Modulation of Cardiac Performance by Motor Protein Gene Transfer

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/75444/1/annals.1420.011.pd

Outcomes of 1½- or 2-ventricle conversion for patients initially treated with single-ventricle palliation

ObjectiveAs outcomes for the Fontan procedure have improved, it has become more difficult to select between a single-ventricle repair or biventricular repair for patients with complex anatomy and 2 ventricles. However, late complications after the Fontan procedure remain a concern. Our strategy, which has favored an aggressive preferential approach for biventricular repair in these patients, has also been applied to patients initially treated on a single-ventricle track elsewhere.MethodsNine patients (4 male patients) who had previously undergone the Fontan procedure (n = 3) or bidirectional cavopulmonary shunting (n = 6) with intent for a later Fontan procedure were referred to our center for complex 1½- or 2-ventricle repair over the last 10 years. Indications for conversion in these patients were protein-losing enteropathy (n = 2), pulmonary arteriovenous malformation (n = 1), and preference for biventricular anatomy (n = 6). The conversion mainly consisted of takedown of the Fontan procedure or bidirectional cavopulmonary shunt connection, reconstruction of 1 or both of venae cavae, creation of an intraventricular pathway for left ventricular output, and placement of a right ventricle–pulmonary artery conduit (Rastelli-type operation).ResultsFive patients underwent 1½-ventricle repair, and 4 had complete biventricular repair. Median cardiopulmonary bypass and aortic crossclamp times were 202 minutes (range, 169–352 minutes) and 129 minutes (range, 100–168 minutes), respectively. There were 2 early deaths and 1 late death. At a median follow-up of 27 months (range, 3.3–99.8 months), all survivors are in New York Heart Association class I.ConclusionsPatients initially treated with intent to perform single-ventricle palliation can be converted to 1½- or 2-ventricle physiology with acceptable outcomes

Early Surgical Morbidity and Mortality in Adults with Congenital Heart Disease: The University of Michigan Experience

Objectives.  To review early surgical outcomes in a contemporary series of adults with congenital heart disease (CHD) undergoing cardiac operations at the University of Michigan, and to investigate possible preoperative and intraoperative risk factors for morbidity and mortality. Methods.  A retrospective medical record review was performed for all patients ≥18 years of age who underwent open heart operations by a pediatric cardiothoracic surgeon at the University of Michigan Congenital Heart Center between January 1, 1998 and December 31, 2004. Records from a cohort of pediatric patients ages 1–17 years were matched to a subset of the adult patients by surgical procedure and date of operation. Results.  In total, 243 cardiac surgical operations were performed in 234 adult patients with CHD. Overall mortality was 4.7% (11/234). The incidence of major postoperative complications was 10% (23/234) with a 19% (45/23) minor complication rate. The most common postoperative complication was atrial arrhythmias in 10.8% (25/234). The presence of preoperative lung or liver disease, prolonged cardiopulmonary bypass and aortic cross clamp times, and postoperative elevated inotropic score and serum lactates were significant predictors of mortality in adults. There was no difference between the adult and pediatric cohorts in terms of mortality and morbidity. Conclusions.  The postoperative course in adults following surgery for CHD is generally uncomplicated and early survival should be expected. Certain risk factors for increased mortality in this patient population may include preoperative presence of chronic lung or liver dysfunction, prolonged cardiopulmonary bypass and aortic cross-clamp times, and postoperative elevated inotropic score and serum lactate levels.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/75596/1/j.1747-0803.2008.00170.x.pd

Characterization of the ZBTB42 gene in humans and mice

A 12 kb haplotype upstream of the key signaling protein gene, AKT1, has been associated with insulin resistance and metabolic syndrome (Devaney et al. 2010). The region contains the first exon and promoter sequences of AKT1, but also includes the complete transcript unit for a highly conserved yet uncharacterized zinc finger-containing protein (ZBTB42). One of the component SNPs of the 12 kb haplotype metabolic syndrome haplotype changes a conserved amino acid in the predicted ZBTB42 protein, increasing the potential significance of the ZBTB42 transcript unit for contributing to disease risk. Using RT-PCR of human and mouse cells, we verified that the two exon ZBTB42 was expressed and correctly spliced in human skeletal muscle, and murine C2C12 cells. Production of peptide antibodies showed the expected protein in human (47 kD) and mouse (49 kD) immunoblots, and murine tissue distribution showed strongest expression in muscle and ovary. Immunostaining showed nuclear localization of the ZBTB42 protein in human muscle. Confocal imaging analyses of murine muscle showed ZBTB42 distributed in the nucleoplasm, with particular enrichment in nuclei underlying the neuromuscular junctions. The genetic association data of metabolic syndrome, coupled with the molecular characterization of the ZBTB42 transcript unit and encoded protein presented here, suggests that ZBTB42 may be involved in metabolic syndrome phenotypes

The angiotensin-converting enzyme insertion/deletion polymorphism rs4340 associates with habitual physical activity among European American adults.

BACKGROUND: The angiotensin-converting enzyme (ACE) insertion/deletion (I/D) polymorphism (rs4340) (ACE DIP) accounts for half of the variability in plasma ACE concentrations. ACE has been widely studied for its influence on sports performance; however, research on its influence in physical activity is limited and inconsistent. We examined the influence of the ACE DIP on physical activity among 461 European Americans. METHODS: Subjects completed the Paffenbarger Physical Activity Questionnaire for weekly walking distance. Multivariate analysis of covariance (MANCOVA) tested log-transformed differences in weekly walking distance among ACE DIP genotypes (II, ID, DD) with gender as a fixed factor, and age and body mass index (BMI) as covariates. Because we found a significant ACE DIPxBMI interaction (P = 0.03), we categorized the sample by normal weight (NW: BMI RESULTS: NW adults with ACE II walked 15.8 ± 11.1 km/week, ID 13.2 ± 10.6 km/week, and DD 17.9 ± 13.0 km/week, with ID walking less than II (P = 0.03) and DD (P = 0.01). OW adults with ACE II walked 16.7 ± 12.6 km/week, ID 13.8 ± 11.6 km/week, and DD 9.7 ± 9.0 km/week, with DD walking less than II (P = 0.02). Weekly walking distance was 8.2 ± 2.4 km/week less among OW adults with ACE DD than NW (P = 0.02). CONCLUSION: BMI interacted with ACE DD such that OW walked ~8.2 km/week less than NW, potentially equating to a body weight differential of ~3.5 kg annually

Skunk River Review 2009-10, vol 22

Welcome to the 2009-2010 edition of The Skunk River Review! We received a record number of entries this year, making this volume one of the best and most competitive! We even added a new category called Art & Literary Analysis to include a growing number of submissions dedicated to inspiration and critique. Each year we continue to receive many fine examples of student writing. Selection is a challenging process but enjoyable as the submissions range from a variety of topics and styles. Selected entries were only minimally edited for clarity. The Skunk River Review focuses on students from various DMACC campuses. It includes selections from College Preparatory Writing classes, Composition I and Composition II classes. All entries generally begin as class assignments and are supported by the instructor.https://openspace.dmacc.edu/skunkriver/1001/thumbnail.jp

PPAR alpha L162V underlies variation in serum triglycerides and subcutaneous fat volume in young males

Background: Of the five sub-phenotypes defining metabolic syndrome, all are known to have strong genetic components ( typically 50 - 80% of population variation). Studies defining genetic predispositions have typically focused on older populations with metabolic syndrome and/or type 2 diabetes. We hypothesized that the study of younger populations would mitigate many confounding variables, and allow us to better define genetic predisposition loci for metabolic syndrome. Methods: We studied 610 young adult volunteers ( average age 24 yrs) for metabolic syndrome markers, and volumetric MRI of upper arm muscle, bone, and fat pre- and post-unilateral resistance training. Results: We found the PPARa L162V polymorphism to be a strong determinant of serum triglyceride levels in young White males, where carriers of the V allele showed 78% increase in triglycerides relative to L homozygotes ( LL = 116 +/- 11 mg/ dL, LV = 208 +/- 30 mg/ dL; p = 0.004). Men with the V allele showed lower HDL ( LL = 42 +/- 1 mg/ dL, LV = 34 +/- 2 mg/ dL; p = 0.001), but women did not. Subcutaneous fat volume was higher in males carrying the V allele, however, exercise training increased fat volume of the untrained arm in V carriers, while LL genotypes significantly decreased in fat volume ( LL = - 1,707 +/- 21 mm(3), LV = 17,617 +/- 58 mm(3); p = 0.002), indicating a systemic effect of the V allele on adiposity after unilateral training. Our study suggests that the primary effect of PPARa L162V is on serum triglycerides, with downstream effects on adiposity and response to training. Conclusion: Our results on association of PPARa and triglycerides in males showed a much larger effect of the V allele than previously reported in older and less healthy populations. Specifically, we showed the V allele to increase triglycerides by 78% ( p = 0.004), and this single polymorphism accounted for 3.8% of all variation in serum triglycerides in males ( p = 0.0037)

MC4R Variant Is Associated With BMI but Not Response to Resistance Training in Young Females

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/93697/1/oby_2147_sm_1.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/93697/2/oby.2010.180.pd

AKT1 polymorphisms are associated with risk for metabolic syndrome

Converging lines of evidence suggest that AKT1 is a major mediator of the responses to insulin, insulin-like growth factor 1 (IGF1), and glucose. AKT1 also plays a key role in the regulation of both muscle cell hypertrophy and atrophy. We hypothesized that AKT1 variants may play a role in the endophenotypes that make up metabolic syndrome. We studied a 12-kb region including the first exon of the AKT1 gene for association with metabolic syndrome-related phenotypes in four study populations [FAMUSS cohort (n = 574; age 23.7 ± 5.7 years), Strong Heart Study (SHS) (n = 2,134; age 55.5 ± 7.9 years), Dynamics of Health, Aging and Body Composition (Health ABC) (n = 3,075; age 73.6 ± 2.9 years), and Studies of a Targeted Risk Reduction Intervention through Defined Exercise (STRRIDE) (n = 175; age 40–65 years)]. We identified a three SNP haplotype that we call H1, which represents the ancestral alleles at the three loci and H2, which represents the derived alleles at the three loci. In young adult European Americans (FAMUSS), H1 was associated with higher fasting glucose levels in females. In middle age Native Americans (SHS), H1 carriers showed higher fasting insulin and HOMA in males, and higher BMI in females. In older African-American and European American subjects (Health ABC) H1 carriers showed a higher incidence of metabolic syndrome. Homozygotes for the H1 haplotype showed about twice the risk of metabolic syndrome in both males and females (p < 0.001). In middle-aged European Americans with insulin resistance (STRRIDE) studied by intravenous glucose tolerance test (IVGTT), H1 carriers showed increased insulin resistance due to the Sg component (p = 0.021). The 12-kb haplotype is a risk factor for metabolic syndrome and insulin resistance that needs to be explored in further populations

Genetic Characterization of Physical Activity Behaviours in University Students Enrolled in Kinesiology Degree Programs

Studies of physical activity behaviours have increasingly shown the importance of heritable factors such as genetic variation. Non-synonymous polymorphisms of alpha-actinin 3 (ACTN3) and the β-adrenergic receptors 1 and 3 (ADRB) have been previously associated with exercise capacity and cardiometabolic health. We thus hypothesized that these polymorphisms are also related to physical activity behaviors in young adults. To test this hypothesis we examined relationships between ACTN3 (R577X), ARDB1 (Arg389Gly) and ADRB3 (Trp64Arg), and physical activity behaviors in university students. We stratified for student enrollment in kinesiology degree programs compared to non-majors as we previously found this to be a predictor of physical activity. We did not identify novel associations between physical activity and ACTN3. However, the minor alleles of ADRB1 and ADRB3 were significantly underrepresented in kinesiology students compared to non-majors. Furthermore, carriers of the ADRB1 minor allele reported reduced participation in moderate physical activity and increased afternoon fatigue compared to ancestral allele homozygotes. Together, these findings suggest that the heritability of physical activity behaviours in young adults may be linked to non-synonymous polymorphisms within β-adrenergic receptors.The accepted manuscript in pdf format is listed with the files at the bottom of this page. The presentation of the authors' names and (or) special characters in the title of the manuscript may differ slightly between what is listed on this page and what is listed in the pdf file of the accepted manuscript; that in the pdf file of the accepted manuscript is what was submitted by the author