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J J Heffron

Publications and source records attributed to J J Heffron.

At least 19 recordsLinked to original sources
PubMed1991

Diagnosis of susceptibility to malignant hyperthermia with flanking DNA markers.

OBJECTIVE: To define the region on human chromosome 19 carrying the gene for malignant hyperthermia susceptibility and to evaluate the use of flanking DNA markers in diagnosing susceptibility. DESIGN: Prospective molecular genetic linkage studies in a large malignant hyperthermia pedigree. SETTING: Irish malignant hyperthermia testing centre. SUBJECTS: A large Irish malignant hyperthermia pedigree. MAIN OUTCOME MEASURES: Routine diagnosis of susceptibility to malignant hyperthermia with in vitro contracture test on muscle biopsy specimens and genetic linkage between susceptibility and polymorphic DNA markers in a malignant hyperthermia family. RESULTS: Genetic typing of polymorphic DNA markers in a large Irish malignant hyperthermia pedigree generated a lod score of greater than 3 for the marker D19S9 and showed that the gene for susceptibility is flanked by the markers D19S9 and D19S16. These tightly linked flanking markers allowed non-invasive presymptomatic diagnosis of susceptibility in five untested subjects in the large pedigree with an accuracy of greater than 99.7%. CONCLUSIONS: DNA markers flanking the gene for susceptibility to malignant hyperthermia can be used with high accuracy to diagnose susceptibility in subjects in large known malignant hyperthermia pedigrees and may replace the previous in vitro contracture test for diagnosing this inherited disorder in large families with malignant hyperthermia.

Chromosomes, Human, Pair 19↗
PubMed1991

The caffeine contracture test for malignant hyperthermia: caffeine citrate, caffeine benzoate or caffeine free base?

The aim of the present study was to investigate whether the three different caffeine preparations--caffeine citrate, caffeine benzoate and the free base--used for in vitro diagnosis of malignant hyperthermia susceptibility--produced the same amount of contracture in rat diaphragm. At equimolar caffeine concentrations, the pure base generated more tension in the rat diaphragm muscle than caffeine benzoate or caffeine citrate. The citrate lowers the pH and the free Ca2+ concentration of the test bath and thus suppresses the caffeine contracture. The benzoate is believed to inhibit the caffeine contracture by its carbonyl group in a way similar to the effect of benzocaine.

Animals↗
PubMed1990

Localization of the malignant hyperthermia susceptibility locus to human chromosome 19q12-13.2.

Malignant hyperthermia (MH) is an inherited human skeletal muscle disorder and is one of the main causes of death due to anaesthesia. The reported incidence of MH varies from 1 in 12,000 in children to 1 in 40,000 in adults. MH is triggered in susceptible people by all commonly used inhalational anaesthetics; it is characterized by a profoundly accelerated muscle metabolism, contractures, hyperthermia and tachycardia. Susceptibility to MH (MHS) is predicted by contracture tests on muscle tissue obtained by biopsy. An almost identical disorder known as porcine MH exists in pigs. The genetics of the porcine syndrome have been extensively studied; the locus controlling expression of porcine MH is genetically linked to the glucose phosphate isomerase locus (GPI). In man, GPI has been mapped to the q12-13.2 region of chromosome 19 (refs 10-12). We have now investigated genetic linkage in several extended Irish pedigrees in which MHS is segregating as an autosomal dominant trait. Here we show linkage between MHS and DNA markers from the GPI region of human chromosome 19 with a maximum log likelihood ratio (lod score) of 5.65 at the CYP2A locus. These results indicate that human and porcine MH are most probably due to mutations in homologous genes, and also provide a potentially accurate and noninvasive method of diagnosis for MHS.

Animals↗
PubMed1990

Recent developments in the molecular genetics of malignant hyperthermia: implications for future diagnosis at the DNA level.

Molecular genetic linkage studies on the inherited human disorder malignant hyperthermia have resulted in the mapping of the locus for malignant hyperthermia susceptibility (MHS) to the twenty centimorgan genetic interval in the q12-13.2 region of chromosome 19 defined by the anonymous polymorphic DNA markers D19S9 and BCL3. The mapping of the MHS locus to this interval now allows diagnosis of MHS in selected families with an accuracy of 97.5% using closely linked polymorphic DNA markers.

Chromosomes, Human, Pair 19↗
PubMed1990

Current views of the molecular basis of the malignant hyperthermia syndrome.

The muscle disease malignant hyperthermia is a disorder of intracellular free Ca2+ regulation in both humans and pigs. Current evidence indicates that the Ca2+ channel of the sarcoplasmic reticulum of MH muscle is abnormally sensitive to Ca2+ and to halothane. Mitochondria, the sarcolemma and the transverse tubule appear not to be involved in primary pathogenesis of MH. Molecular genetic studies indicate that the MH gene is on human chromosome 19 and that the likely candidate gene is that coding for the Ca2+ channel.

Calcium↗
PubMed1979

Skeletal muscle sarcoplasmic reticulum in porcine malignant hyperthermia.

To examine the function of sarcoplasmic reticulum (SR) in malignant hyperthermia, SR was isolated from semitendinosus muscle of normal and genetically susceptible Poland China swine. Determinations included rate of calcium binding (oxalate absent), rate and capacity of calcium uptake (oxalate present), and spontaneous calcium release (in the absence of ionic depolarization or calcium) with and without halothane, using the millipore filtration technique. Rate of calcium binding, and rate and capacity of calcium uptake were decreased, and spontaneous calcium release was greater in SR fragments from susceptible swine as compared to those from normal swine. Halothane 0.5% slightly increased the rate of calcium binding in susceptible and normal SR. Above 1%, halothane decreased calcium binding rate, and uptake rate and capacity, and increased calcium release similarly in susceptible and normal SR. These differences in SR function were insufficient to explain the etiology of malignant hyperthemia, nor did the effect of halothane account for its triggering action.

Animals↗
PubMed1978

Fine structure of the homologous tergo-coxal muscles of flying and flightless beetles.

The flight-related tergo-coxal muscles of flying and flightless beetles are compared. In the flying beetle, Pachynoda sinuata, the myofibrils and cylindrical and the myofilaments packed in double hexagonal arrays. The sarcomeres are short (2.8 micrometer) and wide with many large, closely packed adjacent mitochondria but the sarcoplasmic reticulum is poorly developed in this fibrillar (asynchronous) muscle. Sarcoplasmic glycogen in rosette form is abundant. In the flightless beetle, Anthia thoracica, the myofibrils are lamellar-like with sarcomeres of 5.3 micrometer. The myosin filaments form a single hexagonal array each thick filament having an orbital of 11 to 12 thin filaments. The width of the Z-line (120 nm) of A. thoracia muscle was twice that of the Z-line of P. sinuata muscle. The sarcoplasmic reticulum and T-system are well-developed in this afibrillar (synchronous) muscle. Few glycogen granules are present. Triangular projections of the sarcolemma occur regularly opposite the Z-lines in A. thoracica and they appear to extend into the Z-lines. Membranous connections joint adjacent Z-lines in A. thoracica and occasionally in P. sinuata.

Animals↗
PubMed1977

Porcine malignant hyperthermia: role of skeletal muscle in increased oxygen consumption.

During malignant hyperthermia (MH) induced by halothane and succinylcholine, oxygen consumption (VO2) of whole body, muscle and the splanchnic area was calculated from measurements of blood flow and arteriovenous oxygen content difference. Caudal body blood flow was isolated and measured (six animals) for determination of average muscle VO2 in the hind limbs, buttocks, and flanks. The increase in muscle VO2 was extrapolated to total skeletal muscle and compared with the increase in whole body VO2 (same six animals). The average increase in VO2 for both total muscle and whole body during the period of maximum increase was about 6 ml O2/min/kg body weight. Splanchnic VO2 (four animals) tended to decrease during MH. The data support the hypothesis that the metabolic changes in MH are due to a disorder of skeletal muscle and that the increase in whole body VO2 is due to the increase in muscle VO2.

Animals↗