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J E Fletcher

Publications and source records attributed to J E Fletcher.

149 records · Page 9Linked to original sources
PubMed1969

Binding of long-chain fatty acids to bovine serum albumin.

We have studied the binding of long-chain free fatty acids (FFA) to crystalline bovine serum albumin (BSA) that had been extracted with charcoal to remove endogenous fatty acids. The data were analyzed in terms of a model consisting of six high-energy binding sites and a large number of weak binding sites. The high-energy sites were resolved into two distinct classes, each containing three sites. At 37 degrees C and pH 7.4, k'(1) (the apparent association constant of a class of binding sites) was about 10(6) m(-1) for binding to the three primary sites, and k'(2) was about 10(5) m(-1) for binding to the three secondary sites. The number of weak (tertiary) sites was estimated to be 63 with a k'(3) of 10(3) m(-1). In general, palmitate and palmitoleate were bound more tightly than oleate, linoleate, stearate, or myristate, and much more tightly than laurate. The association of palmitate with human and rabbit albumin also was analyzed in terms of this model. Palmitate was bound less firmly by human or rabbit albumin than by BSA. Palmitate binding to BSA was dependent upon the pH and temperature of the incubation medium. Long-chain hydrocarbons that did not contain a free carboxyl group (methyl palmitate, cetyl alcohol, and hexadecane) were bound to a limited extent and weakly. The presence of positively charged protein sites and native protein tertiary structure were required for maximal binding of palmitate to BSA. Of nine other proteins tested, only -lactoglobulin exhibited a significant capacity to bind palmitate.

Animals↗
PubMedDate not supplied

Malignant hyperthermia susceptibility in X-linked muscle dystrophies.

To evaluate malignant hyperthermia (MH) susceptibility in X-linked muscular dystrophies, halothane and caffeine contracture tests were performed on muscle fiber bundles from five patients with Duchenne muscular dystrophy (DMD) and two patients with Becker muscular dystrophy (BMD). Two DMD patients and one BMD patient had positive contracture tests. Since a positive contracture test is currently the best indicator of anesthetic susceptibility in the MH population, and episodes of MH in dystrophic patients have been reported, patients with DMD and BMD may be at risk for developing similar anesthetic complications. Awareness of this potential anesthetic risk is of importance because orthopedic interventions are increasingly more common in these patients.

Adolescent↗
PubMedDate not supplied

Similarities and differences in mechanisms of cardiotoxins, melittin and other myotoxins.

Myonecrosis induced in vivo by cardiotoxin, melittin, and Asp49 and Lys49 phospholipase A2 (PLA2) myotoxins involves rapid lysis of the sarcolemma, myofibril clumping, and hypercontraction of sarcomeres. In contrast, skeletal muscle necrosis induced by crotamine and myotoxin a is much slower, consisting of mitochondrial and sarcoplasmic reticulum swelling, myofibril degeneration, and lack of sarcolemma or transverse tubule damage. The mechanisms contributing to the myonecrosis induced by these peptides were evaluated. Two cardiotoxins and two Lys49 PLA2 myotoxins lysed primary cultures of human skeletal muscle within 24 hr at a concentration of 0.25 microM, while melittin, crotamine, and myotoxin a, and an Asp49 PLA2 myotoxin were non-cytolytic at concentrations up to 5.0 microM, suggesting that cytolysis is not a good measure of myotoxicity. Crotamine and the Lys49 PLA2 myotoxin altered Ca2+ ion flux in human heavy sarcoplasmic reticulum by opening the ryanocine receptor. Whole-cell patch-clamp studies demonstrated that administrating crotamine intracellularly increased Na+ currents. Free fatty acids, liberated by activation of tissue phospholipase C or by the PLA2 activity of the myotoxins, were monitored for crotamine, myotoxin a and a Lys49 PLA2 myotoxin in cell cultures in which the lipids had been radiolabeled. Only the Lys49 myotoxin produced significant amounts of fatty acid in cell cultures, supporting a potential role for fatty acid production only in the mechanism of sarcolemma-destroying myotoxins. These findings, coupled with those in the literature, support a hypothesis in which the myotoxins and/or products of lipase activity (e.g. fatty acids) are acting at a site existing on both the Na+ channel and a protein involved in Ca2+ release and probably serving a modulatory function for ion regulation. Based on the similarities in mechanisms between the toxins and fatty acids, the most likely site would be a fatty acid binding site on the protein (either similar to that on fatty acid binding proteins, or an acylated cysteine residue) or in the membrane.

Bee Venoms↗
PubMedDate not supplied

Use of a physiologic scoring system during interhospital transport of pediatric patients.

OBJECTIVE: To determine the incidence of physiologic deterioration in critically ill and injured pediatric patients during interhospital transport with air and ground ambulance DESIGN: Prospective, descriptive study SETTING: All children were treated in regional hospitals and then transported to a pediatric tertiary care center. PATIENTS: Children (n = 100) with a median age of 1.4 years (range 1 week to 18 years) MAIN RESULTS: Three sets of physiologic scores were calculated: at the time of referral, on departure from the referring hospital, and arrival at the tertiary care center. The incidence of significant physiologic deterioration based on the calculated physiologic scores was 5.6% (n = 4) during ground and 3.4% (n = 1) during air ambulance transports. Critical events occurred in 15% of ground and 31% of air ambulance transports. CONCLUSION: No difference existed in the incidence of adverse events or physiologic deterioration when air ambulance transports were compared with ground ambulance transports for critically ill children by our team. The physiologic scoring system we chose is simple and easy to use for quality assurance.

Adolescent↗