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Biomedical subjects

J P Connolly

Publications and source records attributed to J P Connolly.

17 recordsLinked to original sources
PubMed1999

Mutational analysis of the engrailed homeodomain recognition helix by phage display.

The homeodomain (HD) is a ubiquitous protein fold that confers DNA binding function on a superfamily of eukaryotic gene regulatory proteins. Here, the DNA binding of recognition helix variants of the HD from the engrailed gene of Drosophila melanogaster was investigated by phage display. Nineteen different combinations of pairwise mutations at positions 50 and 54 were screened against a panel of four DNA sequences consisting of the engrailed consensus, a non-specific DNA control based on the lambda repressor operator OR1 and two model sequence targets con-taining imperfect versions of the 5'-TAAT-3' consensus. The resulting mutant proteins could be divided into four groups that varied with respect to their affinity for DNA and specificity for the engrailed consensus. The altered specificity phenotypes of several mutant proteins were confirmed by DNA mobility shift analysis. Lys50/Ala54 was the only mutant protein that exhibited preferential binding to a sequence other than the engrailed consensus. Arginine was also demonstrated to be a functional replacement for Ala54. The functional combinations at 50 and 54 identified by these experiments recapitulate the distribution of naturally occurring HD sequences and illustrate how the engrailed HD can be used as a framework to explore covariation among DNA binding residues.

Animals↗
PubMed1999

Repeat prescribing management--a cause for concern?

BACKGROUND: No existing studies of repeat prescribing management have been carried out on statistically adequate samples permitting an extrapolation of results with regard to the population of general practitioners (GPs). AIM: To provide adequate regional evidence of the quality of repeat prescribing management for the profession and its administrators, and to test a scoring system for quality assurance in repeat prescribing practice. METHOD: A semi-structured questionnaire was administered by one observer to a statistically representative population sample of Northern Ireland's general practices to investigate the extent to which they adopted recommended procedures for the management of repeat prescribing. Responses to 26 of these questions were used to score the quality of management. The subjects were a random sample of 57 practices stratified for number of partners, geographical area, and fundholding status. RESULTS: The main outcome measures were the percentage adoption of recommended procedures at the time of repeat prescription issue and at the review consultation, use of computing for repeat prescribing and the effects of fundholding; and quality assurance scores. During issue of repeats, essential checks are often omitted; the potential of computerization for improving management is often not realized. At review consultation, the opportunities for quality assurance are often missed. Fundholders manage repeat prescribing significantly better than non-fundholders, but in neither group is the mean management score exemplary. CONCLUSION: We have identified and quantified serious deficiencies in repeat prescribing management in a representative sample large enough to permit extrapolation to the regional population of GPs. In response, we have devised guidelines that GPs might use to address this problem. We have tested and proved a scoring system for repeat prescribing evaluation.

Drug Prescriptions↗
PubMed1995

Glucocorticoids coordinately regulate type I collagen pro alpha 1 promoter activity through both the glucocorticoid and transforming growth factor beta response elements: a novel mechanism of glucocorticoid regulation of eukaryotic genes.

Glucocorticoids have previously have shown to decrease Type I collagen synthesis in vivo and in fibroblast cell culture. Several studies have demonstrated that glucocorticoids decrease Type I procollagen gene expression. These latter studies have included uridine incorporation into pro alpha 1 (I) and pro alpha 2 (I) mRNAs and nuclear run-off experiments. Using the ColCat 3.6 plasmid, which contains part of the 5' flanking region of the pro alpha 1 (I) collagen gene and the reporter gene, chloramphenicol acetyltransferase, the present studies demonstrate by stable transfection of fetal rat skin fibroblasts that dexamethasone down regulates the promoter activity of the pro alpha 1 (I) collagen gene. The glucocorticoid-mediated down-regulation of procollagen gene expression was demonstrated using the ColCat 3.6, 2.4, 1.7, or 0.9 plasmid. In addition, competitive oligonucleotide transfection experiments and site specific mutation of the glucocorticoid response element (GRE) in the whole ColCat 3.6 plasmid did not eliminate the effect. The possibility existed that another cis-element in the 5' flanking region of the pro alpha 1 (I) collagen gene was also required for the collagen glucocorticoid-mediated down-regulation of procollagen gene expression, since TGF-beta has been shown to stimulate in a decrease of transforming growth factor-beta (TGF-beta) secretion into the media. Gel mobility studies demonstrated that glucocorticoid treatment of rat skin fibroblasts decreased glucocorticoid receptor binding to the GRE and TGF-beta activator protein to the TGF-beta element which were brought back to control values by coordinate exogenous TGF-beta treatment. Thus the interaction of these TGF-beta molecules with cellular membrane receptors and subsequent transduction is dramatically decreased resulting in less signals to regulate collagen gene expression. These data indicate that glucocorticoids coordinately regulate procollagen gene expression through both the GRE and TGF-beta elements. Depression of procollagen gene expression by glucocorticoids through the TGF-beta element is mediated by decreased TGF-beta secretion, possibly involving a secondary effect on regulatory protein(s) encoded by noncollagenous protein gene(s). The present studies provide the basis for a novel mechanism of glucocorticoid-mediator regulation of eukaryotic genes containing the TGF-beta element.

Animals↗
PubMed1993

Hemoptysis as a presentation of mild hemophilia A in an adult.

It is not unusual for mild hemophilia A to escape detection into adolescent years and it is often detected following dental extractions or other mild trauma. The present report describes a patient shown to have only 8 to 9 percent factor VIII activity at age 30 years. The presentation of recurrent mild hemoptysis with upper respiratory tract infections is unusual and of interest in the differential diagnosis of hemoptysis.

Adult↗
PubMed1991

Intrathoracic osteosarcoma diagnosed by CT scan and pleural biopsy.

Osteosarcoma rarely presents as a primary lesion in the chest, whereas pulmonary metastases are common. The diagnosis of primary intrathoracic osteosarcoma has invariably been by thoracotomy or autopsy. We present a case of a densely calcified, primary intrathoracic osteosarcoma where diagnosis was made antemortem by pleural biopsies and computed tomography scan.

Aged↗
PubMed1991

Asthma in the Navy and Marine Corps.

Today, asthma is an increasing health problem in young Americans. In some cases, it can be quite difficult to diagnose. Many individuals enter military service each year with undiagnosed asthma, which subsequently limits their performance of duty. We review the patterns of asthma in children and young adults and relate this to Navy and Marine Corps personnel. We also review the current evaluation of this disease in the U.S. Navy Medical Department and suggest future improvements in this evaluation.

Adolescent↗
PubMed1990

Torulopsis glabrata fungemia in a diabetic patient.

We have presented a case of a stable diabetic outpatient who had an acute illness that proved to be Torulopsis glabrata fungemia responsive to amphotericin B therapy. Her only apparent additional predisposition was a nonobstructing renal calculus. Fungemia with this organism in an outpatient is most unusual. T glabrata should be an additional consideration in outpatient as well as inpatient illnesses, especially in diabetic women.

Amphotericin B↗