Differentially Expressed miRNAs Influence Metabolic Processes in Pituitary Oncocytoma

Neurochemical Research - Spindle cell oncocytomas (SCO) of the pituitary are rare tumors accounting for 0.1–0.4% of all sellar tumors. Due to their rarity, little information is available...     

Epidemiology and factor analysis of obesity, type II diabetes, hypertension, and dyslipidemia (syndrome X) on the Island of Kosrae, Federated States of Micronesia

OBJECTIVES: Obesity, type II diabetes, hypertension, and dyslipidemia are major causes of morbidity and mortality throughout the world. Though these disorders often cluster in individuals and families and are collectively known as syndrome X, the basis for this aggregation is not well understood. To further understand the pathogenesis of syndrome X, a comprehensive epidemiological study was undertaken on the Pacific Island of Kosrae, Federated States of Micronesia (FSM). METHODS: The entire adult (>20 years of age) population of Kosrae underwent a clinical evaluation that included a questionnaire that noted the participants' sex, family data including listing of biological parents, siblings, and children, smoking status, village of residence, age and health status. The medical evaluation included: anthropometric measures (weight, height, waist, hip), serum chemistries (leptin, fasting blood sugar (FBS), insulin, total cholesterol (TC), triglycerides (TG), and apolipoproteins B and A-I (apo B and apo A-I) and blood pressure (BP) measurements. RESULTS: Obesity (BMI >/=35) was found in 24%, diabetes (FBS >/=126 or 2-hour oral glucose tolerance test >/=200) in 12%, hypertension (SBP >/=140 or DBP >/=90) in 17%, and dyslipidemia (TC >/=240 or TG >/=200 or apo B >/=120 or apo A-I 相似文献   

Ascertainment and anticipation in family studies

Many human diseases show anticipation; that is, disease occurs earlier (or with greater severity) in successive generations. In a computer simulation, we assessed the degree of anticipation that one would expect to see in two-generation breast cancer families. Under reasonable assumed distributions for age at cancer onset, number of children, and mortality, we find a consistent earlier mean age at diagnosis in daughters than in mothers, but the same mean age at diagnosis in affected aunts and nieces. We compare these results with published pedigree data for familial breast cancer that show substantial anticipation in affected daughters compared to their mothers. We find that at least some anticipation is expected in human disease families even when the disease is stable and families are ascertained without obvious sampling bias. We further demonstrate that such anticipation is reduced when comparing affected children to the parents' affected siblings.     

A Transmission/Disequilibrium Test That Allows for Genotyping Errors in the Analysis of Single-Nucleotide Polymorphism Data

The present study assesses the effects of genotyping errors on the type I error rate of a particular transmission/disequilibrium test (TDT(std)), which assumes that data are errorless, and introduces a new transmission/disequilibrium test (TDT(ae)) that allows for random genotyping errors. We evaluate the type I error rate and power of the TDT(ae) under a variety of simulations and perform a power comparison between the TDT(std) and the TDT(ae), for errorless data. Both the TDT(std) and the TDT(ae) statistics are computed as two times a log-likelihood difference, and both are asymptotically distributed as chi(2) with 1 df. Genotype data for trios are simulated under a null hypothesis and under an alternative (power) hypothesis. For each simulation, errors are introduced randomly via a computer algorithm with different probabilities (called "allelic error rates"). The TDT(std) statistic is computed on all trios that show Mendelian consistency, whereas the TDT(ae) statistic is computed on all trios. The results indicate that TDT(std) shows a significant increase in type I error when applied to data in which inconsistent trios are removed. This type I error increases both with an increase in sample size and with an increase in the allelic error rates. TDT(ae) always maintains correct type I error rates for the simulations considered. Factors affecting the power of the TDT(ae) are discussed. Finally, the power of TDT(std) is at least that of TDT(ae) for simulations with errorless data. Because data are rarely error free, we recommend that researchers use methods, such as the TDT(ae), that allow for errors in genotype data.     

Effects of fenofibrate on lipid parameters in obese rhesus monkeys

Fenofibrate is a member of the fibrate class of hypolipidemic agents used clinically to treat hypertriglyceridemia and mixed hyperlipidemia. The fibrates were developed primarily on the basis of their cholesterol and triglyceride lowering in rodents. Fibrates have historically been ineffective at lowering triglycerides in experimentally-induced dyslipidemia in nonhuman primate models. The spontaneously obese rhesus monkey is a well-recognized animal model for the study of human obesity and type 2 diabetes, and many of these monkeys exhibit naturally occurring lipid abnormalities, including elevated triglycerides and low HDL cholesterol (HDL-C), similar to patients with type 2 diabetes. To explore whether the obese rhesus model was predictive of the lipid lowering effects of fibrates, we evaluated fenofibrate in six hypertriglyceridemic, hyperinsulinemic, nondiabetic animals in a 20-week, dose-escalating study. The study consisted of a 4-week baseline period, two treatment periods of 10 mg/kg twice daily (b.i.d) for 4 weeks and 30 mg/kg b.i.d. for 8 weeks, and a 4-week washout period. Fenofibrate (30 mg/kg b.i.d) decreased serum triglycerides 55% and LDL-C 27%, whereas HDL-C increased 35%. Apolipoproteins B-100 and C-III levels were also reduced 70% and 29%, respectively. Food intake, body weight, and plasma glucose were not affected throughout the study. Interestingly, plasma insulin levels decreased 40% during the 30 mg/kg treatment period, suggesting improvement in insulin sensitivity. These results support the use of obese rhesus monkey as an excellent animal model for studying the effects of novel hypolipidemic agents, particularly agents that impact serum triglycerides and HDL-C.     

A principal-components approach based on heritability for combining phenotype information

For many traits, genetically relevant disease definition is unclear. For this reason, researchers applying linkage analysis often obtain information on a variety of items. With a large number of items, however, the test statistic from a multivariate analysis may require a prohibitively expensive correction for the multiple comparisons. The researcher is faced, therefore, with the issue of choosing which variables or combinations of variables to use in the linkage analysis. One approach to combining items is to first subject the data to a principal components analysis, and then perform the linkage analysis of the first few principal components. However, principal-components analyses do not take family structure into account. Here, an approach is developed in which family structure is taken into account when combining the data. The essence of the approach is to define principal components of heritability as the scores with maximum heritability in the data set, subject to being uncorrelated with each other. The principal components of heritability may be calculated as the solutions to a generalized eigensystem problem. Four simulation experiments are used to compare the power of linkage analyses based on the principal components of heritability and the usual principal components. The first of the experiments corresponds to the null hypothesis of no linkage. The second corresponds to a setting where the two kinds of principal components coincide. The third corresponds to a setting in which they are quite different and where the first of the usual principal components is not expected to have any power beyond the type I error rate. The fourth set of experiments corresponds to a setting where the usual principal components and the principal components of heritability differ, but where the first of the usual principal components is not without power. The results of the simulation experiments indicate that the principal components of heritability can be substantially different from the standard principal components and that when they are different, substantial gains in power can result by using the principal components of heritability in place of the standard principal components in linkage analyses.     

Accuracy of transrectal ultrasonography for determination of pregnancy in sheep: effect of fasting and handling of the animals

The present study was performed to investigate the effect of previous fasting and lifting of the abdomen of the ewes during transrectal ultrasonographic scanning on the results of early pregnancy diagnosis. Ewes of four flocks (A, B, C and D; all Awassi x Merino ewes, n = 1247 ) aged 0.7-10 years were used in this study. These ewes were estrus synchronized and artificially inseminated. From 2 weeks later onwards, fertile rams were kept with the ewes of flocks A, B and C ( n=949 ) for natural breeding, while ewes of flock D ( n=298 ) were re-inseminated 17 days later. Transrectal ultrasonography (5 MHz) was carried out in ewes of flocks A, B and C on four separate occasions but only once in ewes of flock D. For final analysis, animals were divided over two groups: ewes of Group 1 ( n=949 scans) were scanned in a standing position within the milking parlor. Animals of Group 2 ( n=764 scans) were scanned by the same operator and with the same scanning technique, but these ewes were fasted for 12h prior to scanning and the abdominal wall was lifted, just in front of the udder during scanning. The sensitivity of the test for diagnosing pregnancy at Days 18-24, 25-30, 31-40 and 41-50 was 21.8, 32.3, 63.3 and 50% in Group 1, and 46, 92.5, 92.3 and 96.8% in Group 2, respectively. Only within Group 1, the sensitivity of the test was higher in young ewes (0.7-2 years) than in older ones (>2-10 years). Significant differences were observed at scan periods Days 18-24 and Days 41-50 of gestation. It is concluded that, fasting prior to scanning and lifting the abdomen during scanning significantly improve the accuracy of transrectal ultrasonographic pregnancy diagnosis in Awassi x Merino ewes.     

Glucose ingestion attenuates the exercise-induced increase in circulating heat shock protein 72 and heat shock protein 60 in humans

Heat shock protein (Hsp) 72 is a cytosolic stress protein that is highly inducible by several factors including exercise. Hsp60 is primarily mitochondrial in cellular location, plays a key role in the intracellular protein translocation and cytoprotection, is increased in skeletal muscle by exercise, and is found in the peripheral circulation of healthy humans. Glucose deprivation increases Hsp72 in cultured cells, whereas reduced glycogen availability elevates Hsp72 in contracting human skeletal muscle. To determine whether maintained blood glucose during exercise attenuates the exercise-induced increase in intramuscular and circulating Hsp72 and Hsp60, 6 males performed 120 minutes of semirecumbent cycling at approximately 65% maximal oxygen uptake on 2 occasions while ingesting either a 6.4% glucose (GLU) or sweet placebo (CON) beverage throughout exercise. Muscle biopsies, obtained before and immediately after exercise, were analyzed for Hsp72 and Hsp60 protein expression. Blood samples were simultaneously obtained from a brachial artery, a femoral vein, and the hepatic vein before and during exercise for the analysis of serum Hsp72 and Hsp60. Leg and hepatosplanchnic blood flow were measured to determine Hsp72-Hsp60 flux across these tissue beds. Neither exercise nor glucose ingestion affected the Hsp72 or Hsp60 protein expression in, or their release from, contracting skeletal muscle. Arterial serum Hsp72 increased (P < 0.05) throughout exercise in both trials but was attenuated (P < 0.05) in GLU. This may have been in part because of the increased (P < 0.05) hepatosplanchnic Hsp72 release in CON, being totally abolished (P < 0.05) in GLU. Serum Hsp60 increased (P < 0.05) after 60 minutes of exercise in CON before returning to resting levels at 120 minutes. In contrast, no exercise-induced increase in serum Hsp60 was observed in GLU. We detected neither hepatosplanchnic nor contracting limb Hsp60 release in either trial. In conclusion, maintaining glucose availability during exercise attenuates the circulating Hsp response in healthy humans.     

Light-directed 5'-->3' synthesis of complex oligonucleotide microarrays

Light-directed synthesis of high-density microarrays is currently performed in the 3'-->5' direction due to constraints in existing synthesis chemistry. This results in the probes being unavailable for many common types of enzymatic modification. Arrays that are synthesized in the 5'-->3' direction could be utilized to perform parallel genotyping and resequencing directly on the array surface, dramatically increasing the throughput and reducing the cost relative to existing techniques. In this report we demonstrate the use of photoprotected phosphoramidite monomers for light-directed array synthesis in the 5'-->3' direction, using maskless array synthesis technology. These arrays have a dynamic range of >2.5 orders of magnitude, sensitivity below 1 pM and a coefficient of variance of <10% across the array surface. Arrays containing >150,000 probe sequences were hybridized to labeled mouse cRNA producing highly concordant data (average R(2) = 0.998). We have also shown that the 3' ends of array probes are available for sequence-specific primer extension and ligation reactions.