Biomedical subjects
Publications and source records attributed to J D Baxter.
Two hundred and four cases of acute epiglottitis treated at the Montreal Children's Hospital between 1951 and 1978 are reviewed. The comparison of tracheostomy vs. nasotracheal intubation is discussed. Nasotracheal intubation has been found to be the treatment of choice as long as the necessary services are available in the hospital.
After a careful dissection of trabecular tissue from recent postmortem specimens, human trabecular cells were established in tissue culture with 250 ng/ml fibroblast growth factor (FGF), Dulbecco's modified Eagle's medium (DME), and 10% human serum. These conditions have allowed propagation of human trabecular cells for a number of passages at high density without apparent cellular degeneration. FGF increased the rate of cell division and the plating efficiency for trabecular cells but was not needed after cells had achieved confluency. Human trabecular cells had a pattern of growth which differed from human corneal keratocytes and human corneal endothelial cells compared at a similar passage. Propagation of human trabecular cells in vitro may provide a valuable source of experimental material to study the functional aspects of these cells which line the trabecular meshwork.
Modalities of local medical treatment of chronic otitis media in Inuit elementary school children were evaluated over a period of three and a half years in a project associated with the provision of amplification (hearing aids) for students who had significant conductive hearing deficits which interfered with their ability to communicate. The significant medical and educational benefits derived are reviewed.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Mechanisms whereby glucocorticoids might inhibit growth are reviewed from the perspective of glucocorticoid effects on cell metabolism and growth. Although glucocorticoids given to patients decrease levels of growth hormone and possible somatomedins, the effect of glucocorticoids on growth is not reversed when growth hormone is given. Glucocorticoids inhibit cell growth in culture. Cell inhibition correlates with binding of steroids to the glucocorticoid receptors. Some tissues are very sensitive; others are insensitive. In cell culture, changes in sensitivity can be associated with changes in binding, but this is not always the case in tissues of the animal. The mechanisms of inhibition of cell growth are not known. It could be due to steroid-induced synthesis of inhibitory proteins or to blocking by receptor-steroid complexes of the synthesis of RNA. Steroids may affect uptake of substrates, e.g., glucose or amino acids, which in turn affects growth. The inhibitory actions of glucocorticoids on individual tissues may explain why these steroids inhibit growth in the animal. It is not known, however, how the steroid inhibits linear growth in mass or which cell types are most important targets for such effects.
Ten patients with atrophic rhinitis were treated surgically with silastic implants. The details and principles of the surgical technique are emphasized. These patients have been observed for up to nine years. They all improved, with 70 per cent of them showing a "marked improvement" and the remaining 30 per cent showing a satisfactory one.
The primary structure of DNA containing the sequence for rat pituitary growth hormone mRNA has been determined. DNA was obtained by reverse transcription of polyadenylated RNA from cultured pituitary cells and from recombinant bacterial plasmids. The amino acid sequences for rat growth hormone and its precursor form have been deduced from the determined nucleotide sequences.
DNA complementary to mRNA coding for the human polypeptide hormone, chorionic somatomammotropin, has been purified by specific restriction endonuclease digestion and religation before cloning into bacterial plasmids. The primary structure of a major portion of this mRNA species is deduced from the nucleotide sequence of the recombinant DNA.
Explore the source record for details and available documents.
Cultured rat pituitary cells (GC) respond to thyroid and glucocorticoid hormones by increases in growth hormone production and growth hormone mRNA. When these cells are transferred from medium containing normal animal serum (with 1.8 mug of thyroxine per dl) to a medium containing serum from a thyroidectomized calf, "hypothyroid medium" (with no detectable thyroid hormone), growth hormone production decreases markedly. In cells maintained for 5 days in hypothyroid medium, triiodothyronine induces within 50 hr a 17-fold increase in growth hormone production whereas glucocorticoids, during the same time, produce a negligible (3-fold or less) stimulation. In combination, the two hormones promote a 45-fold stimulation. In all instances the changes in growth hormone production are paralleled by changes in the levels of growth hormone mRNA as measured by cell-free translation. The transfer to hypothyroid medium and the hormonal induction do not affect the relative activities of other mRNAs whose products are detectable on polyacrylamide gels. These studies indicate that thyroid hormone can be an activator of the expression of the growth hormone gene. The results also show that triiodothyronine controls the magnitude of the effect of glucocorticoids on growth hormone mRNA, and provide a model for "permissive" triiodothyronine action. The synergistic effect of these two classes of hormone suggests that they increase levels of growth hormone mRNA by different mechanisms.
Thyroid and glucocorticoid hormones stimulate growth hormone synthesis in cultured rat pituitary cells (GC). We have compared changes in growth hormone production and mRNA in these cells. Triiodothyronine (10 nM) and dexamethasone (1 micron) stimulated increases in growth hormone production by 2.5- and 3.8-fold, respectively. There were corresponding increases in the capacity of RNA from hormone-treated cells to direct synthesis of pregrowth hormone in a wheat germ cell-free translation system, suggesting hormone-regulated increases in growth hormone mRNA. Hormone-induced changes in mRNA were also demonstrated by determining the kinetics of hybridization of a cDNA probe prepared from RNA enriched (about 70%) for growth hormone translational activity with RNA from control and hormone-treated cells. These results suggest that thyroid and glucocorticoid hormones can regulate growth hormone production by influencing the levels of its mRNA.
l-Thyroxine is converted to 3,5,3'-l-triiodothyronine (T(3)) as well as to 3,3',5'-l-triiodothyronine (reverse T(3)). One product of further deiodination is 3,3'-diiodothyronine (3,3'T(2)). The serum levels of reverse T(3) and 3,3'T(2) change considerably in various physiological and disease states. We previously found that reverse T(3) and 3,3'T(2) bind to the solubilized hepatic nuclear "receptors" for thyroid hormones. This led us to study binding and actions of these metabolites in cultured rat pituitary cells in which glucose consumption and growth hormone production are regulated by T(3) and l-thyroxine. Reverse T(3) and 3,3'T(2) stimulated growth hormone production and glucose consumption and inhibited nuclear binding of radioactive T(3). Either metabolite produced maximal effects that equaled those of T(3), and neither inhibited the T(3) response. Further, additive effects were observed when reverse T(3) was combined with submaximal concentrations of T(3). In serum-free and serum-containing media, concentrations of 3,3'T(2) 50- to 70- and 10- to 100-fold greater, respectively, than those of T(3) were required for equivalent stimulations and for inhibition of nuclear binding by T(3). The relative activity differences under the two conditions can be attributed to weaker serum protein binding of 3,3'T(2) than T(3). With cells in serum-free media, reverse T(3) was a less avid competitor than 3,3'T(2) for T(3) binding by the nuclear receptors, and was less potent than 3,3'T(2) (0.001 the potency of T(3)) in inducing growth hormone production or glucose oxidation. In incubations with serum-containing media, reverse T(3) was an ineffective competitor for T(3) binding, and had only 0.1 the inducing potency of 3,3'T(2) (0.001 the potency of T(3)). The weaker activity of reverse T(3) relative to 3,3'T(2) in serum-containing media could be explained by stronger serum binding of reverse T(3) than 3,3'T(2). In addition, after long-term incubation of cells with radioactive reverse T(3), much of the cell-associated radioactivity was recovered as 3,3'T(2). These studies suggest that reverse T(3) and 3,3'T(2) can stimulate thyroid hormone-regulated functions as weak agonists by acting via the same receptors that mediate T(3) actions. Moreover, some of the effects of reverse T(3) may be due to 3,3'T(2) produced by deiodination of reverse T(3).
Chronic otitis media and hearing loss is a major health problem today in the Canadian Eskimo. The subject is reviewed and the findings of projects and a survey that have been carried out recently are discussed. A modality of treatment is proposed which is based upon the findings of the projects, the survey and other information that is available at the present time.
Acute epiglottitis is the most treacherous inflammatory process that can affect the respiratory tract. It can be a cause of sudden death in children. The clinical features of this entity are reviewed and our experience with its management at The Montreal Children's Hospital during the past 25 years is presented. The establishment of a "secure" airway by tracheostomy and in recent years, by nasotracheal intubation has decreased to practically nil the mortality of children who arrive alive at this hospital with acute epiglottitis.
Acute epiglottitis is a pediatric airway emergency. No deaths occurred in 61 cases treated by elective tracheostomy at The Montreal Children's Hospital between 1966 and 1974. Seven patients (11.5%) showed evidence of aspiration pneumonia prior to tracheostomy and seven others developed pulmonary atelectasis in the first 24 hours following tracheostomy but only 9.8% of the total had a complication which continued in evidence 24 hours following surgery. A further 19.5% developed further complications unrelated to this earlier morbidity prior to discharge from hospital. The mean cannulation time was seven days and the mean hospital stay was nine days. Of these patients, 32 (52.4%) were seen between a year and seven-and-a-half years later. Twenty were completely asymptomatic with a small, neat scar. Twelve patients had experienced some upper respiratory problem or minor problems related to the tracheostomy incision.
In summary, a general approach is presented to purify and sequence DNA fragments of a specific gene starting with a heterogeneous mixture of mRNAs. The methodology has been applied to the determination of the DNA sequence of a portion of the gene for human chorionic somatomammotropin. Most of the possible translation codons of the genetic code were found to be used. Some selectivity in the codon choices was found, and this may be important for RNA or gene regulation or structure. The stop codon UAG was found and a second stop codon in the same reading frame was found nine bases farther down. Finally, a "palindrome" sequence was detected in the 3' noncoding region.