherosclerosis and congestive heart failure. The expanding role of angiotensin II implies that multiple signal transduction pathways are likely to be activated in a tissue-specific manner. Recent data show that angiotensin II stimulates not only cytoplasmic tyrosine kinases including c-Src, focal adhesion kinase (FAK), and Janus kinases (JAK2 and TYK2), but also may transactivate receptor tyrosine kinases such as Axl and PDGF by as yet undefined autocrine/paracrine mechanisms. Finally, tyrosine kinases, which mediate tyrosine phosphorylation of key signal mediators such as Shc, Raf, and phospholipase C-gamma following angiotensin II stimulation, remain to be defined. These tyrosine kinases, activated by angiotensin II, appear to be required for angiotensin II effects such as vasoconstriction, proto-oncogene expression, protein synthesis, and cell proliferation. Thus, it is important to understand angiotensin II-mediated signaling events, especially those related to tyrosine kinase activity, to develop new therapies for cardiovascular diseases.
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PMID:Angiotensin II signal transduction in vascular smooth muscle cells: role of tyrosine kinases. 921 88

In this review, the signal events regulated by angiotensin II (AngII) in vascular smooth muscle are analyzed based on activation of specific tyrosine kinases. AngII has been shown to play a critical role in the pathogenesis of hypertension, inflammation, atherosclerosis, and congestive heart failure. The expanding role of AngII indicates that multiple signal transduction pathways are likely to be activated in a tissue-specific manner. Although at least three AngII receptors have been characterized, it seems that the AngII type I receptor (AT1R) is physiologically most important since pharmacologic inhibitors of the AT1R block most AngII signal events and have beneficial effects on cardiovascular disease. The AT1R is a seven transmembrane-spanning G protein-coupled receptor that regulates intracellular signal events by activation of Gq and Gi. However, many recent data indicate that activation of tyrosine kinases by several different mechanisms contributes to AngII effects in target tissues. Tyrosine kinases activated by AngII include c-Src, focal adhesion kinase (FAK), Pyk2 (CADTK), Janus kinases (JAK2 and TYK2), and the receptor tyrosine kinases Ax1, epidermal growth factor, and platelet-derived growth factor. Finally, unknown tyrosine kinases may mediate tyrosine phosphorylation of paxillin, Shc, Raf, and phospholipase C-gamma after AngII stimulation. These AngII-regulated tyrosine kinases seem to be required for AngII effects such as vasoconstriction, proto-oncogene expression, and protein synthesis based on studies with tyrosine kinase inhibitors. Thus, understanding AngII-stimulated signaling events, especially those related to tyrosine kinase activity, may form the basis for the development of new therapies for cardiovascular diseases.
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PMID:Angiotensin II signal transduction in vascular smooth muscle: pathways activated by specific tyrosine kinases. 989 42

Apoptosis of cardiac myocytes is thought to be a feature of many pathological disorders, including congestive heart failure (CHF) and ischemic heart disease (IHD). Because recent investigations indicate that endothelin-1 (ET-1) plays an important role in CHF and IHD, we investigated the effect of ET-1 on cardiomyocyte apoptosis. The presence of apoptosis in rat cardiomyocytes (H9c2 and neonatal) was evaluated by morphological criteria, electrophoresis of DNA fragments, 4',6'-diamidine-2'-phenylindole staining, and TUNEL analysis. ET-1, but not angiotensin II, prevented apoptosis induced by serum deprivation via ETA receptors in a dose-dependent manner (1 to 100 nmol/L). ET-1 also prevented cytochrome c release from mitochondria to the cytosol. The use of specific pharmacological inhibitors demonstrated that the antiapoptotic effect of ET-1 was mediated through a tyrosine kinase pathway (genistein and AG490) but not through protein kinase C (PKC; calphostin C), mitogen-activated protein kinases (PD98059 and SB203580), or PKA (KT5270) pathways. Adenovirus-mediated gene transfer of kinase-inactive (KI) c-Src reversed the antiapoptotic effect of ET-1. We further investigated whether Bcl-xL, an antiapoptotic molecule, would be upregulated by using a luciferase-based reporter system. ET-1 upregulated Bcl-xL, and this upregulation was inhibited by genistein or AG490 but not by calphostin C. The experiments with KI mutants for various tyrosine kinases revealed that c-Src and Pyk2 (but not JAK1, Jak2, Syk, and Tec) are involved in ET-1-induced upregulation of Bcl-xL expression. These findings suggest that ET-1 prevents apoptosis in cardiac myocytes through the ETA receptor and the subsequent c-Src/Bcl-xL-dependent pathway.
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PMID:Antiapoptotic effect of endothelin-1 in rat cardiomyocytes in vitro. 1266 84

The rising costs of the Swiss health care system are currently a source of discussion. Precise facts about the treatment costs in Switzerland are not available. The aim of this paper is to assess the price of the acute therapy of multiple trauma patients at the University Hospital of Zurich. We analysed the exact treatment costs of 16 patients with an average Injury Severity Score (ISS) of 33.9. All these cases had a private or a supplementary insurance coverage, were foreigners or were otherwise invoiced according to the so-called hospital tariff (Spitalleistungskatalog/SLK). We developed a concept to measure the expenditure not covered by the insurance of those with a basic insurance, who entail the largest percent of all hospitalized patients. The average amount invoiced was 128,135 Swiss Francs (31,266-310,358 CHF). After subtracting the profit, gained on cases charged according to the SLK, the remaining deficit per ordinary insured was 42-65% or 33,703-138,829 CHF The range of this amount depends on the insurance status of the afflicted person. If hospitals are required to work with a balanced budget, then these losses can no longer be neglected. New forms of invoicing multiply trauma patients must be found in Switzerland.
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PMID:[Cost analysis of acute therapy of polytrauma patients]. 1472 95

We investigated application of the OS-EM method to the (123)I-IMP ARG method to measure regional cerebral blood flow (rCBF). First, scan time and subsets were fixed at 20 min and 16, respectively, and the influence of iteration on the CCF and quantitative rCBF values obtained by the ARG method was investigated when the iteration number was set at 2, 4, 8, 16, 32, and 90. Next, with the number of iterations set at 4, we compared the scanning times of OS-EM and FBP. We determined that the CCF values remained at the same level irrespective of iteration number. Quantitative rCBF values had no association with iteration number, either. Using the quantitative rCBF values obtained by 20-min. scanning with FBP as a standard, the time period for collecting SPECT data was 10 min, without sacrificing image quality or quantification. Quantitative rCBF obtained by OS-EM was estimated to be higher than that by FBP.
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PMID:[Application of the OS-EM method to the 123I-IMP ARG method: comparison between FBP and OS-EM methods]. 1521 2

The renin-angiotensin system is a central component of the physiological and pathological responses of cardiovascular system. Its primary effector hormone, angiotensin II (ANG II), not only mediates immediate physiological effects of vasoconstriction and blood pressure regulation, but is also implicated in inflammation, endothelial dysfunction, atherosclerosis, hypertension, and congestive heart failure. The myriad effects of ANG II depend on time (acute vs. chronic) and on the cells/tissues upon which it acts. In addition to inducing G protein- and non-G protein-related signaling pathways, ANG II, via AT(1) receptors, carries out its functions via MAP kinases (ERK 1/2, JNK, p38MAPK), receptor tyrosine kinases [PDGF, EGFR, insulin receptor], and nonreceptor tyrosine kinases [Src, JAK/STAT, focal adhesion kinase (FAK)]. AT(1)R-mediated NAD(P)H oxidase activation leads to generation of reactive oxygen species, widely implicated in vascular inflammation and fibrosis. ANG II also promotes the association of scaffolding proteins, such as paxillin, talin, and p130Cas, leading to focal adhesion and extracellular matrix formation. These signaling cascades lead to contraction, smooth muscle cell growth, hypertrophy, and cell migration, events that contribute to normal vascular function, and to disease progression. This review focuses on the structure and function of AT(1) receptors and the major signaling mechanisms by which angiotensin influences cardiovascular physiology and pathology.
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PMID:Angiotensin II cell signaling: physiological and pathological effects in the cardiovascular system. 1687 Aug 27

One of the major manifestations of obesity is an increased production of the adipocyte-derived 16-kDa peptide leptin, which acts mainly on hypothalamic leptin receptors. Leptin receptors are widely distributed in various tissues, including the heart. Whereas increased plasma leptin levels have been reported in patients with congestive heart failure, systemic alterations induced by obesity can affect cardiac hypertrophy, and the direct effects of leptin on cardiac structure and function still remain to be determined. We first exposed primary cardiac myocytes from neonatal rats to leptin for 48 h. This resulted in a significant increase in myocyte long-axis length (P < 0.05 at 50 ng/ml) but not in the short-axis width. Leptin induced the rapid phosphorylation of STAT3 and its DNA binding in cardiac myocytes. Administration of a JAK2 inhibitor, AG-490, completely inhibited all of these effects by leptin. Furthermore, we examined the effect of continuous infusion of leptin for 4 wk following myocardial infarction in mice. Echocardiography demonstrated that left ventricular fractional shortening in the leptin-infused group (28.4 +/- 2.8%) was significantly higher than that in the PBS-infused group (18.4 +/- 2.2%) following myocardial infarction. Interestingly, left ventricular diastolic dimension in the leptin-infused group (4.56 +/- 0.12 mm) was also higher than that in the PBS-infused group (4.13 +/- 0.09 mm). These results demonstrate that leptin induces the elongation of cardiac myocytes via a JAK/STAT pathway and chronic leptin infusion causes eccentric dilatation with augmented systolic function after myocardial infarction.
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PMID:Leptin induces elongation of cardiac myocytes and causes eccentric left ventricular dilatation with compensation. 1722 Jan 91


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