Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0024591 (malignant hyperthermia)
 2,353 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Elective diagnosis of malignant hyperthermia depends on halothane and caffeine contracture testing of biopsied skeletal muscle. Ryanodine-induced contractures may provide greater sensitivity and specificity for malignant hyperthermia (MH) diagnosis. This study investigated the effects of ryanodine concentration and stimulus frequency to distinguish between MH susceptible (MHS) and MH non-susceptible (MHN) dogs. Increasing ryanodine concentrations (1, 2.5 and 5 microM) increased peak isometric contracture tension, but similar responses in MHS and MHN muscle precluded use for diagnosis. Time to tension onset and to peak tension decreased with increasing ryanodine concentration, and these times were shorter in MH skeletal muscle. Increasing stimulus frequency (0.1, 0.5 and 1 Hz) decreased the time to tension onset and to peak tension, but the effect was greater in MHN muscle which decreased the difference between MHN and MHS muscle responses. When ryanodine contracture tension onset time was selected to detect MHS muscle, combinations of either 0.1 Hz and 1 microM ryanodine or 0.5 Hz and 1 microM ryanodine reduced the probabilty of a false diagnosis to less than 1%. Similar studies performed on human muscle might identify optimal stimulus frequency and ryanodine concentration for detecting MH in patients.
J Pharmacol Exp Ther 1997 Sep
PMID:Changes in ryanodine-induced contractures by stimulus frequency in malignant hyperthermia susceptible and malignant hyperthermia nonsusceptible dog skeletal muscle. 931 43

Staphylococcal leukocidin and gamma-hemolysin consist of LukF and LukS for leukocidin and LukF and Hlg2 for gamma-hemolysin. In this report, we identify the minimum segment responsible for the LukS-specific function of leukocidin. After chemical analysis and homology study of the amino acid sequence of the C-terminal region between LukS and Hlg2, we found a unique 5-residue sequence I242K243R244S245T246 in LukS in which the 4-residue KRST is identical with that of the phosphorylated segment of a protein phosphorylated by protein kinase A. To elucidate whether the 5-residue segment is essential for the LukS function, we created plasmids containing a series of mutant genes corresponding to the 5-residue sequence and expressed them in Escherichia coli. The mutant proteins were purified and assayed for their leukocytolytic activity with LukF. The mutant MLS-TS, in which the T246 in the 5-residue sequence was replaced by S, showed leukocidin activity 10 times higher than that of the intact LukS. However, neither mutant MLS-TY nor MLS-TA, in which T246 was replaced by Y or A, respectively, showed leukocidin activity. The 5-residue segment was found to be deleted in Hlg2. The mutant of Hlg2, in which the 5-residue segment was inserted at the position that the segment is deleted, showed leukocidin activity. The boiled LukS, MLS-TS, and MHS-Z were strongly phosphorylated with [gamma-32P]ATP in the presence of protein kinase A in a cell-free system. Thus, we conclude that the 5-residue segment 1242K243R244S245T246 is the pivotal segment of LukS responsible for the LukS function of staphylococcal leukocidin.
FEBS Lett 1997 Sep 22
PMID:Identification of the minimum segment in which the threonine246 residue is a potential phosphorylated site by protein kinase A for the LukS-specific function of staphylococcal leukocidin. 932 77

The aim of this study was to find, using modern techniques, any histological differences in muscle biopsies between malignant hyperthermia (MH) susceptible (MHS), MH equivocal (MHE) and MH negative (MHN) patients. On the basis of the European MH contracture test carried out in 83 patients, 23 were shown to be MHS, nine MHE and 51 MHN. Four lesions were found with a significantly high frequency in MHS and MHE biopsies: muscle fibre hypertrophy and atrophy, internal nuclei and myofibrillar necrosis. These four lesions were observed together in 35% of MHS but in none of the MHE or MHN biopsies. Three of these lesions occurred together in 57% of MHS, 33% of MHE and 4% of MHN biopsies. Our results support a histological difference between MHE, MHS and MHN biopsies and attempt to contribute towards a better definition of MHE status.
Br J Anaesth 1997 Sep
PMID:Histological support for the difference between malignant hyperthermia susceptible (MHS), equivocal (MHE) and negative (MHN) muscle biopsies. 938 50

Malignant hyperthermia (MH) is a potentially fatal autosomal dominant disorder of skeletal muscle and is triggered in susceptible people by all commonly used inhalation anaesthetics and depolarizing neuromuscular blocking agents. To date, eight mutations in the skeletal muscle ryanodine receptor gene (RYR1) have been identified in malignant hyperthermia susceptible (MHS) and central core disease (CCD) cases. We have screened the RYR1 gene in affected individuals for novel MHS mutations by single stranded conformational polymorphism (SSCP) analysis and have identified a G to T transition mutation which results in the replacement of a conserved arginine (Arg) at position 614 with a leucine (Leu). The Arg614Leu mutation was present in three unrelated MHS individuals of 151 investigated. The mutation was not detected in 148 normal chromosomes and segregated precisely with MHS in family members from one of the probands where DNA was available for analysis. This mutation occurs at the same position as the previously identified Arg to Cys mutation reported in all cases of porcine MH and in approximately 5% of human MH. A comparison of the phenotypes of the Arg614Leu and Arg614Cys probands is presented.
Br J Anaesth 1997 Sep
PMID:Detection of a novel mutation at amino acid position 614 in the ryanodine receptor in malignant hyperthermia. 938 51

31P nuclear magnetic resonance spectroscopy was performed on 19 to 55 kg weighing pigs of different MHS genotypes to study the changes of phosphorus components (inorganic phosphate --Pi, phosphocreatine--PCr and adenosine triphosphate--ATP) of muscle metabolism as well as intramuscular pH under application of halothane. Aim of the present study was to observe the changes in energy metabolism and to perform a comparison with also measured blood parameters. Both, NN and Nn pigs did not show any changes during halothane exposure in phosphorus spectra, but in all animals a partially metabolically compensated respiratoric acidosis was found. In all MHS positive pigs a rapid fall of PCr and a corresponding raise of Pi levels in muscle was observed.
Dtsch Tierarztl Wochenschr 1997 Sep
PMID:[In vivo investigations of stress susceptibility in pigs by means of magnetic resonance spectroscopy]. 941 Jul 28

Hyphomonas MHS-3 (MHS-3) elaborates a diffuse capsular material, primarily composed of polysaccharide, which has been implicated to serve as the holdfast of this prosthecate marine bacterium. A purified polysaccharide (fr2ps) from this capsular material exhibits a relatively large affinity for (Ge), or more precisely for the Ge oxide surface film. In its natural habitat MHS-3 attaches to marine sediments. This suggests that molecular properties of fr2ps have evolved to render it adhesive toward mineral oxides. In order to characterize these molecular interactions, the effect of divalent cations and pH on the adsorption of fr2ps to Ge has been measured using attenuated total internal reflection Fourier transform infrared (ATR/FT-IR) spectroscopy. The effect of adsorption of fr2ps on the Ge oxide film has been investigated using X-ray photoelectron spectroscopy (XPS). The results indicate that divalent cations participate in binding of fr2ps to Ge oxide and that atomic size of the cation is important. Evidence for significant participation of hydrogen bonding to the oxide surface is lacking. Copyright 1998 Academic Press.
J Colloid Interface Sci 1998 Sep 01
PMID:Influence of Divalent Cations and pH on Adsorption of a Bacterial Polysaccharide Adhesin. 971 May 2

Objective markers of exposure to semen provide a more valid assessment of condom failure and failure to use condoms than self-reports. The present study evaluated three of the assays commonly used in forensic medicine for detecting semen exposure: acid phosphatase (AP) activity, prostate specific antigen (PSA), and the human seminal plasma antigen (MHS-5). 20 US women were intravaginally inoculated with 6 measured, increasingly larger amounts of their partners' semen. Vaginal fluid was collected with swabs by study participants and tested for the three markers. Before semen inoculation, PSA levels were consistently low (median, 0.11 ng/ml; range, 0-1.25 ng/ml) while those of AP were highly variable (median, 13.4 U/l; range, 0-350 U/l); all preinoculation samples were negative for MHS-5. The median PSA concentration increased consistently with increasing volumes of semen, while median AP and MHS-5 levels showed an inconsistent pattern. All 120 swabs obtained after intravaginal inoculation with semen were positive for PSA, 64 (55%) were positive for AP, and 14 (12%) were positive for MHS-5. These findings indicate that self-sampling of vaginal secretions followed by the PSA immunoassay represents a simple, accurate marker of semen exposure. Because the PSA assay is available in most hospital laboratories for prostate cancer screening, the methodology used in the present study is suitable for widespread application.
Sex Transm Dis 1998 Sep
PMID:Objective markers of condom failure. 977 37

The mitochondrial myopathies are a rare group of conditions affecting the respiratory chain and oxidative phosphorylation. The anesthetic management of a 6-year-old girl with complex I respiratory chain deficiency requiring surgery for a fractured hip is presented and discussed. Potential problems were masseter spasm, tendency to develop lactate acidosis, and malignant hyperthermia susceptibility. These problems were avoided by the use of a laryngeal mask airway, allowing the patient to spontaneously ventilate; caudal analgesia; and maintenance of anesthesia with a proprofol infusion.
J Clin Anesth 1998 Sep
PMID:Anesthesia for a child with complex I respiratory chain enzyme deficiency. 979 22

The skeletal muscle ryanodine receptor (RYR1) is a calcium release channel that mediates efflux of calcium ions from the sarcoplasmic reticulum into the myoplasm during excitation-contraction coupling. Mutations in the RYR1 gene have been detected in about 50% of the patients suffering from malignant hyperthermia (MH), but evidence is accumulating that other genetic defects can also lead to MH in humans. MH is a life-threatening disorder induced by exposure to volatile anesthetics and/or the muscle relaxans succinylcholin during surgical procedures in affected patients. MH leads to skeletal muscle rigidity, hypermetabolism and rapid rise in body temperature. MH is also known in pigs where it is triggered by stress and therefore often referred to as porcine stress syndrome. The existence of an animal model has greatly faciliated the elucidation of the basis for the human disease. This review describes recent advances in the understanding of the physiological action of ryanodine receptors and new insights regarding the relation between different RYR1 mutations and distinct phenotypical appearances.
Int J Mol Med 1998 Sep
PMID:Ryanodine receptors and their role in genetic diseases (review). 985 1

Two groups of 21 three-month-old Landrace x Large White pigs were sedated with either azaperone (2 mg/kg), butorphanol (0.2 mg/kg) and ketamine (5 mg/kg) (group A), or detomidine (100 microg/kg), butorphanol (0.2 mg/kg) and ketamine (5 mg/kg) (group D) administered intramuscularly, before being anaesthetised with halothane, oxygen and nitrous oxide for a bilateral stifle arthrotomy. The pigs' heart rate, respiratory rate, mean arterial blood pressure, electrocardiogram, arterial oxygen saturation, arterial blood gases, and oesophageal and rectal temperature were measured while they were anaesthetised and five minutes after they were disconnected, and their recovery times and any complications were recorded. Both groups were well sedated. Their heart rate was unchanged during the period of anaesthesia but increased when they recovered. The respiratory rate, mean arterial blood pressure and rectal temperature were lower in group A than in group D (P<0.05). Mild respiratory acidosis developed during anaesthesia in both groups. Both groups recovered equally rapidly and complications were generally minor, though two pigs in group D appeared to develop malignant hyperthermia.
Vet Rec 1999 Sep 04
PMID:Comparison of two combinations of sedatives before anaesthetising pigs with halothane and nitrous oxide. 1057 38


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