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Biomedical subjects

P Clancy

Publications and source records attributed to P Clancy.

13 recordsLinked to original sources
PubMed2000

The Escherichia coli signal transducers PII (GlnB) and GlnK form heterotrimers in vivo: fine tuning the nitrogen signal cascade.

The PII protein is Escherichia coli's cognate transducer of the nitrogen signal to the NRII (NtrB)/NRI (NtrC) two-component system and to adenylyltransferase. Through these two routes, PII regulates both amount and activity of glutamine synthetase. GlnK is the recently discovered paralogue of PII, with a similar trimeric x-ray structure. Here we show that PII and GlnK form heterotrimers, in E. coli grown in nitrogen-poor medium. In vitro, fully uridylylated heterotrimers of the two proteins stimulated the deadenylylation activity of adenylyltransferase, albeit to a lower extent than homotrimeric PII-UMP. Fully uridylylated GlnK did not stimulate, or hardly stimulated, the deadenylylation activity. We propose that uridylylated PII/GlnK heterotrimers fine-regulate the activation of glutamine synthetase. The PII/GlnK couple is a first example of prokaryotic signal transducer that can form heterotrimers. Advantages of hetero-oligomer formation as molecular mechanism for fine-regulation of signal transduction are discussed.

Bacterial Proteins↗
PubMed1999

Aorto-right ventricular fistula: a late complication of aortic valve replacement.

We report the case of a patient who was found to have an aorto-right ventricular fistula 17 years after receiving a Björk-Shiley prosthetic aortic valve. A pseudoaneurysm had formed at the aortotomy suture line, and it had extended into the interventricular septum and had eventually opened into the right ventricle. Using transesophageal echocardiography, we identified the defect in the ascending aorta, and a left-to-right shunt. Aortography was used to confirm these findings. The pseudoaneurysm was successfully resected and the ascending aorta was replaced with a Dacron graft. To the best of our knowledge, no similar late complication of aortic valve replacement has been reported in the medical literature.

Aged↗
PubMed1993

Molecular dynamics simulations of a winter flounder "antifreeze" polypeptide in aqueous solution.

A winter flounder antifreeze polypeptide (HPLC-6) has been studied in vacuo and in aqueous solution using molecular dynamics computer simulation techniques. The helical conformation of this polypeptide was found to be stable both in vacuum and in solution. The major stabilizing interactions were found to be the main-chain hydrogen bonds, a salt-bridge interaction, and solute-solvent hydrogen bonds. A significant bending in the middle of the polypeptide chain was observed both in vacuo and in solvent at 300 K. Possible causes of the bending are discussed. From simulations of mutant polypeptide molecules in vacuo, it is concluded that the bend in the native polypeptide was caused by side chain to backbone hydrogen bond competition involving the Thr 24 side chain and facilitated by strains on the helix resulting from the Lys 18-Glu 22 salt bridge.

Amino Acid Sequence↗
PubMed1991

Hemodynamic and metabolic effects of venoarterial cardiopulmonary support in coronary artery disease.

Coronary angioplasty was performed on 14 high-risk patients supported with venoarterial partial cardiopulmonary bypass. Hemodynamic, metabolic and physiologic parameters were monitored to assess the effect of cardiopulmonary support in conscious patients. Cardiopulmonary support caused a decrease in systolic (45 +/- 17 to 27 +/- 14 mm Hg, p less than 0.001), diastolic (23 +/- 12 to 14 +/- 8 mm Hg, p less than 0.005) and mean (29.7 +/- 13.2 to 18 +/- 9 mm Hg, p less than 0.001) pulmonary artery pressures. Aortic systolic (129 +/- 18 to 106 +/- 17 mm Hg, p less than 0.001), mean (89 +/- 19 to 84 +/- 19 mm Hg, p less than 0.05) and pulse (64 +/- 17 to 37 +/- 16 mm Hg, p less than 0.00001) pressures also decreased. Heart rate and aortic diastolic pressures were unchanged. End-systolic wall stress (122 +/- 48 x 10(3) to 96 +/- 44 x 10(3) dynes/cm2, p less than 0.001) and left ventricular end-diastolic diameter (5.7 +/- 0.8 to 5.5 +/- 0.9 cm, p less than 0.05) were reduced during partial cardiopulmonary bypass. After initiation of cardiopulmonary support, normal lactate extraction across the coronary circulation was diminished or converted to lactate production (38 +/- 23 to 2 +/- 29%, p less than 0.005). There was a marked reduction in hematocrit (41 +/- 4 to 28 +/- 5%, p less than 0.0001) and platelet count (259,000 +/- 57,600/ml to 145,900 +/- 46,000/ml, p less than 0.0001) after bypass. Cardiopulmonary bypass successfully supported all patients during balloon inflation, for an optimal angioplasty result.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1991

Monoclonal antibodies to Kunjin and Kokobera viruses.

Five monoclonal antibodies (MoAb) were produced to the envelope (E) protein of Kunjin (KUN) virus. Three of these were specific for the KUN/West Nile complex, and two reacted with epitopes that were common to the flavivirus family. These MoAb defined at least four distinct epitopes on the E protein of KUN virus. Eight MoAb were also produced to unidentified proteins of Kokobera (KOK) virus. Seven were specific for KOK, while the remaining antibody cross-reacted with Stratford virus and an unregistered flavivirus CS946. The application of these MoAb to arboviral surveillance is discussed.

Animals↗
PubMed1990

Epitope analysis of the envelope and non-structural glycoproteins of Murray Valley encephalitis virus.

Previous studies have shown that antibodies produced against strategic flavivirus epitopes play an important role in recovery and immunity. Definition of the conformation and location of these epitopes and the degree of their conservation among flaviviruses is important to understanding the humoral response to flavivirus infection. In this study we have examined epitopes recognized by 14 monoclonal antibodies (MAbs) produced to the envelope (E) and non-structural (NS1) proteins of Murray Valley encephalitis virus (MVE). These antibodies were analysed for specificity, neutralization, haemagglutination inhibition (HI) and competitive binding. We have identified six distinct epitopes on the E protein which are located in four non-overlapping domains. MAbs to epitopes in one domain neutralized virus, were specific for MVE and Japanese encephalitis virus, and reacted with epitopes resistant to reduction. Two other E domains, one specific to MVE and the other shared by all flaviviruses, also contained neutralization sites and were stabilized by disulphide bonds. The fourth domain on E was conserved among the flaviviruses, sensitive to SDS denaturation and did not induce neutralizing antibody. Studies with MVE NS1 MAbs revealed that they were mostly type-specific, unreactive with conserved epitopes, and unreactive in HI and neutralization tests. The six epitopes identified on NS1 did not overlap and represent antigenic domains either resistant or sensitive to reduction. Immunoblotting of viral proteins in MVE-infected C6/36 cells revealed two distinct forms of NS1 and high Mr proteins of 97K and 108K that represented disulphide-linked heterodimers of E and NS1.

Animals↗
PubMed1987

Refresher education policy: results of a survey.

Occupational Therapy experiences chronic manpower shortage. This is in part, due to loss of trained,experienced manpower. In many cases, female occupational therapists, like other women, drop-out of the work force to re-enter later. In an attempt to delineate refresher education policy for re-entering, a mail survey of randomly selected members of Ontario occupational therapists and occupational therapy managers was conducted. The results of the survey suggested refresher education should be mandatory after an absence of 3-5 years, should be under the jurisdiction, at least in part, of the provincial association, should be oriented to specialists training and have a variety of formats including clinical practice.

Data Collection↗