Determining the health of muscle cells by in vivo imaging could impact the diagnosis and monitoring of a large number of congenital and acquired muscular or cardiac disorders. However, currently used technologies are hampered by insufficient resolution, lack of specificity, or invasiveness. We have combined intrinsic optical second-harmonic generation from sarcomeric myosin with a novel mathematical treatment of striation pattern analysis, to obtain measures of muscle contractile integrity that correlate strongly with the neuromuscular health of mice suffering from genetic, acquired, and age-related decline in skeletal muscle function. Analysis of biopsies from a pilot group of human volunteers suggests a similar power in quantifying sarcopenic changes in muscle integrity. These results provide the first strong evidence that quantitative image analysis of sarcomere pattern can be correlated with physiological function, and they invite the application of SHG imaging in clinical practice, either in biopsy samples or via microendoscopy.

No abstract

Individuals whose androgen receptors have short polyglutamine tracts (resulting from CAG repeats) may have greater receptor signaling activity of the androgen receptor. We evaluated the association between bone mineral density (BMD) and CAG repeats in 91 older men with normal (control) and low femoral neck (EN) BMD (OP) or a history of femoral fracture (FX). Bioavailable testosterone (BioT) and physical performance, including composite score (EPESE) and physical activity (PASE), were also measured. Comparing FX, OP, and control subjects, we observed BMD Tscores of -2.16 +/- 1.08, -2.26 +/- 0.74, and -0.20 +/- 0.40 (p < 0.001); CAG repeat lengths of 21.9 +/- 2.7, 22.5 +/- 2.4, and 22.3 +/- 2.9 (p = 0.63); BioT levels of 2.29 +/- 1.25, 2.19 +/- 1.11, and 3.99 +/- 1.25 nmol/L (p < 0.001); EPESE scores of 8.0 +/- 3.0, 9.7 +/- 2.0, and 11.3 +/- 0.9 (p < 0.001); and PASE scores of 91 +/- 66, 122 +/- 66, and 200 +/- 55 (p < 0.001), respectively. There were no significant correlations between CAG repeats and BioT or physical performance. Men with osteoporosis or fracture had lower BioT, physical performance, and physical activity than controls. This study found no association between CA G repeats and FN BMD in older men with normal or low BMD or FX.

The number of polyglutamine repeats at the amino terminal determine the androgen receptor polymorphism. The number of polyglutamine repeats is influenced by the number of CAG repeats in the androgen receptor gene. Studies have evaluated the association between CAG repeat polymorphism and bone mineral density, bone turnover markers, and fractures. Both men and women were studied. While differences in CAG repeat polymorphism appear to affect androgen receptor function, the current data do not indicate any consistent effect of androgen receptor gene polymorphism on bone. This could be secondary to a small effect of polymorphism in a complex polygenic disease such as osteoporosis and may require much more extensive study. (The Endocrinologist 2005;15: 23-26) Learning Objectives • Recall what available studies have shown about how polymorphism of CAG repeat length in the androgen receptor gene may relate to bone mass and bone metabolism in men and women. • Describe what is known about how differences in CAG repeat length may influence androgen receptor function. • Give examples of abnormalities in bone and other tissues that may be associated with CAG repeat length.A ndrogen deficiency results in bone loss and androgen treatment can increase bone mass. This can occur both by direct genomic effects mediated by the androgen receptor 1 and by conversion of androgens to estrogens. Recent studies have suggested that a polymorphism of the androgen receptor ͓gene located in long arm of X chromosome (Xq11-12)͔ consisting of variable numbers of polyglutamine repeats (determined by AR gene CAG repeat length) in the N-terminal domain may affect bone metabolism. 2,3 This polymorphism was originally identified in men with the syndrome of spinal and bulbar muscular atrophy (Kennedy syndrome) in which a large (usually between 40 and 62) number of CAG repeats is found. 4,5 There may also be effects on androgen responsiveness within the usual range of CAG repeat from 9 to 40. Shorter repeat lengths are associated with increased transactivation activity of the androgen receptor. 6 Moreover, shorter CAG repeat are associated with more rapid declines in testosterone levels with aging 7-9 and with an increased prevalence of prostate cancer in black men. 10 -12 In this review, we will examine the available data on the association between CAG repeat length and bone metabolism, including our own unpublished study. These studies vary in their conclusions concerning the role of androgen receptor polymorphisms. Thus, at this point, there can be no definite answer as to the role of this genetic variation. The fact that women carry 2 X chromosomes (one of the X chromosomes undergoes random inactivation) and men carry a single X chromosome makes it difficult to interpret study findings. The selection of either the maternal or paternal X chromosome for inactivation occurs by a process involving random choice between the 2 Xs. 13 This random inactivation of X chromosomes in women results in 2 alleles with different CAG repeat lengths of equal distr...

No abstract