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Biomedical subjects

E Schultz

Publications and source records attributed to E Schultz.

At least 91 records · Page 5Linked to original sources

Hindlimb suspension suppresses muscle growth and satellite cell proliferation.

The effects of long-term hindlimb unweighting by tail suspension on postnatal growth of 20-day rat extensor digitorum longus (EDL) and soleus muscles were studied. Morphological assay indicated that radial growth of soleus myofibers was completely inhibited between 3 and 10 days of suspension and reduced thereafter, leading to a severe attenuation (-76% from control) over the total experimental period. Longitudinal growth rate, however, was accelerated 40% over weight-bearing controls. In addition, myofibers were arranged parallel to the long axis of the muscle, an orientation associated with chronologically younger muscles, suggesting morphological maturation of the soleus muscle had been delayed by suspension. In contrast, radial and longitudinal growth of EDL myofibers were minimally affected under similar conditions and remained within approximately 5% of control at all times. Suspension also influenced the normal changes that occur in satellite cell and myonuclear populations during postnatal growth. Both the number and proliferative activity of satellite cells were severely reduced in individual myofibers after only 3 days in both soleus and EDL muscles. The reduced number of satellite cells within 3 days of initiating hindlimb suspension appeared to be the result of their incorporation into myofibers while the long-lasting reduction appeared to be the added effects of decreased proliferative activity. In the soleus, this reduction in number and proliferation of satellite cells persisted throughout the experimental period and resulted in an overall 43% fewer myonuclei and 45% fewer satellite cells than control at 50 days of age. In contrast, both the total number and mitotic activity of satellite cells in the EDL rapidly returned to weight-bearing control levels by day 10 of suspension, resulting in no overall reduction in myonuclear accretion.

Animals↗

[Imaging properties of a high-resolution CT system].

This paper provides an overview of the most important imaging properties of a high-resolution computed tomography system. Spatial and contrast resolution (inplane as well as crossplane) are described, while the trade-off between those two characteristics is pointed out. Furthermore, it is shown that extremely small structures are imaged, but not with realistic Hounsfield units. Finally, the noise is set into relation to the contrast resolution.

Humans↗

Satellite cell behavior during skeletal muscle growth and regeneration.

Satellite cells play an integral role in normal development of skeletal muscle by providing a source for postmitotic myonuclei and in repair of injured myofibers by serving as the source of myoblasts that participate in the regeneration response. The population of satellite cells in a muscle undergoes an ordered change both in relative and absolute numbers over the course of the postnatal growth period. Quantitative studies have shown that the changes are not the same among muscles or even among the individual myofibers within a muscle. In general, oxidative muscles have a much higher density of satellite cells than do glycolytic muscles. Although the exact reasons for the differences in the population densities are unknown, differences in the growth patterns of muscles or in their activity levels may be related factors. These differences point to the fact that the mechanisms that regulate satellite cell mitotic and fusion behavior are also not the same in all muscles. The activity state of muscle is an important factor in the regulation of satellite cell behavior. Increased functional demand that induces a hypertrophic response results in increased satellite cell mitotic activity, and decreased activity that results in atrophy results in decreased mitotic activity. Finally, elevated satellite cell mitotic activity can be a sensitive indicator of muscle damage, especially when the damage is minimal and difficult to detect by morphological means.

Exercise↗

Inhibition of catechol-O-methyltransferase activity by two novel disubstituted catechols in the rat.

Catechol-O-methyltransferase (COMT) has an important role in the extraneuronal inactivation of catecholamine neurotransmitters and drugs with a catechol structure. Two novel COMT inhibitors, OR-462 and OR-486, were highly effective (IC50 = 18 and 12 nM, respectively) and selective in inhibiting COMT activity in vitro. Tyrosine hydroxylase was not inhibited until micromolar concentrations of these compounds were used: the IC50 values for OR-462 and OR-486 were 10 and 14 microM, respectively. The IC50 values for dopamine-beta-hydroxylase, dopa-decarboxylase and monoamine oxidase forms A and B were greater than 50 microM. In studies ex vivo oral OR-462 inhibited mainly the COMT activity in the duodenum while OR-486 inhibited COMT activity in the liver and red blood cells as well. Oral OR-462 did not penetrate into the brain in doses up to 30 mg/kg while the same dose of OR-486 had some effect on striatal COMT activity. When tested in combination with levodopa-carbidopa, orally administered OR-462 and OR-486 were more effective in reducing the formation of 3-O-methyldopa from levodopa than was the levodopa-carbidopa treatment alone. These results indicate that OR-462 and OR-486 are effective and long-lasting inhibitors of COMT activity.

Animals↗

Survival of satellite cells in whole muscle transplants.

The ability of satellite cells to survive the ischemic conditions at the core of orthotopically free grafted rat extensor digitorum longus muscles was examined. Cell cultures of isolated core and peripheral regions of whole muscle grafts maintained in vivo for more than 24 hours indicated that no viable cells were present in the core, whereas the number of cells from the peripheral region was greatly increased. Muscles were examined with the electron microscope to determine the fate of satellite cells of the core at various times after transplantation. The population of satellite cells in the core was reduced beginning at 18 hours and had virtually disappeared by 24-28 hours. This reduction did not appear to be the result of satellite cell death. Although there was abundant morphological evidence that myonuclei as well as myofiber cytoplasmic organelles were degenerating, there was little indication of satellite cell death in situ any time period studied. These studies suggest that satellite cells cannot survive, but migrate from the ischemic core to more peripheral regions of whole muscle transplants. In addition, they suggest that migration is an important aspect of the regeneration response in the free graft system and permits the myogenic population to contribute en masse to the centripetal wave of regeneration from the time it is initiated at the muscle periphery.

Animals↗

Bone density of the radius, spine, and proximal femur in osteoporosis.

Bone mineral density (BMD) was measured in 140 normal young women (aged 20 to 39 years) and in 423 consecutive women over age 40 referred for evaluation of osteoporosis. Lumbar spine and proximal femur BMD was measured using dual-photon absorptiometry (153Gd), whereas the radius shaft measurement used single-photon absorptiometry (125I). There were 324 older women with no fractures, of which 278 aged 60 to 80 years served as age-matched controls. There were 99 women with fractures including 32 with vertebral and 22 with hip fractures. Subsequently, another 25 women with hip fractures had BMD measured in another laboratory; their mean BMD was within 2% of that of the original series. The mean age in both the nonfracture and fracture groups was 70 +/- 5 years. The BMD in the age-matched controls was 20% to 25% below that of normal young women for the radius, spine, and femur, but the Ward's triangle region of the femur showed even greater loss (35%). The mean BMD at all sites in the crush fracture cases was about 10% to 15% below that of age-matched controls. Spinal abnormality was best discriminated by spine and femoral measurements (Z score about 0.9). In women with hip fractures, the BMD was 10% below that of age-matched controls for the radius and the spine, and the BMD for the femoral sites was about 25% to 30% below that of age-matched control (Z score about 1.6). Femoral densities gave the best discrimination of hip fracture cases and even reflected spinal osteopenia. In contrast, neither the spine nor the radius reflected the full extent of femoral osteopenia in hip fracture.

Adult↗

Hyperplasia of jejunal smooth muscle in the myenterically denervated rat.

Application of a cationic surfactant, benzalkonium chloride, to the serosa of rat jejunum results in an increase in thickness of both longitudinal and circular smooth muscle layers. The increase in thickness is due primarily to an increase in the number of smooth muscle cells (hyperplasia). Little cellular hypertrophy was observed. The time sequence of surfactant-induced effects on the muscle layers was determined. Within 24 h, total destruction of the longitudinal muscle and partial destruction of the circular muscle was evident. The myenteric plexus was also necrotic; however, the submucosal plexus remained intact. By 48 h after surfactant treatment, the smooth muscle cells remaining in the circular muscle layer had begun to divide, as indicated by the presence of mitotic figures and incorporation of 3H-thymidine. A repopulation of the longitudinal muscle layer began at this time, apparently the result of migration of cells arising in the circular muscle layer. By 5 days post-treatment, both muscle layers had regenerated to their original states. The myenteric plexus was totally absent. The denervated smooth muscle cells proceeded to divide until approximately day 15, resulting in hyperplasia of both muscle layers. Between 15 and 105 days, the number of muscle cells in the circular layer progressively declined, eventually returned to the value seen in control tissue. In contrast, the number of smooth muscle cells in the longitudinal layer remained elevated through the period of study (165 days). We hypothesize that the smooth muscle hyperplasia observed after serosal benzalkonium chloride application results from loss of the myenteric nerves.

Animals↗

Studies on cardiac myofibrillogenesis with antibodies to titin, actin, tropomyosin, and myosin.

Cardiac myofibrillogenesis was examined in cultured chick cardiac cells by immunofluorescence using antibodies against titin, actin, tropomyosin, and myosin. Primitive cardiomyocytes initially contained stress fiber-like structures (SFLS) that stained positively for alpha actin and/or muscle tropomyosin. In some cases the staining for muscle tropomyosin and alpha actin was disproportionate; this suggests that the synthesis and/or assembly of these two isoforms into the SFLS may not be stoichiometric. The alpha actin containing SFLS in these myocytes could be classified as either central or peripheral; central SFLS showed developing sarcomeric titin while peripheral SFLS had weak titin fluorescence and a more uniform stain distribution. Sarcomeric patterns of titin and myosin were present at multiple sites on these structures. A pair of titin staining bands was clearly associated with each developing A band even at the two or three sarcomere stage, although occasional examples of a titin band being associated with a half sarcomere were noted. The appearance of sarcomeric titin patterns coincided or preceded sarcomere periodicity of either alpha actin or muscle tropomyosin. The early appearance of titin in myofibrillogenesis suggests it may have a role in filament alignment during sarcomere assembly.

Actins↗

Pulmonary intravascular macrophages and hemodynamic effects of liposomes in sheep.

We studied the effects of liposomes on the pulmonary circulation of sheep and found a close correlation between liposome retention in the lung and the intravascular macrophages. A test dose of liposomes (5.5 mumol of total lipids) injected intravenously transiently increased pulmonary arterial pressure from 24 +/- 2 to 55 +/- 16 (SD) cmH2O. The pulmonary arterial pressure responses were dose dependent and reproducible. The rise in pulmonary arterial pressure was blocked completely by indomethacin and 75% by a thromboxane synthase inhibitor. Systemic arterial thromboxane B2 concentration increased from a base-line level of less than 50 pg/ml to 250 +/- 130 pg/ml at the peak of the pressor response. Larger doses of liposomes (220 mumol of total lipids) infused intravenously over 1 h increased pulmonary arterial pressure maximally within the first 15 min. Lymph flow increased and lymph protein concentration decreased, suggesting venoconstriction. Over half (62.4 +/- 15.7%) of 111In-labeled liposomes remained in the lung after 2 h. Fluorescence and transmission electron microscopy showed that greater than 90% of the liposomes were associated with mononuclear cells in the lumen of the alveolar wall microvessels. We conclude that liposomes affect pulmonary arterial pressure transiently by a mechanism involving the arachidonate cascade, principally thromboxane. Our observations suggest that a population of pulmonary intravascular macrophages is likely to be the source of the thromboxane and the pulmonary hemodynamic and lymph dynamic changes that occur in a dose-dependent fashion, although interactions between liposomes, leukocytes, or endothelial cells, in addition to the macrophages, have not been completely ruled out. We believe this is the first demonstration that pulmonary intravascular macrophages may be the source of the arachidonate metabolites rather than endothelial cells, neutrophils, or perivascular interstitial cells.

Animals↗

Exercise-induced satellite cell activation in growing and mature skeletal muscle.

The time course and extent of satellite cell activation were studied in the soleus (m-SOL) and extensor digitorum longus (m-EDL) muscles of untrained growing and mature rats after a single bout of prolonged eccentric treadmill running. At 24, 48, 72, and 120 h postexercise, satellite cell mitotic activity was quantitated in autoradiographs of whole-fiber segments after injection of [3H]thymidine. Fiber damage and localization of labeled cells were also examined in muscle cross sections. Labeling in growing muscles progressively increased to peak levels (approximately 250% of control) at 72 h postexercise, whereas mature muscles exhibited an earlier peak (approximately 250% of control) at 24 (m-SOL) and 48 (m-EDL) h, followed by a more rapid decline to control levels by 120 h postexercise. In all exercised muscles the calculated satellite cell activation was far greater than required to repair the small number (less than 3.0%) of necrotic fibers identified at the light-microscopic level. These results suggest that satellite cells were activated not only on fibers exhibiting overt necrosis but also on those with lesions not discernible with light microscopy.

Aging↗

[Phantom substances for quantitative evaluation of MRT images. III. Effect of various protein concentrations on MRT intensity values].

The use of heavy water (D2O) in paramagnetic agar phantoms can yield tissue equivalent values of the proton spin density p. In this manner all the MRI parameters that are typical of tissues can be realised in phantom substances. It is shown that the use of heavy water results in some enhancement of relaxation time, T2, that can be easily controlled via the agar concentration.

Electron Spin Resonance Spectroscopy↗

Absence of exogenous satellite cell contribution to regeneration of frozen skeletal muscle.

Rat extensor digitorum longus (EDL) muscles were repeatedly frozen and thawed to kill completely all cellular constituents. Within four days, blood vessels and phagocytic cells invaded the muscle. Migrating or circulating myoblasts were not among the invading cells, and could be induced to invade the frozen muscle only when a physical bridge was created with an adjacent intact muscle. A further requirement for migration was that the connective tissue investments of both the frozen EDL and adjacent muscle had to be disrupted. This study demonstrates that regeneration of a muscle is primarily dependent upon the intrinsic satellite cell population, although under some circumstances recruitment of extrinsic cells is possible.

Animals↗

Potassium supplementation in blacks with mild to moderate essential hypertension.

Potassium chloride (KCl) salt (65 mmol) daily reduced BP from 153/104 to 146/101 mmHg in 32 hypertensive black females during a 6-week placebo controlled crossover study. The fall in BP was independent of the order of randomization and was significant for systolic (SBP; P less than 0.01) and diastolic (DBP; P less than 0.05) pressure after 4 weeks. Analysis of the 95% confidence intervals in this and in five other studies, two of which were reported as showing no beneficial effect, suggests that potassium supplementation does lower BP, but that the change is small and within the confidence levels of all six trials. Thus, apparent discrepancies in the literature are not genuine statistically.

Adult↗