Trp1-dependent enhancement of salivary gland fluid secretion: role of store-operated calcium entry.
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Adenoviridae↗
Biomedical subjects
D Liao
Publications and source records attributed to D Liao.
Arterial distensibility and physical activity in the ARIC study.
PURPOSE: Arterial distensibility decreases with age. This decrease may be associated with the initiation and/or progression of hypertension and atherosclerosis and may be attenuated by positive lifestyle habits, including habitual physical activity. We tested the hypothesis that self-reported sport, leisure, and work physical activity is associated with greater arterial distensibility (i.e., carotid artery pulsatile diameter changes). METHODS: The Atherosclerosis Risk in Communities (ARIC) study assessed left common carotid arterial diameters and intimal-medial wall thickness (IMT) using B-mode ultrasound techniques, in 10,644 African-American and white men and women aged 45-64 yr and free of cardiovascular disease. RESULTS: Work activity, but not sports or leisure activity, was weakly associated with greater arterial distensibility in an ANCOVA model adjusted for blood pressure and other covariates (diastolic arterial diameter, pulse pressure, pulse pressure squared, age, race, sex, smoking, dietary fat intake, height, education, and clinical center) (P for linear trend = 0.03). Vigorous sports activity was weakly positively associated with arterial distensibility (arterial diameter change (mean +/- SE in mm) 0.42 +/- 0.004 vs 0.41 +/- 0.002 for the 12.7% of participants reporting any vs no vigorous activity, P = 0.02), and this association was not attenuated by adjustment for IMT, body mass index, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, or diabetes. Repeated analyses with traditional arterial stiffness indices showed similar findings for vigorous but not work activity. CONCLUSION: In contrast to several smaller studies, these findings do not support the hypothesis that habitual physical activity has a strong, consistent positive effect on arterial distensibility.
Arteries↗
Association of hemostatic variables with MRI-detected cerebral abnormalities: the atherosclerosis risk in communities study.
OBJECTIVES: Population-based and clinical prospective studies have shown independent associations of several hemostatic factors with ischemic heart disease and stroke. MRI-detected cerebral infarcts and white matter lesions are often detected in elderly individuals without clinical disease. It has been hypothesized that these types of lesions are often the consequence of cerebral ischemic damage and may be the precursors of clinical stroke. METHODS: This study examined the relation between a range of hemostatic factors measured at baseline in middle-aged participants who were free of diagnosed cardiovascular disease in the Atherosclerosis Risk in Communities Study and MRI-detected cerebral abnormalities at a 6-year follow-up examination. RESULTS: Plasma fibrinogen and perhaps von Willebrand factor were associated positively, and protein C was associated negatively, with cerebral infarctions. Adjusted for other risk factors, the odds ratio for cerebral infarction was 1.21 (95% confidence interval, CI = 1.02-1.44) per standard deviation increment for fibrinogen, 1.15 (95% CI = 0.97-1.37) per standard deviation increment for von Willebrand factor, and 0.77 (95% CI = 0.62-0.95) per standard deviation increment for protein C. No hemostatic factor, however, was associated with white matter disease. CONCLUSIONS: This study has only a follow-up MRI, and it is likely that some MRI lesions were present at baseline. Nevertheless, increased levels of fibrinogen and von Willebrand factor and reduced levels of protein C appear to be associated with cerebral infarction identified by MRI.
Aged↗
Abnormal glucose tolerance and increased risk for cardiovascular disease in Japanese-Americans with normal fasting glucose.
OBJECTIVE: To compare the American Diabetes Association (ADA) fasting glucose and the World Health Organization (WHO) oral glucose tolerance test (OGTT) criteria for diagnosing diabetes and detecting people at increased risk for cardiovascular disease (CVD). RESEARCH DESIGN AND METHODS: Study subjects were 596 Japanese-Americans. Fasting insulin, lipids, and C-peptide levels; systolic and diastolic blood pressures (BPs); BMI (kg/m2); and total and intra-abdominal body fat distribution by computed tomography (CT) were measured. Study subjects were categorized by ADA criteria as having normal fasting glucose (NFG), impaired fasting glucose (IFG), and diabetic fasting glucose and by WHO criteria for a 75-g OGTT as having normal glucose tolerance (NGT), impaired glucose tolerance (IGT), and diabetic glucose tolerance (DGT). RESULTS: Of 503 patients with NFG, 176 had IGT and 20 had DGT These patients had worse CVD risk factors than those with NGT . The mean values for NGT, IGT, and DGT, respectively, and analysis of covariance P values, adjusted for age and sex, are as follows; intra-abdominal fat area by CT 69.7, 95.0, and 101.1 cm2 (P < 0.0001); total CT fat area 437.7, 523.3, and 489.8 cm2 (P < 0.0001); fasting triglycerides 1.40, 1.77, and 1.74 mmol/l (P = 0.002); fasting HDL cholesterol 1.56, 1.50, and 1.49 mmol/l (P = 0.02); C-peptide 0.80, 0.90, 0.95 nmol/l (P = 0.002); systolic BP 124.9, 132.4, and 136.9 mmHg (P = 0.0035); diastolic BP 74.8, 77.7, and 78.2 mmHg (P = 0.01). CONCLUSIONS: NFG patients who had IGT or DGT had more intra-abdominal fat and total adiposity; higher insulin, C-peptide, and triglyceride levels; lower HDL cholesterol levels; and higher BPs than those with NGT. Classification by fasting glucose misses many Japanese-Americans with abnormal glucose tolerance and less favorable cardiovascular risk profiles.
Adult↗
[The experimental study of Sr-HAP on reconstructing mandibular bone defect].
OBJECTIVE: Different ration of Sr-HAP was implanted in animals to study the bioreactions in order to prepare for the clinical applications in future. METHODS: 24 rabbits were divided into 3 groups for study. Bone defect of 6 mm x 12 mm x 4 mm was made at the mandibular angle of rabbits and Sr-HAP of different proportion (10%, 5%, 0%) was applied to reform the defect. One group of animals were killed at 1 month, 3 months, 6 months to evaluate the biologic capacity with anatomy, histology, SEM, tetracycline fluorescent marker, ECT and ration histology. RESULTS: Sr-HAP had hardly been rejected by hosts, and in early period after operation the new bone in the Sr-HAP was found with great quantities as the degradation of Sr-HAP much more than that in the pure HA, and the difference of bone quantity can be shown in statistics. CONCLUSIONS: 1. Sr-HAP has a better biocompatibility, biodegradation than pure HA and a excellent osteoinductivity. The existence of Sr-HAP improves the total new bone quantity and the interface of bone, also prolongs the period of new bone increasing. 2. Sr-HAP has a good biodegradation and suitable speed of biodegradating, so the reconstruction effect with Sr-HAP is fairly satisfactory.
Animals↗
Activity identification of anti-caspase-3 mRNA hammerhead ribozyme in both cell-free condition and BRL-3A cells.
OBJECTIVE: To study the transcription effects and cleavage activities of rat caspase-3 specific hammerhead ribozyme (Rz107) in both cell-free conditions and BRL-3A cells. METHODS: Rat caspase-3 gene fragment was cloned into the pGEM-T EASY vector under the T7 promoter control. The 32P-labeled caspase-3 transcript was the target-RNA. Rz107 genes designed against caspase-3 mRNA were cloned into vector p1.5 between 5'-cis-Rz and 3'-cis-Rz. 32P-labeled ribozyme transcripts were incubated with target-RNAs at different conditions and autoradiographed after denaturing gel-electrophoresis. Rz107 was electroporated into BRL-3A cells and the Rz107 expression was analyzed by RT-PCR. RESULTS: In cell-free conditions, Rz107 was active at 37 degrees C. The optimal temperature was 50 degrees C. The Km and Kcat were 14.13 nmol/L and 2.31.min-1 respectively. Intracellular cleavage efficiency of Rz107 was 37%, as analyzed by RT-PCR. This indicated that the design of Rz107 was correct, and Rz107 had the activity of common enzymes. CONCLUSIONS: Rz107 in cell-free conditions possessed perfect specific catalytic cleavage activity, and it can also cleave the target RNA successfully in cells. The results illustrate the feasibility of ribozyme therapy as a potential alternative approach for treating liver disease caused by apoptosis.
Animals↗
Association of educational achievement with pulsatile arterial diameter change of the common carotid artery: the Atherosclerosis Risk in Communities (ARIC) Study, 1987-1992.
Education is strongly inversely associated with common carotid artery intima-media thickness in the Atherosclerosis Risk in Communities (ARIC) Study. The authors extended the ARIC study of preclinical atherosclerosis by evaluating the cross-sectional association of education with common carotid artery elasticity. This study included 10,091 Black and White men and women aged 45-64 years who were free of clinical coronary heart disease and stroke/transient ischemic attack. Arterial elasticity was assessed by pulsatile arterial diameter change (PADC), derived from phase-locked echo-tracking. The smaller the PADC, the stiffer the artery. Education was categorized into grade school, high school without graduation, high school with graduation, vocational school, some college, and graduate/professional school. PADC was directly associated with educational attainment. The mean PADCs, adjusted for age, height, diastolic diameter, systolic blood pressure, pulse pressure (linear and squared), ethnicity, gender, and smoking status, in successively higher education strata were 402 (standard error (SE) 5), 403 (SE 4), 407 (SE 3), 413 (SE 4), 416 (SE 2), and 417 (SE 4) microm (p = 0.007). To the authors' knowledge, this is the first time such an association has been reported. If arterial dilation impairment precedes arterial wall thickening in the atherosclerotic process, as recent studies on endothelial dysfunction suggest, these results indicate that low socioeconomic status may be associated with early arterial pathophysiologic changes-an effect that appears to be mediated by established cardiovascular disease risk factors.
Anthropometry↗
Low heart rate variability in a 2-minute rhythm strip predicts risk of coronary heart disease and mortality from several causes: the ARIC Study. Atherosclerosis Risk In Communities.
BACKGROUND: Low heart rate variability (HRV) is associated with a higher risk of death in patients with heart disease and in elderly subjects and with a higher incidence of coronary heart disease (CHD) in the general population. METHODS AND RESULTS: We studied the predictive value of HRV for CHD and death from several causes in a population study of 14 672 men and women without CHD, aged 45 to 65, by using the case-cohort design. At baseline, in 1987 to 1989, 2-minute rhythm strips were recorded. Time-domain measures of HRV were determined in a random sample of 900 subjects, for all subjects with incident CHD (395 subjects), and for all deaths (443 subjects) that occurred through 1993. Relative rates of incident CHD and cause-specific death in tertiles of HRV were computed with Poisson regression for the case-cohort design. Subjects with low HRV had an adverse cardiovascular risk profile and an elevated risk of incident CHD and death. The increased risk of death could not be attributed to a specific cause and could not be explained by other risk factors. CONCLUSIONS: Low HRV was associated with increased risk of CHD and death from several causes. It is hypothesized that low HRV is a marker of less favorable health.
Aged↗
Serum albumin level as a predictor of incident coronary heart disease: the Atherosclerosis Risk in Communities (ARIC) study.
Various studies have reported an inverse association between serum albumin level and incident coronary heart disease (CHD), though biologic mechanisms have not been established. The authors examined the association between serum albumin level and CHD in the Atherosclerosis Risk in Communities cohort, comprising 14,506 White and African-American middle-aged men and women. The mean albumin level in this population was 3.9 g/dl (standard deviation 0.3). During 5.2 years of follow-up, 470 incident CHD events occurred. The hazard ratio for incident CHD associated with a 1-standard deviation decrease in serum albumin level was 1.26 (95% confidence interval (CI): 1.15, 1.38) after adjustment for age, gender, and ethnicity and 1.18 (95% CI: 1.07, 1.30) after additional adjustment for covariates related to CHD. Hazard ratios were similar across gender and ethnic groups. However, there was statistically significant effect modification by smoking status, with hazard ratios of 1.01 (95% CI: 0.84, 1.22) among never smokers, 1.09 (95% CI: 0.92, 1.30) among former smokers, and 1.35 (95% CI: 1.17, 1.54) among current smokers. Further adjustment for factors related to renal disease, nutrition, platelet aggregation, inflammation, use of angiotensin-converting enzyme inhibitors, and hemostasis factors attenuated the albumin-CHD relation only slightly. In this study, serum albumin was inversely associated with incident CHD at the baseline examination in current smokers but not in never or former smokers. Albumin level may be a marker of susceptibility to the inflammatory response that results from smoking.
Biomarkers↗
Gene conversion drives within genic sequences: concerted evolution of ribosomal RNA genes in bacteria and archaea.
Multiple copies of a given ribosomal RNA gene family undergo concerted evolution such that sequences of all gene copies are virtually identical within a species although they diverge normally between species. In eukaryotes, gene conversion and unequal crossing over are the proposed mechanisms for concerted evolution of tandemly repeated sequences, whereas dispersed genes are homogenized by gene conversion. However, the homogenization mechanisms for multiple-copy, normally dispersed, prokaryotic rRNA genes are not well understood. Here we compared the sequences of multiple paralogous rRNA genes within a genome in 12 prokaryotic organisms that have multiple copies of the rRNA genes. Within a genome, putative sequence conversion tracts were found throughout the entire length of each individual rRNA genes and their immediate flanks. Individual conversion events convert only a short sequence tract, and the conversion partners can be any paralogous genes within the genome. Interestingly, the genic sequences undergo much slower divergence than their flanking sequences. Moreover, genomic context and operon organization do not affect rRNA gene homogenization. Thus, gene conversion underlies concerted evolution of bacterial rRNA genes, which normally occurs within genic sequences, and homogenization of flanking regions may result from co-conversion with the genic sequence.
Archaea↗
GRASP-1: a neuronal RasGEF associated with the AMPA receptor/GRIP complex.
The PDZ domain-containing proteins, such as PSD-95 and GRIP, have been suggested to be involved in the targeting of glutamate receptors, a process that plays a critical role in the efficiency of synaptic transmission and plasticity. To address the molecular mechanisms underlying AMPA receptor synaptic localization, we have identified several GRIP-associated proteins (GRASPs) that bind to distinct PDZ domains within GRIP. GRASP-1 is a neuronal rasGEF associated with GRIP and AMPA receptors in vivo. Overexpression of GRASP-1 in cultured neurons specifically reduced the synaptic targeting of AMPA receptors. In addition, the subcellular distribution of both AMPA receptors and GRASP-1 was rapidly regulated by the activation of NMDA receptors. These results suggest that GRASP-1 may regulate neuronal ras signaling and contribute to the regulation of AMPA receptor distribution by NMDA receptor activity.
Amino Acid Sequence↗
Activation of p53 or loss of the Cockayne syndrome group B repair protein causes metaphase fragility of human U1, U2, and 5S genes.
Infection by adenovirus 12, transfection with the Ad12 E1B 55 kDa gene, or activation of p53 cause metaphase fragility of four loci (RNU1, PSU1, RNU2, and RN5S) each containing tandemly repeated genes for an abundant small RNA (U1, U2, and 5S RNA). We now show that loss of the Cockayne syndrome group B protein (CSB) or overexpression of the p53 carboxy-terminal domain induces fragility of the same loci; moreover, p53 interacts with CSB in vivo and in vitro. We propose that CSB functions as an elongation factor for transcription of structured RNAs, including some mRNAs. Activation of p53 would inhibit CSB, stalling transcription complexes and locally blocking chromatin condensation. Impaired transcription elongation may also explain the diverse clinical features of Cockayne syndrome.
Acetylation↗
Treatment preferences among depressed primary care patients.
OBJECTIVE: To understand patient factors that may affect the probability of receiving appropriate depression treatment, we examined treatment preferences and their predictors among depressed primary care patients. DESIGN: Patient questionnaires and interviews. SETTING: Forty-six primary care clinics in 7 geographic regions of the United States. PARTICIPANTS: One thousand one hundred eighty-seven English- and Spanish-speaking primary care patients with current depressive symptoms. MEASUREMENTS AND MAIN RESULTS: Depressive symptoms and diagnoses were determined by the Composite International Diagnostic Interview (CIDI) and the Center for Epidemiological Studies Depression Scale (CES-D). Treatment preferences and characteristics were assessed using a self-administered questionnaire and a telephone interview. Nine hundred eight-one (83%) patients desired treatment for depression. Those who preferred treatment were wealthier (odds ratio [OR], 3.7; 95% confidence interval [95% CI], 1.8 to 7.9; P =.001) and had greater knowledge about antidepressant medication ( OR, 2.6; 95% CI, 1.6 to 4.4; P </=.001) than those who did not want treatment. A majority ( 67%, n = 660) of those preferring treatment preferred counseling, with African Americans (OR, 2.2; 95% CI, 1.0 to 4.8, P =. 04 compared to whites) and those with greater knowledge about counseling (OR, 2.1; 95% CI, 1.6 to 2.7, P </=.001) more likely to choose counseling. Three hundred twelve ( 47%) of the 660 desiring counseling preferred group over individual counseling. Depression severity was only a predictor of preference among those already in treatment. CONCLUSIONS: Despite low rates of treatment for depression, most depressed primary care patients desire treatment, especially counseling. Preferences for depression treatment vary by ethnicity, gender, income, and knowledge about treatments.
Adolescent↗
Adenovirus E1B 55-kilodalton oncoprotein inhibits p53 acetylation by PCAF.
The adenovirus E1B 55-kDa protein binds to cellular tumor suppressor p53 and inactivates its transcriptional transactivation function. p53 transactivation activity is dependent upon its ability to bind to specific DNA sequences near the promoters of its target genes. It was shown recently that p53 is acetylated by transcriptional coactivators p300, CREB bidning protein (CBP), and PCAF and that acetylation of p53 by these proteins enhances p53 sequence-specific DNA binding. Here we show that the E1B 55-kDa protein specifically inhibits p53 acetylation by PCAF in vivo and in vitro, while acetylation of histones and PCAF autoacetylation is not affected. Furthermore, the DNA-binding activity of p53 is diminished in cells expressing the E1B 55-kDa protein. PCAF binds to the E1B 55-kDa protein and to a region near the C terminus of p53 encompassing Lys-320, the specific PCAF acetylation site. We further show that the E1B 55-kDa protein interferes with the physical interaction between PCAF and p53, suggesting that the E1B 55-kDa protein inhibits PCAF acetylase function on p53 by preventing enzyme-substrate interaction. These results underscore the importance of p53 acetylation for its function and suggest that inhibition of p53 acetylation by viral oncoproteins prevent its activation, thereby contributing to viral transformation.
Acetylation↗
Parental history of stroke predicts subclinical but not clinical stroke: the Atherosclerosis Risk in Communities Study.
BACKGROUND AND PURPOSE: An individual with a positive family history of a disease may be at increased risk for the disease. We sought to examine whether parental history of stroke is associated with subclinical or clinical stroke in the Atherosclerosis Risk in Communities (ARIC) Study, and whether any observed association is independent of established stroke risk factors. METHODS: Parental history of stroke was determined by home interview at the baseline examination. Cerebral MRI was performed on individuals from 2 ARIC field centers. Subclinical cerebral infarct cases (n=202) were defined by the presence of cerebral infarcts >3 mm. The comparison group for the subclinical cases included all individuals participating in the MRI examination who were not identified as a subclinical case (n=1533). Incidence of clinical ischemic stroke was determined by following the ARIC cohort for potential cerebrovascular events. Two hundred sixty-one validated ischemic strokes were identified; 13 775 individuals from the ARIC cohort did not experience an ischemic event. RESULTS: Parental history of stroke was significantly associated with subclinical stroke after adjusting for age, gender, and race (OR 1.67, 95% CI1.23 to 2.26) and after further adjustment for multiple stroke risk factors (OR1. 64, 95% CI1.20 to 2.24). Parental history of stroke was not a significant predictor of clinical stroke in either adjustment model. CONCLUSIONS: The observed increased risk of subclinical stroke among individuals with a parental history of stroke is consistent with the expression of genetic susceptibility, a shared environment, or both in the etiology of stroke. This effect did not appear to be mediated by established stroke risk factors. Parental history of stroke does not confer an increased risk of clinical stroke in this sample of middle-aged Americans.
Age Factors↗
Arterial stiffness and the development of hypertension.
Evidence is accumulating in support of the plausible notion that lower arterial elasticity is associated with an increased risk of cardiovascular disease manifestations. Conventional indices of arterial stiffness are compared to a newer method (blood pressure-adjusted pulsatile arterial diameter change) in terms of blood pressure dependence. Impaired elasticity of larger arteries is an antecedent factor in the natural history of blood pressure elevation at the population level. Strong evidence supports the notion that lower arterial elasticity in the medium-sized arteries is associated with the development of hypertension.
Arteries↗
[Preparation and identification of hammerhead ribozyme in vitro against rat caspase-3 mRNA fragment].
OBJECTIVE: To study the transcript effect and cleavage activity in vitro of rat Caspase-3 specific ribozyme (Rz107 and Rz544). METHODS: Rat caspase-3 gene fragment was cloned into T-vector under the control of T7 promoter. (32)P-labeled caspase-3 transcript was target-RNA. Rz107 and Rz544 genes against caspase-3 mRNA were cloned and transcribed in vitro. Cleavage reaction was detected. RESULTS: It was found that Rz107 was active at 37 degrees C and more so at higher temperature within allowing temperature range. The optimal temperature was 50 degrees C. For Rz107, Km and kcat was 14.13 nmol/L and 2.31 min(-1), respectively. However, the Rz544 had no cleavage activity at all. CONCLUSION: Rz107 prepared in vitro possesses the perfect specific catalytic cleavage activity. It is hopeful that Rz107 would be developed to be a new nucleic acid drug that could effectively inhibit the inflammation of hepatitis through cleaving the key gene, caspase-3, in apoptosis in vivo.
Animals↗
Striking bimodal methylation of the repeat unit of the tandem array encoding human U2 snRNA (the RNU2 locus).
The genes encoding human U2 small nuclear RNA are arrayed in tandem (the RNU2 locus) and have undergone concerted evolution for >35 Myr. Tandem organization of repetitive sequences may facilitate recombination that underlies concerted evolution, but could risk instability. Since DNA methylation plays a crucial role in genome stability, we investigated the methylation status of the RNU2 locus to understand the forces maintaining array stability and homogeneity. We found that a region of approximately 1.5 kb spanning the U2 promoter, U2 gene sequence, and CT microsatellite is completely unmethylated, whereas the rest of the repeat is heavily methylated. Since the U2 transcription enhancer DSE and CT microsatellite mark the boundaries between methylated and unmethylated domains, they might function as cis-acting elements for establishing and maintaining proper methylation at the RNU2 locus. Interestingly, the RNU2 locus in human fibrosarcoma line HT1080 is hypomethylated, and de novo methylation did not occur in an artificial U2 tandem array introduced by stable transfection. The observed bimodal methylation pattern may be important for both efficient transcription of U2 gene and maintenance of nearly perfect tandem arrays in somatic cells.
Cell Line↗