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)

Data are controversial as to the role of menarche age as a risk factor of high-risk human papillomavirus (HR-HPV) infections. The objective of this study was to analyse the risk estimates for age at menarche as determinant of cervical intraepithelial neoplasia (CIN) and HR-HPV infections. A cohort of 3187 women were stratified into three groups according to their age at menarche: (i) women <13 years of age; (ii) those between 13 and 14 years and (iii) women >15 years of age. These groups were analysed for predictors of (a) HR-HPV, (b) high-grade CIN and (c) outcome of HR-HPV and cytological abnormalities during prospective follow-up. All the three groups had identical prevalence of HR-HPV, Papanicolaou smear abnormalities and CIN grades. In contrast to menarche age itself, the time from menarche to the first intercourse (TMI), to the first pregnancy (TMP) and to the first delivery (TMD) were all significant (P = 0.0001) predictors of HR-HPV (but not CIN2) in univariate analysis, but lost their significance in a multivariate model. Outcome of cervical disease and HR-HPV infection was unrelated to menarche age, the latter and the three intervals being not predictors of CIN2 in a multivariate model. In conclusion, age at menarche and the intervals between menarche and (i) onset of sexual activity, (ii) first pregnancy and iii) first delivery, are not independent predictors of HR-HPV infections and CIN2 in multivariate analysis.
Int J STD AIDS 2008 Jan
PMID:Age at menarche is not an independent risk factor for high-risk human papillomavirus infections and cervical intraepithelial neoplasia. 1827 41

The growth and metabolic actions of growth hormone (GH) are believed to be mediated through the GH receptor (GHR) by JAK2 activation. The GHR exists as a constitutive homodimer, with signal transduction by ligand-induced realignment of receptor subunits. Based on the crystal structures, we identify a conformational change in the F'G' loop of the lower cytokine module, which results from binding of hGH but not G120R hGH antagonist. Mutations disabling this conformational change cause impairment of ERK but not JAK2 and STAT5 activation by the GHR in FDC-P1 cells. This results from the use of two associated tyrosine kinases by the GHR, with JAK2 activating STAT5, and Lyn activating ERK1/2. We provide evidence that Lyn signals through phospholipase C gamma, leading to activation of Ras. Accordingly, mice with mutations in the JAK2 association motif respond to GH with activation of hepatic Src and ERK1/2, but not JAK2/STAT5. We suggest that F'G' loop movement alters the signalling choice between JAK2 and a Src family kinase by regulating TMD realignment. Our findings could explain debilitated ERK but not STAT5 signalling in some GH-resistant dwarfs and suggest pathway-specific cytokine agonists.
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PMID:An agonist-induced conformational change in the growth hormone receptor determines the choice of signalling pathway. 1848 18

The purpose of this study was to determine whether a brief (6-8 sessions) cognitive-behavioral treatment for temporomandibular dysfunction-related pain could be efficacious in reducing pain, pain-related interference with lifestyle and depressive symptoms. The patients were 101 men and women with pain in the area of the temporomandibular joint of at least 3 months duration, randomly assigned to either standard treatment (STD; n=49) or standard treatment+cognitive-behavioral skills training (STD+CBT; n=52). Patients were assessed at posttreatment (6 weeks), 12 weeks, 24 weeks, 36 weeks, and 52 weeks. Linear mixed model analyses of reported pain indicated that both treatments yielded significant decreases in pain, with the STD+CBT condition resulting in steeper decreases in pain over time compared to the STD condition. Somatization, self-efficacy and readiness for treatment emerged as significant moderators of outcome, such that those low in somatization, or higher in self-efficacy or readiness, and treated with STD+CBT reported of lower pain over time. Somatization was also a significant moderator of treatment effects on pain-related interference with functioning, with those low on somatization reporting of less pain interference over time when treated in the STD+CBT condition. It was concluded that brief treatments can yield significant reductions in pain, life interference and depressive symptoms in TMD sufferers, and that the addition of cognitive-behavioral coping skills will add to efficacy, especially for those low in somatization, or high in readiness or self-efficacy.
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PMID:Brief cognitive-behavioral treatment for TMD pain: long-term outcomes and moderators of treatment. 2065 62