Activation of the skeletal α-actin promoter during muscle regeneration

Little is known conerning promoter regulation of genes in regenerating skeletal muscles. In young rats, recovery of muscle mass and protein content is complete within 21 days. During the initial 5–10 days of regeneration, mRNA abundance for IGF-I, myogenin and MyoD have been shown to be dramatically increased. The skeletal -actin promoter contains E box and serum response element (SRE) regulatory regions which are directly or indirectly activated by myogenin (or MyoD) and IGF-I proteins, respectively. We hypothesized that the skeletal -actin promoter activity would increase during muscle regeneration, and that this induction would occur before muscle protein content returned to normal. Total protein content and the percentage content of skeletal -actin protein was diminished at 4 and 8 days and re-accumulation had largely occurred by 16 days post-bupivacaine injection. Skeletal - actin mRNA per whole muscle was decreased at day 8, and thereafter returned to control values. During regeneration at day 8, luciferase activity (a reporter of promoter activity) directed by –424 skeletal -actin and –99 skeletal -actin promoter constructs was increased by 700% and 250% respectively; however, at day 16, skeletal -actin promoter activities were similar to control values. Thus, initial activation of the skeletal - actin promoter is associated with regeneration of skeletal muscle, despite not being sustained during the later stages of regrowth. The proximal SRE of the skeletal -actin promoter was not sufficient to confer a regeneration-induced promoter activation, despite increased serum response factor protein binding to this regulatory element in electrophoretic mobility shift assays. Skeletal -actin promoter induction during regeneration is due to a combination of regulatory elements, at least including the SRE and E box. © Kluwer Academic Publishers.     

Changes in muscle recruitment patterns during skill acquisition

The control of movement is predicated upon a system of constraints of musculoskeletal and neural origin. The focus of the present study was upon the manner in which such constraints are adapted or superseded during the acquisition of motor skill. Individuals participated in five experimental sessions, in which they attempted to produce abduction-adduction movements of the index finger in time with an auditory metronome. During each trial, the metronome frequency was increased in eight steps from an individually determined base frequency. Electromyographic (EMG) activity was recorded from first dorsal interosseous (FDI), first volar interosseous (FVI), flexor digitorum superficialis (FDS), and extensor digitorum communis (EDC) muscles. The movements produced on the final day of acquisition more accurately matched the required profile, and exhibited greater spatial and temporal stability, than those generated during initial performance. In the early stages of skill acquisition, an alternating pattern of activation in FDI and FVI was maintained, even at the highest frequencies. In contrast, as the frequency of movement was increased, activity in FDS and EDC was either tonic or intermittent. As learning proceeded, alterations in recruitment patterns were expressed primarily in the extrinsic muscles (EDC and FDS). These changes took the form of increases in the postural role of these muscles, shifts to phasic patterns of activation, or selective disengagement of these muscles. These findings suggest that there is considerable flexibility in the composition of muscle synergies, which is exploited by individuals during the acquisition of coordination.     

The dynamics of isometric bimanual coordination

Eight right-handed subjects performed rhythmic isometric applications of torque in the directions of pronation and supination of the forearm, in single limb and bimanual conditions. Bimanual movements were executed in either in-phase (homologous muscles simultaneously active) or anti-phase (non-homologous muscles active simultaneously) modes of coordination, in self-paced and frequency-scaled conditions. In the inphase (frequency-scaled) condition, subjects were required to synchronise (applications of torque) with each beat of a metronome, either in the direction of pronation or supination. In the anti-phase (frequency-scaled) condition, subjects were required to synchronise (applications of torque) with each beat of the metronome, either to the left or to the right. Departures from the anti-phase mode of coordination were observed as pacing frequency was increased. However, these departures were of short duration and the anti-phase mode was always re-established. These findings are in marked contrast to those obtained when there is free motion of the limbs. There also existed systematic differences between the stability of the pronation and supination phases of torque application. These differences were, in turn, modified through coincidence with the pacing signal. These results are discussed with reference to the constraints imposed upon the coordination dynamics by the intrinsic properties of the neuromuscular-skeletal system.     

Norepinephrine-induced cardiac hypertrophy of the cat heart.

Norepinephrine administration causes progressive hypertrophy of the mammalian heart as measured by myocardial mass. The purpose of this study was to determine the growth response of the myocardial tissue components as well as the myocardial cell itself to norepinephrine. Young, adult cats were given low doses of norepinephrine in dextrose or dextrose alone twice daily for 15 days. On day 16, there were no changes in the animals body weight, right ventricular systolic pressure, right ventricular end-diastolic pressure, heart rate, cardiac index, or blood pressure. However, the right ventricle/body weight, the left ventricle/body weight and the total heart weight/body weight were increased significantly in the norepinephrine treated animals. The increase was on the order of 40%. The cardiac muscle cell was also significantly increased in size and both the right and left ventricular cardiac muscle cells exhibited a dramatic increase in size as measured by cross sectional area. Upon stereological examination it was found that the amount of hypertrophy as seen in the cardiac muscle cells was paralleled by the hypertrophy seen in the other tissue components of the myocardium. The volume density of the muscle cells, the interstitial components, as well as the blood vessel compartment were identical in the control and in the norepinephrine-treated groups. In conclusion, this study demonstrates that the response of the myocardium to norepinephrine is similar to that seen in response to a volume overload rather than that seen in response to pressure overload.     

Central and peripheral mediation of human force sensation following eccentric or concentric contractions

Fatigue was induced in the triceps brachii of the experimental arm by a regimen of either eccentric or concentric muscle actions. Estimates of force were assessed using a contralateral limb-matching procedure, in which target force levels (25 %, 50 % or 75 % of maximum) were defined by the unfatigued control arm. Maximum isometric force-generating capacity was reduced by 31 % immediately following eccentric contractions, and remained depressed at 24 (25 %) and 48 h (13 %) post-exercise. A less marked reduction (8.3 %) was observed immediately following concentric contractions. Those participants who performed prior eccentric contractions, consistently (at all force levels), and persistently (throughout the recovery period), overestimated the level of force applied by the experimental arm. In other words, they believed that they were generating more force than they actually achieved. When the forces applied by the experimental and the control arm, were each expressed as a proportion of the maximum force that could be attained at that time, the estimates matched extremely closely. This outcome is that which would be expected if the estimates of force were based on a sense of effort. Following eccentric exercise, the amplitude of the EMG activity recorded from the experimental arm was substantially greater than that recorded from the control arm. Cortically evoked potentials recorded from the triceps brachii (and extensor carpi radialis) of the experimental arm were also substantially larger than those elicited prior to exercise. The sense of effort was evidently not based upon a corollary of the central motor command. Rather, the relationship between the sense of effort and the motor command appears to have been altered as a result of the fatiguing eccentric contractions. It is proposed that the sense of effort is associated with activity in neural centres upstream of the motor cortex.     

Facio-cardio-renal (Eastman-Bixler) syndrome

We report on a 5-year-old boy with moderate mental retardation, horseshoe kidneys, tricuspid valve prolapse, and a characteristic face with broad nasal root, prominent ears, and a cleft palate. These manifestations suggested the diagnosis of the Eastman-Bixler syndrome. Our patient also had an isolated growth hormone deficiency which responded successfully to treatment.     

Hepatitis E virus infection in chimpanzees: a retrospective analysis

Summary.  Different patterns of disease were observed among 11 chimpanzees who were inoculated intravenously with hepatitis E virus (HEV) positive fecal specimens from four different outbreaks (Nepal 1981, Uzbekistan 1981, Pakistan 1985, and Mexico 1986). Five chimpanzees had marginal or no liver enzyme elevations within 70 days of inoculation. Two of the chimpanzees had limited viremia, but did not produce detectable antibody. The four remaining chimpanzees had liver enzyme elevations, viral shedding, viremia, seroconversion to anti-HEV, and detectable HEV antigen in liver biopsy specimens. These results may reflect the range of infection patterns that develop in humans after natural exposure to the HEV. Received December 29, 1999/Accepted February 21, 2000     

Giant lymph-node hyperplasia, plasma-cell type, of the mediastinum, with peripheral neuropathy.

A case of mediastinal giant lymph-node hyperplasia, plasma-cell type, is described. The patient had progressive peripheral neuropathy for which no apparent cause was found. Giant lymph-node hyperplasia with associated peripheral neuropathy has not been reported previously.     

A Randomized Pilot Study of DASH Patterned Groceries on Serum Urate in Individuals with Gout

The Dietary Approaches to Stop Hypertension (DASH) diet reduces serum urate (SU); however, the impact of the DASH diet has not been previously evaluated among patients with gout. We conducted a randomized, controlled, crossover pilot study to test the effects of ~$105/week ($15/day) of dietitian-directed groceries (DDG), patterned after the DASH diet, on SU, compared with self-directed grocery shopping (SDG). Participants had gout and were not taking urate lowering therapy. Each intervention period lasted 4 weeks; crossover occurred without a washout period. The primary endpoint was SU. Compliance was assessed by end-of-period fasting spot urine potassium and sodium measurements and self-reported consumption of daily servings of fruit and vegetables. We randomized 43 participants (19% women, 49% black, mean age 59 years) with 100% follow-up. Mean baseline SU was 8.1 mg/dL (SD, 0.8). During Period 1, DDG lowered SU by 0.55 mg/dL (95% CI: 0.07, 1.04) compared to SDG by 0.0 mg/dL (95% CI: −0.44, 0.44). However, after crossover (Period 2), the SU difference between groups was the opposite: SDG reduced SU by −0.48 mg/dL (95% CI: −0.98, 0.01) compared to DDG by −0.05 mg/dL (95% CI: −0.48, 0.38; P for interaction by period = 0.11). Nevertheless, DDG improved self-reported intake of fruit and vegetables (3.1 servings/day; 95% CI: 1.5, 4.8) and significantly reduced total spot urine sodium excretion by 22 percentage points (95% CI: −34.0, −8.6). Though relatively small in scale, this pilot study suggests that dietitian-directed, DASH-patterned groceries may lower SU among gout patients not on urate-lowering drugs. However, behavior intervention crossover trials without a washout period are likely vulnerable to strong carryover effects. Definitive evaluation of the DASH diet as a treatment for gout will require a controlled feeding trial, ideally with a parallel-design.