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Biomedical subjects

J D Baxter

Publications and source records attributed to J D Baxter.

At least 199 records · Page 11Linked to original sources

Arctic audiology: trials, tribulations, and occasional successes.

Efforts to provide audiologic services to the Inuit population of the Baffin Zone have frequently resulted in unexpected problems and frustrations. Often these are the product of two very different cultures coming together. This paper reviews the author's personal experiences in this regard with special reference to hearing aid attitudes, noise exposure, and the making of instructional audio-visual materials. A brief description of a recently revised hearing conservation program at Frobisher Bay is provided.

Arctic Regions↗

Acute epiglottitis in adults.

Fourteen cases of adult acute epiglottitis with their clinical manifestations are presented. The history, etiology, pathophysiology, and diagnosis of the disease are reviewed. The controversies of management are discussed and a concise management protocol is outlined.

Acute Disease↗

The evolving attitude in Canada toward the management of chronic otitis media in the Inuit population.

The reasons for the high incidence of otitis media in the Inuit population are described. The disorder seems to be related to socio-economic conditions including the adoption of many Caucasian habits such as overcrowded housing and bottle feeding. The relative merits of improving socio-economic conditions combined with medical treatment, and of medical treatment alone, and surgical treatment are outlined.

Attitude to Health↗

Detection of glucocorticoid receptors in cultured human trabecular cells.

To evaluate potential direct effects of glucocorticoids on the aqueous outflow pathway, the cellular binding of steroids to cultured human trabecular cells was examined. After incubation of cells with 5 to 40 nM [3H]dexamethasone, specific binding (i.e., binding that could be blocked by an excess of nonlabeled steroid) was detected by measuring the total cell-associated labeled hormone. A binding affinity of 5 nM and 60,000 receptor sites/cell were demonstrated with labeled dexamethasone. Incubation of human trabecular cells with 40 nM [3H]dexamethasone for 60 min revealed that 62% +/- 7 of the specific binding was found in the nuclear fraction and 38% +/- 3 was in the cytoplasmic fraction. In competition studies, dexamethasone had a higher affinity for these sites than cortisol, which in turn had a higher affinity than progesterone. These studies suggest that functional glucocorticoid receptors are present in human trabecular cell cultures. Therefore it is possible that a direct action of glucocorticoids on trabecular cells could contribute to the decreased outflow facility observed in steroid glaucoma.

Cells, Cultured↗

Nuclear accumulation of epidermal growth factor in cultured rat pituitary cells.

Epidermal growth factor (EGF) is a mitogen for epidermal cells in vivo and for a wide variety of cells in culture. Recently, we and others have reported that EGF can also regulate the cellular levels of various hormones and fibronectin at concentrations which only minimally influence cell division. In addition, EGF treatment of GH3 cells affects chromatin structure such that isolated nuclei from treated cells have an increased capacity to bind bacterial RNA polymerase in initiation site complexes. Thus, the data suggest that various nuclear functions are modulated by EGF in GH3 cells despite its failure to affect DNA synthesis or cell proliferation. Recently, Yanker and Shooter have reported on the nuclear accumulation of nerve growth factor (NGF) in PC12 cells in which NGF does not promote cell division but does influence RNA and protein synthesis while inducing overt differentiation (neurite outgrowth). The similarities between the two systems and the various theories regarding the mechanism by which mitogens exert their growth-promoting and other effects led us to investigate whether an interaction between EGF and the cell nucleus can be demonstrated after surface binding and internalization of EGF in GH3 cells. We report here that when its lysosomal degradation is inhibited by chloroquine, EGF accumulates in the nucleus.

Animals↗

Molecular cloning of DNA complementary to bovine growth hormone mRNA.

We have cloned DNA complementary to mRNA coding for bovine growth hormone (bGH). Double-stranded DNA complementary to bovine pituitary mRNA was inserted into the Pst I site of plasmid pBR322 by the dC x dG tailing technique and amplified in E. coli x 1776. A recombinant plasmid containing bGH cDNA ws identified by hybridization to cloned rat growth hormone cDNA. It contains the entire coding and 3'-untranslated regions and 31 bases in the 5'-untranslated region. Nucleotide sequence analysis determined the sequence of the 26-amino acid signal peptide and confirmed the published amino acid sequence of the secreted hormone at all but 2 residues. Codon usage is nonrandom, with 81.7% of the codons ending in G or C. The nucleotide sequence of bGH mRNA is 83.9% homologous with rat GH mRNA and 76.5% homologous with human GH mRNA, while the respective amino acid sequence homologies are 83.5% and 66.8%.

Amino Acid Sequence↗

Cell-free synthesis of acetylcholine receptor polypeptides.

Messenger RNA coding for acetylcholine receptor peptides has been identified. This polyadenylate [poly(A)+]RNA from Torpedo californica directs, in a cell-free system, the synthesis of peptides 60,000, 51,000, 49,000 41,000, and 35,000 daltons which account for approximately 2 percent of the total synthesized proteins. The results suggest that several different messenger RNA's code for the receptor subunits. These proteins react specifically to antiserum to native acteylcholine receptor, suggesting that the primary translational product has conformational features similar to the native receptor. Further, the results support the idea that there is post-translational modification of receptor subunits as the molecular weights of the cell-free synthesized proteins differ from those of purified receptor subunits.

Acetylcholine↗

Genes for growth hormone, chorionic somatommammotropin, and growth hormones-like gene on chromosome 17 in humans.

The human genes for growth hormone (GH), chorionic somatomammotropin (CSH), and a third growth hormone-like gene (GHL) have been located on chromosome 17 in humans. DNA fragments of 2.6, 2.8, and 9.5 kilobase pairs containing GH, CSH, and GHL, respectively, were identified in human genomic DNA, and a 7.5-kilobase DNA fragment related to growth hormone DNA sequences was found in mouse cells. In somatic hybrids of human and mouse cells containing reduced numbers of human chromosomes, but a normal complement of mouse chromosomes, the mouse, 7.5-kolobase DNA fragment was always present, whereas the 2.6-, 2.8-, and 9.5-kilobase human fragments were present only when human chromosome 17 was also present.

Animals↗

Expression of cloned beta-endorphin gene sequences by Escherichia coli.

DNA coding for the opiate peptide beta-endorphin has been cloned into bacterial plasmids in such a way as to direct the synthesis of a hybrid beta-galactosidase/beta-endorphin protein. This hybrid protein can readily be cleaved in vitro to release biologically active beta-endorphin.

Animals↗

Epidermal growth factor and expression of specific genes: effects on cultured rat pituitary cells are dissociable from the mitogenic response.

Cultured rat pituitary tumor cells, GH3/D6, which synthesize both growth hormone and prolactin, have cell-surface epidermal growth factor (EGF) receptor sites (34,000 per cell) that bind 125I-labeled EGF with a high affinity (Kd approximately 1 nM). Prolonged treatment of the cells with EGF did not stimulate cell division but did inhibit thyroid hormone-stimulated cell growth. In addition, EGF altered the morphology of the cells from a rounded to an elongated conformation. EGF also induced a perturbation of chromatin structure in GH3 cell nuclei that was detected by an increase (40%) in the number of rifampicin-resistant initiation sites for bacterial RNA polymerase. This was accompanied by an increased synthesis of prolactin and an inhibition of synthesis of growth hormone. In the presence of EGF, the synthesis of growth hormone was no longer inducible by thyroid hormone, but it remained responsive to glucocorticoids. The results demonstrate that EGF can elicit major effects on the cellular phenotype and expression of specific genes in the absence of a proliferative response. This suggests that EGF can also regulate differentiated cellular functions.

Animals↗

Processing of the precursor to corticotropin and beta-lipotropin in humans.

The biosynthesis of human corticotropin (ACTH) was studied in organ culture of pituitary adenomas and by translating mRNA from an ectopic ACTH-producing tumor in a cell-free system. Peptides similar to human ACTH, beta-lipotropin, and the amino-terminal glycopeptide are cleaved from a common precursor with an apparent molecular weight of 35,000 on sodium dodecyl sulfate/polyacrylamide gels. The precursors synthesized in pituitary and ectopic ACTH-producing tissues are indistinguishable. The cleavage sites of the peptide chain appear to be similar to those previously deduced for murine and bovine ACTH. Immunoprecipitation studies suggest that the primary structure of the precursor peptide is similar in all three species. However, glycosylation is different in the human and murine precursors: the precursor to human ACTH appears to be glycosylated only in the amino-terminal fragment, not in the ACTH or beta-lipotropin sequences. Studies with an autopsied normal human pituitary suggest that neither normal nor adenomatous pituitary tissue glycosylates the ACTH sequence.

Adrenocorticotropic Hormone↗

Recombinant DNA and medical progress.

In the extensive debate surrounding recombinant DNA research, the significant contributions it has already made and their potential for directly affecting medical practice are often lost. The recombinant techniques are described in the context of the already achieved "manufacture" of highly pure insulin and human growth hormone and their promise for practical application in diagnosis and therapy.

Cloning, Molecular↗

Ceruminoma.

A unique case of adenoid cystic carcinoma arising in a ceruminous gland, with widespread pulmonary metastases, is presented. This is the first case in the English literature in which the diagnosis was made from material obtained by needle aspiration from a pulmonary metastasis. The literature is reviewed and the histological features and clinical course are discussed in the paper. Adenoid cystic carcinoma is the most common tumor of ceruminous gland origin, and is the only one which produces widespread metastases in the lungs. Tumors arising from ceruminous glands are slightly more prevalent in females, and pulmonary metastases occur almost three times as often in females as in males. Suggested treatment is wide local excision of the primary tumor and of local recurrences, and excision of distant metastases when possible. Irradiation is useful only for palliation. All patients, but especially females, should be followed carefully for the detection of possible pulmonary metastases.

Carcinoma, Adenoid Cystic↗