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)

The objective of this study is to establish normal ranges for the assessment of lung permeability, using 99mTc DTPA (diethylene triamine penta acetate) aerosol by measuring the half-time of transfer from the lung in asymptomatic HIV-positive patients. Also to audit the use of the test in the clinical management of outpatients with symptoms suggestive of Pneumocystis carinii pneumonia (PCP). A retrospective analysis of data from outpatients' notes for the audit of symptomatic patients, and prospective acquisition of 'normal' data for HIV-positive asymptomatic patients who were non-smokers and smokers was performed. Over a period of 8 years, DTPA scans were performed on 400 asymptomatic HIV-positive patients (121 non-smokers and 279 smokers) and 188 symptomatic HIV-positive patients with symptoms suggestive of PCP. A biphasic curve of transfer of 99mTc DTPA with a half-time of less than 4 min, was considered diagnostic of PCP. The mean half-times (+/-SEM) for asymptomatic non-smokers was 61.4 +/- 3 min and for smokers was 21.9 +/- 0.8 min. In the symptomatic patients, 106 were treated for PCP and in 97 (91.5%) of these, the transfer was biphasic. Of the remaining 82 patients with respiratory pathology other than PCP, 71 (86.6%) had normal scans. The results show that smokers may have abnormal baseline scans 16/ 279 (5.7%) and therefore a baseline scan before symptoms should be recorded or a higher false positive rate can be expected. The test is however highly sensitive for the detection of PCP and allows the attending physician to initiate PCP treatment without delay.
Int J STD AIDS 1997 Aug
PMID:Radioactively labelled diethylene triamine penta acetate lung scan in Pneumocystis carinii pneumonia and asymptomatic HIV-positive patients. 925 95

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

Two 160-d feedlot experiments, each consisting of 20 Angus-Hereford steers (216 +/- 5 kg BW, Exp. 1; 258 +/- 5 kg BW, Exp. 2) and 20 Angus-Hereford heifers (208 +/- 5 kg BW, Exp. 1; 236 +/- 5 kg BW, Exp. 2), were used to investigate the effects of supplementing diets with either roasted soybeans (RSB, roasted at 127 degrees C for 10 min) or soybean meal (SBM) and implanting or not implanting with an estrogenic growth promoter (SYN; Synovex-S, 20 mg of estradiol benzoate plus 200 mg of progesterone or Synovex-H, 20 mg of estradiol benzoate plus 200 mg of testosterone) on performance. The cattle were fed a basal diet of 15% orchardgrass silage, 15% corn silage, and 70% corn-based concentrate. Treatments were 1) no SYN and fed a SBM-supplemented diet, 2) no SYN and fed a RSB-supplemented diet, 3) SYN and SBM, and 4) SYN and RSB. Cattle in the SYN groups were reimplanted at 80 d. Four additional Angus-Hereford steers were used in a digestion and nitrogen balance experiment conducted during the first half of Exp. 1. For the total 160-d feedlot experiments, DMI for RSB compared with SBM was lower (P < .01; 8.5 vs 9.2 kg/d, SEM = .07) and ADG/DMI tended to be higher (P < .10; 165 vs 157 g/kg, SEM = 1.3). Final BW of steers fed RSB was similar (P > .10) to that of steers fed SBM (473 vs 478 kg, SEM = 5.6), as was ADG (1.39 vs 1.43 kg/d, SEM = .02). Dry matter intake for SYN-implanted steers was higher (P < .01) than for steers not implanted (9.2 vs 8.5 kg/d). Likewise, final BW (491 vs 460 kg) and ADG (1.49 vs 1.33 kg/d) were higher (P < .01), and ADG/DMI (166 vs 157 g/kg) tended to be higher (P < .10), for SYN-implanted steers than for steers not implanted. During the more rapid muscle growth period (0 to 80 d), DMI for RSB compared with SBM was lower (P < .01; 7.8 vs 8.6 kg/d, SEM = .07) and ADG/DMI was similar (P > .10; 181 vs 172 g/kg, SEM = 1.8). Dry matter intake for SYN-implanted steers was higher (P < .05) than for steers not implanted (8.4 vs 8.0 kg/d), as was ADG/DMI (P < .01, 182 vs 171 g/kg). During this more rapid growth period, the supplement x implant interaction for ADG was significant (P < .05; 1.35, 1.36, 1.59, and 1.44 kg/d for Treatments 1, 2, 3, and 4, respectively, SEM = .04). There were no differences in digestibilities or N balance. The results suggest that there is no improvement in performance under feedlot conditions when RSB replaces SBM in the diet of beef cattle, and, in young cattle, RSB may reduce the response expected by an estrogenic growth promoter.
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PMID:Performance and digestibilities of beef cattle fed diets supplemented with either soybean meal or roasted soybeans and implanted with Synovex. 1043 6

The effects of initial thermal state on thermoregulatory responses to cold (-10 degrees C) in a 0.2 (still air), 1.0, and 5.0 m. S(-1) wind speed were studied. Eight young male subjects were first preconditioned in thermoneutral (+20 degrees C, TN) or cool (-5 degrees C, CO) environment for 60 min. After preconditioning the subjects were exposed to wind at -10 degrees C in a standing position, facing the wind, for 30 min. Precooling decreased mean skin temperature (Tsk) by 4.0 (SEM 0.1) degrees C (P < 0.001) and increased heat flux by 57 (SEM 2) W x m(-2) (P < 0.001) in comparison to TN. Cooling rate of Tsk was faster (P < 0.001) in TN than in CO at every wind speed. Even so, Tsk ended up at a lower level in CO (P < 0.001-0.01) than in TN at every wind speed. Local skin temperatures of hand, finger, foot and toe were significantly lower in CO than in TN at the end of all exposures to wind. Heat flux from the skin was 8% higher (NS) in TN at 5.0 m x s(-1) wind speed in comparison to CO. A 5.0 m x s(-1) wind speed increased oxygen consumption significantly (P < 0.001) in both CO and TN in comparison to still air. At 5.0 m x s(-1) wind speed the general thermal sensation was the same (cold) in both TN and CO, despite the higher Tsk in TN. In conclusion, Tsk decreased more rapidly in TN, probably due to rapid skin vasoconstriction and redistribution of circulation to the central body. Probably for the same reason, dry heat loss from the skin was at nearly the same level in both TN and CO. Although the initial thermal state did not affect the amount of heat loss, it significantly affected the peripheral temperatures and thermal sensations and should therefore be taken into consideration in the prediction of thermophysiological responses to wind.
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PMID:Thermal responses to cold wind of thermoneutral and cooled subjects. 1075 Nov 1

Insulin-like growth factor I (IGF-I) exerts a negative feedback effect on GH secretion via either direct actions at the pituitary level or indirect ones at the hypothalamic level, through stimulation of somatostatin (SS) and/or inhibition of GHRH release. In fact, recombinant human IGF-I (rhIGF-I) in humans inhibits spontaneous GH secretion as well as the GH response to GHRH and even more to GH/GH-releasing peptides, whose main action is on the hypothalamus, antagonizing SS and enhancing GHRH activity. The aim of the present study was to further clarify in humans the mechanisms underlying IGF-I-induced inhibition of somatotroph secretion. In six normal young volunteers (all women; mean +/- SEM: age, 28.3+/-1.2 yr; body mass index, 21.3+/-1.2 kg/m2) we studied the GH response to GHRH (1 microg/kg, iv, at 0 min), both alone and combined with arginine (ARG; 0.5 g/kg, iv, from 0-30 min), which probably acts via inhibition of hypothalamic SS release, after pretreatment with rhIGF-I (20 microg/kg, sc, at -180 min) or placebo. rhIGF-I increased circulating IGF-I levels (peak at -60 vs. -180 min: 54.9+/-3.9 vs. 35.9+/-3.3 mmol/L; P < 0.05) to a reproducible extent, and these levels remained stable and within the normal range until 90 min. The mean GH concentration over 3 h (from -180 to 0 min) before ARG and/or GHRH was not modified by placebo or rhIGF-I. After placebo, the GH response to GHRH (peak, 23.6+/-2.9 microg/L) was strikingly enhanced (P < 0.05) by ARG coadministration (69.6+/-9.9 microg/L). rhIGF-I blunted the GH response to GHRH (13.1+/-4.5 microg/L; P < 0.05), whereas that to GHRH plus ARG was not modified (59.5+/-8.9 microg/L), although it occurred with some delay. Mean glucose and insulin concentrations were not modified by either placebo or rhIGF-I. In conclusion, ARG counteracts the inhibitory effect of rhIGF-I on somatotroph responsiveness to GHRH in humans. These findings suggest that the acute inhibitory effect of rhIGF-I on the GH response to GHRH takes place on the hypothalamus, possibly via enhancement of SS release, and that ARG overrides this action.
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PMID:Arginine counteracts the inhibitory effect of recombinant human insulin-like growth factor I on the somatotroph responsiveness to growth hormone-releasing hormone in humans. 1106 9

The mechanisms underlying the reduction in the GH-releasing activity of GHRPs in aging are still unclear. Aim of our study was to verify in man whether age-related impairment of the neurohormonal control of GH secretion and/or receptor alterations are involved in the reduced GH response to GHRPs in aging. To this goal, in 16 normal elderly subjects (E, 66-81 yr) and 12 young controls (Y, 24-28 yr) we studied the effects of 1.0, 2.0 and 3.0 micrograms/kg i.v. Hexarelin (HEX), a synthetic hexapeptide, or GHRH, as well as the interaction among HEX (2.0 micrograms/kg), GHRH (2.0 micrograms/kg) and arginine (ARG, 0.5 gr/kg) on GH secretion. In Y the GH response to increasing doses of HEX (1.0 vs. 2.0 vs. 3.0 micrograms/kg; AUC0;v-120 +/- SEM: 1728.4 +/- 406.4 vs. 2265.9 +/- 298.4 vs. 2934.3 +/- 482.2 micrograms/L/h, p < 0.05 for 1.0 vs. 2.0 micrograms/kg) and GHRH (649.6 +/- 111.4 vs. 792.2 +/- 117.6 vs. 1402.6 +/- 363.0 micrograms/L/h) showed a progressive increase. Two micrograms/kg HEX and 1 microgram/kg GHRH were the maximal effective doses. Similarly, in E the GH response to increasing doses of HEX (336.7 +/- 50.0 vs. 742.8 +/- 157.9 vs. 1205.1 +/- 178.1 micrograms/L/h, p < 0.05 for 1.0 vs. 2 micrograms/kg, p < 0.001 for 1.0 vs. 3.0 micrograms/kg and p < 0.03 for 2.0 vs. 3.0 micrograms/kg) and GHRH (183.8 +/- 27.3 vs. 260.9 +/- 17.3 vs. 356.1 +/- 46.3 micrograms/L/h, p < 0.005 for 1.0 vs. 3.0 micrograms/kg and p < 0.05 for 2.0 vs. 3.0 micrograms/kg) showed a progressive increase. In E the GH response to 3 micrograms/kg HEX or GHRH were clearly higher than those to 2 micrograms/kg. However, at each dose the GH responses to HEX or GHRH in E were lower (p < 0.05) than those in Y. In Y the GH response to HEX + GHRH was synergistical (4259.2 +/- 308.0 micrograms/L/h, p < 0.05). ARG strikingly potentiated the GHRH-induced GH rise (2640.8 +/- 273.6 micrograms/L/h, p < 0.01) but not the HEX-induced one (2371.7 +/- 387.2 micrograms/L/h) as well as the synergistical effect of HEX and GHRH (4009.1 +/- 360.8 micrograms/L/h). In E the GH response to HEX and GHRH was still synergistical (1947.7 +/- 306.0 micrograms/L/h, p < 0.05) but these responses were lower than those in young (p < 0.01). On the other hand, in E ARG restored the GH response to GHRH (1858.9 +/- 172.8 micrograms/L/h, p < 0.01) and even those to HEX (2069.5 +/- 528.7 micrograms/L/h, p < 0.01) and HEX + GHRH (4406.0 +/- 1079.2 micrograms/L/h, p < 0.05). Our present results indicate that the impairment of GHRP and GHRH receptor activity may have a role in the reduction of the somatotrope responsiveness in aging. However, the age-related reduction in the GH-releasing activity of GHRPs seems mainly dependent on age-related variations in the neural control, i.e. concomitant GHRH hypoactivity and somatostatinergic hyperactivity.
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PMID:Age-related variations in the neuroendocrine control, more than impaired receptor sensitivity, cause the reduction in the GH-releasing activity of GHRPs in human aging. 1108 Nov 83

VEGF is a key regulator of vascular permeability. However, its signaling pathways are incompletely understood. We tested the hypothesis that VEGF regulates endothelial cell (EC) permeability by activating PKB/akt, NOS, and MAP kinase dependent pathways using human umbilical vein EC (HUVEC). Permeability was measured from FITC-dextran 70-kDa flux across the EC monolayer at baseline and after VEGF at 0.034, 0.068, 1, 10, and 100 nM. VEGF increased HUVEC permeability to FITC-dextran in a dose-dependent manner. VEGF (1 nM) increased permeability from 3.9 x 10(-6) +/- 0.7 x 10(-6) to 14.0 x 10(-6) +/- 1.7 x 10(-6) cm/s (mean +/- SEM; P < 0.001). Permeability changes were also assessed after treatment with 1, 10, and 100 nM wortmannin (PI 3-kinase inhibitor); 0.01, 0.1, and 1.0 nM LY294002 (PI 3-kinase inhibitor); 200 microM l-NMMA (NOS inhibitor); 2.7 microM AG126 (p42/44(MAPK) inhibitor); and 0.006, 0.06, and 0.6 microM SB203580 (p38(MAPK) inhibitor). All inhibitors blocked VEGF-induced permeability changes. Our data demonstrate that (1) VEGF increases permeability of EC monolayers in a dose-dependent fashion, and (2) VEGF-induced permeability is mediated through PI-3 kinase-PKB, NOS, and MAP-kinase signaling cascades. These observations suggest that microvascular hyperpermeability associated with inflammation and vascular disease is mediated by activation of these EC signaling pathways.
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PMID:VEGF increases permeability of the endothelial cell monolayer by activation of PKB/akt, endothelial nitric-oxide synthase, and MAP kinase pathways. 1167 28

An accurate, simple method for assessing energy expenditure in individuals and in free-living populations continues to be elusive. To compare estimates of energy expenditure (EE) from a combination of two previously validated physical activity questionnaires: Tecumseh Occupational (EE(TEC)) and a 4-wk history version of the Minnesota Leisure Time Physical Activity that included household activities (EE(MNLTPA)) and EE from sleep (EE(SLEEP)), to EE obtained from doubly labeled water (EE(DLW)). We studied free-living males (n = 24) eating a controlled diet designed to maintain body weight and determined EE from doubly labeled water (DLW) during 14 days and EE from physical activity instruments used in epidemiological studies (EE(TEC) and EE(MNLTPA)). There was excellent agreement between EE(DLW) (mean +/- SEM, 13.55 +/- 0.38 MJ/d) and EE(TEC) + EE(MNLTPA) + EE(SLEEP) (EE(TOTAL1)) (13.79 +/- 0.89 MJ/d) with a difference of only 1.0% +/- 5.4%. When the EE from watching TV, reading, and childcare activities was added the total EE (EE(TOTAL2)) (14.87 +/- 0.90 MJ/D) overestimated EE(DLW) by 8.9% +/- 5.4%. Both of these estimates of EE had significant regressions against EE(DLW) (EE(TEC) + EE(MNLTPA) + EE(SLEEP), R(2) = 0.38, P < 0.001; EE(TOTAL2), R(2) = 0.39, P < 0.001). Men whose occupations involved significant intermittent moderate activity had the largest disagreement between EE(DLW) and estimates from the questionnaires. This investigation demonstrates that a combination of previously validated physical activity questionnaires can be used to accurately determine the mean energy expenditure of a population of employed males.
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PMID:Estimating energy expenditure from the Minnesota Leisure Time Physical Activity and Tecumseh Occupational Activity questionnaires - a doubly labeled water validation. 1192 8

Ghrelin possesses central and peripheral endocrine actions including influence on the endocrine pancreatic function. To clarify this latter ghrelin action, in seven normal young subjects [age (mean +/- SEM), 28.3 +/- 3.1 yr; body mass index, 21.9 +/- 0.9 kg/m(2)), we studied insulin and glucose levels after acute ghrelin administration (1.0 microg/kg i.v.) alone or combined with glucose [oral glucose tolerance test (OGTT), 100 g orally], arginine (ARG, 0.5 g/kg i.v.) or free fatty acid (FFA, Intralipid 10%, 250 ml). Ghrelin inhibited (P < 0.05) insulin and increased (P < 0.05) glucose levels. OGTT increased (P < 0.01) glucose and insulin levels. FFA increased (P < 0.05) glucose but did not modify insulin levels. ARG increased (P < 0.05) both insulin and glucose levels. Ghrelin did not modify both glucose and insulin responses to OGTT as well as the FFA-induced increase in glucose levels; however, ghrelin administration was followed by transient insulin decrease also during FFA. Ghrelin blunted (P < 0.05) the insulin response to ARG and enhanced (P < 0.05) the ARG-induced increase in glucose levels. In all, ghrelin induces transient decrease of spontaneous insulin secretion and selectively blunts the insulin response to ARG but not to oral glucose load. On the other hand, ghrelin raises basal glucose levels and enhances the hyperglycemic effect of ARG but not that of OGTT. These findings support the hypothesis that ghrelin exerts modulatory action of insulin secretion and glucose metabolism in humans.
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PMID:Effects of ghrelin on the insulin and glycemic responses to glucose, arginine, or free fatty acids load in humans. 1297 Feb 97

This study investigates the molecular mechanisms underlying the blood glucose-lowering effect of a 2-day very low-energy diet (VLED, 1883 kJ/d) in 12 obese (body mass index, 36.3 +/- 1.0 kg/m2 [mean +/- SEM]) type 2 diabetic (HbA(1C) 7.3% +/- 0.4%) patients simultaneously taken off all glucose-lowering therapy, including insulin. Endogenous glucose production (EGP) and glucose disposal ([6,6-2H2]-glucose) were measured before and after the VLED in basal and hyperinsulinemic (40 mU/m2 per minute) euglycemic conditions. Insulin signaling and expression of GLUT-4, FAT/CD36, and triglycerides were assessed in muscle biopsies, obtained before the clamp and after 30 minutes of hyperinsulinemia. Fasting plasma glucose decreased from 11.3 +/- 1.3 to 10.3 +/- 1.0 mmol/L because of a decreased basal EGP (14.2 +/- 1.0 to 11.9 +/- 0.7 micromol/kg per minute, P = .009). Insulin-stimulated glucose disposal did not change. No diet effect was found on the expression of the insulin receptor and insulin receptor substrate-1 or on phosphatidylinositol 3'-kinase activity, or on FAT/CD36 expression pattern, GLUT-4 translocation, or triglyceride distribution in either the basal or insulin-stimulated situation. Unexpectedly, basal PKB/Akt phosphorylation on T308 and S473 increased after the diet, at equal protein expression. In conclusion, a 2-day VLED lowers fasting plasma glucose via a decreased basal EGP without an effect on glucose disposal. Accordingly, no changes in activation of phosphatidylinositol 3'-kinase, triglyceride distribution, FAT/CD36 expression, and GLUT-4 translocation were found in skeletal muscle biopsies.
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PMID:Effect of a 2-day very low-energy diet on skeletal muscle insulin sensitivity in obese type 2 diabetic patients on insulin therapy. 1631 Nov 2


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