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 Odstock dropped foot stimulator (ODFS) is a foot switch controlled single channel neuromuscular stimulator for correction of dropped foot. Following a randomized controlled trial, the ODFS was recommended for use in the United Kingdom's National Health Service and a clinical service established. The patient performance was assessed by measurement of walking speed over 10 m, physiological cost index (PCI), and by questionnaire. After 4.5 months stroke patients (n = 111) showed a mean increase in walking speed of 27% and reduction in PCI of 31% with stimulation and changes of 14% and 19%, respectively, unassisted. Multiple sclerosis patients (n = 21) gained similar orthotic benefit but no carry over. The principal reason cited for using the equipment was that it reduced the effort of walking. The principal reasons identified for discontinuing were an improvement in mobility, electrode positioning difficulties, and deteriorating mobility. A comprehensive clinical follow-up service is essential to achieve the maximum continuing benefit from FES based orthosis.
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PMID:Clinical audit of 5 years provision of the Odstock dropped foot stimulator. 1037 38

Platelet aggregation and subsequent thrombosis are the major cause of ischemic diseases such as heart attack and stroke. ADP, acting via G protein-coupled receptors (GPCRs), is an important signal in thrombus formation and involves activation of phosphoinositide 3-kinases (PI3K). When platelets from mice lacking the G protein-activated PI3Kgamma isoform were stimulated with ADP, aggregation was impaired. Collagen or thrombin, however, evoked a normal response. ADP stimulation of PI3Kgamma-deficient platelets resulted in decreased PKB/Akt phosphorylation and alpha(IIb)beta(3) fibrinogen receptor activation. These effects did not influence bleeding time but protected PI3Kgamma-null mice from death caused by ADP-induced platelet-dependent thromboembolic vascular occlusion. This result demonstrates an unsuspected, well-defined role for PI3Kgamma downstream of ADP and suggests that pharmacological targeting of PI3Kgamma has a potential use as antithrombotic therapy.
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PMID:Resistance to thromboembolism in PI3Kgamma-deficient mice. 1151 14

The serine/threonine protein kinase PKB (also known as Akt) is thought to be a key mediator of signal transduction processes. The identification of PKB substrates and the role PKB phosphorylation plays in regulating these molecules have been a major focus of research in recent years. A recently developed motif-profile scoring algorithm that can be used to scan the genome for potential PKB substrates is therefore a useful tool, although additional considerations, such as the evolutionary conservation of the phosphorylation site, must also be taken into account. Recent evidence indicates that PKB plays a key role in cancer progression by stimulating cell proliferation and inhibiting apoptosis and is also probably a key mediator of insulin signalling. These findings indicate that PKB is likely to be a hot drug target for the treatment of cancer, diabetes and stroke. There are, however, a number of pitfalls of methodologies currently employed to study PKB function, and therefore caution should be used in interpretation of such experiments.
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PMID:PKB/Akt: a key mediator of cell proliferation, survival and insulin responses? 1168 94

The objective of this article is to determine the effect of three different putting grips (conventional, cross-hand, and one-handed) on variations in eye and head movements during the putting stroke. Seven volunteer novice players, ranging in age from 21 to 22 years, participated in the study. During each experimental session, the subject stood on a specially designed platform covered with artificial turf and putted golf balls towards a standard golf hole. The three different types of grips were tested at two distances: 3 and 9 ft. For each condition, 20 putts were attempted. For each putt, data were recorded over a 3-s interval at a sampling rate of 100 Hz. Eye movements were recorded using a helmet-mounted eye movement monitor. Head rotation about an imaginary axis through the top of the head and its center-of-rotation was measured by means of a potentiometer mounted on a fixed frame and coupled to the helmet. Putter-head motion was measured using a linear array of infrared phototransistors embedded in the platform. The standard deviation (STD, relative to the initial level) was calculated for eye and head movements over the duration of the putt (i.e., from the beginning of the backstroke, through the forward stroke, to impact). The averaged STD for the attempted putts was calculated for each subject. Then, the averaged STDs and other data for the seven subjects were statistically compared across the three grip conditions. The STD of eye movements were greater (p < 0.1) for conventional than cross-hand (9 ft) and one-handed (3 and 9 ft) grips. Also, the STD of head movements were greater (p < 0.1; 3 ft) for conventional than cross-hand and one-handed grips. Vestibulo-ocular responses associated with head rotations could be observed in many 9 ft and some 3 ft putts. The duration of the putt was significantly longer (p < 0.05; 3 and 9 ft) for the one-handed than conventional and cross-hand grips. Finally, performance, or percentage putts made, was significantly better (p < 0.05; 9 ft) for cross-hand than conventional grip. The smaller variations, both in eye movements during longer putts and head movements during shorter putts, using cross-hand and one-handed grips may explain why some golfers, based on their playing experience, prefer these over the conventional grip. Also, the longer duration for the one-handed grip, which improves tempo, may explain why some senior players prefer the long-shaft (effectively one-handed grip) putter.
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PMID:Effect of putting grip on eye and head movements during the golf putting stroke. 1280 25

Understanding transcriptional changes in brain after ischemia may provide therapeutic targets for treating stroke and promoting recovery. To study these changes on a genomic scale, oligonucleotide arrays were used to assess RNA samples from periinfarction cortex of adult Sprague-Dawley rats 24 h after permanent middle cerebral artery occlusions. Of the 328 regulated transcripts in ischemia compared with sham-operated animals, 264 were upregulated, 64 were downregulated, and 163 (49.7%) had not been reported in stroke. Of the functional groups modulated by ischemia: G-protein-related genes were the least reported; and cytokines, chemokines, stress proteins, and cell adhesion and immune molecules were the most highly expressed. Quantitative reverse transcription polymerase chain reaction of 20 selected genes at 2, 4, and 24 h after ischemia showed early upregulated genes (2 h) including Narp, Rad, G33A, HYCP2, Pim-3, Cpg21, JAK2, CELF, Tenascin, and DAF. Late upregulated genes (24 h) included Cathepsin C, Cip-26, Cystatin B, PHAS-I, TBFII, Spr, PRG1, and LPS-binding protein. Glycerol 3-phosphate dehydrogenase, which is involved in mitochondrial reoxidation of glycolysis derived NADH, was regulated more than 60-fold. Plasticity-related transcripts were regulated, including Narp, agrin, and Cpg21. A newly reported lung pathway was also regulated in ischemic brain: C/EBP induction of Egr-1 (NGFI-A) with downstream induction of PAI-1, VEGF, ICAM, IL1, and MIP1. Genes regulated acutely after stroke may modulate cell survival and death; also, late regulated genes may be related to tissue repair and functional recovery.
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PMID:Genomics of the periinfarction cortex after focal cerebral ischemia. 1284 83

Erythropoietin (Epo) plays a central role in erythropoiesis but also has neuroprotective properties. Recently, Epo-related neuroprotective studies used a hypoxic-ischemic neonatal model, which is different from focal stroke, a frequent cause of neonatal brain injury. We report on the effects of Epo treatment given after focal stroke and its potential neuroprotective mechanisms in postnatal day 7 rats with focal cerebral ischemia (FCI) achieved by occlusion of the middle cerebral artery. The experimental groups included sham operation, FCI plus vehicle, and FCI plus Epo. In the Epo-treated group, pups received a single intraperitoneal injection of 1000 U/kg 15 min after FCI or three injections of 100, 1000, or 5000 U/kg, starting at 15 min and repeated at 1 and 2 d after FCI. Epo treatment produced significant reductions in the mean infarct area and volume at 1 and 3 d after FCI, demonstrated by 2,3,5-triphenyltetrazolium chloride staining. Terminal deoxynucleotidyltransferase-mediated 2'-deoxyuridine 5'-triphosphate-biotin nick end labeling (TUNEL) staining showed a markedly reduced number of TUNEL-positive cells in the Epo-treated group when compared with the vehicle control 3 d after FCI (p<0.01). The most effective dose after FCI was 1000 U/kg for 3 d. Immunoanalyses showed that Epo induced a significant increase in phosphorylated Janus kinase 2 and signal transducer and activator of transcription-5 expressions at 1 and 3 d and up-regulated Bcl-xL expression by 24 h after FCI but did not affect Epo receptor or NF-kappaB expression. In conclusion, Epo given after FCI in neonatal rats provides significant neuroprotection, mediated possibly by activation of the Janus kinase-signal transducer and activator of transcription-Bcl-xL signaling pathways.
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PMID:Erythropoietin after focal cerebral ischemia activates the Janus kinase-signal transducer and activator of transcription signaling pathway and improves brain injury in postnatal day 7 rats. 1571 73

This study evaluates stroke patients with upper-limb (UL) motor deficits using measures of impairment and "activity limitation" to quantify recovery of UL function poststroke and to identify predictors of UL function and predictors of UL recovery following stroke. The study also compares the recovery of UL function with that of the lower limb (LL). Measures of impairment and "activity limitation" of the UL and LL improved over the first 5 weeks. The Box and Block Test performance improved the most over 5 weeks (standardized response mean [SRM] = 1.34), followed closely by the 5-meter walk test (SRM = 0.97). Performances on measures of UL "activity limitation" measured at 1 week poststroke were the most important predictors of UL function 5 weeks poststroke. The results of this study do not support the belief that recovery of LL function is faster than that of UL.
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PMID:Upper-limb function and recovery in the acute phase poststroke. 1574 51

The purpose of the study was to examine the effect of 1) active (loadless pedaling), 2) passive (assisted pedaling), and 3) inactive (motionless) recovery modes on mean arterial pressure (MAP), cutaneous vascular conductance (CVC), and sweat rate during recovery after 15 min of dynamic exercise in women. It was hypothesized that an active recovery mode would be most effective in attenuating the fall in MAP, CVC, and sweating during exercise recovery. Ten female subjects performed 15 min of cycle ergometer exercise at 70% of their predetermined peak oxygen consumption followed by 20 min of 1) active, 2) passive, or 3) inactive recovery. Mean skin temperature (Tsk), esophageal temperature (Tes), skin blood flow, sweating, cardiac output (CO), stroke volume (SV), heart rate (HR), total peripheral resistance (TPR), and MAP were recorded at baseline, end exercise, and 2, 5, 8, 12, 15, and 20 min postexercise. Cutaneous vascular conductance (CVC) was calculated as the ratio of laser-Doppler blood flow to MAP. In the active recovery mode, CVC, sweat rate, MAP, CO, and SV remained elevated over inactive values (P < 0.05). The passive mode was equally as effective as the active mode in maintaining MAP. Sweat rate was different among all modes after 12 min of recovery (P < 0.05). TPR during active recovery remained significantly lower than during recovery in the inactive mode (P < 0.05). No differences in either Tes or Tsk were observed among conditions. The results indicate that CVC can be modulated by central command and possibly cardiopulmonary baroreceptors in women. However, differences in sweat rate may be influenced by factors such as central command, mechanoreceptor stimulation, or cardiopulmonary baroreceptors.
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PMID:Nonthermoregulatory control of cutaneous vascular conductance and sweating during recovery from dynamic exercise in women. 1603 2

Epidemiological studies have linked the consumption of phenolic acids with reduced risk of cardiovascular diseases. In the present study, we sought to investigate whether caffeic acid, a phenolic acid which is abundant in normal diet, can antagonize angiotensin II (Ang II)-induced vascular smooth muscle cell (VSMC) proliferation in stroke-prone spontaneously hypertensive rats (SHRSP) and Wistar-Kyoto (WKY) rats, and if so, to elucidate the underlying cell signaling mechanisms. We exposed VSMCs to Ang II and caffeic acid and found that caffeic acid significantly inhibited intracellular superoxide anion generation (decreased from 127 +/- 6.3% to 100.3 +/- 6.6% of the control cells) and the cell proliferation induced by Ang II. Furthermore, caffeic acid significantly abolished the tyrosine phosphorylation of JAK2 (decreased from 7.4 +/- 0.6-fold to 2.4 +/- 0.6-fold at 2 min) and STAT1 (decreased from 1.8 +/- 0.2-fold to 0.5 +/- 0.1-fold at 2 min) and the phosphorylation of ERK1/2 (decreased from 99.2 +/- 10.2-fold to 49.8 +/- 10.9-fold at 2 min) that were induced by Ang II. These effects of caffeic acid were consistent with the inhibition of the proliferation of VSMCs by DPI, an NADPH oxidase inhibitor, and by AG-490, a JAK2 inhibitor. In conclusion, our findings suggest that caffeic acid attenuates the proliferative reaction of VSMCs to Ang II stimulation in both SHRSP and WKY rats by inhibiting the generation of reactive oxygen species and then partially blocking the JAK/STAT signaling cascade and the Ras/Raf-1/ERK1/2 cascade.
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PMID:Caffeic acid inhibits vascular smooth muscle cell proliferation induced by angiotensin II in stroke-prone spontaneously hypertensive rats. 1613 68

After a stroke balance can be impaired, that may influence the physical activities which can be undertaken. A person's confidence in performing activities without falling could be as important as the real balance ability in situations of daily living. The aims of the study were to evaluate the relationship between perceived self-confidence in task performance without falling, using the Falls Efficacy Scale, Swedish version, (FES(S)) and observer-assessed balance, measured by the BDL Balance Scale (BDL BS) and also between the FES(S) and gait velocity. Thirty-one subjects with stroke, 32-62 years of age, time since onset between 3 and 104 months, participated The FES(S) was significantly correlated with the BDL BS (r = 0.49, p = 0.008). Furthermore there were significant correlations between the FES(S) and self-selected (r = 0.53, p = 0.003) as well as for maximum (r = 0.55, p = 0.002) gait velocity. The results indicate that the use of the FES(S) can be recommended in subjects with stroke and balance deficit in order to map out the dimension of self-confidence in balance problems. However, in more highly functioning subjects with stroke other fall-efficacy assessments with major demands on balance performance may be preferable due to partly ceiling effect in the study population.
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PMID:Fear of falling, balance, and gait velocity in patients with stroke. 1639 64


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