Adrenal aldosterone-producing adenomas (APAs) are a main cause for primary aldosteronism leading to arterial hypertension. Physiologically, aldosterone production in the adrenal gland is stimulated by angiotensin II and high extracellular potassium. These stimuli lead to a depolarization of the plasma membrane and, as a consequence, an increase of intracellular Ca(2+). Mutations of the plasma membrane Ca(2+)-ATPase ATP2B3 have been found in APAs with a prevalence of 0.6%-3.1%. Here, we investigated the effects of the APA-associated ATP2B3(Leu425_Val426del) mutation in adrenocortical NCI-H295R and human embryonic kidney (HEK-293) cells. Ca(2+) measurements revealed a higher basal Ca(2+) level in cells expressing the mutant ATP2B3. This rise in intracellular Ca(2+) was even more pronounced under conditions with high extracellular Ca(2+) pointing to an increased Ca(2+) influx associated with the mutated protein. Furthermore, cells with the mutant ATP2B3 appeared to have a reduced capacity to export Ca(2+) suggesting a loss of the physiological pump function. Surprisingly, expression of the mutant ATP2B3 caused a Na(+)-dependent inward current that strongly depolarized the plasma membrane and compromised the cytosolic cation composition. In parallel to these findings, mRNA expression of the cytochrome P450, family 11, subfamily B, polypeptide 2 (aldosterone synthase) was substantially increased and aldosterone production was enhanced in cells overexpressing mutant ATP2B3. In summary, the APA-associated ATP2B3(Leu425_Val426del) mutant promotes aldosterone production by at least 2 different mechanisms: 1) a reduced Ca(2+) export due to the loss of the physiological pump function; and 2) an increased Ca(2+) influx due to opening of depolarization-activated Ca(2+) channels as well as a possible Ca(2+) leak through the mutated pump.

The age-related force production characteristics of six muscle groups in 143 women aged 25-74 years were examined. Measures of maximal force (MFR) were obtained on the finger flexors (FF), thumb extensors (TE), forearm flexors (FAF), forearm extensors (FAE), dorsi flexors (DF), and plantar flexors (PF) utilizing a linear voltage differential transducer. The subjects were categorized by age into ten 5-year groups. The magnitude of decline across age in MFR ranged from 36.2% IFAE) to 45.1% (PF). There were differences among muscle groups in the age at which a significant decline in MFR was first detected. The earliest drop off in MFR was observed in FF and FAF (45-49 years), while the latest significant decline across age was noted in FAE (65-69 years). Since the magnitude of maximal force decreases with age, and because these charactemtics can not be entirely explained by age-related decrements in €at-free mass, it appears that the quality in addition to the quantity of senescent muscle tissue may be compromised. However, the magnitude of decline in maximal force is dependent upon the muscle group considered.

No abstract

The purpose of this study was to determine the effects of speed, hip angle, knee angle, and gravity on hamstring to quadriceps (H/Q) torque ratios. Eighteen healthy college-aged men performed three maximal-effort knee extension and flexion repetitions on a Cybex II isokinetic dynamometer at speeds of 15 and 90 degrees /sec. Hamstring and quadriceps torques were measured at 15, 30, 45, 60, 75, and 90 degrees of knee flexion and at the angles at which peak torque occurred. These torques were also measured at 5 and 120 degrees of hip flexion. H/Q torque ratios were calculated with these torques, both corrected and uncorrected for gravitational effects. Analysis of variance revealed that gravity-corrected ratios decreased with increased knee angles from 15 to 60 degrees . The higher hip angle at each speed produced higher ratios at knee angles between 30 and 90 degrees . The effect of speed on ratios was variable and interacted with hip and knee angle. Correction for gravity reduced the ratios at all knee angles except 90 degrees . H/Q torque ratios at selected knee angles ranged from 0.20 to 2.00, differed from H/Q peak torque ratios 40% of the time, and did not always correlate highly with H/Q peak torque ratios (range: r = 0.50-0.90). Thus, H/Q peak torque ratios were not indicative of H/Q torque ratios at selected knee angles. Thus, knee angle-specific H/Q torque ratios may provide different, and perhaps more useful, information about hamstring and quadriceps function than do H/Q peak torque ratios.J Orthop Sports Phys Ther 1988;9(8):287-291.

No abstract