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Biomedical subjects

N McDonald

Publications and source records attributed to N McDonald.

At least 19 recordsLinked to original sources
PubMed2001

Structural insights into the hydrolysis of cellular nitric oxide synthase inhibitors by dimethylarginine dimethylaminohydrolase.

Nitric oxide synthase is inhibited by asymmetric NG-methylated derivatives of arginine whose cellular levels are controlled in part by dimethylarginine dimethylaminohydrolase (DDAH, EC 3.5.3.18). Levels of asymmetric NG,NG-dimethylarginine (ADMA) are known to correlate with certain disease states. Here, the first structure of a DDAH shows an unexpected similarity to arginine:glycine amidinotransferase (EC 2.1.4.1) and arginine deiminase (EC 3.5.3.6), thus defining a superfamily of arginine-modifying enzymes. The identification of a Cys-His-Glu catalytic triad and the structures of a Cys to Ser point mutant bound to both substrate and product suggest a reaction mechanism. Comparison of the ADMA-DDAH and arginine-amidinotransferase complexes reveals a dramatic rotation of the substrate that effectively maintains the orientation of the scissile bond of the substrate with respect to the catalytic residues. The DDAH structure will form a basis for the rational design of selective inhibitors, which are of potential use in modulating NO synthase activity in pathological settings.

Amidohydrolases↗
PubMed2000

Room with a view.

Explore the source record for details and available documents.

Dentists↗
PubMed1999

Navigating ambulatory referral: a standardized process.

Significant funding and structure changes to healthcare in Ontario in the mid-90's led The Hospital for Sick Children in Toronto to examine patient referral processes. In an effort to streamline access and encourage more appropriate referrals, the hospital tested and implemented three major changes. This article outlines these changes using the PDSA (Plan, Do, Study, Act) improvement framework and summarizes the results from this project.

Ambulatory Care↗
PubMed1999

Overcoming inhibitions: subversion of CKI function by viral cyclins.

DNA tumour viruses deregulate the mammalian cell cycle to provide a better environment for their replication. Studies of such deregulation have led to the identification of key regulatory steps that normally control the G1-S phase transition of the cell cycle. The balance between the activities of G1-specific cyclin-CDK complexes and their inhibitors is critical. Recent studies suggest that certain herpesviruses disrupt this balance: the viruses encode a cyclin that generates active complexes even in the presence of high inhibitor levels.

Cell Cycle↗
PubMed1999

Evaluation for tooth stabilization and treatment of traumatized teeth.

Thorough evaluation and correct treatment of traumatized teeth improve their chances for survival. This article provides an overview clinical evaluation and how best to treat the tooth that has been traumatized. The rationale and techniques for tooth stabilization of the traumatized tooth will also be presented.

Contusions↗
PubMed1997

Age-specific distribution of plasma amino acid concentrations in a healthy pediatric population.

Reference values were determined for 23 plasma free amino acids from measurements done in 148 healthy children ranging from 0 to 18 years of age. Amino acid analysis was performed by ion-exchange chromatography. We propose a graphic form of presenting the age-specific distribution of plasma amino acid concentrations where the 10th, 50th, and 90th quantiles are illustrated. Although each amino acid possesses its own pattern of distribution, we can identify five different profiles. Nine amino acids (alanine, arginine, asparagine, methionine, ornithine, phenylalanine, proline, threonine, and tyrosine) demonstrate a decrease in their concentrations during the first year of life; their concentrations then tend to increase throughout childhood and adolescence. Nine others (cystine, glutamine, glycine, histidine, isoleucine, leucine, lysine, tryptophan, and valine) show a steady increase throughout infancy, childhood, and adolescence. Five amino acids (aspartic acid, citrulline, glutamic acid, serine, and taurine) do not follow these two common profiles. For the first time, quantile curves are produced to illustrate the age-dependent variation of amino acid concentrations from infancy to adulthood. This alternative way of presenting amino acid concentrations may facilitate the follow-up of patients with inborn errors of amino acid metabolism.

Adolescent↗
PubMed1995

The incidence of gastroesophageal reflux with the laryngeal mask: a comparison with the face mask using esophageal lumen pH electrodes.

To test the hypothesis that the laryngeal mask airway (LMA) predisposes patients to gastroesophageal reflux, we randomly assigned 55 patients having elective surgery to receive standardized anesthesia with the LMA or with conventional face mask (FM) plus airway. A pH-sensitive probe with two electrodes, 10 cm apart, was passed nasally into the esophagus 1 h before induction of anesthesia, and recordings were made continuously until 30 min after surgery. At the distal electrode, 30 cm from the anterior nares, there was a significant difference in the incidence of reflux: 53.6% with the LMA versus 22.2% with the FM (P < 0.05). At the level of the proximal electrode, 20 cm from the anterior nares, there was no difference between groups. Multiple reflux events, defined as two or more reflux events before, during, or after anesthesia, were significantly more frequent in the LMA group (P < 0.05). Reflux events continued in the postanesthesia care unit (PACU) in both groups with no significant difference between groups. There was no clinical evidence of aspiration of gastric contents in either group. Use of the LMA appears to result in increased reflux to the level of the mid to upper esophagus, and is associated with a more frequent incidence of multiple reflux events than use of the FM.

Adult↗
PubMed1989

Epidermal growth factor binding induces a conformational change in the external domain of its receptor.

To study the properties of the extracellular epidermal growth factor (EGF) binding domain of the human EGF receptor, we have infected insect cells with a suitably engineered baculovirus vector containing the cDNA encoding the entire ectodomain of the parent molecule. This resulted in a correctly folded, stable, 110 kd protein which possessed an EGF binding affinity of 200 nM. The protein was routinely purified in milligram amounts from 1 litre insect cell cultures using a series of three standard chromatographic steps. The properties of the ectodomain were studied before and after the addition of different EGF ligands, using both circular dichroism and fluorescence spectroscopic techniques. A secondary structural analysis of the far UV CD spectrum of the ectodomain indicated significant proportions of alpha-helix and beta-sheet in agreement with a published model of the EGF receptor. The ligand additions to the receptor showed differences in both the near- and far-UV CD spectra, and were similar for each ligand used, suggesting similar conformational differences between uncomplexed and complexed receptor. Steady-state fluorescence measurements indicated that the tryptophan residues present in the ectodomain are buried and that the solvent-accessible tryptophans in the ligands become buried on binding the receptor. The rotational correlation times measured by fluorescence anisotropy decay for the receptor-ligand complexes were decreased from 6 to 2.5 ns in each case. This may indicate a perturbation of the tryptophan environment of the receptor on ligand binding. Ultracentrifugation studies showed that no aggregation occurred on ligand addition, so this could not explain the observed differences from CD or fluorescence.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

The influence of collateral vascularisation on haemodynamic performance during abdominal aortic surgery.

The extent of periaortic collateral vascularisation has been proposed as a possible mechanism of an altered haemodynamic response to infra-renal aortic cross-clamp in patients undergoing by-pass grafting for aorto-iliac occlusive disease (AOD) compared with patients undergoing abdominal aortic aneurysm (AAA) resection. The haemodynamic responses following clamping, during the clamp time and following clamp release were studied in 18 patients undergoing AAA resection and 12 patients undergoing bypass grafting for AOD. The role of preoperative aortography in predicting cardiovascular performance during aortic vascular surgery was assessed. During the cross-clamp period LVSWI and CI decreased while SVR increased in the AAA group while the AOD group showed an improved CI, stable LVSWI and reduced SVR, which correlated with the extent of periaortic vascularisation on preoperative aortography. Chronic collateral circulation associated with AOD may permit continuous lower extremity perfusion during aortic cross-clamp. The extent of periaortic collateralisation may influence the choice of monitoring techniques and anaesthetic management.

Aged↗
PubMed1989

Structure-function relationships of growth factors and their receptors.

The primary amino acid sequences of several receptor tyrosine kinases have recently made it possible to deduce similarities in the molecular organization of these large multidomain proteins. This has allowed a classification of these receptors into three groups (see Waterfield this Issue and for review in Ref.1). Class I includes the EGF receptor and the neu proto-oncogene, Class II includes the insulin and insulin-like growth factor 1 (IGF-1) receptors, and Class III the platelet derived growth factor (PDGF) and the colony stimulating factor 1 (CSF-1) receptors. The conformation of the ligands for the Classes I and II receptors have been defined using X-ray diffraction, 2-D nuclear magnetic resonance (NMR) and knowledge based modelling procedures. It seems that the ligands are more diverse in sequence than the receptor tyrosine kinases so they cannot be classified as rigorously. However, certain features are common to all growth factors (so far defined) which form compact, globular structures and this allows a discussion of possible interactions between the ligand and receptor; but in the absence of a molecular structure for any of the receptors, we can only review biochemical evidence and deductions from predictive and modelling studies. Various models for the signal transduction process are discussed in the light of current work on receptor interactions.

Growth Substances↗
PubMed1988

Experience with the endorectal ileal pullthrough with lateral reservoir for ulcerative colitis and polyposis.

Since 1977, 184 patients with colitis or polyposis underwent colectomy with endorectal ileal pullthrough in two stages with a temporary ileostomy. Five had an S reservoir, three had a J reservoir, and 15 had no reservoir; 97 patients had a lateral reservoir constructed at the second operation and 64 had one constructed at the first operation. Ten patients with no reservoir and one with a J reservoir underwent conversion to a lateral reservoir because of stool frequency. Three patients with an S reservoir and six (3.5%) of 172 patients with a lateral reservoir underwent a permanent ileostomy. Over 65% of complications occurred in the first 50 patients. Late reservoir shortening was necessary in 34 patients. Of the last 110 patients, 107 are functioning well with a mean of six bowel movements per day. A short lateral reservoir (less than 15 cm) constructed at the first operation produces the fewest complications and best results.

Adenomatous Polyposis Coli↗
PubMed1988

Calcium channel blockade does not offer adequate protection from perioperative myocardial ischemia.

This study aimed to detect the difference in hemodynamic and electrocardiographic responses during the prebypass period in patients undergoing coronary bypass grafting who were receiving beta-adrenergic blocking drugs, calcium entry blocking drugs, or both beta-adrenergic and calcium entry blocking drugs. Electrocardiographic evidence of myocardial ischemia was noted significantly more frequently in patients receiving calcium entry blocking drugs alone at induction of anesthesia (P less than 0.03), skin incision (P less than 0.05), and sternotomy (P less than 0.002). Heart rate at sternotomy was significantly higher in patients receiving calcium entry blocking drugs (P less than 0.02) as compared to patients receiving beta-adrenergic blocking drugs or the combination of both drugs. In conclusion, patients treated with calcium entry blocking drugs alone had significantly higher incidence of perioperative ischemic ECG changes compared with patients receiving beta-adrenergic blocking drugs alone or in combination with calcium channel blocking drugs.

Adrenergic beta-Antagonists↗
PubMed1988

Construction of an ileal reservoir in patients with a previous straight endorectal ileal pull-through.

A decade has passed since Martin and associates presented the first series of endorectal ileal pull-through (PT) procedures with straight ileoanal anastomosis for treatment of ulcerative colitis and polyposis. During the ensuing years, several medical centers have reported their results using the PT. Although some children have experienced good results, the majority of adults and children have had severe problems associated with high stool frequency, urgency, and incontinence. Between 1977 and 1987, 12 patients underwent colectomy and straight PT for ulcerative colitis or familial polyposis under the direction of a single surgeon. In this group, the average number of stools varied from six to 45 movements per 24 hours (mean, 18). In seven patients, high stool frequency (mean, 24 per 24 hours), partial fecal incontinence, and urgency that led to moderate to severe limitation in physical, social, work, and sexual activities made it necessary to convert the straight PT to an ileal reservoir. For each of these patients, the ileal PT segment was separated from the rectal muscle cuff, a lateral isoperistaltic reservoir was constructed, and the ileoanal anastomosis was re-established in a one-stage operation. One additional patient decided to return to a conventional ileostomy. All seven patients who underwent conversion to a PT with reservoir had no major complications, and each improved markedly in their clinical status. Daytime stool frequency was reduced by a mean of approximately 50%, whereas nocturnal frequency was decreased by a mean of 60%. Incontinence and fecal urgency were relieved significantly. In conclusion, for patients who develop problems with a straight PT procedure and who desire to avoid a permanent ileostomy, conversion to a PT with a lateral ileal reservoir is a valuable alternative with low risk and a high likelihood of success.

Adenomatous Polyposis Coli↗