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Biomedical subjects

R D King

Publications and source records attributed to R D King.

At least 19 recordsLinked to original sources
PubMed1992

Drug design by machine learning: the use of inductive logic programming to model the structure-activity relationships of trimethoprim analogues binding to dihydrofolate reductase.

The machine learning program GOLEM from the field of inductive logic programming was applied to the drug design problem of modeling structure-activity relationships. The training data for the program were 44 trimethoprim analogues and their observed inhibition of Escherichia coli dihydrofolate reductase. A further 11 compounds were used as unseen test data. GOLEM obtained rules that were statistically more accurate on the training data and also better on the test data than a Hansch linear regression model. Importantly machine learning yields understandable rules that characterized the chemistry of favored inhibitors in terms of polarity, flexibility, and hydrogen-bonding character. These rules agree with the stereochemistry of the interaction observed crystallographically.

Artificial Intelligence↗
PubMed1992

Modelling the structure and function of enzymes by machine learning.

A machine learning program, GOLEM, has been applied to two problems: (1) the prediction of protein secondary structure from sequence and (2) modelling a quantitative structure-activity relationship in drug design. GOLEM takes as input observations and combines them with background knowledge of chemistry to yield rules expressed as stereochemical principles for prediction. The secondary structure prediction was explored on the alpha/alpha class of proteins; on an unrelated test set it yielded 81% accuracy. The rules from GOLEM defined patterns of residues forming alpha-helices. The system studied for drug design was the activities of trimethoprim analogues binding to E. coli dihydrofolate reductase. The GOLEM rules were a better model than standard regression approaches. More importantly, these rules described the chemical properties of the enzyme-binding site that were in broad agreement with the crystallographic structure.

Amino Acid Sequence↗
PubMed1992

IPSA-Inductive Protein Structure Analysis.

The Inductive Structure Protein Analysis (IPSA) project presents a new method for investigating protein structure. IPSA includes the creation of a new database which was designed specifically for the analysis of protein structure by statistics and machine learning. The Protein Representation Language (PRL) database includes explicit and symbolic representations of geometrical, topological and chemophysical information about secondary structures and the relationships between secondary structures. The IPSA methodology consists of: the use of PRL information to produce a new database of examples of secondary structures which associate together (examples of possible super-secondary structures); then the use of a variety of clustering techniques to produce a consensus clustering of these examples (super-secondary structures); these super-secondary structures are finally examined to uncover any biological features of significance. We have applied this method to find simple super-secondary structures consisting of pairs of alpha-helices. We found four well-defined super-secondary structures, one formed exclusively by long range interactions, and another in association with an additional element of secondary structure (alpha t alpha-motif). Examinations were carried out using homologous pairs and conformational fits which confirm our clustering.

Cluster Analysis↗
PubMed1992

Protein secondary structure prediction using logic-based machine learning.

Many attempts have been made to solve the problem of predicting protein secondary structure from the primary sequence but the best performance results are still disappointing. In this paper, the use of a machine learning algorithm which allows relational descriptions is shown to lead to improved performance. The Inductive Logic Programming computer program, Golem, was applied to learning secondary structure prediction rules for alpha/alpha domain type proteins. The input to the program consisted of 12 non-homologous proteins (1612 residues) of known structure, together with a background knowledge describing the chemical and physical properties of the residues. Golem learned a small set of rules that predict which residues are part of the alpha-helices--based on their positional relationships and chemical and physical properties. The rules were tested on four independent non-homologous proteins (416 residues) giving an accuracy of 81% (+/- 2%). This is an improvement, on identical data, over the previously reported result of 73% by King and Sternberg (1990, J. Mol. Biol., 216, 441-457) using the machine learning program PROMIS, and of 72% using the standard Garnier-Osguthorpe-Robson method. The best previously reported result in the literature for the alpha/alpha domain type is 76%, achieved using a neural net approach. Machine learning also has the advantage over neural network and statistical methods in producing more understandable results.

Amino Acid Sequence↗
PubMed1992

Surgery for atrioventricular node reentry tachycardia. Results with surgical skeletonization of the atrioventricular node and discrete perinodal cryosurgery.

Surgical treatment options for interruption of atrioventricular node reentrant tachycardia include (1) skeletonization of the atrioventricular node by dissecting it from most of its atrial inputs and (2) discrete cryosurgery of the perinodal tissues by applying a series of sequential cryolesions to the atrial tissues immediately adjacent to the atrioventricular node. Both these techniques attempt to interrupt one of the dual atrioventricular node conduction pathways while preserving the other. This report describes 17 consecutive patients who underwent surgical treatment, 10 patients with skeletonization of the atrioventricular node and seven patients with discrete perinodal cryosurgery. There were 10 female and seven male patients and their ages ranged from 28 to 56 years (mean 38). Two of the 17 patients had Wolff-Parkinson-White syndrome and their accessory pathways were interrupted before the atrioventricular nodal reentrant tachycardia was ablated. All the procedures were performed in a normothermic beating heart while atrioventricular conduction was monitored closely. In the skeletonization technique, the right atrial septum was mobilized and the atrioventricular node exposed anterior to the tendon of the Todaro. The perinodal cryosurgical procedure was also performed through a right atriotomy and a series of sequential 3 mm cryolesions were placed around the borders of the triangle of Koch on the inferior right atrial septum. There were no operative deaths. Two patients who underwent the skeletonization operation had heart block necessitating pacemaker therapy. At postoperative electrophysiologic study, no echoes or atrioventricular nodal reentrant tachycardia were inducible in any of the 17 patients. All patients have remained free of arrhythmia recurrence and have required no antiarrhythmic therapy after a follow-up of 5 to 28 months (mean 14). In conclusion, both atrioventricular node skeletonization and perinodal cryosurgery successfully ablate atrioventricular nodal reentrant tachycardia; however, perinodal cryosurgery appears to be safer in avoiding heart block, is more easily performed, and is our procedure of choice for the management of medically refractory atrioventricular nodal reentrant tachycardia.

Adolescent↗
PubMed1991

Surgical myocardial revascularization for the 1990s.

After two decades, coronary artery surgery remains a reliable mainstay in the treatment of select patients suffering from ischemic heart disease. However, surgical myocardial revascularization has undergone continuous evolution. Several trends have emerged, including increased use of autogenous artery for bypass conduit, extending indications to include patients with poor ventricular function or following recent myocardial infarction and new techniques, such as surgical angioplasty of the left main coronary artery.

Humans↗
PubMed1990

Machine learning approach for the prediction of protein secondary structure.

PROMIS (protein machine induction system), a program for machine learning, was used to generalize rules that characterize the relationship between primary and secondary structure in globular proteins. These rules can be used to predict an unknown secondary structure from a known primary structure. The symbolic induction method used by PROMIS was specifically designed to produce rules that are meaningful in terms of chemical properties of the residues. The rules found were compared with existing knowledge of protein structure: some features of the rules were already recognized (e.g. amphipathic nature of alpha-helices). Other features are not understood, and are under investigation. The rules produced a prediction accuracy for three states (alpha-helix, beta-strand and coil) of 60% for all proteins, 73% for proteins of known alpha domain type, 62% for proteins of known beta domain type and 59% for proteins of known alpha/beta domain type. We conclude that machine learning is a useful tool in the examination of the large databases generated in molecular biology.

Amino Acid Sequence↗
PubMed1988

Surgical division of Wolff-Parkinson-White pathways utilizing the closed-heart technique: a 2-year experience in 47 patients.

Kent bundle interruption for ventricular preexcitation has been successfully accomplished utilizing several different surgical techniques. The external closed-heart technique of Guiraudon combining surgical dissection and cryoablation has been used to interrupt 52 accessory pathways in 47 consecutive patients since May, 1985. The 35 male and 12 female patients ranged in age from 10 to 67 years (mean, 30 years). There were 25 left free wall, 13 right free wall, 13 posterior septal, and 1 anterior septal accessory pathways. Preoperative and intraoperative electrophysiological studies were performed in all patients to induce the arrhythmia and localize all accessory pathways. The operation consisted of dissection of the atrioventricular fat pad. Following this, the delta wave and retrograde accessory pathway conduction disappeared, thereby indicating successful pathway ablation. In 4 patients with right-sided accessory pathways, interruption of the pathway required cryoablation. Cryolesions (made with cryoprobe at -60 degrees C for two minutes) were created in the region of the accessory pathway insertion. All accessory pathways were successfully ablated without any deaths or heart block. Concomitant surgical procedures were performed in 4 patients. Two patients required a second operation the next day for an accessory pathway not found at the initial operation. Three patients had postpericardiotomy syndrome, and 4 had recurrent atrial fibrillation requiring therapy. The remaining patients have had no arrhythmia recurrence and have remained drug free after a follow-up of 1 month to 22 months (mean, 12.5 months). We conclude that the closed-heart technique of accessory pathway ablation is safe and reproducible, obviates the necessity for aortic cross-clamping and cardioplegic arrest, and allows instantaneous monitoring of conduction over the pathway.

Adolescent↗
PubMed1987

Effects of hypothermia on brainstem auditory evoked potentials in humans.

Ten adult patients who underwent open heart surgery under induced hypothermia had brainstem auditory evoked potentials (BAEPs) recorded at 1 degree- to 2 degrees C-steps as body temperature was lowered from 36 degrees C to 20 degrees C to determine temperature-dependent changes. Hypothermia produced increased latencies of BAEP waves I, III, and V; the prolongation was more severe for the later components with the result that interpeak latencies I-III, III-V, and I-V were also prolonged. The temperature-latency relationship was nonlinear and best expressed by exponential curve. The latencies of waves I, III, V and the interpeak latency I-V increased roughly 7% for each 1 degree C drop; they doubled at a temperature around 26 degrees C. The amplitude of the BAEP components had a quasiparabolic relationship to temperature; the amplitude rose with hypothermia to 28 degrees or 27 degrees C, but decreased linearly with further cooling. All BAEP components were present at temperatures above 23 degrees C and absent below 20 degrees C. With rewarming, the changes reversed and BAEPs returned to initial prehypothermia status.

Acoustic Stimulation↗
PubMed1986

Lesser saphenous vein as an alternative conduit of choice in coronary bypass operations.

Dissatisfaction with the use of the greater cephalic vein and the ease of harvest and overall excellent quality of the lesser saphenous vein have caused us to consider this as our alternate conduit of choice when complete revascularization cannot be obtained with the internal mammary artery and greater saphenous vein. We describe our experience with this conduit and our harvesting technique and review the anatomy of this vein.

Coronary Artery Bypass↗
PubMed1985

Postoperative phrenic nerve palsy in patients with open-heart surgery.

We prospectively studied patients undergoing open-heart surgical procedures to evaluate the role of phrenic nerve palsy in the causation of the high incidence of pulmonary complications reported in these patients. Although atelectasis, or infiltrates, or both developed in the left lower lobe of 98% of the patients (43 of 44) with or without similar changes on the right side, only 5 (11%) of the 44 patients had diaphragmatic dysfunction following operation. In 1, the left phrenic nerve became inexcitable; 2 had paresis of the left hemidiaphragm, and 2 had paresis of the right hemidiaphragm. Although damage to the phrenic nerve can occur during open-heart operations, a relatively low incidence of this complication does not support it as the major cause of postoperative pulmonary complications.

Adult↗
PubMed1978

Occlusion, carbon dioxide, and fungal skin infections.

Occlusion of the skin renders it susceptible to acute fungal skin infections (dermatophytosis and candidiasis). Occlusion also raised carbon-dioxide (CO2) tensions at the skin's surface. Comparable CO2 tnesions have a pronounced effect on the morphology and metabolism of dermatophytes in vitro. It is postulated that dermatophyte conida and hyphae produce infective units under conditions of raised CO2 tensions, and that occlusion of the skin produces the concentrations of CO2 required for the conversion. Fungal skin infections might be prevented or controlled by interference with the action of CO2 or by prevention of its accumulation under wet, occlusive clothing.

Acute Disease↗
PubMed1978

The effect of occlusion on carbon dioxide emission from human skin.

The effect of occlusion on the carbon dioxide (CO2) emission rate (CDER) of human skin was determined. Occlusive plastic tape elevated the CDER 4.5 times (90nl/cm2/hr) over the normal CDER (20nl/cm2/hr). This increase was noted within a 3-hour period. Non-occlusive paper tape had no effect on CDER. Quantitation of the amount of CO2 under plastic tape revealed that CO2 was present at a concentration of 8-10%. Removal of the plastic tape after 24 hours allowed the CDER to return to approximately normal values within 2 hours. The mechanism by which occlusive plastic tape mediates this dramatic effect on CDER as well as the significance of elevated CO2 concentrations under occlusion are discussed.

Adult↗