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)

Transluminal coronary extraction-endarterectomy is an alternative interventional approach for treatment of coronary artery disease. The atherectomy system consists of a catheter assembly including a cutter and torque tube which is rotated at a relatively low rate of 750 rotations per minute, when introduced to the coronary artery over a guide-wire via a guiding catheter. Excised tissue is withdrawn from the coronary artery by suction applied through the catheter by means of an attached vacuum bottle. We report acute results in 18 patients and the clinical outcome of 14 patients who up to now underwent angiographic follow-up catheterization after 6 months. Initial angiographic success (residual stenosis less than 50%) using TEC-atherectomy alone was obtained in 6/18 patients (33%), 11/18 patients (60%) required additional PTCA in order to achieve primary success (9/18) or to treat total occlusion (2/18) after TEC-atherectomy. Major complications consisted in 1-vessel perforation with non-Q-wave-infarction but no need of surgical intervention and 2 occlusions due to dissection (treated with PTCA). 14 patients underwent angiographic follow-up (6 months) and restenosis (greater than 50%) was confirmed in 7 patients (50%). Considering the low primary success rate of TEC-atherectomy alone and the tendency to high restenosis rate, we cannot recommend it as an alternative to conventional PTCA in general clinical practice. Further studies should be designed to directly compare TEC-atherectomy to PTCA in specific patient subgroups (e.g. bypass grafts, intraluminal thrombus, diffuse disease) in order to define the role of this interventional device.
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PMID:[Transluminal coronary extraction atherectomy. Method, acute results, angiographic and clinical follow-up]. 158 9

The fractional rate of cholesterol esterification in very low density lipoprotein- and low density lipoprotein-depleted plasma (FERHDL) was studied in normolipidemic subjects and in individuals with hyperlipidemia and proven coronary artery disease (CAD). The FERHDL was significantly higher than the FER in whole plasma and was significantly higher in normal men than in normal women. In addition, men and women with primary hyperlipidemia had significantly higher FERHDL values relative to their sex-matched controls. The most significant increases in FERHDL values, however, were observed in individuals with CAD. In all patient groups, FERHDL was positively correlated with plasma triglyceride concentration. In addition, FERHDL was negatively related to plasma high density lipoprotein (HDL) cholesterol concentration in all groups except in men with CAD and in normolipidemic women. The gradient gel electrophoretic pattern of HDL from individuals with either low or high FERHDL values indicated an inverse relation between this activity and the relative amount of HDL2b particles. FERHDL likely reflects the metabolic properties of the heterogeneous population of HDL particles in the plasma and may be a function of the relative content of larger and smaller HDL particles. It appears to be a sensitive and reliable functional measure of the particle size distribution in the HDL pool and one of potential clinical value in the assessment of risk for CAD.
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PMID:Cholesterol esterification rates in very low density lipoprotein- and low density lipoprotein-depleted plasma. Relation to high density lipoprotein subspecies, sex, hyperlipidemia, and coronary artery disease. 198 5

The present study was planned to investigate whether the sum of ST segment depression in 12-lead electrocardiogram (sigma STD) in relation to change in heart rate (delta HR) during exercise, sigma STD/delta HR index, could be utilized to predict the extent of underlying coronary artery disease. Two hundred and twenty-six consecutive patients were included in this study, 191 men and 35 women, aged 28-74 years (mean 56). Patients were classified into two groups. Group I consisted of 165 patients with either no coronary disease, single or double vessel disease. Group II included 61 patients with triple vessel or left main stem stenosis. It was found that the sigma STD/delta HR index at 25 mm. beat-1 X min. 10(2) provided the best separation between Groups I and II patients. All but 3 of the 61 patients in Group II had a sigma STD/delta HR index greater than 25. In contrast, all but 4 of the 165 patients in Group I had an index less than 25. The sensitivity, specificity and positive predictive value in the identification of Group II patients by using the index were 95%, 98% and 94% respectively. Utilization of ST segment depression of greater than or equal to 2 mm in a VF alone as a test criterion for the recognition of Group II patients had a low sensitivity (41%), specificity (88%) and positive predictive value (56%).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The value of sum of ST segment depression in 12-lead electrocardiogram in relation to change in heart rate during exercise to predict the extent of coronary artery disease. 363 21

Diabetes mellitus is a major cause of ischemic coronary artery disease. Endothelial dysfunction is implicated in the pathogenesis of diabetic vascular disease. To examine coronary blood flow (CBF) regulation with endothelium-derived nitric oxide (EDNO) in the diabetic state, we compared the effects of both acetylcholine (ACh) and adenosine (Ado) on left circumflex coronary artery (LCX) blood flow in 12 vehicle-treated and 21 dogs made diabetic with alloxan anesthetized with pentobarbital. All dogs were pretreated with aspirin to inhibit endogenous prostaglandins. None of the hemodynamic parameters were significantly different in the two groups. The percent change in coronary vascular resistance (CVR) after ACh (100 ng/kg) infusion was significantly attenuated in diabetic dogs (-56.5 +/- 1.4%) as compared with vehicle-treated dogs (-64.5 +/- 1.2%) (p < 0.01), whereas the effect of Ado (1 microgram/kg) was not different between the two groups (-71.1 +/- 1.5% in vehicle, -67.0 +/- 1.3% in diabetes). After infusion of incremental doses of NG-nitro-L-arginine methyl ester (L-NAME) 10(-5)-10(-3)M, the effect of ACh was progressively inhibited in both groups and was different no longer between the two groups after the maximal dose. L-Arginine (L-ARG), but not D-ARG, significantly restored the effect of ACh in diabetic dogs but did not affect vehicle-treated dogs. The effect of Ado did not change after L- and D-ARG administration. Cu, Zn-superoxide dismutase (Cu, Zn-SOD) had no effect on any of the effects of ACh and Ado in diabetic dogs. Regulation of CBF with EDNO is impaired in dogs with alloxan-induced diabetes, and this impairment is partially restored by L-ARG.
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PMID:Impairment of coronary blood flow regulation by endothelium-derived nitric oxide in dogs with alloxan-induced diabetes. 879 37

The endothelial EDRF/NO-mediated relaxing mechanism is impaired in atherosclerotic and in hypertensive arteries. Recently, it was suggested that primary pulmonary hypertension might be another disease in which the endothelial EDRF/NO pathway is disturbed. We tested the hypothesis that intravenous administration of L-arginine (L-ARG), the physiological precursor of EDRF/NO, stimulates the production of NO, subsequently increasing plasma cGMP levels and reducing systemic and/or pulmonary blood pressure, in patients with coronary artery disease (CAD, n = 16) or with primary pulmonary hypertension (PPH, n = 5). L-ARG (30 g, 150 ml, 15 min) or placebo (150 ml NaCl) was infused in CAD patients, and L-ARG was infused in PPH patients during cardiac catheterization. Mean aortic (Pao) and pulmonary (PAPmean) arterial pressures were continuously monitored. Cardiac output (CO, by thermodilution), total peripheral resistance (TPR), and pulmonary vascular resistance (PVR) were measured before and during the infusions. In CAD patients Pao decreased from 87.2 +/- 4.9 to 81.8 +/- 5.1 mmHg during L-ARG (p < 0.05), whereas PAPmean and PVR were unchanged. TPR decreased from 1008.9 +/- 87.9 to 845.0 +/- 81.7 dyne x sec x cm-5 during L-ARG administration (p < 0.01). CO significantly increased during L-ARG (from 7.3 +/- 2.8 to 8.1 +/- 0.9 l/min, p < 0.05). Placebo did not significantly influence any of the hemodynamic parameters. Plasma cGMP (determined by RIA) slightly increased by 12.2 +/- 9.6% during L-ARG, but slightly decreased during placebo (-12.3 +/- 9.2%) (p < 0.05 for L-ARG vs. placebo). In PPH patients, L-ARG induced no significant change in Pao, TPR, and CO, PAPmean was 59.4 +/- 8.5 mmHg at the beginning of the study and was not significantly reduced by L-ARG nor was PVR (basal: 1042.4 +/- 211.4 dyne x sec x cm-5) changed by L-ARG. Plasma cGMP was not significantly affected by L-ARG in these patients. We conclude that L-ARG stimulates NO production and induces vasorelaxation in CAD patients but not in patients with primary pulmonary hypertension.
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PMID:Differential systemic and pulmonary hemodynamic effects of L-arginine in patients with coronary artery disease or primary pulmonary hypertension. 886 93

Small low density lipoprotein (LDL) particles are thought to be more atherogenic than larger LDL particles, although this association may depend on plasma triglyceride (TG) and high density lipoprotein (HDL) levels. To help prevent coronary artery disease (CAD), it may be useful to understand risk factors during childhood and adolescence. In the present study, we evaluated low density lipoprotein particle size (LDL-size) by 2-16% gradient gel electrophoresis in 70 healthy children (30 boys and 40 girls) along with conventional lipid and lipoprotein parameters which are thought to affect LDL-size. The fractional and molar esterification rates (FER and MER) of cholesterol in plasma and HDL were also determined. As expected, plasma levels of TG, HDL-cholesterol (HDL-C) and apoA-I were closely associated with LDL-sizes in both sexes (boys: r = -0.694, 0.708 and 0.701, girls: r = -0.579, 0.551 and 0.539, P < 0.001). However, a closer association was found between FER in HDL (FER(HDL)) and LDL-size (boys: r= -0.874, girls: r= -0.642, P < 0.001). In a stepwise multiple regression analysis, FER(HDL) alone accounted for 76% and 41% of the variability in LDL-size in boys and girls, respectively. MER in HDL accounted for additional 4% and 19% in boys and girls, respectively. Other parameters, including plasma TG, HDL-C and apoA-I had no significant additional effects. Thus, the determination of FER(HDL) is useful to predict the particle size of LDL in children.
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PMID:Fractional esterification rate of cholesterol in high density lipoprotein is correlated with low density lipoprotein particle size in children. 903 8

A number of studies have suggested that type of dialysis membrane is associated with differences in long-term outcome of patients undergoing hemodialysis, both in terms of morbidity and mortality. The purpose of this study was to determine the relationship of membrane type and specific causes of death. Data from the United States Renal Data System Case Mix Adequacy Study, a national random sample of hemodialysis patients who were alive on December 31, 1990, were used. Our study was limited to patients in this data set who were undergoing dialysis for at least 1 year (n = 4,055). For the main analytic models, membrane type was classified into two categories: unmodified cellulose or MC/SYN (which combines modified cellulose [MC] and synthetic membranes [SYN]). The relationships of membrane type and major causes of mortality were analyzed using Cox proportional hazards models, which adjusted for multiple (21) covariates, including demographics, comorbidity, Kt/V, and other parameters. Patients were censored at transplantation or 60 days after a switch to peritoneal dialysis. Compared with patients dialyzed with unmodified cellulose membranes, the adjusted relative mortality risk (RR) from infection was 31% lower (RR = 0.69; P = 0.03) and from coronary artery disease was 26% lower (RR = 0.74; P = 0.07) for patients dialyzed with MC/SYN membranes. No statistically significant difference (all P > 0.1) was found in mortality risk from cerebrovascular disease (RR = 1.08), other cardiac causes (RR = 0.86), malignancy (RR = 0.90), or other known causes (RR = 0.82) between patients dialyzed with MC/SYN compared with unmodified cellulose membranes. These results offer support to reported experimental and observational clinical studies that have found that unmodified cellulose membranes may increase the risk for both infection and atherogenesis. Further studies are necessary to evaluate the possibility of confounding factors, compare more specific membrane types, and determine the pathophysiology linking membrane type to cause-specific mortality.
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PMID:Relationship of dialysis membrane and cause-specific mortality. 991 61

Many risk factors for coronary artery disease (CAD) have been established by large epidemiological studies. However, some patients without the major risk factors still develop disease. Preliminary analysis of individuals referred for angiography, who had no major risk factors associated with CAD, indicated that apolipoprotein-AI (apoAI) was significantly lower in patients with positive angiograms. The hypothesis that apoAI was an independent risk factor for CAD in low risk populations was put forth. One thousand and seventy-five consecutive patients underwent angiography, lipid analysis, and completed a risk factor questionnaire. Individuals with total cholesterol<5.2 mmol/l, high density lipoprotein (HDL)-cholesterol>0.9 mmol/l, systolic blood pressure<140 mmHg and diastolic blood pressure<90 mmHg, no diabetes, and no family history of premature CAD in first degree relatives were selected. Fifty-four patients met these selection criteria, 29 having positive evidence of CAD and 25 with no evidence of disease. Multivariate analysis revealed that, after adjusting for age and gender, serum apoAI level was the only variable predictive of CAD. This effect was independent of HDL cholesterol level and fractional esterification rate of HDL (FER(HDL)). These results point to an important role for apoAI in the atherogenic process, particularly in populations with no major CAD risk factors. Decreased levels of apoAI or LpAI may initiate atherosclerosis in a highly selected group of low risk patients.
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PMID:Coronary artery disease in patients at low risk--apolipoprotein AI as an independent risk factor. 1122 38

In this study we compared several parameters characterizing differences in the lipoprotein profile between members of families with a positive or negative family history of coronary artery disease (CAD). In addition to regular parameters such as the body mass index (BMI), total plasma cholesterol (TC), low density (LDL-C) and high density (HDL-C) cholesterol and triglycerides (TG) we estimated the fractional esterification rate of cholesterol in apoB lipoprotein-depleted plasma (FER(HDL)) which reflects HDL and LDL particle size distribution. A prevalence of smaller particles for the atherogenic profile of plasma lipoproteins is typical. Log (TG/HDL-C) as a newly established atherogenic index of plasma (AIP) was calculated and correlated with other parameters. The cohort in the study consisted of 29 young (< 54 years old) male survivors of myocardial infarction (MI), their spouses and at least one offspring (MI group; n=116). The control group consisted of 29 apparently healthy men with no family history of premature CAD in three generations, their spouses and at least one offspring (control group; n=124). MI families had significantly higher BMI than the controls, with the exception of spouses. Plasma TC did not significantly differ between MI and the controls. MI spouses had significantly higher TG. Higher LDL-C had MI survivors only, while lower HDL-C had both MI survivors and their spouses compared to the controls. FER(HDL) was significantly higher in all the MI subgroups (probands 25.85+/-1.22, spouses 21.55+/-2.05, their daughters 16.93+/-1.18 and sons 19.05+/-1.33 %/h) compared to their respective controls (men 20.80+/-1.52, spouses 14.70+/-0.98, daughters 13.23+/-0.74, sons 15.7+/-0.76 %/h, p<0.01 to p<0.05). Log(TG/HDL-C) ranged from negative values in control subjects to positive values in MI probands. High correlation between FER(HDL) and Log (TG/HDL-C) (r=0.80, p<0.0001) confirmed close interactions among TG, HDL-C and cholesterol esterification rate. The finding of significantly higher values of FER(HDL) and Log (TG/HDL-C) indicate higher incidence of atherogenic lipoprotein phenotype in members of MI families. The possibility that, in addition to genetic factors, a shared environment likely contributes to the familial aggregation of CAD risk factors is supported by a significant correlation of the FER(HDL) values within spousal pairs (control pairs: r=0.51 p<0.01, MI pairs: r=0.41 p<0.05).
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PMID:Atherogenic lipoprotein profile in families with and without history of early myocardial infarction. 1130 Feb 20

We sought to determine the associations among thoracic aortic atherosclerosis, coronary atherosclerosis and the function of high density lipoprotein (HDL) in a case-control study. The function of HDL can be assessed by the fractional esterification rate of cholesterol in low density lipoprotein (LDL)- and very low density lipoprotein (VLDL)-depleted plasma (FER(HDL)), which reflects a balance of cholesterol uptake by HDL and cholesterol ester (CE) transport in the reverse cholesterol transport (RCT) system in humans. Cases (n=51, age: 64.3+/-8.0 years) and controls (n=51, age: 58.7+/-13.1 years) were defined as subjects with/without angiographically proven coronary artery disease (CAD), respectively and examined for thoracic aortic atherosclerosis (TAA) by transesophageal echocardiography. The severity of TAA was determined by the ratio of average sclerotic areas (ASA) and average sclerotic lengths (ASL). The cases had significantly (P<0.05) higher values of ASA (0.22+/-0.18 vs. 0.10+/-0.11), ASL (0.82+/-0.56 vs. 0.48+/-0.45), ASA/ASL ratio (0.23+/-0.08 vs. 0.17+/-0.09) and FER(HDL) (10.3+/-3.8 vs. 8.3+/-3.5% per hour) and lower HDL-C and apolipoprotein A-I levels than the controls. A receiver operating characteristic (ROC) curve analysis showed that ASA/ASL and FER(HDL) had moderate discriminating ability for CAD and the diagnostic accuracy of ASA/ASL was better than that of FER(HDL) (area under ROC curve: 0.703 and 0.656, respectively). Multivariate logistic regression analysis indicated that ASA/ASL and FER(HDL) were independent indicators for CAD [odds ratio (95% CI): 7.5 (2.4-27), P<0.01 and 4.0 (1.2-15), P<0.05] after adjusting for age, gender and other conventional risk factors, and that a high FER(HDL) value greatly increased the relative risk of CAD associated with a high ASA/ASL. The function of HDL, as assessed by FER(HDL), enhances the ability of TAA to predict CAD.
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PMID:The associations among thoracic aortic atherosclerosis, coronary atherosclerosis and the function of high density lipoprotein. 1173 Aug 21


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