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)

Calcium-induced calcium release and halothane-induced calcium release from pig sarcoplasmic reticulum (SR) were studied. The SR prepared from pigs susceptible to malignant hyperthermia (MH) was shown to release calcium at a much lower level of calcium content than in normal pig SR. The concentration above which halothane can release calcium is 40 microM for both MH-SR and normal SR, although the latter required a high calcium content to demonstrate the calcium release. Dantrolene was shown to inhibit the halothane-induced calcium release. Results suggest that SR plays an important role in pathogenesis of MH.
FEBS Lett 1983 Sep 05
PMID:Calcium-induced Ca2+ release from sarcoplasmic reticulum of pigs susceptible to malignant hyperthermia. The effects of halothane and dantrolene. 688 19

Two fractions of sarcoplasmic reticulum, one light (LSR) and one heavy (HSR), were isolated from gracilis muscle of control and malignant hyperthermia (MH)-susceptible pigs. Part of the gracilis muscle biopsy was used to compare the contracture sensitivity of the muscle to the calcium-releasing effects of caffeine on isolated SR membranes. Gracilis muscle of MH pigs was more sensitive to the contracture-producing effects of caffeine than control pig muscle. The caffeine dose-cumulative contracture response curve for MH muscle was shifted left of that for controls. The amount of caffeine-induced calcium released from SR is a function of the amount of calcium preload and this did not differ between LSR of MH and control muscle. When LSR fractions were optimally loaded with calcium for caffeine-induced calcium release, no difference in calcium-releasing effects of varying caffeine doses was observed between MH and control LSR. At calcium preloads below optimal, the MH-LSR appeared to be more sensitive to caffeine-induced calcium release. The HSR fractions could not be loaded with calcium in a manner similar to the LSR fractions because of an apparent calcium-induced calcium release phenomenon. Therefore, calcium threshold for calcium-induced calcium release was compared between MH and control HSR fraction. The effect of caffeine on the calcium-induced calcium release was also studied. The average calcium concentration threshold for calcium-induced calcium release was markedly lower for MH vs. control HSR; 20 vs. 63 nmol Ca2+/mg, respectively. Caffeine decreased the threshold for calcium-induced calcium release more in the MH than in control HSR. Under all conditions studied, the amount of calcium released did not differ between the two groups. Ruthenium red increased the threshold calcium concentration for calcium-induced calcium release while it reduced the amount of calcium released. Increasing concentrations of Mg2+ increased the Ca2+ threshold for release and the amount of Ca2+ released but did not significantly affect rate of Ca2+ release. Results of the study suggest a defect in the mechanisms causing calcium release from SR in MH-affected muscle.
J Clin Invest 1983 Sep
PMID:Abnormality in calcium release from skeletal sarcoplasmic reticulum of pigs susceptible to malignant hyperthermia. 688 7

Malignant hyperpyrexia (M.H.) is a rare, important and frequently fatal disease provoked by inhalational anaesthetic agents and other drugs. It is manifested most frequently by tachycardia, a rise in core body temperature, muscle stiffness and is associated with profound metabolic effects. It may be transmitted in a predictable familial dominant fashion, but sporadic cases in whom this transference cannot be demonstrated do occur. Susceptibility may be revealed on questioning regarding previous anaesthetic exposure. One such unexpected but successfsully treated case of M.H. is described in detail and the current management and investigation is discussed.
Br J Oral Surg 1980 Sep
PMID:Malignant hyperpyrexia: successful management following oral surgery. 693 2

The introduction of isoflurane to clinical practice follows the search for a nonflammable, potent inhalation anesthetic which, above all, is chemically stable so as to resist biodegradation or attack by other chemicals. These attributes characterize isoflurane (Table 2). The hoped for freedom from hepatic and renal toxicity and from carcinogenic and mutagenic properties is a reality with this drug. Other favorable characteristics include relatively low solubility in blood in relation to anesthetic dose, lack of arrhythmogenic effect, provision of good muscle relaxation, and the absence of central nervous system excitation. Its moderate pungency detracts slightly from the ease of inhaled induction. Disadvantages include respiratory depression, reduced arterial blood pressure, uterine relaxation, decreased uteroplacental blood flow, and likely ability to trigger malignant hyperpyrexia. The frequency and/or significance of tachycardia and dilation of muscle blood vessels in clinical practice remain to be established. We believe isoflurane is a significant improvement over earlier potent inhalation anesthetics.
Anesth Analg 1981 Sep
PMID:Isoflurane: an anesthetic for the eighties? 702 81

Ca-releasing action of halothane on fragmented sarcoplasmic reticulum (FSR) from bullfrog and rabbit skeletal muscle was examined to understand the mechanism of Ca release in reference to the etiology of malignant hyperthermia. Halothane has dual action on FSR: the Ca release and the inhibition of Ca uptake. On addition of halothane to loaded FSR, a rapid Ca release was followed by a sluggish Ca leakage which was probably due to a decreased capacity for Ca uptake. The properties of the rapid Ca release by halothane are similar to those of caffeine. It was inhibited by procaine or high concentrations of Mg2+. It was stimulated by a high concentration of ATP. A low temperature was stimulatory for Ca-releasing action on frog FSR while it was inhibitory on rabbit FSR. The result that caffeine shifted the dose response curve for Ca release by halothane to a steeper relation to a range of much lower concentrations suggests that the action of halothane may not be identical with that of caffeine in spite of many similarities.
J Biochem 1982 Sep
PMID:The Ca-releasing action of halothane on fragmented sarcoplasmic reticulum. 714 26

Ryanodine toxicity in animals has been suggested to constitute a model of malignant hyperthermia. Dantrolene is known to block the development of malignant hyperthermia triggered by halothane in susceptible swine. The authors studied the influences of dantrolene and halothane on the effects of ryanodine in vitro in isolated rat diaphragm muscle segments, and in vivo in mice, to explore the validity of this model. In the diaphragm experiments, dantrolene was found to block or delay the development of contractures produced by ryanodine and to delay the potentiation of ryanodine-induced contractures caused by halothane. In mice, ryanodine at various dosages was injected and animals surviving after one hour were examined. Such survivors appeared grossly to be normal, and may constitute a model for the malignant hyperthermia patient. They were found to be susceptible to halothane and to succinylcholine, being killed by treatment with these two agents at dosages that were not lethal to control mice. Pretreatment of mice for 48 hours with orally administered dantrolene, followed by injection of ryanodine and then halothane anesthesia, decreased the lethality of ryanodine but did not reduce the number of deaths caused by the subsequent exposure to halothane. That the effects of ryanodine in vitro and in vivo are diminished and potentiated by dantrolene and halothane, respectively, would suggest that the ryanodine toxicity model of malignant hyperthermia may have validity and is worthy of further study. A prediction from this model is that the terminal cisternae of skeletal muscle sarcoplasmic reticulum may be altered in MH.
Anesthesiology 1980 Sep
PMID:Modification of ryanodine toxicity by dantrolene and halothane in a model of malignant hyperthermia. 742 33

Anaesthesia-induced malignant hyperthermia (MH) may be caused by specific gene defects in the skeletal muscle ryanodine receptor. We have studied the frequency of occurrence of the C1840T mutation, analogous to the porcine mutation, and three mutations associated both with MH and central core disease (G7301A, C487T and C1209G). We investigated skeletal muscle specimens from up to 137 patients testing negative and 101 patients testing positive for MH susceptibility by the North American MH Group protocol. The presence or absence of the mutations was determined by polymerase chain reaction and restriction enzyme digestion. The frequencies of occurrence of the C1840T and C487T mutations were 2% and 1%, respectively, in MH-positive subjects and were the only two mutations identified. One subject with central core disease did not have any of the three mutations examined associated with this disorder. Therefore, the porcine and central core disease-associated mutations examined in the ryanodine receptor account for a small proportion (approximately 3%) of MH-positive diagnoses. The mutations examined did not occur in any of the MH-negative patients, supporting an association between defects in the ryanodine receptor and a positive diagnosis for MH.(ABSTRACT TRUNCATED AT 250 WORDS)
Br J Anaesth 1995 Sep
PMID:Genotype and phenotype relationships for mutations in the ryanodine receptor in patients referred for diagnosis of malignant hyperthermia. 754 49

The ryanodine receptor gene (RYR1) has been shown to be mutated in a small number of malignant hyperthermia (MH) pedigrees. Missense mutations in this gene have also been identified in two families with central core disease (CCD), a rare myopathy closely associated with MH. In an effort to identify other RYR1 mutations responsible for MH and CCD, we used a SSCP approach to screen the RYR1 gene for mutations in a family exhibiting susceptibility to MH (MHS) where some of the MHS individuals display core regions in their muscle. Sequence analysis of a unique aberrant SSCP has allowed us to identify a point mutation cosegregating with MHS in the described family. The mutation changes a conserved tyrosine residue at position 522 to a serine residue. This mutation is positioned relatively close to five of the six MHS/CCD mutations known to date and provides further evidence that MHS/CCD mutations may cluster in the amino terminal region of the RYR1 protein.
Genomics 1994 Sep 01
PMID:Mutation screening of the RYR1 gene in malignant hyperthermia: detection of a novel Tyr to Ser mutation in a pedigree with associated central cores. 782 78

To test the hypothesis that the mutation associated with porcine stress syndrome (PSS; malignant hyperthermia) was present in a large proportion of North American and English swine, a simple and rapid laboratory protocol was used for cost-effective, large-scale diagnosis of susceptibility to PSS. This PSS test was applied to 10,245 breeding swine of various breeds from 129 farms in the United States, Canada, and England. Approximately 1 of 5 swine was a heterozygous carrier of the PSS mutation, with approximately 1% being homozygotes. Prevalence of the PSS mutation was 97% for 58 Pietrain, 35% for 1,962 Landrace, 15% for 718 Duroc, 19% for 720 Large White, 14% for 496 Hampshire, 19% for 1,727 Yorkshire, and 16% for 3,446 crossbred swine. The PPS gene frequencies for these breeds were 0.72, 0.19, 0.08, 0.10, 0.07, 0.10, and 0.09, respectively. In addition to these breeds, we have identified the PSS mutation in Poland China and Berkshire breeds. These gene frequencies were 30 to 75% lower in Canadian swine than in US swine, with the exception of Yorkshires, for which the gene frequency was threefold higher in Canadian swine. English swine were similarly, or more so, affected than were US swine. Accuracy was estimated at > 99%. Cost to perform the test was < $20/animal. Depending on the perceived net balance of deleterious and beneficial effects of the mutation, the PSS test could be used to eradicate the PSS mutation from herds, or for controlled expression of the mutation.
J Am Vet Med Assoc 1993 Sep 15
PMID:Use of a DNA-based test for the mutation associated with porcine stress syndrome (malignant hyperthermia) in 10,000 breeding swine. 790 Nov 88

The testis-specific human sperm antigen, SP-10, has been designated a 'primary vaccine candidate' by the World Health Organization Taskforce on Contraceptive Vaccines. Molecular cloning and sequencing of the cDNAs coding for human (h) and baboon (b) SP-10 have been reported. To produce large amounts of pure antigen for ongoing studies of the immunogenicity and anti-fertility effects of SP-10, we used an efficient Escherichia coli expression system. The full-length open reading frames for hSP-10 and bSP-10 were placed under the inducible T7 bacteriophage RNA polymerase/promoter system. An in-frame fusion was made such that a His6 stretch was produced at the C terminus of SP-10. Upon induction of gene expression, large amounts of hSP-10 or bSP-10 were synthesized and the recombinant (re-) protein segregated into an insoluble fraction. The protein was then solubilized in 6 M guanidine.HCl and purified by immobilized metal affinity chromatography (IMAC). The yield of purified bSP-10 preparation was approx. 20 micrograms/ml of culture. Immunoreactivity of the purified re-SP-10 with MHS-10, a monoclonal antibody specific to SP-10, and rabbit polyclonal sera raised against SP-10, indicated that the synthesized antigen was suitable for immunization studies. Four female baboons were then immunized with the re-bSP-10 antigen. Immunoblots using pre-immune and immune sera from these animals indicated that all four baboons produced antibodies that reacted with native SP-10 extracted from human sperm in a manner identical to that of MHS-10, the positive control. Immune sera also stained the acrosome region of human and baboon sperm heads by immunofluorescence.(ABSTRACT TRUNCATED AT 250 WORDS)
Gene 1994 Sep 30
PMID:Production in Escherichia coli, purification and immunogenicity of acrosomal protein SP-10, a candidate contraceptive vaccine. 792 98


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