Characterization of epistasis influencing complex spontaneous obesity in the BSB model

There is growing awareness that complex interactions among multiple genes and environmental factors play an important role in controlling obesity traits. The BSB mouse, which is produced by the backcross of (lean C57BL/6J x lean Mus spretus) x C57BL/6J, provides an excellent model of epistatic obesity. To evaluate potential epistatic interactions among six chromosomal regions previously determined to influence obesity phenotypes, we performed novel Bayesian analyses on the basis of both epistatic and nonepistatic models for four obesity traits: percentage of body fat, adiposity index, total fat mass, and body weight, and also for plasma total cholesterol. The epistatic analysis detected at least one more QTL than the nonepistatic analysis did for all obesity traits. These obesity traits were variously influenced by QTL on chromosomes 2, 7, 12, 15, and 16. Interaction between genes on chromosomes 2 and 12 was present for all obesity traits, accounting for 3-4.8% of the phenotypic variation. Chromosome 12 was found to have weak main effects on all obesity traits. Several different epistatic interactions were also detected for percentage of body fat, adiposity index, and total fat mass. Chromosomes 6 and 12 have not only main effects but also strong epistatic effects on plasma total cholesterol. Our results emphasize the importance of modeling epistasis for discovery of obesity genes.     

Complications of controlled tissue expansion in the pediatric burn patient

All patients at the Burn Institute reconstructed with tissue expanders between June of 1984 and June of 1987 were included in this review. There were 122 expanders used in 77 patients. Complications were defined as "absolute" (23 of 122 expanders, 20 percent) if they resulted in loss of expanders or additional surgery or none of preoperative plan was satisfied or "relative" (14 of 122 expanders, 11 percent) if they included spotty alopecia or alopecia greater than 50 percent or the operative plan only partially satisfied, reflecting poor judgment. The most common absolute complication was prosthetic exposure secondary to wound dehiscence occurring in the scalp area. Complications relative to specific anatomic areas were neck and face, 2 of 20 (10 percent); lower extremity, 1 of 4 (25 percent); trunk, 0 of 6 (0 percent); and scalp, 20 of 92 (22 percent). We feel that this high complication rate in the use of tissue expanders may be unique to the pediatric burn patient. Knowledge of indications for use and potential complications is essential to add this entity to the armamentarium of the burn reconstructive surgeon.     

Knee ligament mechanical properties are not influenced by estrogen or its receptors

Women are at greater risk of tearing their knee anterior cruciate ligament (ACL) than men participating in similar athletic activities. There is currently no conclusive explanation for this disparity; however, as ACL injuries in women have been linked with estrogen fluctuations during the menstrual cycle, one hypothesis is that estrogen has a direct detrimental effect on knee ligament mechanical properties. This study investigated the influence of estrogen and its receptors (ER alpha and ER beta) on knee ligament mechanical properties. This was achieved by testing the viscoelastic and tensile mechanical properties of knee medial collateral ligaments (MCL) and ACLs from: 1) male Sprague-Dawley rats treated with either estrogen (17alpha-ethynylestradiol; 0.03 mg/kg) or an ER alpha-specific agonist (propyl pyrazole triol; 2 mg/kg), and 2) female mice with a null mutation of the gene encoding for ER beta. Estrogen treatment had no significant effects on the viscoelastic or tensile mechanical properties of the rat MCL or ACL. Similarly, pharmacological stimulation of ER alpha using a selective agonist in rats and genetic modulation of ER beta by null mutation of its gene in mice did not influence MCL or ACL properties. These data indicate that estrogen does not have a major direct effect on ligament mechanical properties. Energies for the prevention of the disproportionately high rate of knee ligament injuries in women may be better spent focusing on more established and modifiable risk factors, such as abnormalities in neuromuscular control about the knee.     

Linkage analysis of the genetic determinants of high density lipoprotein concentrations and composition: evidence for involvement of the apolipoprotein A-II and cholesteryl ester transfer protein loci

We have tested for evidence of linkage between the genetic loci determining concentrations and composition of plasma high density lipoproteins (HDL) with the genes for the major apolipoproteins and enzymes participating in lipoprotein metabolism. These genes include those encoding various apolipoproteins (apo), including apoA-I, apoA-II, apoA-IV, apoB, apoC-I, apoC-II, apoC-III, apoE, and apo(a), cholesteryl ester transfer protein (CETP), HDL-binding protein, lipoprotein lipase, and the low density lipoprotein (LDL) receptor. Polymorphisms of these genes, and nearby highly polymorphic simple sequence repeat markers, were examined by quantitative sib-pair linkage analysis in 30 coronary artery disease families consisting of a total of 366 individuals. Evidence for linkage was observed between a marker locus D16S313 linked to the CETP locus and a locus determining plasma HDL-cholesterol concentration (P = 0.002), and the genetic locus for apoA-II and a locus determining the levels of the major apolipoproteins of HDL, apoA-I and apoA-II (P = 0.009 and 0.02, respectively). HDL level was also influenced by the variation at the apo(a) locus on chromosome 6 (P = 0.02). Thus, these data indicate the simultaneous involvement of at least two different genetic loci in the determination of the levels of HDL and its associated lipoproteins.