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)

The traditional evaluation of the endothelium-derived nitric oxide (EDNO) pathway involves isolated aortic rings with attached strain gauges. This model is nonphysiologic and does not permit studies lasting longer than several hours. Our objective was to overcome the limitations of these "traditional" methods utilizing a physiologic, whole vessel model as a reproducible assay of EDNO. Canine carotid arteries (n = 4) were removed (maintaining in vivo arterial geometry), mounted in a specially designed, continuous-flow circuit, and perfused at 100 ml/min, 80 mm Hg with Medium-199/10% canine serum. Physiologic pH, pCO2, pO2, and temperature were precisely regulated. A non-contacting, helium-neon laser micrometer was interfaced with the current system to provide continuous measurement of vessel external diameter and to quantitate changes in vessel wall geometry in response to epinephrine (EPI; 2 x 10(-5) to 2 x 10(-3) mg/ml) and acetylcholine (ACh; 0.1 to 100 microM) challenge. Further characterization of the perfusion system included the use of a competitive inhibitor to EDNO production, NG-monomethyl-L-arginine (L-NMMA), and the effect of this compound on ACh-induced vasodilation. The reversibility of this blockade was verified via the sequential addition of L-arginine (L-ARG; 0 to 3 mM). Data are expressed as the ratio of steady-state vessel cross-sectional area (CSA) following administration of vasoactive substance to the CSA prior to vasoactive challenge. Our results indicate that EPI and ACh produced significant dose-dependent vasoconstrictive and vasodilatory responses, respectively (P less than 0.001, ANOVA).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Evaluation of endothelium-derived nitric oxide mediated vasodilation utilizing ex vivo perfusion of an intact vessel. 161 7

By comparing mouth-to-mouth ventilation to other methods, we tested whether there are significant differences among infant mannequin ventilation methods performed by emergency medical technicians-paramedics (EMT-Ps). Fifty-nine participants were evaluated in the performance of six ventilation methods; methods studied were mouth-to-mouth; two mouth-to-mask devices; and infant, pediatric, and adult bag-valve-mask devices. By measuring each breath, the percentage of acceptable ventilations in predetermined ranges, 5 to 25 mL/kg or 10 to 20 mL/kg, was calculated. Methods were compared using repeat measures ANOVA testing. Correlation between ventilation performance and the experience of personnel was expressed as the Pearson correlation coefficient. There were no significant differences in performance between methods, except for inadequate ventilation with the Laerdal Pocket Mask (P less than .05) from poor mask fit. The correlation between years of prehospital experience and the number of resuscitations versus ventilation performance was poor. Single rescuer, EMT-Ps can successfully ventilate an infant mannequin with various size resuscitation bags. The Laerdal Pocket Mask is an ineffective device for infant mannequin ventilation and should not be recommended for infant resuscitation.
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PMID:A comparison of infant ventilation methods performed by prehospital personnel. 272 84

To examine the effects of increased skin blood flow (BFsk) and skin temperature (Tsk) on bioelectric impedance (BIA), 30 young males participated as subjects. All subjects underwent the following measurements: 1) BFsk and Tsk for the chest, biceps, thigh, and calf; 2) body composition using the BIA prediction equations and underwater weighting (UW); and 3) triceps skinfold (SFtri) thickness. After the baseline studies (M1) the subjects exercised for 30 min at approximately 83% of maximal heart rate. The above measurements were repeated immediately after exercise (M2), and at 1-h recovery from exercise (M3). Repeated measures ANOVA showed that mean Tsk and BFsk, and for the four measured sites were significantly increased from M1 to M2 (P < 0.05) and decreased from M2 to M3 (P < 0.05). These changes did not affect BIA measurement for resistance (R) and reactance between M1 and M2 (P > 0.05), and between M2 and M3 (P > 0.05). With regression analysis the following independent variables were identified as strong contributing factors for predicting fat-free mass (FFM): 1) SFtri and total body water for M1 and M3; and 2) WT, SFtri, and Tsk of the chest for M2. Two FFM equations have little multicolinearity (M1 and M2), e.g., they have low root mean square errors (< or = 2.6 kg), very high values for R2 (> or = 0.94), and relatively low values for coefficient of variations (< or = 5.65%). Differences (P < 0.05) were observed between the UW method and the Lukasi equation for estimating FFM for M1 and M3, but not for M2.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of skin blood flow and temperature on bioelectric impedance after exercise. 828 9

Four Holstein steers (159 kg) surgically fitted with abomasal-infusion cannulas were used in a 4 x 4 Latin square study to test amino acid (AA) and casein (CAS) infusions on nitrogen balance and hormonal status of steers consuming vegetative wheat (Triticum aestivum L.) silage (12.3% CP). Treatments were 5-d infusions of 1) water (CONT), 2) arginine (ARG; 13.69 g/d), 3) limiting amino acids (LAA, 13.69 g/d arginine + 10.92 g/d histidine + 28.97 g/d lysine + 10.88 g/d methionine + 16.96 g/d threonine, and 4) Na-CAS (300 g/d). Whole blood was collected for plasma AA, growth hormone (GH), insulin, and IGF-I concentrations. Data were analyzed by ANOVA, and the following orthogonal contrasts were used to separate treatment means: CONT vs ARG; ARG vs LAA; and LAA vs CAS. Urinary N increased (P < .02) for CAS vs LAA. Arginine increased N retention, as did CAS, compared to LAA. Total plasma essential AA were decreased by arginine. Mean plasma insulin concentrations were increased by CAS (P < .034). Arginine increased mean plasma GH levels, but not IGF-I. The CAS treatment increased (P < .015) IGF-I levels, but not GH. These data suggest that performance of steers fed wheat silage was limited by duodenal AA flow and that arginine was the first-limiting AA. Casein infusion increased plasma insulin and IGF-I, which would explain the improved growth noted in calves and lambs fed forages supplemented with ruminally undegraded protein.
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PMID:Nitrogen metabolism and hormonal responses of steers fed wheat silage and infused with amino acids or casein. 937 20

Lectins or agglutinins are proteins with affinity for specific sugar residues. Peanut agglutinin (PNA) and the lectin from the edible mushroom (Agaricus bisporus, ABL) both bind to the disaccharide galactosyl beta-1,3-N-acetyl galactosamine alpha-. This is expressed in keratinocytes as an O-linked chain on CD44, a polymorphic membrane glycoprotein. Many lectins are mitogens and PNA is a mitogen for colonic epithelial cells. However, ABL reversibly inhibits proliferation of colonic cancer cell lines without cytotoxicity and thus has therapeutic potential in situations such as psoriasis where proliferation is increased. We have therefore investigated the effect of ABL on the growth of normal human cultured keratinocytes and a human papilloma virus (HPV)-transformed cell line. In a 5-day dose-response study, keratinocyte growth was greatly reduced by 1.0 microg/mL ABL and completely inhibited by 3.0 microg/mL ABL (ANOVA, P < 0.0001). Exposure to 1.0 microg/mL ABL for only 8 h gave the same growth inhibition as did continued exposure for 3 days. No cytotoxic or morphological changes were observed. An HPV-immortalized cell line was relatively resistant to ABL: in a 5-day dose-response study, exposure to 30 microg/mL was required to inhibit cell growth completely. Topical application of ABL 0.01% or 0.1% to normal human skin caused no change in skin erythema, blood flow or thickness compared with vehicle or baseline (n = 6). ABL 0. 1% in white soft paraffin was compared with vehicle in 11 psoriatic patients, using comparative contralateral plaques. Twice daily application for 2 weeks showed no significant difference from vehicle-treated sites, although the skin thickness of plaques fell from 5.3 +/- 0.4 (n = 11, mean +/- SEM) to 4.1 +/- 0.3 mm. In view of the in vitro results further studies are warranted, particularly if means can be found to improve the epidermal penetration of the relatively large ABL molecule (60 kDa).
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PMID:The antiproliferative effect of lectin from the edible mushroom (Agaricus bisporus) on human keratinocytes: preliminary studies on its use in psoriasis. 1021 68

The purpose of this study was to determine the relationship between educational level and time of decline to AIDS mortality. A total of 1578 death certificates were matched and processed with reported Louisiana male AIDS cases to assess the relation between decline to AIDS mortality with educational background, age, race, and transmission group. A 2 (race) x 4 (age group) x 2 (transmission group) x 3 (educational background) ANOVA was performed. In addition, descriptive statistics were utilized to show patterns of the association. A significant (P < 0.05) main effect of educational background on decline to death was found. However, inconsistent educational level effect on mortality was found across different subgroups regarding race and AIDS transmission group. Those with higher educational levels demonstrated least severity of decline to death. Furthermore, a significant 3-way interaction in the well-educated black intravenous drug user (IDU) population suggests a call to expand current models of counselling for this clientele.
Int J STD AIDS 1999 Mar
PMID:The relationship between educational background and decline to death in a sample of Louisiana male AIDS cases. 1034 Feb 1

The current study retrospectively examined the association between insulin resistance and plasma triglycerides (TG) in a group of subjects with normal glucose tolerance. Among 1,434 subjects consecutively undergoing a standard oral glucose tolerance test (OGTT) between 1993 and 1998, 567 (age, 15 to 78 years) were classified as having a normal glucose tolerance according to the 1999 World Health Organization (WHO) criteria and were selected for the study. Serum insulin was measured by radioimmunoassay (INSI-CTK, Dia Sorin, Saluggia, Italy). Intra-assay and interassay coefficients of variation for the method were less than 4% and less than 8.5%, respectively. Insulin resistance was calculated by a homeostasis model assessment (HOMA(IR) = fasting serum insulin [mU/mL] x fasting blood glucose [mmol/L]/22.5). A very significant correlation was found between HOMA(IR) and plasma TG (r = 0.27, P < 1.02E(-10)). Multiple regression analyses confirmed plasma TG as independent variables explicative of HOMA(IR). When subjects were evaluated according to tertiles of TG, those in the upper two tertiles were older (P <.001) and presented higher body mass index (BMI) values (P <.0001) in comparison to subjects in the lower tertile. A positive trend (analysis of variance [ANOVA]) was found in regard to systolic (P <.05) and diastolic blood pressure (P <.0001), fasting blood glucose (P <.01), fasting serum insulin (P <.0001), and total cholesterol (P <.0001), while a negative trend was found in regard to high-density lipoprotein cholesterol (HDL-C) (P <.0001). Insulin resistance, calculated as HOMA(IR), was higher in the upper two tertiles of TG in comparison to the lower tertile (P <.001 and P <.0001, respectively), with a statistically significant trend for the entire group (first tertile, 1.85 +/- 0.94; second tertile, 2.28 +/- 1.10; third tertile, 2.65 +/- 1.71; ANOVA: P <.0001). In conclusion, this study shows an association between high levels of circulating TG and insulin resistance in patients with normal glucose tolerance seen in an atherosclerosis prevention clinic. This association is also present at levels of plasma TG considered to be normal and is associated with a cluster of cardiovascular risk factors.
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PMID:Hypertriglyceridemia is associated with increased insulin resistance in subjects with normal glucose tolerance: evaluation in a large cohort of subjects assessed with the 1999 World Health Organization criteria for the classification of diabetes. 1275 93

Hydration is recommended in order to decrease the overload on the cardiovascular system when healthy individuals exercise, mainly in the heat. To date, no criteria have been established for hydration for hypertensive (HY) individuals during exercise in a hot environment. Eight male HY volunteers without another medical problem and 8 normal (NO) subjects (46 +/- 3 and 48 +/- 1 years; 78.8 +/- 2.5 and 79.5 +/- 2.8 kg; 171 +/- 2 and 167 +/- 1 cm; body mass index=26.8 +/- 0.7 and 28.5 +/- 0.6 kg/m2; resting systolic (SBP)=142.5 and 112.5 mmHg and diastolic blood pressure (DBP)=97.5 and 78.1 mmHg, respectively) exercised for 60 min on a cycle ergometer (40% of VO2peak) with (500 ml 2 h before and 115 ml every 15 min throughout exercise) or without water ingestion, in a hot humid environment (30 masculine C and 85% humidity). Rectal (Tre) and skin (Tsk) temperatures, heart rate (HR), SBP, DBP, double product (DP), urinary volume (Vu), urine specific gravity (Gu), plasma osmolality (Posm), sweat rate (S R), and hydration level were measured. Data were analyzed using ANOVA in a split plot design, followed by the Newman-Keuls test. There were no differences in Vu, Posm, Gu and S R responses between HY and NO during heat exercise with or without water ingestion but there was a gradual increase in HR (59 and 51%), SBP (18 and 28%), DP (80 and 95%), Tre (1.4 and 1.3%), and Tsk (6 and 3%) in HY and NO, respectively. HY had higher HR (10%), SBP (21%), DBP (20%), DP (34%), and Tsk (1%) than NO during both experimental situations. The exercise-related differences in SBP, DP and Tsk between HY and NO were increased by water ingestion (P<0.05). The results showed that cardiac work and Tsk during exercise were higher in HY than in NO and the difference between the two groups increased even further with water ingestion. It was concluded that hydration protocol recommended for NO during exercise could induce an abnormal cardiac and thermoregulatory responses for HY individuals without drug therapy.
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PMID:Thermoregulation in hypertensive men exercising in the heat with water ingestion. 1506 Jul 11

Treatment of cancers with cytotoxic agents such as alkylating drugs often, but not always results in transient to permanent testicular dysfunction. The present study was planned to investigate the effects of dacarbazine [5-(3,3-dimethyltriazeno) imidazole-4-carboxamide] on testicular function in mice. Swiss albino mice (9-12 weeks old) were treated with 0, 5, 25, 50, or 100mg/kg body weight/day dacarbazine (i.p.) for 5 days at intervals of 24h between treatments. Mice were sacrificed on days 7, 14, 21, 28, 35, 49, and 70 after the last treatment (6 mice/dose/sample time), and the epididymal sperm count, sperm motility, sperm morphology, testicular histopathology (qualitative histopathology, seminiferous tubular diameter and epithelial height), and intra-testicular levels of testosterone and lactate dehydrogenase were assessed. Dacarbazine decreased the body weight only on day 28 at 25mg/kg dose-level, but increased the paired testes weights at 50mg/kg on day 7, at 25-100mg/kg on day 14, and at 25 and 50mg/kg on day 21 (P<0.05-0.01; one-way ANOVA and Bonferroni's post hoc test). The sperm count was decreased on all sampling days except at 5 and 25mg/kg dose-levels on day 70, but with severe oligospermia on days 28 and 35 (P<0.05-0.001). The sperm motility was decreased at 100mg/kg on days 14 and 21, at 5, 25, and 100mg/kg on day 28, and at all dose-levels on day 35 (P<0.05-0.001). Dacarbazine induced both head and tail abnormalities and some sperms with cytoplasmic droplets, but significant increase was seen in all dose groups on days 14 and 21, and at 100mg/kg dose-level on day 35. Drug-induced epithelial sloughing was seen on days 14-35 and other histopathological changes observed were vacuoles and abnormal cells. The STD was increased at 25-100mg/kg on day 7, at all dose-levels on day 14, at 50-100mg/kg on days 21 and 28, but without any effects on days 35-70 (P<0.05-0.001), and the tubular lumen was found dilated. The SE was increased on days 7, 21 and 28 at 100mg/kg and on day 14 at 50-100mg/kg. Dacarbazine reduced the intra-testicular testosterone level at 100mg/kg on day 7, at 5, 50 and 100mg/kg on day 14, at all dose-levels on days 21, 28, and 35, and at 50mg/kg on day 49 (P<0.05-0.001). The intra-testicular lactate dehydrogenase concentration increased at all dose-levels up to day 35, but without any effect on days 49 and 70 (P<0.05-0.001). There was no particular dose-response of dacarbazine on any parameters tested. The sperm count (except on day 7-positive correlation; Pearson product moment correlation) or sperm motility did not have any relation but increase in abnormal sperms showed negative correlation with decrease in testosterone level on days 7, 21 and 28. Decrease in sperm count was in negative correlation on days 14 and 35, and increase in abnormal sperms showed positive correlation on day 35 with increase in LDH level. Finally, the decrease in sperm motility had no correlation with increase in abnormal sperm shapes. We conclude that dacarbazine is genotoxic and cytotoxic to the mouse testis in a transient fashion, and these effects are exerted along with decrease in testosterone and increase in lactate dehydrogenase levels in the testis.
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PMID:Dacarbazine induces genotoxic and cytotoxic germ cell damage with concomitant decrease in testosterone and increase in lactate dehydrogenase concentration in the testis. 1679 27

This study evaluated the microtensile bond strength (microTBS) of dual-cured adhesive systems when the different components were either light activated or left in the uncured state prior to cementation of an indirect composite restoration. Occlusal dentin surfaces of 40 human third molars were flattened. The teeth were randomly assigned to 8 groups (n = 5) according to the dual-cured systems (bonding agents/resin cements) and curing modes: All Bond 2/Duolink (AB2-BISCO Inc) and Optibond Solo Plus Dual Cure/Nexus 2 (SOLO-Kerr). Resin cements were applied to pre-cured resin composite discs (2 mm thick/Z-250/3M ESPE), which were fixed to dentin surfaces containing adhesive resin in either cured (LP) or uncured states (SP). The restored teeth were light activated according to the manufacturers' instructions (LRC-XL3000/3M ESPE) or allowed to self-cure (SRC). The restored teeth were water-stored at 37 degrees C for 24 hours. They were then both mesial-distally and buccal-lingually sectioned to obtain bonded specimens (1.2 mm2). Each specimen was tested in tension at a crosshead speed of 0.6 mm/minute until failure. Data (MPa (SD)) were analyzed by two-way ANOVA and Tukey's post-hoc test (p < .05). AB2/SP exhibited higher microTBS than AB2/LP (p = .00001); however, no significant differences were noted between SOLO/LP and SOLO/SP. Results suggested that dual-cured adhesive systems were as strong or even stronger when they were left in the uncured state prior to indirect resin composite cementation.
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PMID:Effect of curing mode on microtensile bond strength to dentin of two dual-cured adhesive systems in combination with resin luting cements for indirect restorations. 1728 27


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