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OBJECTIVE - The present study evaluated differences in gene expression associated with age and gender in the human parotid gland.
DESIGN - Parotid gland tissue was analysed using the Affymetrix GeneChip HGU133plus2.0 array.
RESULTS - Differential gene expression, defined as a statistically significant difference with a 1.5-fold or greater change, was detected in 787 gene probe sets; 467 (approximately 59%) showed higher expression in females. Several genes associated with saliva secretion were differentially expressed in male and female parotid glands including vesicle-associated membrane protein 3 VAMP3, synaptosomal-associated protein SNAP23, RAS oncogene family member RAB1A and the syntaxin binding protein STXBP1. Evaluation of gene expression in the youngest and the oldest female subjects revealed that the expression of 228 probe sets were altered during aging; 155 genes were up-regulated in the aged female parotid gland. However, of the genes that were altered during aging, 22 of the 30 probes (73%) classified as being associated with immune responses were down-regulated in the aged parotid gland. A panel of differentially expressed, age- and gender-related genes was selected for validation by quantitative, real-time RT-PCR. Comparable differences in gene expression were detected by both Affymetrix array and quantitative, real-time RT-PCR methods.
CONCLUSIONS - Our data suggest that salivary gland function may be adversely affected in the aged population due, at least in part, to the altered regulation of several categories of genes. Moreover, the gender specific differences in gene expression identified in the present study correlate with the previously observed sexual dimorphism in salivary gland function.
PURPOSE - We performed this analysis of possible first night effects (FNEs) on sleep and respiratory parameters in order to evaluate the need for two serial night polysomnograms (PSGs) to diagnose obstructive sleep apnea (OSA) in epilepsy patients.
METHODS - As part of a pilot multicenter clinical trial investigating the effects of treating sleep apnea in epilepsy, two nights of PSG recording were performed for 40 patients with refractory epilepsy and OSA symptoms. Sleep architecture was examined in detail, along with respiratory parameters including apnea/hypopnea index (AHI) and minimum oxygen saturation. Analysis included two-tailed t-tests, Wilcox sign rank analysis, and Bland Altman measures of agreement.
RESULTS - Total sleep time differed between the two nights (night 1,363.8 min + 59.4 vs. 386.3 min + 68.6, p = 0.05). Rapid eye movement (REM) sleep and percentage of REM sleep were increased during night two (night 1: 12.3% + 5.9 vs. night 2: 15.5% + 6.2, p = 0.007), and the total minutes of slow-wave sleep (SWS) were increased (night 1: 35.6 + 60.7 vs. night 2: 46.4 + 68.1, p = 0.01). No other sleep or respiratory variables differed between the two nights. Given an AHI inclusion criterion of five apneas per hour, the first PSG identified all but one patient with OSA.
DISCUSSION - Respiratory parameters showed little variability between the first and second nights. Sleep architecture was mildly different between the first and second PSG night. Performing two consecutive baseline PSGs to diagnose OSA may not be routinely necessary in this population.
It has previously been observed that during isometric dorsiflexion exercise, the time course of T2-weighted signal intensity (SI) changes is spatially heterogeneous. The purpose of this study was to test the hypothesis that this spatial heterogeneity would increase at higher contraction intensities. Eight subjects performed 90-s isometric dorsiflexion contractions at 30% and 60% of maximum voluntary contraction (MVC) while T2-weighted (repetition time/echo time=4000/35 ms) images were acquired. SI was measured before, during and after the contractions in regions of interest (ROIs) in the extensor digitorum longus (EDL) muscle and the deep and superficial compartments of the tibialis anterior (D-TA and S-TA, respectively). For all ROIs at 30% MVC, SI changes were similar. The maximum postcontraction SI was greater than the SI during exercise. At 60% MVC, SI changes during contraction were greater in the S-TA than in the D-TA and EDL. For the EDL and D-TA, the maximum postcontraction SI was greater than those during exercise. For the S-TA, the maximum postcontraction change was greater than the changes at t=8, 20 and 56 s but not the end-exercise value. We conclude that spatial heterogeneity increases during more intense dorsiflexion contractions, possibly reflecting regional differences in perfusion or neural activation of the muscle.
OBJECTIVE - To develop a model that uses individual and lesion characteristics to help surgeons choose lesions that have a high probability of containing histologically confirmed endometriosis.
DESIGN - Secondary analysis of prospectively collected information.
SETTING - Government research hospital in the United States.
PATIENT(S) - Healthy women 18-45 years of age, with chronic pelvic pain and possible endometriosis, who were enrolled in a clinical trial.
INTERVENTION(S) - All participants underwent laparoscopy, and information was collected on all visible lesions. Lesion data were randomly allocated to a training and test data set.
MAIN OUTCOME MEASURE(S) - Predictive logistic regression, with the outcome of interest being histologic diagnosis of endometriosis.
RESULT(S) - After validation, the model was applied to the complete data set, with a sensitivity of 88.4% and specificity of 24.6%. The positive predictive value was 69.2%, and the negative predictive value was 53.3%, equating to correct classification of a lesion of 66.5%. Mixed color; larger width; and location in the ovarian fossa, colon, or appendix were most strongly associated with the presence of endometriosis.
CONCLUSION(S) - This model identified characteristics that indicate high and low probabilities of biopsy-proven endometriosis. It is useful as a guide in choosing appropriate lesions for biopsy, but the improvement using the model is not great enough to replace histologic confirmation of endometriosis.
OBJECTIVES - To examine the relationships of religious involvement and affiliation with health behavior and conditions.
METHODS - A survey (n = 3014) conducted for the Nashville REACH 2010 project included questions about religious affiliation and practice as well as health behaviors and conditions.
RESULTS - Bivariate analyses indicated negative associations between religious involvement and health, along with differences between religious affiliations/groups. This relationship changed, however, after controlling for demographic differences and individual differences in religious involvement.
CONCLUSIONS - Religious groups share not only beliefs, but also socioeconomic, ethnic, and cultural similarities that must be taken into account in research examining religion and health.
Protein kinase C enzymes play an important role in signal transduction, regulation of gene expression and control of cell division and differentiation. The fsI and betaII isoenzymes result from the alternative splicing of the PKCbeta gene (PRKCB1), previously found to be associated with autism. We performed a family-based association study in 229 simplex and 5 multiplex families, and a postmortem study of PRKCB1 gene expression in temporocortical gray matter (BA41/42) of 11 autistic patients and controls. PRKCB1 gene haplotypes are significantly associated with autism (P<0.05) and have the autistic endophenotype of enhanced oligopeptiduria (P<0.05). Temporocortical PRKCB1 gene expression was reduced on average by 35 and 31% for the PRKCB1-1 and PRKCB1-2 isoforms (P<0.01 and <0.05, respectively) according to qPCR. Protein amounts measured for the PKCbetaII isoform were similarly decreased by 35% (P=0.05). Decreased gene expression characterized patients carrying the 'normal' PRKCB1 alleles, whereas patients homozygous for the autism-associated alleles displayed mRNA levels comparable to those of controls. Whole genome expression analysis unveiled a partial disruption in the coordinated expression of PKCbeta-driven genes, including several cytokines. These results confirm the association between autism and PRKCB1 gene variants, point toward PKCbeta roles in altered epithelial permeability, demonstrate a significant downregulation of brain PRKCB1 gene expression in autism and suggest that it could represent a compensatory adjustment aimed at limiting an ongoing dysreactive immune process. Altogether, these data underscore potential PKCbeta roles in autism pathogenesis and spur interest in the identification and functional characterization of PRKCB1 gene variants conferring autism vulnerability.
This study tested for alpha-2 adrenergic mediation of the inverse relationship between resting blood pressure and acute pain sensitivity in healthy individuals. It also replicated limited prior work suggesting this inverse blood pressure/pain association is altered in chronic pain, and provided the first test of whether chronic pain-related changes in alpha-2 adrenergic function contribute to these alterations. Resting blood pressure was assessed in 32 healthy controls and 24 chronic low back pain participants prior to receiving placebo or an intravenous alpha-2 adrenergic receptor antagonist (yohimbine hydrochloride, 0.4 mg/kg) in a randomized crossover design. Participants experienced three acute pain tasks during both sessions. A significant Systolic Blood Pressure x Participant Type x Drug interaction on finger pressure McGill Pain Questionnaire-Sensory ratings (P < .05) reflected significant hyperalgesic effects of yohimbine in chronic pain participants with lower systolic blood pressures (P < .05) but not those with higher systolic pressures, and no significant effects of yohimbine in controls regardless of blood pressure level. A Drug x Systolic Blood Pressure interaction on finger pressure visual analog scale unpleasantness indicated the inverse blood pressure/pain association was significantly stronger under yohimbine relative to placebo (P < .05). Significant Participant Type x Systolic Blood Pressure interactions (P's < .05) were noted for finger pressure visual analog scale pain intensity and unpleasantness, ischemic pain threshold, and heat pain threshold, reflecting absence or reversal of inverse blood pressure/pain associations in chronic pain participants. Results suggest that blood pressure-related hypoalgesia can occur even when alpha-2 adrenergic systems are blocked. The possibility of upregulated alpha-2 adrenergic inhibitory function in chronic pain patients with lower blood pressure warrants further evaluation.
Peak bone mass (PBM) is a complex trait, determined by both genetic and environmental factors and also their interactions. Vitamin D receptor (VDR) estrogen receptor alpha (ERalpha), interleukin 6 (IL6), parathyroid hormone (PTH), collagen type I alpha 2 (COL1A2), bone Gla protein (BGP), alpha2-HS glycoprotein (AHSG) are among the important candidate genes of bone metabolism. The study aims to detect significant effect of potential inter-genic action underlying PBM in Chinese females. 361 unrelated healthy premenopausal Chinese females (aged 20 -44 years) with Han ethnicity were recruited from the Shanghai city in China. Bone mineral density (BMD) at the hip and the lumbar spine (L1-4) was measured using a Hologic QDR 2000 + dual-energy X-ray absorptiometry (DXA) scanner. Eight polymorphisms among the seven genes were genotyped, i. e. Apa I in VDR, Pvu II and Xba I in ERa (ERX and ERP, respectively), BsrB I in IL6, BstB I in PTH, Msp I in COL1A2, Hind III in BGP, and Sac I in AHSG, using PCR-RFLP (polymerase chain reaction-restriction fragment length polymorphism) methods. Two-way analysis of variance (ANOVA) showed significant effects of IL6 x ERP interaction on PBM at the total hip (P = 0.019), intertrochanter (P = 0.016), and femoral neck (P =0. 019). The BMD difference between GGPp carriers and GGpp subjects (at these two loci) amounted to 18.0%, 19.5%, and 14.8% at the hip,intertrochanter,and femoral neck,respectively. The potential interaction effect of AHSG x IL6 was observed on femoral neck PBM (P = 0.046). GGSS individuals (at these two loci) had, on average, 18.8% higher femoral neck BMD than those subjects with GGSs genotype. The population-level statistical analysis indicates that IL6 x ERP and AHSG x IL6 have significant inter-genic effect on the genetic determination of PBM in Chinese females.