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)

Six young, healthy male subjects performed a series of experiments in a climatic chamber in different environmental conditions wearing protective ventilated NBC clothing. Ambient temperature, TA, ranged from -20 to 35 degrees C, relative humidity, RH, from 20 to 85%, and air velocity, VA, from 0 center dot 1 to 5 center dot 0 ms-1. In addition, thermal radiation, measured by the temperature of the globothermometer, TG, was artificially increased in some experiments. A total of 32 experiments were performed. The subject had to exercise on a bicycle ergometer at a mechanical power of 60 W for 120 min. Heart rate, HR, oxygen uptake, VO2, skin temperature, Tsk, and rectal temperature, Tre, were measured during the experiments together with the temperature of the space between skin and garment, Tmu. Sweat loss was determined as the difference of the body weight before and after the experiment. Tmu was well correlated with the chamber environmental parameters. During heat exposure work duration began to decrease progressively from a Tmu > 30 degrees C, reducing to 40 min at the highest thermal load. About the same value of Tmu marked the departure of HR, VO2, Tsk and Tre from the values measured during the same work load in neutral conditions. Also, during cold exposure at -20 degrees C work duration was reduced below 1 h, but the limit appeared to be the cold at the extremities. From these findings it appears that Tmu is a good indicator of the thermal load and is related to the environmental condition by the equation: Tmu = 9 center dot 93 + 0 center dot 56 TA + 0 center dot 023 TG + 0 center dot 14 RH (T in degrees C, RH in %). For better comfort and performance Tmu should be monitored whenever a subject has to work wearing an NBC garment and the ventilating system must be adequate to fulfil the needs imposed on the subject by an adverse environment, in particular a high relative humidity.
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PMID:Work tolerance and physiological responses to thermal environment wearing protective NBC clothing. 885 82

The impairment of endothelial function in hypercholesterolaemic animals and humans is known to be reversed by intravenous infusions of L-arginine (L-ARG), the precursor of NO. 22 patients with peripheral arterial obstructive disease (PAOD) received L-ARG (60 mmol) as intravenous infusions, each lasting three hours, daily for seven consecutive days. This treatment resulted in elongation of the painfree and maximum walking distances, as well as shortening of the period of time required for pain relief after walking the maximum distance. A rise in the ankle/arm pressure ratio (AAPR) was associated with an increase of arterial blood flow in both calves. The transcutaneous oxygen tension (tcpO2) in the ischaemic foot was also increased. After the 1st and the 7th infusion of L-ARG the spontaneous (PAR) as well as the ADP- and collagen-induced platelet aggregation were suppressed, the euglobulin clot lysis time (ECLT) shortened, plasma levels of platelet activator inhibitor (PAI) decreased, and cGMP levels increased. These data indicate beneficial effects of L-ARG as a therapeutic agent in patients with PAOD. We presume that in these patients high doses of exogenous L-ARG can be partially converted to NO.
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PMID:Treatment with L-arginine is likely to stimulate generation of nitric oxide in patients with peripheral arterial obstructive disease. 886 84

We have previously reported that, following continuous exercise, a prolonged elevated plateau of esophageal temperature (Tes) was directly related to the Tes at the time of cutaneous vasodilation (Thdil) during exercise. In order to investigate the hypothesis that the factors which result in an increase of the post-exercise Thdil and define the post-exercise Tes elevation are related to pre-exercise Tes, nine healthy, young [24.0 (1.9) years], non-training males rested at 29 degrees C, 50% humidity for > 1 h (control). They then completed three successive cycles of 15 min treadmill running at 70% maximal oxygen consumption (VO2max) followed by 30 min rest. Esophageal, rectal (Tre) and skin (Tsk) temperatures and forearm cutaneous blood flow were recorded at 5-s intervals throughout. Laser-Doppler flowmetry of forearm skin blood flow was used to identify the Thdil during exercise. Pre-exercise Tes was 36.74 (0.25) degrees C and post-exercise Tes fell to stable and significant (P < 0.05) elevations above pre-exercise values at 37.22 (0.27) degrees C, 37.37 (0.27) degrees C and 37.48 (0.26) degrees C following each successive work bout respectively. Correspondingly, Thdil during each work bout rose in proportion to, and was not different than, the post-exercise Tes in the following recovery [37.20(0.23) degrees C, 37.41 (0.24) degrees C and 37.58 (0.24) degrees C]. Although the increases were less with each successive exercise bout, the differences between each exercise bout, in terms of post-exercise Tes and Thdil values, were significant (P < 0.05). These results reinforce our previous observations of elevations in Thdil and post-exercise Tes after a single exercise bout and lead to the tentative conclusions that (1) pre-exercise Tes has a direct influence on Thdil and post-exercise Tes, and (2) the exercise-induced increase of Thdil persists into recovery, influencing post-exercise thermal recovery.
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PMID:Post-exercise thermal homeostasis as a function of changes in pre-exercise core temperature. 889 32

The effect of the blockade of the renin angiotensin system (RAS) on thermoregulatory, cardiovascular and renal function during moderate exercise in a hot [mean (SEM) 34.4 (0.1) degrees C] environment was evaluated. Six men and three women cycled at 60% peak oxygen uptake for 45 min following acute administration of a placebo (PLAC) or enalapril (ENAL), an angiotensin converting enzyme inhibitor (ACE-I). Resting mean arterial pressure (MAP) was reduced by ENAL, but the pressor response to exercise was unaffected [delta MAP = 7.8 (1.4)mmHg for both trials (P > 0.05)]. Peak esophageal temperature [T(es) = 38.7 (1.0) degrees C (PLAC) vs 38.4 (0.2) degrees C (ENAL)] and mean skin temperatures [Tsk = 36.5 (0.1) degrees C (PLAC) vs 36.6 (0.1) degrees C (ENAL)] were similar for both drug treatments during the exercise. Both aldosterone and plasma renin activity (PRA) increased five fold above resting values during exercise; however, only the PRA response [16.7 (3.2) ng angiotensin I (Ang I).ml-1.h-1 (ENAL) vs 7.4 (1.2)ng Ang I.ml-1.h-1 (PLAC)] was significantly altered by ENAL treatment (P < 0.05). Urine flow, sodium excretion and glomerular filtration rates, determined from creatinine clearance, were similarly reduced following exercise for both ENAL and PLAC treatments. These results suggest acute administration (5 mg) of ACE-I does not impair thermoregulatory, cardiovascular or renal responses during moderate exercise in the heat.
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PMID:Influence of angiotensin II blockade during exercise in the heat. 892 29

The effects of prolonged (20 day) hyperbaric exposure (HBO) to oxygen on non adrenergic non cholinergic (NANC) contractile and relaxant responses of rat trachea were examined. The electrical field stimulation (EFS) of rat tracheal rings was performed at 30 Hz and contractile and relaxant responses were assessed in the absence or in the presence of pretreatment with L-nitro-arginine-methyl-ester (L-NAME), an inhibitor of NO synthase, and L-Arginine (L-ARG), a precursor of NO synthesis, plus L-NAME. Our data demonstrated that L-NAME significantly (p < 0.05) enhanced the contractile responses induced by EFS (controls 30.6 +/- 0.99%; L-NAME 76.07 +/- 2.00%) and statistically (p < 0.05) reduced the relaxant component of EFS (controls 31.10 +/- 0.46; L-NAME 15.00 +/- 0.12); these effects were reversed when tissues were pretreated with L-ARG plus L-NAME, suggesting that NO plays a modulatory role in cholinergic neurotransmission and participates in EFS relaxant responses. Moreover, prolonged HBO exposure (20 days) at 202.6 and 303.9 kPa did not modify the contractile or relaxant responses induced by EFS, nor modify the L-NAME or L-ARG effects on EFS responses.
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PMID:Effects of hyperbaric oxygen exposure on non-adrenergic non-cholinergic responses of rat trachea. 905 53

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

During extracorporeal circulation (ECC) a continuous monitoring of venous oxygen saturation yields a quantitative impression of the equilibrium of oxygen supply and oxygen consumption in steady state conditions. The aim of the investigation was to study whether the measurements of venous oxygen saturation and haemoglobin of a continuous on-line monitor (CDI-100) agree with those of the ABL-4 bloodgasmonitor or the haemoglobincyanid method in hospital laboratory. The study group consisted of 21 patients, with comparable conditions of anesthesia and ECC set-up. Measurements of saturation and haemoglobin were compared at three moments, resulting in a total of 189 measurements. Analysis was based on the Bland Altman method, using the differences between correspondent measurements, which contain all the information needed to decide whether the methods agree. Bias of saturation measurement (CDI-100 versus ABL-4) is -3.4, 3.0 and -3.5% at times 1,2 and 3. All values are situated within the limits of agreement. Bias of haemoglobin measurement (CDI-100 versus ABL-4) is 0.3, 0.3, and 0.2 gr/dl at times 1, 2 and 3. All values (except one value) are situated within the limits of agreement. Bias of hemoglobin measurement (CDI-100 versus hospital laboratory) is 0.2, 0.0 and 0.1 gr/dl, and all values are situated within the limits of agreement. The results confirm that the CDI-100, in the set-up as described, can be used as a reliable instrument to monitor venous oxygen saturation and haemoglobin during ECC.
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PMID:Comparison between CDI-100 continuous SO2, Hb, and Hct monitoring, intermittent ABL-4 saturation and Hb monitoring, and lab Hb and Hct monitoring. 909 48

The purpose of the present study was to examine the effects of long term cold exposure on thermal responses and physical performance in men while wearing nuclear, biological and chemical (NBC) protective clothing. Six healthy men performed 60 min work/60 min rest cycles during 8 hours at an ambient temperature of -10 degrees C. Work was performed by stepping on a 20 cm high bench 15 times.min-1. Subjects were tested while wearing two different types of NBC clothing: impermeable rubber suit (IP) or semipermeable charcoal impregnated suit (SP) with cold weather underwear layers, as well as rubber gloves, boots and a full-face mask. During the tests oxygen consumption (VO2), rectal (Tre) and skin temperatures and sweat production were measured. Rectal and skin temperatures and body heat content followed the work/rest cycles in both types of NBC clothing. T(re) averaged 37.1 +/- 0.04 and 37.3 +/- 0.1 degrees C for IP and SP (NS), respectively. On average, mean skin temperature (Tsk) was 28.6 +/- 0.2 and 29.7 +/- 0.2 degrees C for IP and SP (p < 0.01), respectively. Finger skin temperature decreased rapidly to below 10 degrees C in both ensembles during the rest periods. During work the finger rewarming rate was 0.49 +/- 0.06 and 0.70 +/- 0.02 degree C.min-1 for IP and SP (p < 0.01), respectively. Decrease in body heat storage (S) during cold exposure was smaller in SP than in IP and S was restored to the level of -0.6 +/- 0.3 and -3.0 +/- 0.6 kJ.kg-1 in SP and IP (p < 0.01), respectively, during the work. Work load, according to VO2 measurements, was 1.5 +/- 0.1 and 1.3 +/- 0.11.min-1 for IP and SP (p < 0.05), respectively. Furthermore, during rest VO2 was 30% (p < 0.001) higher in IP than in SP. In conclusion, both types of NBC protective clothing could be used for long periods in cold conditions at a moderate work load without marked whole body heat debt or heat load. However, peripheral parts of the body experienced a rapid and severe cooling during the rest periods. The semipermeable suit enabled higher body heat storage and faster rewarming of extremities during work than the impermeable suit.
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PMID:Thermal responses and physiological strain in men wearing impermeable and semipermeable protective clothing in the cold. 911 32

The cytotoxic and photodynamic activities of the commercially-available biological stains methylene blue (MB), 1,9-dimethyl MB (Taylor's Blue) and a newly synthesised compound, 1-methyl MB, were measured against the murine mammary tumour cell line, EMT-6. Both 1-methyl MB and 1,9-dimethyl MB exhibited increased dark toxicity with concomitant higher phototoxicity compared to MB at a light dose of 7.2 J cm-2. While increasing the light dose as a function of the fluence rate increased the photocytotoxicity of MB, this had little effect on the methylated derivatives. In vitro chemical testing proved that successive methylation rendered the phenothiazinium chromophore both more resistant to reduction to its inactive leuco form, and also led to increased levels of singlet-oxygen production, thus providing a possible explanation for the increased toxicities of the methylated derivatives. Comparisons are made with the benzo[a]phenothiazinium photosensitizer, EtNBS.
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PMID:Increased cytotoxicity and phototoxicity in the methylene blue series via chromophore methylation. 937 12

The purpose of this review is to give an update of the recent progress in research on erythropoietin (Epo), the hormone that regulates red blood cell production. Epo is a glycoprotein with a molecular mass of approx 30 kDa, which circulates in plasma of the human with 165 amino acids with three N-linked and one O-linked acidic oligosaccharide side chains in the molecule. Both the alpha (39% CHO) and beta (24% CHO) forms are available for clinical use, and there does not appear to be any difference in the pharmacokinetics of these two forms of Epo. Radioimmunoassays and enzyme-linked immunoabsorbant (ELISA) assays are available in a kit form. Serum levels of Epo in normal human subjects range between 1 and 27 mmu/ml or approx 5 pmol/l. It seems clear that the cells in the adult mammalian kidney which produce Epo are the interstitial cells in the peritubular capillary bed and the perivenous hepatocytes in the liver. Expression of the human Epo gene sequences that direct expression in the kidney are located 6-14 kilobases 5' to the gene; whereas the sequences that control hepatocyte-specific expression are located within 0.7 KS to the 3'-flanking region and 0.5 KS to the 5'-flanking region. The signal transduction pathways postulated to be involved in the expression of Epo are: kinases A, G and C; both a constitutive factor and a second hypoxia-inducible factor-1 (HIF-1) located in the 5' end of an hypoxia inducible enhancer region of the Epo gene; and reactive oxygen species. The primary target cell in the bone marrow acted on by Epo is the colony-forming unit erythroid (CFU-E) which has the highest number of Epo receptors. It has been postulated that Epo decreases the rate which Epo-dependent progenitor cells undergo programed cell death (apoptosis). There are two major signal transduction pathways activated by the Epo receptor: the JAK2-STAT5 pathway and the ras pathway. Both pathways involve tyrosine phosphorylation. The approved clinical uses of Epo are the anemias associated with end-stage renal disease, cancer chemotherapeutic agents, and patients with HIV infection receiving AZT. Other anemias reported to respond to Epo therapy are anemia of prematurity, rheumatoid arthritis, and myelodysplasia. Other uses of Epo under investigation are in perioperative surgery and preoperative autologous blood donation.
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PMID:Erythropoietin: physiologic and pharmacologic aspects. 940 40


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