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 relationship between the physical fitness level (maximal O2 consumption, VO2max) and thermoregulatory reactions was studied in 17 adult males submitted to an acute cold exposure. Standard cold tests were performed in nude subjects, lying for 2 h in a climatic chamber at three ambient air temperatures (10, 5, and 1 degrees C). The level of physical fitness conditioned the intensity of thermoregulatory reactions to cold. For all subjects, there was a direct relationship between physical fitness and 1) metabolic heat production, 2) level of mean skin temperature (Tsk), 3) level of skin conductance, and 4) level of Tsk at the onset of shivering. The predominance of thermogenic or insulative reactions depended on the intensity of the cold stress: insulative reactions were preferential at 10 degrees C, or even at 5 degrees C, whereas colder ambient temperature (1 degree C) triggered metabolic heat production abilities, which were closely related to the subject's physical fitness level. Fit subjects have more efficient thermoregulatory abilities against cold stress than unfit subjects, certainly because of an improved sensitivity of the thermoregulatory system.
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PMID:Physical fitness and thermoregulatory reactions in a cold environment in men. 320 45

A number of cellular processes, such as proliferation, differentiation, and transformation, are regulated by cell-extracellular matrix interactions. Previous studies have identified a novel tyrosine kinase, the focal adhesion kinase p125FAK, as a component of cell adhesion plaques. p125FAK was identified as a 125-kDa tyrosine-phosphorylated protein in cells transformed by the v-src oncogene. p125FAK is an intracellular protein composed of three domains: a central domain with homology to protein tyrosine kinases, flanked by two noncatalytic domains of 400 amino acids which bear no significant homology to previously cloned proteins. p125FAK is believed to play an important regulatory role in cell adhesion because it localizes to cell adhesion plaques and because its phosphorylation on tyrosine residues is regulated by binding of cell surface integrins to the extracellular matrix. Recent studies have shown that Src, through its SH2 domain, stably associates with pp125FAK and that this association prevents dephosphorylation of pp125FAK in vitro by protein tyrosine phosphatases. In this report, we identify Tyr-397 as the primary in vivo and in vitro site of p125FAK tyrosine phosphorylation and association with Src. Substituting phenylalanine for tyrosine at position 397 significantly reduces p125FAK tyrosine phosphorylation and association with Src but does not abolish p125FAK kinase activity. In addition, p125FAK kinase is able to trans-phosphorylate Tyr-397 in vitro in a kinase-deficient p125FAK variant. Phosphorylation of Tyr-397 provides a site [Y(P)AEI] that fits the consensus sequence for the binding of Src.
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PMID:Identification of Tyr-397 as the primary site of tyrosine phosphorylation and pp60src association in the focal adhesion kinase, pp125FAK. 773 63

We present a case of FES (fat embolism syndrome) with very serious neurologic signs (convulsions, deep coma, decerebrate response to noxious stimuli), without lung lesions. Nuclear magnetic resonance imaging revealed vascular alterations of the cerebral hemisphere, truncus, and cerebellum. The patient recovered without neurologic sequelae.
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PMID:Neurologic symptoms in fat embolism syndrome: case report. 801 21

Absidiosis was produced experimentally in rabbits by intravenous inoculation of 1.4 x 10(5) spores of Absidia corymbifera. Infected rabbits exhibited a rise in body temperature, anorexia, dullness, listlessness, diarrhoea, occasional blindness, convulsions and death in some cases. Mortality occurred mainly between 6 to 9 days post infection (DPI) and overall mortality was 50 per cent during the three week observation period. No significant difference was observed in erythrocytic indices viz., Hb, PCV, TEC in control and infected rabbits. However, erythrocyte sedimentation rate was considerably increased in the infected rabbits. A state of leucocytosis was observed in the infected rabbits, which was due to increase in the relative percentage of neutrophils and decrease in lymphocytes. There was a significant increase in blood urea nitrogen concentrations of infected rabbits from 3 to 14 DPI as compared to controls, but serum creatinine values were not significantly altered at any stage of infection. The cause of death was attributed to kidney failure and uraemia in infected rabbits. The rabbit was found to be a suitable model for the study of absidiosis.
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PMID:Experimental Absidia corymbifera infection in rabbits: clinicopathological studies. 881 36

A two-component Cole-Cole model was used to obtain statistically significant fits to 100-Hz-10-MHz impedance data for EMT-6 mouse tumors during the progressive histological changes induced by hyperthermia. The resulting fitting parameters were used to deconvolute and reconstruct the two dispersions which confer the predominant impedance features to this tissue. The time-dependent changes of these two dispersions were correlated with the concurrent, heat-induced morphological changes of the tumors' cells. The higher frequency dispersion (fc approximately 1 MHz) was identified with a Maxwell-Wagner relaxation process linked to the overall volume response of the cells. The lower frequency dispersion (fc approximately 10 kHz) represented an alpha-relaxation associated with the surface morphology and integrity of the plasma membranes. Thus, two aspects of the characteristic cellular damage sequence in these tumors were found to be separately discernable and trackable in real-time using the impedance data.
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PMID:Deconvolved electrical impedance spectra track distinct cell morphology changes. 898 65

The aim of this paper is to perform a critical review of the effectiveness of interventions for the purpose of enhancing adherence to antiretroviral therapy. The overall evaluation indicates that research is in its early stages. Although pilot studies provide support for the feasibility of their protocols, and preliminary results also suggest their capacity to improve adherence, only three major trials have reported significant improvement in adherence. The issues that will have to be addressed by future studies include: (a) the need for a theoretical and empirical understanding of the phenomena; (b) adoption of a format that fits the attributes of the population; (c) the use of multiple strategies involving key providers; (d) a concise and precise schedule governing the frequency and intensity of the intervention; (e) a careful selection of direct outcome; and (f) appropriate time measurement. In sum, greater efforts to design and evaluate interventions are needed to lead to an increase in adherence and improvement in treatment effectiveness.
Int J STD AIDS 2005 May
PMID:Efficacy of interventions in improving adherence to antiretroviral therapy. 1594 60

The t(9;22)(q34;q11) translocation occurs in chronic myeloid leukemia (CML) and adult B-cell acute lymphoblastic leukemia (ALL), leading to fusion of BCR to ABL1 and constitutive activation of ABL1 tyrosine kinase activity. The main BCR-ABL1 breakpoints result in P190 BCR-ABL1 or P210 BCR-ABL1 fusion proteins. The latter is found in almost all cases of CML and in one third of the cases of t(9;22)-positive adult B-ALL. P190 BCR-ABL1 is found in the remaining two thirds of t(9;22)-positive adult B-ALL cases but only exceptionally in CML. We describe here the first case of t(9;22)(q34;q11) associated with t(10;11)(p13;q14) in acute monocytic leukemia. The recurrent t(10;11)(p13;q14) translocation, usually found in acute myeloid leukemia (AML) and T-ALL, merges PICALM to MLLT10. RT-PCR enabled identification of PICALM-MLLT10 and BCR-ABL1 e1-a2 fusion transcripts; in the context of chronic and acute myeloid leukemia, the latter usually has a monocytic presentation. We also identified overexpression of HOXA9, a gene essential to myeloid differentiation that is expressed in PICALM-MLLT10 and MLL-rearranged acute leukemias. This case fits with and extends a recently proposed multistage AML model in which constitutive activation of tyrosine kinases by mutations (BCR-ABL1) are associated with deregulation of transcription factors central to myeloid differentiation (HOXA9 secondary to PICALM-MLLT10).
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PMID:Acute monocytic leukemia with coexpression of minor BCR-ABL1 and PICALM-MLLT10 fusion genes along with overexpression of HOXA9. 1651 48

The aim of this study was to determine the proportion of genitourinary (GU) medicine patients attending a mixed urban/rural clinic who would welcome patient-delivered partner therapy (PDPT) as a partner management option. Five hundred patients completed the questionnaire. Acceptability of traditional partner referral was 87% (435), partner referral with infection specific guidance was 82% (411) and PDPT was 81% (405). Significantly fewer patients, 71% (354) would find a partner home sampling kit acceptable and provider referral was the least popular option at 23% (117). PDPT is not used in the UK mainly due to concerns of health professionals regarding the legal status of PDPT and the lack of UK evidence. The outcome of the Medical Research Council randomized controlled trial on accelerated partner therapy (which fits in with General Medical Council advice on remote prescribing) is eagerly awaited as professionals would welcome evidence-based guidance and our study suggests that patients are willing to consider this form of partner management as an additional treatment option.
Int J STD AIDS 2008 Jul
PMID:Patient-delivered partner therapy in the UK: what do patients think? 1905 Feb 26

The aim of this study was to investigate consultant genitourinary (GU) physicians' and health advisers' views regarding acceptability of patient-delivered partner therapy (PDPT) in the United Kingdom (UK). A postal questionnaire was sent to all consultant GU physicians and senior health advisers: 206 (65%) physician questionnaires and 153 (77%) health-adviser questionnaires were returned. One hundred and three (50%) physicians and 31 (22%) health advisers reported ever having used PDPT. Approximately one-third of professionals are strongly opposed to PDPT. However, the majority of both professional groups are cautiously prepared to consider PDPT, but only if there is no other option and only if a health professional first makes contact with the partner. Chief concern among health professionals is the legal status of PDPT in the UK. Here, the current General Medical Council (GMC) guidance on remote prescribing is helpful. The outcome of the Medical Research Council randomized controlled trial on accelerated partner therapy, which fits in with GMC guidance, is eagerly awaited as professionals would welcome evidence-based national guidance.
Int J STD AIDS 2008 Jul
PMID:Patient-delivered partner therapy in the UK: what do the professionals think? 1857 12

Neuronal Per Arnt Sim domain protein 4 (NPAS4), a brain-specific basic helix-loop-helix transcription factor, has recently been shown to regulate the development of the GABAergic inhibitory synapses and transcription program for contextual memory formation in the hippocampus. We previously reported that chronic social isolation or restriction stress in mice resulted in an impairment in memory and emotional behavior, which was associated with a decrease in Npas4 mRNA levels. In this study, we investigated the role of NPAS4 in neuronal function in vitro and in vivo. Differentiation medium-induced neurite outgrowth was inhibited in Npas4 knockdown Neuro2a cells, whereas overexpression of NPAS4 accelerated the neurite outgrowth in Neuro2a cells. Furthermore, depolarization-induced neurite outgrowth was abolished in Npas4 KO hippocampal neurons. NPAS4 overexpression increased cyclin-dependent kinase 5 (CDK5)-dependent synapsin I phosphorylation in Neuro2a cells and primary cultured hippocampal neurons. A CDK5 inhibitor, roscovitine, inhibited the neurite outgrowth and the increase in phosphorylated synapsin I (p-SYN I) levels in Npas4-overexpressed Neuro2a cells. Interaction of NPAS4 with promoters of Cdk5 and NeuN genes was demonstrated by a chromatin immunoprecipitation assay. In an in vivo study, pentylenetetrazole-induced convulsions in mice resulted in an increase in NPAS4 and p-SYN I levels in the prefrontal cortex of wild-type mice, although no changes in p-SYN I levels were observed in Npas4 knock-out mice. These results suggest that NPAS4 plays an important role in the structural and functional plasticity of neurons.
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PMID:Neuronal Per Arnt Sim (PAS) domain protein 4 (NPAS4) regulates neurite outgrowth and phosphorylation of synapsin I. 2317 25


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