Biomedical subjects

S R Max

Publications and source records attributed to S R Max.

At least 37 records · Page 2Linked to original sources

PubMed1987

Skeletal muscle glucocorticoid receptor and glutamine synthetase activity in the wasting syndrome in rats treated with 2,3,7,8-tetrachlorodibenzo-p-dioxin.

This study demonstrated specific changes in rat skeletal muscles after a single oral dose (100 micrograms/kg) of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). The development of the wasting syndrome was characterized by marked body weight loss, as well as atrophy of plantaris and gastrocnemius muscles. Fourteen days after administration of TCDD, gastrocnemius muscle cytosolic glucocorticoid receptor binding, measured at a single saturating concentration of [3H]triamcinolone acetonide, was significantly diminished, while plantaris muscle glutamine synthetase activity was strikingly elevated, indicating that specific biochemical alterations occur in skeletal muscle in the wasting syndrome.

Animals↗

PubMed1987

Evaluation of the endogenous glucocorticoid hypothesis of denervation atrophy.

We studied the effects of oral administration of RU38486, a potent and selective glucocorticoid antagonist, on muscle weight, non-collagen protein content, and selected enzyme activities (choline acetyltransferase, glucose-6-phosphate dehydrogenase, and glutamine synthetase) following denervation of rat skeletal muscle. Neither decreases in muscle weight, protein content, and choline acetyltransferase activity, nor increases in the activities of glucose-6-phosphate dehydrogenase and glutamine synthetase were affected by RU38486. These data do not support the hypothesis that denervation atrophy results from enhanced sensitivity of muscle to endogenous glucocorticoids.

Animals↗

PubMed1987

Glucocorticoid receptor-mediated induction of glutamine synthetase in skeletal muscle cells in vitro.

We studied the regulation by glucocorticoids of glutamine synthetase in L6 muscle cells in culture. Glutamine synthetase activity was strikingly enhanced by dexamethasone. The dexamethasone-mediated induction of glutamine synthetase activity was blocked by RU38486 [11 beta-(4-dimethylaminophenyl)17 beta-hydroxy-17 alpha-(prop-1-ynyl)estra-4,9-dien-3-one], a glucocorticoid antagonist, indicating the involvement of intracellular glucocorticoid receptors in the induction process. RU38486 alone was without effect. Northern blot analysis revealed that dexamethasone-mediated enhancement of glutamine synthetase activity involves increased levels of glutamine synthetase mRNA. Increased enzyme activity was specific for glucocorticoids; other steroid hormones were essentially without effect. The induction of glutamine synthetase was selective, in that glutaminase activity was not induced by dexamethasone treatment of L6 cells. Thus, glucocorticoids regulate the expression of glutamine synthetase mRNA in cultured muscle cells via interaction with intracellular receptors. Such regulation may be relevant to control of glutamine production by muscle.

Animals↗

PubMed1986

Altered cellular functions in a PC-12 cell clone chronically infected with retrovirus.

We characterized retrovirus-induced changes in PC-12 cell function and neuronal differentiation. PC-12 cells were infected with a neurotropic retrovirus (temperature-sensitive Moloney murine leukemia virus, mutant BA-1). We isolated a cell clone from this infected culture that displayed altered response to nerve growth factor; increased choline acetyltransferase activity; and decreased basal and nerve growth factor-stimulated acetylcholinesterase activity. In addition, Kirsten murine sarcoma virus infection of and subsequent expression of the v-ras oncogene in PC-12 cells induced neurite extension, enhanced choline acetyltransferase activity, and limited the growth potential of the infected cells.

Acetylcholinesterase↗

PubMed1986

A possible role for endogenous glucocorticoids in orchiectomy-induced atrophy of the rat levator ani muscle: studies with RU 38486, a potent and selective antiglucocorticoid.

We employed RU 38486, a potent and selective antiglucocorticoid, to study a possible role for endogenous glucocorticoids in atrophy of the levator ani muscle secondary to castration of male rats. RU 38486 was shown to block [3H]triamcinolone acetonide binding to cytosol from levator ani muscle. Daily oral administration of RU 38486 to castrated rats partially prevented atrophy of the levator ani muscle, as well as a decrease in RNA concentration. In a control group receiving RU 38486 alone, the levator ani underwent significant (20%) hypertrophy. Administration of exogenous dexamethasone also caused pronounced atrophy of the levator ani muscle. This atrophy was prevented, to a significant degree, by simultaneous oral administration of RU 38486. It is concluded that endogenous glucocorticoids, the actions of which are blocked by RU 38486, may be involved in regulation of the mass of the levator ani muscle in intact rats.

Animals↗

PubMed1986

Thyroid hormone actions on a cholinergic neuroblastoma cell line (S-20Y).

Thyroid hormone (T3) has a multiplicity of effects on the developing nervous system. We have investigated T3 action using a cholinergic neuroblastoma cell line (S-20Y) as a model. S-20Y contains a nuclear receptor for T3 with binding properties similar to those of other T3 target tissues. In addition, these cells can carry out 5'-deiodination, which is necessary to produce active thyroid hormone in vivo. The enzyme involved in this process appears to be a type I deiodinase, based on its reaction kinetics and its susceptibility to inhibition by propylthiouracil. S-20Y cells maintained in T3-depleted medium showed decreased choline acetyltransferase (ChAT) activity. ChAT activity was restored to the control level in a dose-dependent manner by T3 repletion. Neither cell density nor viability was influenced by the hypothyroid state. The presence of a T3 receptor and the enzyme activity for T3 production, together with an effect of T3 on ChAT activity, demonstrate that S-20Y cells are a target for T3 action and suggest that these cells represent an excellent model system for studies of T3 effects on nervous tissues.

Animals↗

PubMed1986

Neural control of muscle androgen receptors.

The number of cytosolic androgen receptors in rat skeletal muscle increases following denervation and disuse. This increase was postulated to represent altered intracellular distribution and consequent diminished sensitivity of skeletal muscle to androgens. To test this hypothesis, we measured total (homogenate) androgen receptor levels after denervation. Total (homogenate) androgen receptor binding did not change in response to denervation of leg muscles from adult male rats. An increase in cytosolic receptor number with no increase in total (homogenate) receptor levels supports the hypothesis of altered intracellular distribution of androgen receptors in denervated muscle. Cytosolic androgen receptor binding in muscle from male rats increased by 40% after denervation, whereas in females the increase was 17%. These increases could not be altered by endocrine manipulations of males or females.

Animals↗

PubMed1986

Effects of cell division, cell density, and cyclic nucleotides on choline acetyltransferase activity in a cholinergic neuroblastoma cell line (S-20Y).

We investigated the effects of a number of experimental perturbations on choline acetyltransferase (ChAT) in a cholinergic mouse neuroblastoma cell line (S-20Y). ChAT specific activity increased by 4.5-fold during growth, suggesting that enzyme activity is dependent on increased cell density. This was confirmed by assessing enzyme activity at differential initial seeding densities. ChAT activity was also markedly enhanced by 1 mM dibutyryl cyclic-3',5'-AMP (dBcAMP), an effect that was blocked by cycloheximide. Confirmation of the dBcAMP effect was achieved with forskolin, a compound known to enhance intracellular cyclic AMP; forskolin (100 microM) caused a significant increase in ChAT activity. After a 20-h latent interval ChAT activity was also enhanced significantly by cytosine arabinoside. The common element in these diverse effects on ChAT activity may be cessation of cell division, although cell-cell interactions at the level of the cell membrane may also be important in the control of ChAT in S-20Y.

Animals↗

PubMed1986

Blockade of glucocorticoid receptor binding and inhibition of dexamethasone-induced muscle atrophy in the rat by RU38486, a potent glucocorticoid antagonist.

Glucocorticoid hormones cause marked muscular atrophy, the mechanism of which is unknown. We employed a potent glucocorticoid antagonist, RU38486 [11 beta-(4-dimethylaminophenyl)17 beta-hydroxy-17 alpha-(prop-1-ynyl)estra-4,9-dien-3-one], to determine whether intracellular glucocorticoid receptors are involved. RU38486 was shown to be an effective blocker of glucocorticoid receptor binding in vivo and in vitro. Furthermore, this compound significantly blocked the loss of body and muscle weight caused by injection of dexamethasone. These data indicate that intracellular glucocorticoid receptors are important in the etiology of steroid myopathy. Studies with glucocorticoid antagonists may lead to the design of specific therapeutic modalities for the treatment of both endogenously and exogenously produced steroid myopathies.

Animals↗

PubMed1985

Deletions of proximal 15q and non-classical Prader-Willi syndrome phenotypes.

A deletion of the long arm of chromosome 15 (usually involving bands 15q11-q12) has been seen in approximately 50% of Prader-Willi syndrome (PWS) patients [Ledbetter et al, 1982]. However, 14 patients with non-PWS (or atypical PWS) phenotype with 15q deletion indicate great clinical variability. A deletion was found in a propositus with a de novo translocation [45,XY, -15, -22, +rec(15;22) (22pter----22q13.2::15q14----15qter)], who had anomalies not normally observed in PWS patients. Activities of several enzymes mapped to the involved chromosomes were studied in the patient and control individuals. A 50% decrease in the level of arylsulfatase-A confirmed a small deletion in 22q(22q13.2----qter), and additional studies localized more precisely the loci for alpha-mannosidase (cytoplasmic) and beta-galactosidase.

Cerebroside-Sulfatase↗

PubMed1985

Fibre-type specificity and effect of thyroid hormone on glucose 6-phosphate dehydrogenase activity in normal and denervated skeletal muscles of the rat.

Glucose-6-phosphate dehydrogenase activity increases following denervation of rat skeletal muscle. The specificity of this effect to muscle fibre type was studied. Basal activity of the dehydrogenase was higher in soleus, a muscle composed predominantly of type I fibres, than in extensor digitorum longus, a muscle composed predominantly of type IIa and b fibres. The enzymatic activity of the soleus was also greater than that of the red (RQ) and white (WQ) portions of quadriceps muscle (predominantly type IIa and type IIb fibres, respectively). Following denervation, glucose-6-phosphate dehydrogenase increased in extensor digitorum longus and RQ, but not in WQ or the soleus. Following chronic treatment of rats with 3,3',5-triiodothyronine, which converts type I muscle fibres to type II, the dehydrogenase activity increased in both denervated soleus and extensor digitorum longus. It is concluded that the effect of denervation on glucose-6-phosphate dehydrogenase activity is selective for type IIa (fast oxidative-glycolytic) muscle fibres.

Animals↗

PubMed1985

Effects of 2,4-dichlorophenoxyacetic acid (2,4-D) on the contractile properties of reinnervated rat skeletal muscle.

2,4-Dichlorophenoxyacetic acid (2,4-D), a common herbicide, was administered to rats (100 mg/kg, i.p.) during 24 days to determine whether or not it is toxic to regenerating peripheral nerve and reinnervating muscle. The peroneal nerve was crushed 1 cm proximal to the extensor digitorum longus muscle and recordings made in vivo after 1 to 24 days. Functional reinnervation was observed by day 10 and recovery was similar in rats receiving 2,4-D or vehicle. Distal motor latencies and muscle action potentials returned toward normal during the 24 days in a similar manner in 2,4-D and controls. Isometric twitch tensions per muscle weight on indirect stimulation returned to intact values by 17 days, but in the 2,4-D animals they became larger (P less than 0.01) than controls by day 24. The twitch:tetanus ratios were increased at day 10 and returned toward normal values in the controls but remained increased (P less than 0.01) in the 2,4-D animals at 24 days. Similar results were obtained on direct muscle stimulation. The data suggest that 2,4-D is not toxic to nerve during regeneration or muscle reinnervation in the rat, but that it does affect both twitch and tetanus tensions suggesting proliferation as well as disruption of myofibrils.

2,4-Dichlorophenoxyacetic Acid↗

PubMed1985

2,4-Dichlorophenoxyacetic acid (2,4-D) reduces acetylcholinesterase activity in rat muscle.

A single dose (200 mg/kg body weight, i.p.) of 2,4-dichlorophenoxyacetic acid (2,4-D), commonly used as a herbicide, caused significant decreases in acetylcholinesterase (AChE) activity in diaphragm and other muscles of the rat. The 4S, 10S, and 16S forms of AChE were affected. The effect was maximal 15 to 24 h after injection. Choline acetyltransferase (CAT) activity was not affected. Neither AChE nor CAT activities changed in sciatic nerve from 2,4-D-treated animals. Spontaneous locomotor activity decreased dramatically 4 h after 2,4-D treatment. Myotonia that was present 1.5 h after 2,4-D injection became maximal at 2 to 6 h. Twenty-four hours after drug injection, when animals were recovering from myotonia, spontaneous locomotor activity was still depressed to 50% of control values. Prolonged distal motor latencies were observed 15 to 24 h after drug administration. AChE activity and spontaneous locomotor activity returned to control values at 48 h. Thus, 2,4-D causes a decrement of end-plate AChE, as well as behavioral and electrophysiologic changes. Decreased activity of AChE may be an early step in development of the myopathy that occurs after large dose 2,4-D.

2,4-Dichlorophenoxyacetic Acid↗

PubMed1985

2,4-Dichlorophenoxyacetic acid (2,4-D) does not cause polyneuropathy in the rat.

2,4-Dichlorophenoxyacetic acid (2,4-D), a component of Agent Orange, was injected intraperitoneally into adult male Fisher rats for 3-12 weeks. During the period of study gait and toe-spreading reflexes remained normal and distal motor latencies, motor and mixed nerve conduction velocities and amplitudes remained similar (P greater than 0.05) in animals receiving 2,4-D or vehicle. This study suggests that 2,4-D is not toxic to peripheral nerves in the rat.

2,4-Dichlorophenoxyacetic Acid↗

PubMed1985

Testosterone and muscle hypertrophy in female rats.

The effects of chronic treatment with testosterone propionate on compensatory muscle hypertrophy secondary to synergist removal were studied in female rats. Synergist removal resulted in a significant (2-fold) increase in muscle wet weight, with no changes in protein concentration. As reported previously, oxidation of [2-14C]pyruvate to 14CO2 was significantly decreased in hypertrophic muscles. In addition, malate dehydrogenase and lactate dehydrogenase activities were significantly decreased in overloaded muscles on a wet weight basis but not on the basis of noncollagen protein. These data suggest that specific metabolic adaptations may occur in response to overload of muscle. Administration of testosterone propionate in subcutaneously implanted Silastic capsules resulted in a 20-fold increase in serum testosterone levels. This treatment had no effect on body weight, muscle weight, pyruvate oxidation, or malate and lactate dehydrogenase activities in both control and hypertrophic muscles, although there was an effect on the noncollagen protein content of overloaded muscles. These results do not support the hypothesis that androgens, in conjunction with weight-bearing exercise in female subjects, are effective in increasing muscle mass or function in female subjects.

Animals↗

PubMed1985

Effects of suspension hypokinesia/hypodynamia on rat skeletal muscle.

We studied the effects of suspension hypokinesia/hypodynamia (H/H) on properties of soleus and plantaris muscles of rats. Our objective was to compare the effects of this model to those of disuse atrophy. After 12 d of H/H, there were significant decreases in soleus and plantaris muscle wet weight and citrate synthase activity. Soleus muscle was affected to a greater extent than plantaris muscle. There was a significant decrease in non-collagen protein content of H/H soleus muscle. Triceps brachii muscles did not display significant changes in any parameters measured, suggesting that observed changes were not due to systemic factors. There was no significant change in the water content of H/H soleus or plantaris muscles. Suspension H/H causes muscle changes different from those secondary to limb immobilization, in which soleus and plantaris muscles are equally affected.

Animals↗

PubMed1984

Androgen-estrogen synergy in rat levator ani muscle: glucose-6-phosphate dehydrogenase.

The effects of castration and hormone administration on the activity of glucose-6-phosphate dehydrogenase in the rat levator ani muscle were studied. Castration caused a decrease in enzyme activity and in wet weight of the levator ani muscle. Chronic administration of testosterone propionate increased glucose-6-phosphate dehydrogenase activity in the levator ani muscle of castrated rats; the magnitude of the recovery of enzyme activity was related to the length of time of exposure to testosterone propionate after castration as well as to the length of time the animals were castrated. The longer the period of castration before exposure to testosterone propionate, the greater the effect. This result may be related to previously reported castration-mediated increases in androgen receptor binding in muscle. Dihydrotestosterone was less effective than testosterone propionate in enhancing glucose-6-phosphate dehydrogenase activity in the levator ani muscle from castrated rats; estradiol-17 beta alone was ineffective. Combined treatment with estradiol-17 beta and dihydrotestosterone, however, was as effective as testosterone alone. Thus, androgens and estrogens may exert synergistic effects on levator ani muscle.

Androgens↗

PubMed1984

Increased cytosolic androgen receptor binding in rat striated muscle following denervation and disuse.

We investigated the effects of denervation and disuse on cytosolic androgen receptor binding by rat striated muscle. Denervation of the extensor digitorum longus and tibialis anterior muscles caused a 40-50% increase in cytosolic androgen receptor concentration with no change in apparent binding affinity. This effect was evident at 6 h postdenervation, maximal at 24 h, and declined to 120% of the control level 72 h after denervation. A 40% increase in cytosolic androgen receptor concentration was also noted 24 hr after denervation of the hormone-sensitive levator ani muscle. The effect of denervation on androgen receptors was not blocked by in vivo injection of cycloheximide; therefore, de novo receptor synthesis probably is not involved in the observed increase. Disuse, produced by subperineurial injection of tetrodotoxin into the tibial and common peroneal branches of the sciatic nerve, mimicked the effect of denervation on androgen receptor binding, suggesting that neuromuscular activity is important in regulation of receptor concentration. Possible mechanisms subserving this effect are discussed.

Animals↗