OBJECTIVE: To test the hypotheses that the accumulation of 30 min of moderate intensity, intermittent exercise, 5 daweek 71 , for 32 weeks, will increase aerobic capacity, alter body composition and improve blood lipids, insulin and glucose. Secondly, to identify individuals who may respond to moderate intensity, intermittent exercise. SUBJECTS: Thirteen sedentary, moderately obese females, aged 43 AE 11 (y), body mass index (BMI) 32.7 AE 7.7 (kgaM 2 ), body fat 40.6 AE 8.8 (%), VO 2 max 24.0 AE 4.6 (mlakg 71 amin 71 ). MEASUREMENTS: Aerobic capacity, body composition, blood lipids, fasting insulin and glucose, energy intake. RESULTS: Group data showed no signi®cant changes for aerobic capacity, body composition, blood lipids, insulin or glucose. However, 7 of the 13 subjects increased aerobic capacity, lost fat weight and improved insulin. Adherence to the exercise regimen was excellent with 82.6 AE 10.0% of the prescribed exercise completed. CONCLUSIONS: Moderate intensity, intermittent exercise for a total of 30 min, 5 daweek, 71 for 32 weeks duration, was not a suf®cient stimulus to signi®cantly increase aerobic capacity, alter weight, body composition or improve blood lipids, insulin or glucose for the entire group. However, those subjects who increased aerobic capacity and decreased fat weight were signi®cantly older, had lower maximal aerobic capacity and greater body fat at baseline compared to the six subjects who did not increase aerobic capacity and decrease fat weight. For both groups, moderate intensity, intermittent exercise showed excellent adherence and this may be a useful model for future research studies.

We studied 19 symptomatic female carriers of the Duchenne muscular dystrophy (DMD) gene. Most of these dystrophinopathy patients had had an erroneous or ambiguous diagnosis prior to dystrophin immunofluorescence testing. We assessed clinical severity by a standardized protocol, measured X-chromosome inactivation patterns in blood and muscle DNA, and quantitated the dystrophin protein content of muscle. We found that patients could be separated into two groups: those showing equal numbers of normal and mutant dystrophin genes in peripheral blood DNA ("random" X-inactivation), and those showing preferential use of the mutant dystrophin gene ("skewed" X-inactivation). In the random X-inactivation carriers, the clinical phenotype ranged from asymptomatic to mild disability, the dystrophin content of muscle was > 60% of normal, and there were only minor histopathologic changes. In the skewed X-inactivation patients, clinical manifestations ranged from mild to severe, but the patients with mild disease were young (5 to 10 years old). The low levels of dystrophin (< 30% on average) and the severe symptoms of the older patients suggested a poor prognosis for those with skewed X-inactivation, and they all showed morphologic changes of dystrophy. The random inactivation patients showed evidence of biochemical "normalization," with higher dystrophin content in muscle than predicted by the number of normal dystrophin genes. Seventy-nine percent of skewed X-inactivation patients (11/14) showed genetic "normalization," with proportionally more dystrophin-positive nuclei in muscle than in blood. In 65% of the skewed X-inactivation patients, dystrophin was not produced by dystrophin-positive nuclei; an average of 20% of myofiber nuclei were genetically dystrophin-positive but did not produce stable dystrophin. Biochemical normalization seems to be the main mechanism for rescue of fibers from dystrophin deficiency in the random X-inactivation patients. In the skewed X-inactivation patients, genetic normalization is active, but production failure of dystrophin by dystrophin-normal nuclei may counteract any effect of biochemical normalization. In the skewed X-inactivation patients, the remodeling of the muscle through cycles of degeneration and regeneration led to threefold increase in the number of dystrophin-competent nuclei in muscle myofibers (3.3 +/- 4.6), while dystrophin content was on the average 1.5-fold less then expected (-1.54 +/- 3.38). Our results permit more accurate prognistic assessment of isolated female dystrophinopathy patients and provide important data with which to estimate the potential effect of gene delivery (gene therapy) in DMD.

The combined effects of exercise and energy restriction on changes in body fat and fat-free mass (FFM) are controversial. This study was conducted to determine whether muscle hypertrophy is possible during weight loss. Fourteen obese females received a 3360-kJ/d liquid diet for 90 d. Seven subjects received a weight training (WT) regimen and seven subjects remained sedentary (C). Biopsy samples were obtained from the vastus lateralis muscle at baseline and after 90 d of treatment. The average weight loss over the 90-d period was 16 kg with approximately 24% of the weight loss from FFM and 76% from fat. The amount and composition of the weight loss did not differ between WT and C groups. The cross-sectional area of slow twitch and fast twitch fibers was unchanged by treatment in C subjects but significantly increased in WT subjects. It appears that weight training can produce hypertrophy in skeletal muscle during severe energy restriction and large-scale weight loss.