PubMed Health⌕ Search

Biomedical subjects

M S Phillips

Publications and source records attributed to M S Phillips.

6 recordsLinked to original sources
PubMed1992

Malignant hyperthermia.

In humans genetically predisposed to malignant hyperthermia, anesthesia can induce skeletal muscle rigidity, hypermetabolism, and high fever, which, if not immediately reversed, can lead to tissue damage or death. The corresponding condition in swine leads to stress-induced deaths and devalued meat products. Abnormalities in the Ca2+ release channel of skeletal muscle sarcoplasmic reticulum (the ryanodine receptor) have been implicated in the cause of both the porcine and human syndromes by physiological and biochemical studies and genetic linkage analysis. In swine, a single founder mutation in the ryanodine receptor gene (RYR1) can account for all cases of malignant hyperthermia in all breeds, but a series of different RYR1 mutations are likely to be uncovered in human families with MH. Moreover, lack of linkage between malignant hyperthermia and RYR1 in some families indicates a heterogeneous genetic basis for the human syndrome.

Animals↗
PubMed1992

Refinement of diagnostic assays for a probable causal mutation for porcine and human malignant hyperthermia.

The substitutions of T for C1843 in the porcine ryanodine receptor (RYR1) gene, which deletes a HinPI restriction endonuclease site and creates a HgiAI site, and of T for C1840 in human RYR1, which deletes a RsaI site, lead to Cys for Arg substitutions in the ryanodine receptors and are probable causal mutations for malignant hyperthermia (MH). To improve the restriction endonuclease assay of these sites, thereby providing an accurate, reliable diagnosis for MH, introns flanking the exon containing the mutation were sequenced, permitting identification and PCR amplification of a 659-bp porcine gene sequence that contains both constant and variant HgiAI sites and a 922-bp human gene sequence that contains both constant and variant RsaI sites. As a result, these PCR-amplified sequences contain constant internal controls for the reliable differentiation by restriction endonuclease digestion of normal, heterozygous, and MH genotypes.

Animals↗
PubMed1992

The role of the skeletal muscle ryanodine receptor gene in malignant hyperthermia.

Malignant hyperthermia (MH) is an inherited, potentially lethal condition in which sustained muscle contracture with attendant hypermetabolism and hyperthermia is triggered in humans, heterozygous for the gene defect, by inhalational anaesthetics and skeletal muscle relaxants, and in pigs, homozygous for the defect, by stress. Because muscle contracture could result from a defective Ca2+ release channel, we have focussed our attention on the linkage of MH to defects in the gene (RYR1) encoding the skeletal muscle Ca2+ release channel. We have cloned and sequenced human RYR1 cDNA and found restriction fragment length polymorphisms (RFLPs) in the human gene. We also localized RYR1 to human chromosome 19q13.1. Studies of the cosegregation of MH with these RFLPs established RYR1/MH linkage on human chromosome 19q13.1 (lod score of 4.2; recombinant fraction 0.0). We then sequenced MH and normal porcine RYR1 cDNAs. Mutation of C1843 to T, leading to substitution of Cys for Arg615, was the sole amino acid change noted between MH and normal animals. Linkage of this mutation to MH was established in a study of 338 informative meioses (lod score of 102; recombinant fraction 0.0). We identified the corresponding mutation in 1 of 35 human MH families studied and found cosegregation of the mutation and MH. The combination of a high lod score with crossing of a species barrier supports the causal nature of this mutation. Future studies are aimed at finding the major human MH mutations and establishing assays for their accurate diagnosis.

Amino Acid Sequence↗
PubMed1991

Patients who reoffend while on warrants of the Lieutenant-Governor.

Occasionally, psychiatric patients detained in institutions against their will or residing in the community under legal restraints elope and commit serious offenses. The authors looked at the frequency with which this occurred with patients on warrants of the Lieutenant-Governor in Ontario. Using the files of the Ontario Lieutenant-Governor's Board of Review, they examined the records and isolated such recorded incidents over a 16 year period. In spite of the limitations identified by the authors, their findings indicate a lower than expected occurrence. As well, they point to the risk management implications of certain diagnostic groups being treated in a less than secure setting.

Adult↗
PubMed1979

Sprengel's deformity. Radiology of the pathologic deformation.

A unique specimen of unilateral Sprengel's deformity, and contralateral normal pectoral girdle, were studied morphologically and roentgenographically. The cervical spine exhibited multiple abnormalities involving both the vertebral centra as well as the posterior elements (Klippel-Feil abnormality). A small spina bifida involving C5 and C6 was present. Abnormalities of the spinous processes included an articulation with a well-formed omovertebral bone that also articulated with the vertebral (infraspinatus) margin of the scapula. Secondary (presumed epiphyseal) ossification was present in the omovertebral bone at the distal end. The scapula was deformed, especially in the supraspinatus portion. The clavicle was shorter and had a different contour.

Abnormalities, Multiple↗