Muscle Cellular and Molecular Physiologyhttp://hdl.handle.net/10547/1322262024-03-16T05:39:51Z2024-03-16T05:39:51ZVasoreactivity before and after handgrip training in chronic heart failure patientsCredeur, Daniel P.Mariappan, NithyaFrancis, JosephThomas, DavidMoraes, DenzilWelsch, Michael A.http://hdl.handle.net/10547/5947702020-04-23T08:42:06Z2012-11-01T00:00:00ZVasoreactivity before and after handgrip training in chronic heart failure patients
Credeur, Daniel P.; Mariappan, Nithya; Francis, Joseph; Thomas, David; Moraes, Denzil; Welsch, Michael A.
The purpose of this study was to investigate the vasodilatory and vasoconstrictor responses of the brachial artery in patients with chronic heart failure (CHF) and controls (CON) before and after a period of training and detraining.
2012-11-01T00:00:00ZThe missing risk: MRI and MRS phenotyping of abdominal adiposity and ectopic fat.Thomas, E. LouiseParkinson, James R.Frost, Gary S.Goldstone, Anthony P.Doré, Caroline J.McCarthy, JohnCollins, Adam L.Fitzpatrick, JulieDurighel, GiulianaTaylor-Robinson, Simon D.Bell, Jimmy D.http://hdl.handle.net/10547/5947672020-04-23T07:34:19Z2012-01-01T00:00:00ZThe missing risk: MRI and MRS phenotyping of abdominal adiposity and ectopic fat.
Thomas, E. Louise; Parkinson, James R.; Frost, Gary S.; Goldstone, Anthony P.; Doré, Caroline J.; McCarthy, John; Collins, Adam L.; Fitzpatrick, Julie; Durighel, Giuliana; Taylor-Robinson, Simon D.; Bell, Jimmy D.
Individual compartments of abdominal adiposity and lipid content within the liver and muscle are differentially associated with metabolic risk factors, obesity and insulin resistance. Subjects with greater intra-abdominal adipose tissue (IAAT) and hepatic fat than predicted by clinical indices of obesity may be at increased risk of metabolic diseases despite their "normal" size. There is a need for accurate quantification of these potentially hazardous depots and identification of novel subphenotypes that recognize individuals at potentially increased metabolic risk. We aimed to calculate a reference range for total and regional adipose tissue (AT) as well as ectopic fat in liver and muscle in healthy subjects. We studied the relationship between age, body-mass, BMI, waist circumference (WC), and the distribution of AT, using whole-body magnetic resonance imaging (MRI), in 477 white volunteers (243 male, 234 female). Furthermore, we used proton magnetic resonance spectroscopy (MRS) to determine intrahepatocellular (IHCL) and intramyocellular (IMCL) lipid content. The anthropometric variable which provided the strongest individual correlation for adiposity and ectopic fat stores was WC in men and BMI in women. In addition, we reveal a large variation in IAAT, abdominal subcutaneous AT (ASAT), and IHCL depots not fully predicted by clinically obtained measurements of obesity and the emergence of a previously unidentified subphenotype. Here, we demonstrate gender- and age-specific patterns of regional adiposity in a large UK-based cohort and identify anthropometric variables that best predict individual adiposity and ectopic fat stores. From these data we propose the thin-on-the-outside fat-on-the-inside (TOFI) as a subphenotype for individuals at increased metabolic risk.
2012-01-01T00:00:00ZTelomere maintenance genes SIRT1 and XRCC6 impact age-related decline in telomere length but only SIRT1 is associated with human longevityKim, SangkyuBi, XiuhuaCzarny-Ratajczak, MalwinaDai, JianliangWelsh, David A.Myers, LeannWelsch, Michael A.Cherry, Katie EArnold, JonathanPoon, Leonard W.Jazwinski, S. Michalhttp://hdl.handle.net/10547/5947642020-04-23T07:34:19Z2012-04-01T00:00:00ZTelomere maintenance genes SIRT1 and XRCC6 impact age-related decline in telomere length but only SIRT1 is associated with human longevity
Kim, Sangkyu; Bi, Xiuhua; Czarny-Ratajczak, Malwina; Dai, Jianliang; Welsh, David A.; Myers, Leann; Welsch, Michael A.; Cherry, Katie E; Arnold, Jonathan; Poon, Leonard W.; Jazwinski, S. Michal
Leukocyte telomere length is widely considered a biomarker of human age and in many studies indicative of health or disease. We have obtained quantitative estimates of telomere length from blood leukocytes in a population sample, confirming results of previous studies that telomere length significantly decreases with age. Telomere length was also positively associated with several measures of healthy aging, but this relationship was dependent on age. We screened two genes known to be involved in telomere maintenance for association with the age-related decline in telomere length observed in our population to identify candidate longevity-associated genes. A single-nucleotide polymorphism located in the SIRT1 gene and another in the 3' flanking region of XRCC6 had significant effects on telomere length. At each bi-allelic locus, the minor variant was associated with longer telomeres, though the mode of inheritance fitting best differed between the two genes. No statistical interaction was detected for telomere length between the SIRT1 and XRCC6 variants or between these polymorphisms and age. The SIRT1 locus was significantly associated with longevity (P < 0.003). The frequency of the minor allele was higher in long-lived cases than in young controls, which coincides with the protective role of the minor variant for telomere length. In contrast, the XRCC6 variant was not associated with longevity. Furthermore, it did not affect the association of SIRT1 with exceptional survival. The association of the same variant of SIRT1 with longevity was near significant (P < 0.07) in a second population. These results suggest a potential role of SIRT1 in linking telomere length and longevity. Given the differences between this gene and XRCC6, they point to the distinct impact that alternate pathways of telomere maintenance may have on aging and exceptional survival.
2012-04-01T00:00:00ZReduction of total lung capacity in obese men: comparison of total intrathoracic and gas volumesWatson, R.A.Pride, N.B.Thomas, E. LouiseFitzpatrick, JulieDurighel, GiulianaMcCarthy, JohnMorin, Stanislas X.Ind, P.W.Bell, Jimmy D.http://hdl.handle.net/10547/5947322020-04-23T07:38:57Z2010-03-18T00:00:00ZReduction of total lung capacity in obese men: comparison of total intrathoracic and gas volumes
Watson, R.A.; Pride, N.B.; Thomas, E. Louise; Fitzpatrick, Julie; Durighel, Giuliana; McCarthy, John; Morin, Stanislas X.; Ind, P.W.; Bell, Jimmy D.
Restriction of total lung capacity (TLC) is found in some obese subjects, but the mechanism is unclear. Two hypotheses are as follows: 1) increased abdominal volume prevents full descent of the diaphragm; and 2) increased intrathoracic fat reduces space for full lung expansion. We have measured total intrathoracic volume at full inflation using magnetic resonance imaging (MRI) in 14 asymptomatic obese men [mean age 52 yr, body mass index (BMI) 35–45 kg/m2] and 7 control men (mean age 50 yr, BMI 22–27 kg/m2). MRI volumes were compared with gas volumes at TLC. All measurements were made with subjects supine. Obese men had smaller functional residual capacity (FRC) and FRC-to-TLC ratio than control men. There was a 12% predicted difference in mean TLC between obese (84% predicted) and control men (96% predicted). In contrast, differences in total intrathoracic volume (MRI) at full inflation were only 4% predicted TLC (obese 116% predicted TLC, control 120% predicted TLC), because mediastinal volume was larger in obese than in control [heart and major vessels (obese 1.10 liter, control 0.87 liter, P = 0.016) and intrathoracic fat (obese 0.68 liter, control 0.23 liter, P < 0.0001)]. As a consequence of increased mediastinal volume, intrathoracic volume at FRC in obese men was considerably larger than indicated by the gas volume at FRC. The difference in gas volume at TLC between the six obese men with restriction, TLC < 80% predicted (OR), and the eight obese men with TLC > 80% predicted (ON) was 26% predicted TLC. Mediastinal volume was similar in OR (1.84 liter) and ON (1.73 liter), but total intrathoracic volume was 19% predicted TLC smaller in OR than in ON. We conclude that the major factor restricting TLC in some obese men was reduced thoracic expansion at full inflation.
2010-03-18T00:00:00Z