Search PubMed⌕ Search

Biomedical subjects

A A Smith

Publications and source records attributed to A A Smith.

At least 73 records · Page 4Linked to original sources
PubMed1982

Evidence that ectoderm influences the differentiation of muscle in the limb of the embryonic chick.

Intact limb buds from stage 19 to 21 embryos differentiate to contain both cartilage and muscle in culture. If the limb ectoderm is removed, the limb mesoderm cells differentiate as cartilage and connective tissue but not as muscle. Intact limb buds from stage 19 embryos differentiate both cartilage and muscle when grafted to the chorioallantoic membrane, but differentiate only cartilage and connective tissue if the ectoderm is removed. The significance of limb ectoderm to muscle differentiation can be observed as late as stage 24. Both the prospective cartilage region and the prospective soft tissue region from the limb of a stage 24 embryo differentiate cartilage and muscle in the presence of limb ectoderm, but differentiate little, if any, muscle in the absence of limb ectoderm. The results indicate that the dorsal and ventral ectoderm have some influence on muscle differentiation.

Animals↗
PubMed1980

Inhibition of growth in young mice treated with pentazocine: reversal by naltrexone.

One week old mice were injected subcutaneously once daily with d,1-methadone (5 mg/kg), pentazocine, naltrexone, naloxone, nalorphine or nalbuphine, each at 10 mg/kg. The remaining half of each litter was used as control. Only methadone and pentazocine groups showed reduced weight gain after 3 weeks of treatment (P < 0.01). Injection of pentazocine in dosages of 5-20 mg/kg inhibited weight gain and protein synthesis in a dose-related manner. The incorporation of labeled leucine was followed in brain, liver and muscles. Methadone and pentazocine groups showed a significant decrease in protein synthesis in all tissues studied. The nalbuphine, nalorphine, naloxone, and naltrexone-treated groups incorporated leucine normally, correlating with normal weight gain. These data suggest that pentazocine, unlike the other mixed agonist-antagonists and antagonists, adversely affects the growth of very young animals when administered chronically. A specific opioid effect is suggested by the fact that naltrexone given concomitantly with the pentazocine prevents development of the biochemical lesion.

Animals↗
PubMed1980

Calibration of time derivatives of forced vital capacity by explosive decompression.

A simple, portable, inexpensive device is described that simulates expiratory flow curves for calibration of spirometers. A 4-L metal cylinder filled with copper mesh is fitted with a precision manometer. The pressure is increased to twice atmospheric and released by explosive decompression through 4 easily interchangeable resistors. The ratio of forced expiratory volume in one second to forced vital capacity ranged from 0.80 to 0.25, thus encompassing the range from normal to severe obstruction. Accuracy was defined by 25 measurements of forced vital capacity that differed by no more than 0.5% from the actual cylinder volume. Repeatability was reflected by a standard deviation of at most 0.04 L/s for one-second forced expiratory volume, mid-expiratory flow, and instantaneous flows at 50 and 25% of the forced vital capacity. Peak flow was less reproducible. Calibrations of a water spirometer at increased altitude and at temperatures from 4 degrees to 37 degrees C revealed no significant changes in volume or flow rates. Standard values have remained unchanged for 2.5 yr. Three volume spirometers and 2 primary flow devices were tested extensively.

Altitude↗
PubMed1978

Inhibition by d,l-methadone of RNA and protein synthesis in neonatal mice: antagonism by naloxone or naltrexone.

Neonatal mice were injected once daily with d,l-methadone in a dosage of 2 mg/kg. The remaining half of the litter was injected with saline. After one week the incorporation of labeled uridine and labeled leucine was significantly (P less than 0.05) reduced in skeletal muscle. Longer treatment with methadone impaired RNA and protein synthesis in liver, heart, skeletal muscle and brain. The percentage reduction RNA was log-dose related. When methadone was discontinued for 1 week following 4 weeks of treatment, incorporation of precursors into RNA and protein was found to be normal. A specific opioid effect is suggested by the finding that naltrexone or in part, naloxone, given concomitantly with with the methadone prevents development of the biochemical lesion.

Animals↗
PubMed1977

Inhibition of growth in young mice treated with d,1-methadone.

Neonatal mice were treated with d,1-methadone, 1-alpha-acetylmethadol (LAAM) or the narcotic antagonists, naloxone, nalorphine or levallorphan. Litter mates were injected with normal saline solution and handled in the same way. Treatment began on the second postpartum day and continued daily or on alternate days for up to 6 weeks. Injection of methadone in dosages of 2 mg/kg to mg/kg inhibited weight gain in a log dose-related fashion. LAAM, 1 mg/kg or 2 mg/kg also retarded weight gain. Mice gained weight normally when naloxone, 10 mg/kg was injected with methadone, 2 mg/kg. Furthermore the daily injection of d-methadone, 4 mg/kg, did not inhibit weight gain nor did any of the narcotic antagonists. There findings indicate that growth inhibition induced by methadone is a stereospecific, opioid effect.

Animals↗
PubMed1976

Further characterization of the androgen receptor in rat testis.

Immature rat testes contain a specific binding protein for testosterone (T) and 5alpha-dihyrotestosterone (DHT) with physico-chemical properties similar to the cytoplasmic androgen receptors in the epididymis and ventral prostate but different from the testicular androgen-binding protein (ABP). Like the androgen receptors in the prostate and epididymis, it has a sedimentation coefficient of about 7 S at low ionic strength, is eluted in or close to the void volume on Sephadex G-200 gel filtration (Stokes radius greater than 80 A), has an isoelectric point of about 5.6-6.0 (mean) 5.8 and a relative mobility (Rf) of 0.4 in 3.25% acrylamide gels. Following the injection of 3H-labeled testosterone, T and DHT are bound selectively by the receptor. Relatively more [3H]T than [3H]DHT is present in bound and free fractions as well as in total testicular 105,000 g supernatant. Similar results are obtained from testicular incubations with equimolar amounts of [3H]T and [3H]DHT at 0 degrees C in vitro. Saturation of receptor sites is achieved by incubation of testis supernatants with increasing amounts of [3H]T at 0 degrees C. The number of available binding sites following post-hypophysectomy regression is estimated to be about 9 fmoles/mg protein, and the apparent equilibrium constant of dissociation is 7 X 10(-10) M. The temperature stability and sulfhydryl dependence of the testicular androgen receptor are similar to androgen receptors in other organs. Binding is destroyed by heating the supernatants at 50 degrees C for 30 min and by exposure to p-chloromercuriphenylsulfonate (1 mM) at 0 degrees C for 60 min. Furthermore, like other androgen receptors, the half-time of dissociation of testicular androgen-receptor complexes at 0 degrees C is extremely slow (t1/2 greater than 35 h). Separation of seminiferous tubules from interstitial tissue showed that a major portion of these receptors were localized within the seminiferous tubules.

Animals↗
PubMed1975

Interaction of biogenic amines with ethanol.

Ethanol through its primary catabolite, acetaldehyde, competitively inhibits oxidation of aldehyde dehydrogenase substrates. As a consequence biogenic amines form increased quantities of alcohols rather than the corresponding acids. During this biotransformation, condensation reactions between deaminated and intact amines may occur which can yield tetrahydropapaverolines. These compounds are closely related to precursors of opioids which is cause to link ethanol abuse to morphine addiction. There is, however, no pharmacological or clinical evidence suggesting similarities between ethanol dependence or opiod addiction. Acetaldehyde plays an additional role in alkaloidal formation in vitro. Biogenic amines may react with acetaldehyde to form isoquinoline or carboline compounds. Some of these substances have significant pharmacological activity. Furthermore, they may enter neural stores and displace the natural neurotransmitter. Thus, they can act as false neurotransmitters. Some investigators believe that chronic ethanol ingestion leads to significant formation of such aberrant compounds which may then upset autonomic nervous system balance. This disturbance may explain the abnormal sympathetic activity seen in withdrawal. While these ideas about the etiology of alcohol abuse have a definite appeal, they are naturally based on in vitro preliminary work. Much study of the quantitative pharmacology of these compounds in animals is required before judgement can be made as to the merits of the proposed hypotheses. In the meantime, pharmacological studies on the ability of ethanol to depress respiration in the mouse has revealed that unlike opioids or barbituates, respiratory depression induced by ethanol requires the presence in brain of serotonin. This neurotransmitter also mediates the respiratory effects of several other alcohols but curiously, not chloral hydrate, yet this compound is purported to alter biogenic amine metabolism much like ethanol. Thus, the response to ethanol can be pharmacologically separated from other major narcotic classes such as opioids and barbiturates by respiratory depression effects. The specific requirement for serotonin mediation exhibited by ethanol and several other alcohols opens the door for a rational therapeutic approach to the treatment of alcohol abuse. At the same time, this finding tends to lessen the probability that alcoholism is in some way connected with the formation of addictive alkaloids.

Acetaldehyde↗
PubMed1975

Androgen receptor in nuclei of rat testis.

Testis nuclei of hypophysectomized rats selectively accumulate labeled testosterone and 5alpha-dihydrotestosterone following the injection of tritiated testosterone in vivo. Testosterone and 5alpha-dihydrotestosterone are bound to macromolecules in nuclei and can be extracted with 0.5 M KCl. Accumulation of protein bound radioactive androgens in nuclei of isolated seminiferous tubules is similar to that of whole testis. The relative amounts of testosterone and dihydrotestosterone in purified nuclei were similar to the relative amounts bound to cytoplasmic receptors, suggesting that cytoplasmic androgen-receptor complexes may be transported into the nuclei. Binding of labeled androgen is saturable and inhibited by prior injection of unlabeled testosterone or cyproterone acetate. Nuclear binding sites are destroyed by the proteolytic enzyme pronase, but not by DNase. Like the cytoplasmic androgen-receptor complexes in rat testis, nuclear androgen-protein complexes are heat labile and dissociate slowly at 0 degrees C. androgens fail to accumulate in testis nuclei of the Stanley-Gumbreck androgen insensitive rat, a species lacking cytoplasmic androgen receptors in testis and other androgen target tissues.

Animals↗