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C W Hogue

Publications and source records attributed to C W Hogue.

At least 19 recordsLinked to original sources
PubMed2000

A fast method to sample real protein conformational space.

A fast computer program, FOLDTRAJ, to generate plausible random protein structures is reported. All-atom proteins are made directly in continuous three-dimensional space starting from primary sequence with an N to C directed build-up method. The method uses a novel pipelined residue addition approach in which the leading edge of the protein is constructed three residues at a time for optimal protein geometry, including the placement of cis proline. Build-up methods represent a classic N-body problem, expected to scale as N(2). When proteins become more collapsed, build-up methods are susceptible to backtracking problems which can scale exponentially with the number of residues required to back out of a trapped walk. We have provided solutions to both these problems, using a multiway binary tree that makes the N-body problem of bump-checking scale as NlogN, and speeding up backtracking by varying the number of tries before backtracking based on available conformational space. FOLDTRAJ is independent of energy potentials, other than that implicit in the geometrical properties derived by statistical studies of known structures, and in atomic Van der Waals radii. WHAT-CHECK shows that the program generates chirally and physically valid proteins with all bond lengths, angles and dihedrals within allowable tolerances. Random structures built using sequences from PDB files 1SEM, 2HPR, and 1RTP typically have 5-15% alpha-helical content (according to DSSP) and on the order of 20% beta-strand/extended content. Ensembles of random structures are compared with polymer theory and with experimentally determined fluorescence resonance energy transfer distances. Reasonably sized structure ensembles do sample most of the conformational space available to proteins. The method is also capable of protein reconstruction using Calpha--Calpha direction vectors, and it compares favorably with methods that reconstruct protein backbones based on alpha-carbon coordinates, having an average backbone and Cbeta root mean square deviation of 0.63 A for nine different protein folds. Proteins 2000;39:112-131.

Algorithms↗
PubMed2000

Atrial fibrillation after cardiac operation: risks, mechanisms, and treatment.

Atrial fibrillation (AF) is a common complication of cardiac operations that leads to increased risk for thromboembolism and excessive health care resource utilization. Advanced age, previous AF, and valvular heart operations are the most consistently identified risk factors for this arrhythmia. Dispersion of repolarization leading to reentry is believed to be the mechanism of postoperative AF, but many questions regarding the pathophysiology of AF remain unanswered. Treatment is aimed at controlling heart rate, preventing thromboembolic events, and conversion to sinus rhythm. Multiple investigations have examined methods of preventing postoperative AF, but the only firm conclusions that can be drawn is to avoid beta-blocker withdrawal after operation and to consider beta-blocker therapy for other patients who may tolerate these drugs. Preliminary investigations showing sotalol and amiodarone to be effective in preventing postoperative AF are encouraging, but early data have been limited to selective patient populations and have not adequately evaluated safety. Newer class III antiarrhythmic drugs under development may have a role in the treatment of postoperative AF, but the risk of drug-induced polymorphic ventricular tachycardia must be considered. Nonpharmacologic interventions under consideration for the treatment of AF in the nonsurgical setting, such as automatic atrial cardioversion devices and multisite atrial pacing, may eventually have a role for selected cardiac surgical patients.

Adrenergic beta-Antagonists↗
PubMed2000

BIND--a data specification for storing and describing biomolecular interactions, molecular complexes and pathways.

MOTIVATION: Proteomics is gearing up towards high-throughput methods for identifying and characterizing all of the proteins, protein domains and protein interactions in a cell and will eventually create more recorded biological information than the Human Genome Project. Each protein expressed in a cell can interact with various other proteins and molecules in the course of its function. A standard data specification is required that can describe and store this information in all its detail and allow efficient cross-platform transfer of data. A complete specification must be the basis for any database or tool for managing and analysing this information. RESULTS: We have defined a complete data specification in ASN.1 that can describe information about biomolecular interactions, complexes and pathways. Our group is using this data specification in our database, the Biomolecular Interaction Network Database (BIND). An interaction record is based on the interaction between two objects. An object can be a protein, DNA, RNA, ligand, molecular complex or an interaction. Interaction description encompasses cellular location, experimental conditions used to observe the interaction, conserved sequence, molecular location, chemical action, kinetics, thermodynamics, and chemical state. Molecular complexes are defined as collections of more than two interactions that form a complex, with extra descriptive information such as complex topology. Pathways are defined as collections of more than two interactions that form a pathway, with additional descriptive information such as cell cycle stage. A request for proposal of a human readable flat-file format that mirrors the BIND data specification is also tendered for interested parties. AVAILABILITY: The ASN.1 data specification for biomolecular interaction, molecular complex and pathway data is available at ftp://bioinfo.mshri.on.ca/pub/BIND/Spec/bind.asn. An interactive browser for this document is available through our homepage at http://bioinfo.mshri.on.ca/BIND/asn-browser/.

DNA↗
PubMed2000

Sinus nodal function and risk for atrial fibrillation after coronary artery bypass graft surgery.

BACKGROUND: Nonsurgical patients with sinus node dysfunction are at high risk for atrial tachyarrhythmias, but whether a similar relation exists for atrial fibrillation after coronary artery bypass graft surgery is not clear. The purpose of this study was to evaluate sinus nodal function before and after coronary artery bypass graft surgery and to evaluate its relation with the risk for postoperative atrial arrhythmias. METHODS: Sixty patients without complications having elective coronary artery bypass graft surgery underwent sinus nodal function testing by measurement of sinoatrial conduction time (SACT) and corrected sinus nodal recovery time (CSNRT). Patients were categorized based on whether postoperative atrial fibrillation developed. RESULTS: Twenty patients developed atrial fibrillation between postoperative days 1 through 3. For patients remaining in sinus rhythm (n = 40), sinoatrial conduction times were no different and corrected sinus nodal recovery times were shorter after surgery when compared with measurements obtained after anesthesia induction. Sinus node function test results before surgery were similar between the sinus rhythm and the atrial fibrillation groups. After surgery, patients who later developed atrial fibrillation had longer sinoatrial conduction times compared with the sinus rhythm group (P = 0.006), but corrected sinus nodal recover time was not different between these groups. A sinoatrial conduction time > 96 ms measured at this time point was associated with a 7.3-fold increased risk of postoperative atrial fibrillation (sensitivity, 62%; specificity, 81%; positive and negative predictive values, 56% and 85%, respectively; area under the receiver operator characteristic curve, 0.72). CONCLUSIONS: These data show that sinus nodal function is not adversely affected by uncomplicated coronary artery bypass surgery. Patients who later developed atrial fibrillation, however, had prolonged sinoatrial conduction immediately after surgery compared with patients remaining in sinus rhythm. These results suggest that injury to atrial conduction tissue at the time of surgery predisposes to postoperative atrial fibrillation and that assessment of sinoatrial conduction times could provide a means of identifying patients at high risk for postoperative atrial fibrillation.

Aged↗
PubMed1999

Risk factors for early or delayed stroke after cardiac surgery.

BACKGROUND: Stroke after cardiac surgery is a devastating complication that leads to excess mortality and health resource utilization. The purpose of this study was to identify risk factors for perioperative stroke, including strokes detected early after cardiac surgery or postoperatively. METHODS AND RESULTS: Data were obtained from 2972 patients undergoing coronary artery bypass graft and/or valve surgery. Patients >/=65 years old and those with a history of symptomatic neurological disease underwent preoperative carotid artery ultrasound scanning. Intraoperative epiaortic ultrasound to assess for ascending aorta atherosclerosis was performed in all patients. New strokes were considered as a single end point and were categorized with respect to whether they were detected immediately after surgery (early stroke) or after an initial, uneventful neurological recovery from surgery (delayed stroke). Strokes occurred in 48 patients (1.6%); 31 (65%) were delayed strokes. By multivariate analysis, prior neurological event, aortic atherosclerosis, and duration of cardiopulmonary bypass were independently associated with early stroke, whereas predictors of delayed stroke were prior neurological event, diabetes, aortic atherosclerosis, and the combined end points of low cardiac output and atrial fibrillation. Female sex was associated with a 6.9-fold increased risk of early stroke and a 1.7-fold increased risk of delayed stroke. In-hospital mortality of patients with early (41%) and delayed (13%) strokes was higher than that of other patients (3%, P=0.0001). CONCLUSIONS: Most strokes after cardiac surgery occurred after initial uneventful recovery from surgery. Women were at higher risk to suffer early and delayed perioperative strokes. Atrial fibrillation had no impact on postoperative stroke rate unless it was accompanied by low cardiac output syndrome.

Aged↗
PubMed1999

Antiischemic effects of nicardipine and nitroglycerin after coronary artery bypass grafting.

BACKGROUND: We assessed the efficacy of a continuous infusion of nicardipine and nitroglycerin in reducing the incidence and severity of perioperative myocardial ischemia during elective coronary artery bypass grafting procedures in a prospective, randomized, controlled study. METHODS: Patients received either nicardipine infusion (0.7 to 1.4 microg x kg(-1) x min(-1); n = 30) or nitroglycerin (0.5 to 1 microg x kg(-1) x min(-1); n = 30) or neither medication (n = 17) after aortic occlusion clamp release and for 24 hours postoperatively. Myocardial ischemic episodes (MIE) were considered to have occurred with ST-segment depressions or elevations of at least 1 mm and at least 2 mm (for both depressions or elevations), each at J + 60 ms and lasting at least 1 minute, using a two-channel Holter monitor. RESULTS: Only nicardipine significantly decreased the duration (p = 0.02) of the 1-mm or greater minutes per hour (3.2 +/- 1.2 minutes per hour) and eliminated the number (p = 0.02) of the 2-mm or greater minutes per hour (zero minutes per hour) when compared with control patients (17.2 +/- 5.6 minutes per hour and 0.17 minutes per hour, respectively) during the intraoperative postbypass period. CONCLUSIONS: Our results suggest that nicardipine lessened the severity of myocardial ischemia shortly after coronary revascularization and could be considered as an alternative to standard antiischemic therapy.

Aged↗
PubMed1999

Effects of nicardipine and nitroglycerin on perioperative myocardial ischemia in patients undergoing coronary artery bypass surgery.

Perioperative myocardial ischemic episodes are predictive of adverse cardiac outcomes after coronary artery bypass surgery. We compared the efficacy of continuous infusions of nicardipine (group NIC) and nitroglycerin (group NTG) in reducing the frequency and severity of myocardial ischemic episodes. Patients received either a nicardipine infusion, 0.7 to 1.4 microg/kg/min (n = 30), nitroglycerin infusion, 0.5 to 1 microg/kg/min (n = 30), or neither medication (group C; n = 17) after aortic occlusion clamp release and for 24 hours postoperatively. Myocardial ischemic episodes were considered as ST segment depressions or elevations of 1 mm or greater from baseline, each at J + 60 milliseconds and lasting 1 minute or greater, using a two-channel Holter monitor. Only nicardipine significantly decreased the duration (3.2 +/- 1.2 min/h) and the area under the ST time curve (AUC; 5.7 +/- 15.7 AUC/h) of 1-mm or greater myocardial ischemic episodes compared with group C (17.2 +/- 5.6 min/h and 30.1 +/- 49 AUC/h, respectively) during the intraoperative postbypass period. A trend toward lower frequency, duration, and area under the ST time curve of myocardial ischemic episodes was observed in group NIC compared with group NTG. Cardiac indices and mixed venous oxygen saturations were significantly greater, whereas systemic pressures were less in group NIC compared with group NTG for the same period. These results suggest that nicardipine, but not nitroglycerin, decreased the duration and area under the ST time curve of myocardial ischemic episodes shortly after coronary revascularization. Larger studies are required to verify the efficacy of nicardipine in reducing the severity of myocardial ischemia during cardiac surgery.

Calcium Channel Blockers↗
PubMed1999

Neurological complications of cardiac surgery: the need for new paradigms in prevention and treatment.

Neurological injury is a devastating complication of cardiac surgery that results in a longer duration of hospitalization, increased costs, and increased likelihood of death. Such injury can affect any level of the central nervous system, and its manifestations are broad, ranging from neurocognitive dysfunction to frank stroke. Many variables have been found to be indicative or risk for perioperative neurological injury, but the predictive models are more useful for stroke risk than for neurocognitive dysfunction. Strategies aimed at reducing neurological injury during cardiac surgery have focused, for the most part, on the technical aspects of cardiopulmonary bypass. The concomitant performance of carotid endarterectomy and cardiac surgery continues to be controversial, although the management of patients with symptomatic carotid stenosis is better defined. Cerebral embolism, including atheroembolism from the ascending aorta, has an important role in the pathogenesis of neurological injury of all types. Epiaortic ultrasound imaging of the aorta is a sensitive technique for the identification of atherosclerosis of the ascending aorta at the time of surgery, which can allow it to be avoided and therefore reduce the risk for atheroembolism. Results of laboratory investigations have provided insight into the mechanisms of ischemic neuronal injury and a basis for the development of neuroprotective drugs. Neuroprotection may best be accomplished during cardiac surgery because, in contrast to nonsurgical situations, potential agents can be administered before the neurological insult occurs. Reducing the incidence of perioperative stroke will require a multidisciplinary approach that includes novel diagnostic and therapeutic strategies.

Aortic Diseases↗
PubMed1998

RR interval dynamics before atrial fibrillation in patients after coronary artery bypass graft surgery.

BACKGROUND: Atrial fibrillation/flutter (AF) is a frequent complication of coronary artery bypass graft surgery (CABG) that leads to increased costs and morbidity. We hypothesized that heart rate variability (HRV), an indicator of cardiac sympathovagal balance, is altered before the onset of postoperative AF. Because nonlinear methods of HRV analysis provide information about heart rate dynamics not evident from usual HRV measures, we also hypothesized that approximate entropy (ApEn), a nonlinear measure of HRV, might have predictive value. METHODS AND RESULTS: Analysis of HRV was performed in 3 sequential 20-minute intervals preceding the onset of postoperative AF (24 episodes in 18 patients). These data were compared with corresponding intervals in 18 sex- and age-matched postoperative control subjects who did not develop AF. Patients had left ventricular ejection fractions >45% before surgery and were not receiving beta-blockers during ambulatory ECG monitoring after surgery. Logistic regression demonstrated that on the basis of averaged values for the three 20-minute intervals, increased heart rate and decreased ApEn were independently associated with AF. Heart rate dynamics before AF was associated with either lower (n= 19) or higher (n=5) RR interval variation by traditional measures of HRV or quantitative Poincaré analysis, suggesting the possibility of divergent autonomic conditions before AF onset. CONCLUSIONS: In the hour before AF after CABG surgery, higher heart rate and lower heart rate complexity compared with values in control patients were independent predictors of AF. Decreased ApEn occurs in patients with either increased or decreased HRV by traditional measures and may provide a useful tool for risk stratification or investigation of mechanisms.

Aged↗
PubMed1998

Effects of metal binding affinity on the chemical and thermal stability of site-directed mutants of rat oncomodulin.

Tryptophan fluorescence was used to study the stability and unfolding behavior of several single tryptophan mutants of the metal-binding protein rat oncomodulin (OM); F102W, Y57W, Y65W and the engineered protein CDOM33 which had the 12 residues of the CD loop replaced with a more potent metal binding site. Both the thermal and the chemical stability were improved upon binding of metal ions with the order apo < Ca2+ < Tb3+. During thermal denaturation, the transition midpoints (T(un)) of Y65W was the lowest, followed by Y57W and F102W. The placement of the Trp residue in the F-helix in F102W made the protein slightly more thermostable, although the fluorescence response was readily affected by chemical denaturants, which acted through the disruption of hydrogen bonds at the C-terminal end of the F-helix. Under both thermal and chemical denaturation, the engineered protein showed the highest stability. This indicated that increasing the number of metal ligating oxygens in the binding site, either by using a metal ion with a higher coordinate number (i.e., Tb3+) which binds more carboxylate ligands, or by providing more ligating groups, as in the CDOM33 replacement, produces notable improvements in protein stability.

Acrylamide↗
PubMed1998

UNC-73 activates the Rac GTPase and is required for cell and growth cone migrations in C. elegans.

unc-73 is required for cell migrations and axon guidance in C. elegans and encodes overlapping isoforms of 283 and 189 kDa that are closely related to the vertebrate Trio and Kalirin proteins, respectively. UNC-73A contains, in order, eight spectrin-like repeats, a Dbl/Pleckstrin homology (DH/PH) element, an SH3-like domain, a second DH/PH element, an immunoglobulin domain, and a fibronectin type III domain. UNC-73B terminates just downstream of the SH3-like domain. The first DH/PH element specifically activates the Rac GTPase in vitro and stimulates actin polymerization when expressed in Rat2 cells. Both functions are eliminated by introducing the S1216F mutation of unc-73(rh40) into this DH domain. Our results suggest that UNC-73 acts cell autonomously in a protein complex to regulate actin dynamics during cell and growth cone migrations.

Animals↗
PubMed1998

Structure databases.

Explore the source record for details and available documents.

Computational Biology↗
PubMed1998

Intraabdominal hemorrhage during combined coronary artery bypass and carotid endarterectomy.

Intraabdominal complications during cardiopulmonary bypass are extremely rare, with an incidence of less than 1% in multiple retrospective studies. These complications are associated with a high mortality, and their rapid diagnosis is critical to the outcome of the patient. We present a case of spontaneous intraabdominal hemorrhage after combined carotid endarterectomy and four-vessel coronary artery bypass grafting, which was diagnosed through a diaphragmatic window.

Coronary Artery Bypass↗
PubMed1998

Perioperative myocardial ischemic episodes are related to hematocrit level in patients undergoing radical prostatectomy.

BACKGROUND: The anemia associated with perioperative blood conservation has raised concerns regarding the safety of these strategies in patients with ischemic cardiovascular disease. Therefore the relationship between hematocrit level and myocardial ischemic episodes in a group of elderly patients undergoing elective noncardiac surgery was studied. STUDY DESIGN AND METHODS: One hundred ninety patients undergoing radical prostatectomy were randomly assigned to one of three blood conservation groups: preoperative autologous blood donation, acute normovolemic hemodilution, and preoperative erythropoietin therapy with acute normovolemic hemodilution. Patients underwent ambulatory electrocardiography monitoring to evaluate for myocardial ischemia at randomization (baseline), 7 days preoperatively, throughout surgery, and for 24 hours after surgery. RESULTS: Myocardial ischemic episodes occurred in 61 (34%) of 181 evaluable patients. Patients with hematocrit levels < 28 percent immediately after surgery were significantly (p = 0.05) more likely to have intraoperative and postoperative ECG ischemic episodes. Intraoperative ischemia and tachycardia correlated (r = 0.21, p = 0.008) with hematocrit levels. Hematocrit levels after surgery were associated with postoperative ischemia (r = 0.14, p = 0.03) and duration of myocardial ischemic episodes (r = 0.14, p = 0.04). After adjusting for other risk factors, intraoperative tachycardia episodes, hematocrit level < 28 percent immediately after surgery, and risk factors for coronary artery disease were independently associated with the likelihood of intraoperative ischemia (r = 0.36, p = 0.002, area under receiver operating characteristic curve = 0.73). Similarly, tachycardia episodes and hematocrit levels < 28 percent immediately after surgery were independently associated with ischemic episodes during the first postoperative day (r = 0.30, p = 0.004, area under receiver operating characteristic curve = 0.71). CONCLUSION: A hematocrit level < 28 percent is independently associated with risk for myocardial ischemia during and after noncardiac surgery. Avoidance of cardiac complications may require higher transfusion thresholds, closer attention to tachycardia, or better monitoring for ischemia.

Electrocardiography↗
PubMed1997

Preparation of enantiomerically pure L-7-azatryptophan by an enzymatic method and its application to the development of a fluorimetric activity assay for tryptophanyl-tRNA synthetase.

The reaction of D,L-7-azatryptophan (D,L-7AW) with tryptophanyl-tRNA synthetase (TrpRS), adenosine triphosphate (ATP), and Mg2+ in the presence of inorganic pyrophosphatase results in the formation of a highly fluorescent l-7AW-adenylate complex. Detection of this complex is based on its enhanced fluorescence at 315 nm excitation and 360 nm emission after the addition of ATP. This stereoselective reaction was used to develop an activity assay for TrpRS using commercially available racemic D,L-7AW. The assay can be used to determine the activity of TrpRS from samples which contain less than 1 nmol of enzyme in 250 microL of sample. Thus the enzyme activity can be assessed without resorting to a radioactive assay of tRNATrp acylation. A secondary use of the stereoselective assay was for confirming the presence of pure L-7AW, D-7AW, or mixtures of the two enantiomers. D-7AW and L-7AW were prepared by reacting D,L-7AW with chloroacetic anhydride to form N-chloroacetyl-D,L-7AW (ClAc-7AW) followed by stereospecific proteolytic digestion of ClAc-7AW using carboxypeptidase A to produce the free L-7AW. The L-7AW could be separated from unreacted N-chloroacetyl-7AW by reverse-phase HPLC. The TrpRS-based assay was able to unambiguously discriminate between the two enantiomers of 7AW. The assay was then used to identify which enantiomer of 7AW was present in resolved fractions of the tripeptide L-lysyl-D,L-7-azatryptophyl-L-lysine. Digestion of the resolved tripeptides with protease enzymes produced the free L or D enantiomer of 7AW, which was easily identified using the TrpRS assay procedure.

Adenosine Triphosphate↗