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Biomedical subjects

C Brady

Publications and source records attributed to C Brady.

35 records · Page 2Linked to original sources

Purification of three pectin esterases from ripe peach fruit.

Three isoforms of pectin esterase (PE1-PE3) (pectin pectyl-hydrolase, EC 3.1.1.11.) were purified to homogeneity from ripe peach fruit (Prunus persica cv. Coronet). The three enzymes were basic proteins of M(r) 34,000 as determined by denaturing polyacrylamide gel electrophoresis but were separated by FPLC cation-exchange chromatography. The proteins were N-terminally blocked but amino acid sequences were obtained for peptides released from two of the three isoforms. The sequences revealed a threonine/lysine substitution in a comparison between isoform PE2/isoform PE3, and there were regions of sequence similarity with other plant pectin esterases. The proteins did not bind to concanavalin A and were not stained by the periodate-Schiff reagent suggesting a low or zero level of glycosylation. Polyclonal antisera to isoform PE3 also bound to isoforms PE1 and PE2. The study provides the enzyme protein sequence and immunological basis for an evaluation of the role of pectin esterases in normal and abnormal ripening of peach fruit.

Amino Acid Sequence↗

The efficacy of CGS 20267 in suppressing estrogen biosynthesis in patients with advanced stage breast cancer.

The pharmacologic inhibition of aromatase activity has been the focus of clinical trials in patients with advanced stage breast cancer. Recent developments with imidazole compounds that inhibit aromatase activity suggest their clinical use as potent inhibitors of estrogen biosynthesis in postmenopausal breast cancer patients. In this Phase I, open-label, dose-range finding study, we examined the inhibitory potency of CGS 20267 on blood and urine levels of estradiol, estrone and estrone sulfate in 8 patients with metastatic breast cancer. Studies included evaluation of adrenal and thyroid function to look for evidence of general hydroxylase inhibition at dose levels effective for aromatase blockade. Patients were administered CGS 20267 at doses of 0.1 and 0.25 mg, once a day in ascending doses over a 12-week period. Preliminary data reveal that CGS 20267 elicits a striking suppression in plasma estradiol, estrone and estrone sulphate which was observed in some patients as quickly as within 24 h of the first dose. Estrogen suppression of over 90% was achieved within 2 weeks of therapy. No alterations in either baseline or ACTH (cortrosyn) stimulated cortisol and aldosterone levels were observed through the 12 weeks of therapy. In addition, 24 h urine sodium and potassium values were not appreciably altered during therapy. We conclude that CGS 20267 is a potent, specific inhibitor of estrogen biosynthesis in postmenopausal patients with metastatic breast cancer and effectively reduces blood and urine estrogens to undetectable levels.

Aldosterone↗

Whiplash and temporomandibular joint dysfunction.

This article examines the relationship between Temporomandibular joint dysfunction and rear-end (whiplash) motor vehicle accidents. The clinical and statistical evidence relating TMJ damage to whiplash is reviewed. The sequence of events regarding the head, neck and jaw movements which occur in these accidents is considered. The jaw movements are discussed in detail. An analysis of the forces resulting from these movements indicates that tensile, compressive and shear forces occur which challenge the integrity of the soft tissues of the Temporomandibular joint. An overview of the mechanisms whereby damage may occur is considered. A more detailed analysis of these mechanisms will be dealt with in further articles, to evaluate the precise magnitude and direction of forces in all phases of the accident.

Accidents, Traffic↗

Emergency percutaneous dilatational cricothyroidostomy: use of modified nasal speculum.

The authors devised a percutaneous dilatational method which they believe trained physicians and nonphysicians (emergency medical technicians and paramedics) can use with safety and speed. With one blade of a modified nasal speculum embedded in a tapered small pigtail-dilator catheter, the closed, flattened instrument is forced through the cricothyroid ligament, with a twisting motion, and then opened. Only the skin is incised 1 cm in length. Then a free flow of air via attached syringe is sought before any further penetration. This guarantees accurate and safe entry into the airway. The operator forces the J-tipped dilator and speculum inward as the needle is withdrawn. At the proper depth the speculum is opened transversely, and a cuffed tracheostomy tube with an internal diameter of 6 mm is inserted. The instrument is removed and immediate suctioning and active ventilation is possible. The authors developed the use of this instrument in trials on a mannequin and on 25 cadavers.

Cricoid Cartilage↗

The Florida breastfeeding promotion project: a coalition effort to improve hospital practices and policies.

The Florida Healthy Mothers, Healthy Babies-Coalition initiated a breastfeeding promotion project. The Coalition focused on hospital policies because of their impact on breastfeeding success and because of the potential for working with other state efforts directed at pregnant women or new mothers. The Florida Healthy Mothers, Healthy Babies Coalition developed a three-part program. It consists of model hospital policies concerning breastfeeding, a lecture series which educates hospital nursing staff on the implementation of these model policies and a workshop through which trainers are prepared to present the educational program. Nurses' Association of the American College of Obstetrics and Gynecology (NAACOG), Special Supplemental Food Program for Women, Infants, and Children (WIC), and Florida Lactation Consultant Association (FLCA) all contributed to this project.

Breast Feeding↗

W mutant mice with mild or severe developmental defects contain distinct point mutations in the kinase domain of the c-kit receptor.

Mutations at the mouse W/c-kit locus lead to intrinsic defects in stem cells of the melanocytic, hematopoietic, and germ cell lineages. W alleles vary in the overall severity of phenotype that they confer, and some alleles exhibit an independence of pleiotropic effects. To elucidate the molecular basis for these biological differences, we analyzed the c-kit locus and the c-kit-associated autophosphorylation activities in five different W mutants representative of a range of W phenotypes. Mast cell cultures derived from mice or embryos homozygous for each W allele were deficient in c-kit autophosphorylation activity, the extent of which paralleled the severity of phenotype conferred by a given W allele both in vivo and in an in vitro mast cell coculture assay. The mildly dominant, homozygous viable alleles W44 and W57 were found to express reduced levels of an apparently normal c-kit protein. In contrast, c-kit kinase defects conferred by the moderately dominant, homozygous viable alleles W41 or W55 or the homozygous lethal allele, W37, were attributed to single-point mutations within the kinase domain of the c-kit polypeptide, which result in point substitutions of amino acid residues highly conserved in the family of protein tyrosine kinases. The nature and location of these amino acid substitutions account for the relative severity of phenotypes conferred by these W alleles and demonstrate that the pleiotropic developmental defects associated with the W/c-kit locus arise as the result of dominant loss-of-function mutations in a transmembrane receptor tyrosine kinase.

Alleles↗

Effect of rioprostil on aspirin-induced gastrointestinal mucosal changes in normal volunteers.

Rioprostil, a 15-deoxy-16-methyl prostaglandin E1, was evaluated for its effect on aspirin-induced gastrointestinal mucosal changes in normal volunteers. Fifty-six normal male volunteers were evaluated by endoscopy in a double-blind, placebo-controlled study. Aspirin was given at a dose of 975 mg four times per day. Rioprostil was given at doses of 60, 120, and 300 micrograms four times per day. Rioprostil, at both antisecretory and subantisecretory doses, prevented or reduced aspirin-induced injury. Increased stool frequency was the most common side effect and appeared to be a dose-related effect of rioprostil occurring at only antisecretory doses.

Adolescent↗

v-erbA cooperates with sarcoma oncogenes in leukemic cell transformation.

The v-erbB, v-src, v-fps, v-sea, and v-Ha-ras oncogenes induce avian erythroid progenitor cells to self-renew in an erythropoietin-independent manner. These transformed erythroblasts retain both their capacity to differentiate into erythrocytes and their requirement for complex growth media. However, previous studies showed that erythroblasts transformed by v-erbB plus v-erbA (which by itself is not oncogenic) are blocked in differentiation and grow in standard media. Here we show that the introduction of v-erbA into erythroblasts transformed with v-src, v-fps, v-sea, or v-Ha-ras likewise induces a fully transformed phenotype. It also reduces the capacity of ts sea- and ts erbB-transformed erythroblasts to differentiate terminally in an erythropoietin-dependent manner after a temperature shift. Cooperativity involving v-erbA also occurs in vivo since chicks infected with a retroviral construct encoding v-erbA and v-src develop both acute erythroblastosis and sarcomas.

Alpharetrovirus↗

The relationship between function and DNA sequence in an intercistronic regulatory region in phage lambda.

rho factor-mediated transcription termination at the tr1 terminator site of bacteriophage lambda is examined. Mutations affecting the termination event are characterised. These mutations define features of the site which seem to be important to terminator function. In addition, other related transcriptional and translational regulatory elements are defined within the region surrounding the termination site. The potential molecular interactions and structural overlaps of these control signals apparently couple the regulation of the decision between lytic and lysogenic growth patterns by phage lambda.

Base Sequence↗

The incidence of systemic lupus erythematosus in North American Indians.

The annual incidence (AI) of systemic lupus erythematosus (SLE) was determined in 75 highly inbred North American Indian tribes, a total of approximately 800,000 people, during the fiscal years 1971-1975. Seventy-two of the Indian tribes had an AI of SLE which was of similar magnitude to previously published studies from Sweden, Rochester (Minn.), Alabama, New York City, and San Francisco. However, Three tribes, the Crow, Arapahoe, and Sioux Indians, had a markedly elevated AI of SLE. These three tribes share common historical, geographic, and cultural characteristics. Further, they all reside in the northern half of the United States, in states that do not receive intense sun exposure, thereby eliminating photosensitivity as a major determinant of this increased prevalence. Finally, the AI of SLE in the Sioux Indians was highest for "full-blooded" members and lowest for genetic admixtures.

Humans↗