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Biomedical subjects

J M Steffen

Publications and source records attributed to J M Steffen.

At least 19 recordsLinked to original sources

Skeletal muscle atrophy in response to 14 days of weightlessness: vastus medialis.

The vastus medialis (VM) from rats after 14 days of microgravity on COSMOS 2044 (F) was compared with VM from tail-suspended hindlimb-unloaded rats (T) and ground controls, including vivarium (V), synchronous (S), and basal (B) animals. The VM is composed chiefly of fast-twitch fibers; however, it contains a deep portion closer to the bone with mixed slow- and fast-twitch fibers. In the mixed-fiber portion, type I and II fiber areas were significantly reduced in F animals. In the homogeneous portion with chiefly fast-twitch fibers, F rats also showed reductions in cross-sectional areas compared with T, V, and B but not S rats. Fiber densities (fibers/mm2) were greatest in VM from F rats. Capillary density changes paralleled fiber density changes. F animals have significantly greater density of capillaries in the mixed-fiber portion. Concentrations of protein, RNA, and DNA were highest in V controls, whereas F rats had the lowest level of total RNA. Lactate dehydrogenase activity, one measure of anaerobic capacity, was greater in F than in S rats. Citrate synthase activity, a measure of oxidative capacity, showed no significant differences between groups. Although triglyceride stores of VM were greater in F than in T rats, there were no significant differences from any of the control groups. It was concluded that VM wet weights may be a less sensitive measure of atrophy than the fiber area measurements. Fiber area decreases and fiber density increases in F animals were quantitatively comparable to those in soleus and extensor digitorum longus after 7 days of weightless flight in Spacelab 3. Our results suggest that VM shows measurable responses to weightlessness.

Anaerobiosis

Rat cardiovascular responses to whole body suspension: head-down and non-head-down tilt.

The rat whole body suspension technique mimics responses seen during exposure to microgravity and was evaluated as a model for cardiovascular responses with two series of experiments. In one series, changes were monitored in chronically catheterized rats during 7 days of head-down tilt (HDT) or non-head-down tilt (N-HDT) and after several hours of recovery. Elevations of mean arterial (MAP), systolic, and diastolic pressures of approximately 20% (P < 0.05) in HDT rats began as early as day 1 and were maintained for the duration of suspension. Pulse pressures were relatively unaffected, but heart rates were elevated approximately 10%. During postsuspension (2-7 h), most cardiovascular parameters returned to presuspension levels. N-HDT rats exhibited elevations chiefly on days 3 and 7. In the second series, blood pressure was monitored in 1- and 3-day HDT and N-HDT rats to evaluate responses to rapid head-up tilt. MAP, systolic and diastolic pressures, and HR were elevated (P < 0.05) in HDT and N-HDT rats during head-up tilt after 1 day of suspension, while pulse pressures remained unchanged. HDT rats exhibited elevated pretilt MAP and failed to respond to rapid head-up tilt with further increase of MAP on day 3, indicating some degree of deconditioning. The whole body suspended rat may be useful as a model to better understand responses of rats exposed to microgravity.

Animals

Morphometric and metabolic indices of disuse in muscles of hibernating ground squirrels.

1. Morphological, biochemical and metabolic characteristics of hindlimb muscles from summer-active (SA), winter-active (WA) and hibernating (H) golden-mantled ground squirrels (Spermophilus lateralis) were examined to identify alterations resulting from seasonal periods of inactivity. 2. Cross-sectional areas of fibers from the soleus were reduced in both WA and H, although only significantly (P less than 0.05) in WA. Fibers in the EDL exhibited significant reductions in cross-sectional areas in both H and WA groups. Muscle fiber and capillary densities were altered in quantitative agreement with changes in cross-sectional areas. 3. Protein content was reduced 20% (P less than 0.05) in EDL from H and WA groups, but reductions (10%) in the soleus were not statistically significant. RNA content in WA and H groups was significantly decreased in soleus (20%) and EDL (35%) compared with SA, but DNA content was unchanged. 4. In the plantaris, triglyceride content was unchanged, but citrate synthase activity in H (210 +/- 13 mumol min-1 g-1) was significantly greater than in SA (177 +/- 10). In contrast, LDH activity in H was reduced by 25% (P less than 0.05) compared with SA. 5. These results demonstrate atrophic effects associated with seasonal inactivity in hibernating ground squirrels, but suggest the existence of natural mechanisms which limit the response.

Adaptation, Physiological

Biochemical changes in skeletal muscles of denning bears (Ursus americanus).

1. Biopsies of the extensor hallucis longus (EHL) and gastrocnemius (G) muscles of four captive black bears (Ursus americanus) were obtained prior to denning (PRE), during denning (DEN) and following the Spring arousal (POST). 2. Glycogen, triglyceride and protein concentrations did not differ significantly between the three groups. Likewise, the activity of citrate synthase, a mitochondrial oxidative enzyme, was not significantly different between the three groups. 3. DNA concentrations in DEN samples increased 30% compared to other groups while RNA concentrations were significantly elevated in POST samples. The RNA/DNA ratios were significantly depressed during DEN. 4. These results suggest a degree of muscle atrophy during DEN, with the potential for an increased capacity for muscle protein synthesis following the Spring arousal.

Adaptation, Physiological

Lip bumper therapy for gaining arch length.

With the use of pretreatment and posttreatment lateral cephalograms and study models, lip bumper therapy for two groups of 20 patients was evaluated. One group was treated with lip bumpers fabricated from stainless steel round wire covered with shrink tubing and activated every 2 to 3 months. The second group was treated with larger prefabricated lip bumpers covered with acrylic shields from canine to canine and activated every 4 to 5 weeks. Yearly rates of treatment change indicate that the type of lip bumper used and the method of clinical manipulation have no effect on mandibular incisor position. Both groups showed similar rates of controlled incisal tipping with the center of rotation at the apex. Dental movements of the posterior segment were significantly different between groups. The second group displayed significantly more molar tipping than the first group. The second group also showed significantly greater transverse expansion of the canines, first premolars, and first molars.

Acrylic Resins

Age effects on rat hindlimb muscle atrophy during suspension unloading.

Disuse can induce numerous adaptive alterations in skeletal muscle. In the present study the effects of hindlimb unloading on muscle mass and biochemical responses were examined and compared in adult (450 g) and juvenile (200 g) rats after 1, 7, or 14 days of whole body suspension. Quantitatively and qualitatively the soleus (S), gastrocnemius (G), plantaris (P), and extensor digitorum longus (EDL) muscles of the hindlimb exhibited a differential sensitivity to suspension and weightlessness unloading in both adults and juveniles. The red slow-twitch soleus exhibited the most pronounced atrophy under both conditions, with juvenile responses being greater than adult. In contrast, the fast-twitch EDL hypertrophied during suspension and atrophied during weightlessness, with no significant difference between adults and juveniles. Determination of biochemical parameters (total protein, RNA, and DNA) indicated a less rapid rate of response in adult muscles. This was corroborated by assessment of muscle alpha-actin mRNA levels, which indicated a rapid (within 1 day) and significant (P less than 0.05) effect in juveniles but not in adults. The results of this investigation indicate 1) a qualitatively similar differential effect of unloading on muscles of adults and juveniles, 2) a quantitatively reduced and less rapid effect of suspension on adult muscles, and 3) a close similarity of adult and juvenile muscle responses during suspension and spaceflight, suggesting that this ground-based model simulates many of the unloading effects of weightlessness.

Age Factors

Skeletal muscle response to spaceflight, whole body suspension, and recovery in rats.

Comparisons of soleus and extensor digitorum longus (EDL) muscles from male Sprague-Dawley rats (350-400 g) after 7 days of weightlessness, 7 and 14 days of whole body suspension (WBS), and 7 days of recovery from WBS and from vivarium controls were made. Muscle mass loss of approximately 30% was observed in soleus after 7 and 14 days of WBS. Measurement of slow- and fast-twitch fibers showed significant alterations. Reductions in cross-sectional areas and increases in fiber densities in soleus after spaceflight and WBS were related to previous findings of muscle atrophy during unloading. Capillary density also showed a marked increase with unloading. Seven days of weightlessness were sufficient to effect a 20 and 15% loss in absolute muscle mass in soleus and EDL, respectively. However, the antigravity soleus was more responsive in terms of cross-sectional area reductions. After 7 days of recovery from WBS, with normal ambulatory loading, the parameters studied showed a reversal to control levels. Muscle plasticity, in terms of fiber and capillary responses, indicated differences in responses in the two types of muscles and further amplified that antigravity posture muscles are highly susceptible to unloading. Studies of recovery from spaceflight for both muscle metabolism and microvascular modifications are further justified.

Animals

Transcriptional regulation of decreased protein synthesis during skeletal muscle unloading.

Muscle atrophy resulting from disuse is associated with marked decrements in protein synthesis. The objective of the present investigation was to determine levels of total muscle RNA and the content and composition of the mRNA fraction as a qualitative assessment of the potential regulatory role of transcriptional alterations in unloaded skeletal muscles. Hindlimb muscle unloading was produced by whole-body suspension of rats for up to 7 days. The soleus, gastrocnemius, and extensor digitorum longus (EDL) were excised from 1-, 3-, and 7-day suspended and pair-fed controls, and RNA was extracted by homogenization in 5 M guanidinium thiocyanate. Total RNA and mRNA contents were lower in soleus and gastrocnemius after 7 days of suspension compared with pair-fed controls, but total RNA and mRNA concentrations (per g muscle and per microgram total RNA, respectively) were unaltered. alpha-Actin mRNA, assessed by dot blot hybridization, was significantly reduced in soleus after 1 (37%), 3 (28%), and 7 (59%) days of suspension and in gastrocnemius after 3 (44%) and 7 (41%) days. However, alpha-actin mRNA was unchanged in the EDL after suspension. Protein synthesis directed by RNA extracted from soleus and EDL indicated marked (30-400%) alterations in mRNAs coding for several small (15- to 25-kDa) proteins. The results of this study suggest that altered transcription and availability of specific mRNAs could contribute significantly to the regulation of protein synthesis during unloading of skeletal muscle.

Actins

Glucose, glycogen, and insulin responses in the hypothermic rat.

The rat appears to be unable to utilize glucose during hypothermia. The objective of this study was to examine carbohydrate homeostasis during induction, hypothermia, and rewarming phases. Groups of normothermic animals were euthanized to serve as time controls for comparison. Hypothermia (15 degrees C) was produced by exposure to helox (80% helium:20% oxygen) at 0 +/- 1 degree C. Hyperglycemia was noted during the induction process (169 +/- 8 in control vs 326 +/- 49 mg/dl). Serum glucose increased further during 4 hr of hypothermia, but following rewarming (Tre of 33 +/- 1 degrees C) was reduced (153 +/- 16 mg/dl) significantly (P less than 0.05). Serum insulin was depressed during hypothermic induction (from 48 +/- 4 in controls to 19 +/- 3 microU/ml in hypothermic rats) and increased only slightly during the arousal process, remaining significantly lower than in normothermic subjects. Initial hepatic, skeletal muscle, and cardiac glycogen concentrations were reduced 34, 68, and 75%, respectively, during hypothermic induction. While liver glycogen decreased further during 4 hr of hypothermia, skeletal and cardiac stores increased markedly. During rewarming, hepatic glycogen was markedly decreased, while skeletal and cardiac stores were maintained. These data suggest that hyperglycemia in the hypothermic rat can be accounted for by glycogenolysis and hypoinsulinemia. In addition, this study indicates repletion of skeletal and cardiac muscle glycogen during maintained hypothermia and sparing of muscle glycogen during rewarming.

Animals

Disuse atrophy, plasma corticosterone, and muscle glucocorticoid receptor levels.

A suspension model, characterized by differential atrophy of disused hindlimb skeletal muscles, was utilized to investigate plasma levels of and tissue sensitivity to glucocorticoids. The three objectives were determination of time course and extent of plasma corticosterone changes during 1 week of whole-body suspension; comparison of glucocorticoid receptor site concentrations in muscles differing in morphology and antigravity function; and investigation of the effect of disuse on tissue glucocorticoid receptor site concentrations. Plasma corticosterone increased significantly (p less than 0.01) on the first and third days of suspension, but returned to control levels by day 7. Muscle glucocorticoid receptors exhibited a characteristic hormonal specificity. In controls, receptor site concentration in the slow-twitch soleus (48 +/- 5 fmol/mg prot.) was comparable to that in the fast-twitch gastrocnemius (47 +/- 6) and plantaris (58 +/- 4) muscles but significantly (p less than 0.02) less than the extensor digitorum longus (66 +/- 5). Seven days of suspension resulted in significant differential effects on muscle receptor levels, with a large increase in the soleus (140%), lesser increments in the gastrocnemius (55%) and plantaris (45%), and only a small, statistically insignificant alteration in the EDL (10%). Receptor levels in the soleus remained elevated following 14 d of suspension, but levels in other muscles returned to control values. These results suggest that circulating glucocorticoids, as well as increased tissue hormonal sensitivity, may be related to muscle responses in this model of disuse.

Animals

Spaceflight effects on adult rat muscle protein, nucleic acids, and amino acids.

Exposure to conditions of weightlessness has been associated with decrements in muscle mass and strength. The present studies were undertaken to determine muscle responses at the cellular level. Male Sprague-Dawley rats (360-410 g) were exposed to 7 days of weightlessness during the Spacelab-3 shuttle flight (May 1985). Animals were killed 12 h postflight, and soleus (S), gastrocnemius (G), and extensor digitorum longus (EDL) muscles were excised. Muscle protein, RNA, and DNA were extracted and quantified. Differential muscle atrophy was accompanied by a significant (P less than 0.05) reduction in total protein only in S muscles. There were no significant changes in protein concentration (mg/g) in the muscles examined. In S muscles from flight animals, sarcoplasmic protein accounted for a significantly greater proportion of total protein that in ground controls (37.5 vs. 32.5%). Tissue concentrations (nmol/g) of asparagine-aspartate, glutamine-glutamate, glycine, histidine, and lysine were significantly reduced (from 17 to 63%) in S muscles from flight animals, but only glutamine-glutamate levels were decreased in the G and EDL. Muscle DNA content (microgram) was unchanged in the tissues examined, but S muscle DNA concentration (micrograms/mg) increased 27%. RNA content (micrograms) was significantly (P less than 0.025) reduced in S (-28%) and G(-22%) muscles following spaceflight. These results identify specific alterations in rat skeletal muscle during short term (7-day) exposure to weightlessness and compare favorably with observations previously obtained from ground-based suspension simulations.

Amino Acids

Thymic involution in the suspended rat: adrenal hypertrophy and glucocorticoid receptor content.

The thymus gland and skeletal muscle are sensitive to the catabolic effects of glucocorticoids (GC). Previous studies using suspended rats demonstrated that muscle disuse atrophy resulting from hindlimb unloading was associated with an increase in glucocorticoid receptor site concentration. The objectives of the current studies were: to assess the temporal relationship between adrenal hypertrophy and thymic involution in suspended rats, to evaluate the role of positioning--antiorthostatic, (AO) vs. orthostatic (O)--in the thymic and adrenal responses, and to determine whether or thymic involution, like muscle disuse atrophy, was associated with an increase in GC receptor site concentration. The wet weight of the thymus was reduced by 50% (p less than 0.001) during 7 d of AO suspension. Suspended (AO) rats exhibited a significant (p less than 0.001) hypertrophy of the adrenal glands (33%), primarily on the initial day of suspension. Recovery for 7 d was associated with a return of thymus weight to control levels, but adrenal hypertrophy was not completely reversed. Rats suspended in an O position exhibited thymic and adrenal responses comparable to those of AO rats. Thymic involution in both AO and O rats was associated with a 20% (p less than 0.001) decrease in glucocorticoid receptor site concentration (pmol X mg-1 protein). However, when expressed relative to tissue weight, receptor site concentrations were not significantly different from control values. These results suggest a temporal correlation between adrenal hypertrophy and thymic involution in the suspended rat, but neither of these responses were dependent upon AO positioning.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Gland Diseases