Nemaline myopathy is a hereditary disease of skeletal muscle defined by a distinct pathology of electron-dense accumulations within the sarcomeric units called rods, muscle weakness and, in most cases, a slow oxidative (type 1) fiber predominance. We generated a transgenic mouse model to study this disorder by expressing an autosomal dominant mutant of alpha-tropomyosin(slow) previously identified in a human cohort. Rods were found in all muscles, but to varying extents which did not correlate with the amount of mutant protein present. In addition, a pathological feature not commonly associated with this disorder, cytoplasmic bodies, was found in the mouse and subsequently identified in human samples. Muscle weakness is a major feature of this disease and was examined with respect to fiber composition, degree of rod-containing fibers, fiber mechanics and fiber diameter. Hypertrophy of fast, glycolytic (type 2B) fibers was apparent at 2 months of age. Muscle weakness was apparent in mice at 5-6 months of age, mimicking the late onset observed in humans with this mutation. The late onset did not correlate with observed changes in fiber type and rod pathology. Rather, the onset of muscle weakness correlates with an age-related decrease in fiber diameter and suggests that early onset is prevented by hypertrophy of fast, glycolytic fibers. We suggest that the clinical phenotype is precipitated by a failure of the hypertrophy to persist and therefore compensate for muscle weakness.

SUMMARY1. Single fast-twitch fibres from the extensor digitorum longus muscle of the rat, Rattus norvegicus, and single twitch fibres from the iliofibularis muscle of the cane toad, Bufo marinus, were mechanically skinned and then used to measure maximally Ca2+-activated ([Ca21] > 003 mmol 1-1) isometric force production, myofibrillar MgATPase activity and fibre stiffness at different sarcomere lengths. MgATP hydrolysis was linked by an enzyme cascade to the oxidation of NADH (nicotinamide adenine dinucleotide, reduced form) and was monitored by a microfluorimetric system. Fibre stiffness was measured from the amplitude of force oscillations generated by small sinusoidal length changes.2. At sarcomere lengths which were optimal for isometric force production (around 2-7,am for rat and 22,um for toad fibres) the myofibrillar MgATPase activity (mean +S.E.M.) at 21-22°C was found to be 3-80+ 053 molecules MgATP hydrolysed s-' per myosin head for eight rat fibres and 6-35+0O77 s-1 per myosin head for four toad fibres.3. At sarcomere lengths shorter than 2-7 ,um in rat fibres and 2-2 ,um in toad fibres, MgATPase and stiffness remained elevated and close to their respective values at 2-7 ,um in rat fibres and 2-2 ,um in toad fibres even when the isometric force decreased to near zero levels.4. The dissociation at short sarcomere lengths of myofibrillar MgATPase activity and fibre stiffness from isometric force suggests that the cross-bridge cycle is not greatly affected by double actin filament overlap with the myosin filaments at short sarcomere lengths. Moreover, the results suggest that cross-bridges can be formed by myosin with actin filaments projecting from the nearest Z-line and from the Z-line in the other half of the sarcomere.5. These results help to reconcile energetic and mechanical data obtained by others at short sarcomere lengths and can be explained within the framework of the sliding filament theory.

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Objective To assess the effect of respiratory training (RT) on lung function, activity tolerance and acute exacerbation frequency with chronic obstructive pulmonary disease (COPD). Design A randomised controlled trial. Setting Outpatient clinic and home of the COPD patients, Zhengzhou City, China. Subjects Sixty participants with COPD were randomised into two groups: an intervention group ( n = 30) which received the RT in self-management and a control group ( n = 30) that received an education program during the study. Intervention Pulmonary function, activity tolerance and frequency of acute exacerbation of these COPD patients were evaluated before and after the program. The intervention and control programs were delivered at monthly outpatient clinic visits over a period of 12 months. The pulmonary rehabilitation (PR) program was conducted by a physiotherapist (who delivered RT to the participant over a minimum of 1 h per visit) for the intervention group, whereas the control group received routine health education provided by physiotherapists. The intervention group patients were then instructed to perform exercises at home as taught in the RT at least 5 days per week at home. Results After 12 months of RT, the lung function and the activity tolerance of the COPD patients in the intervention group were significantly improved and the exacerbation frequency was also decreased. Conclusion Long-term RT can improve lung function and activity tolerance while decreasing the frequency of acute exacerbation for COPD patients.

Fluorometric recordings of NADH (nicotinamide adenine dinucleotide) were made on rabbit papillary muscles. The specimens were placed between the UV light source and a small window of the detection stage. As the muscle was moved over the window in a transverse direction, simultaneous measurements could be taken of transmitted UV light and fluorescent light for various thicknesses of tissue. It is concluded that a muscle thickness of 0.65 mm is optimal before absorption of the incident light decreases the fluorescence signal.