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)

We have studied HLA haplotypes, autoimmune diseases and circulating autoantibodies in 23 families with multiple cases of rheumatoid arthritis; 76 per cent of rheumatoid arthritis and 70 per cent of non-rheumatoid individuals were positive for HLA-DR4. The haplotypes Bw44-Bf*S-DR4; B40-Bf*S-DR4; and B15-Bf*S-DR4 were found in 13, 9 and 7 per cent of probands respectively and the B15-Bf*S-DR4 haplotype was found between four and five times more frequently in DR4-positive rheumatoid arthritis than in DR4 positive, non-rheumatoid arthritis families. Rheumatoid arthritis segregated with a DR4 positive haplotype in 13 families and with a DR4 negative haplotype in seven. Analysis of HLA haplotype sharing showed greater than random sharing by affected siblings which is in keeping with genes within the MHS influencing susceptibility to rheumatoid arthritis. Autoimmune thyroid disorders were seen in 8 per cent of family members investigated. They were significantly more frequent in those families in which rheumatoid arthritis segregated with a non-DR4 bearing HLA haplotype. This suggests that genes for autoimmune thyroid disease might predispose to rheumatoid arthritis independently of DR4. These genes are probably not HLA-linked, as there was no trend for HLA haplotype sharing to be increased in sibling pairs with either rheumatoid arthritis and thyroid disease or rheumatoid arthritis and thyroid autoantibodies respectively.
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PMID:Clinical and immunogenetic studies in multicase rheumatoid families. 633 66

Electron microprobe analysis was used to determine cellular concentrations of potassium and sodium in renal cortical cells of hypertensive rats of the Milan strain (MHS) and spontaneously hypertensive rats of the stroke prone strain (SHRSP) and their respective controls. Potassium concentrations in proximal and distal tubular cells were similar in both strains of hypertensive rats compared with their normotensive controls. In MHS rats proximal tubular cell sodium concentration was lower than in controls by 3.1 mmol/kg ww, whereas in both proximal and distal tubular cells of SHRSP sodium concentrations were higher than in controls by 5.3 and 4.3 mmol/kg ww, respectively. These results indicate that changes in the transport characteristics of the renal tubular epithelium are a feature of both models of hypertension.
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PMID:Sodium and potassium concentrations of renal cortical cells two animal models of primary arterial hypertension. 659 94

Young pre-hypertensive rats of the Milan strain (MHS) have a faster glomerular filtration rate (GFR) and a higher urine flow in vivo than matched normotensive controls (MNS). Kidneys from both MHS and MNS at different ages were perfused in vitro with cell-free artificial medium, in order to further clarify the nature of these differences, in the absence of extrarenal uncontrolled factors. Isolated kidneys from young MHS showed a faster GFR, a larger tubular Na+ reabsorption and urine flow as compared to matched MNS: such differences endured throughout the 2 h of perfusion. These results support an intrinsic kidney abnormality as causing the above described differences between young rats of the two strains. Isolated kidneys from adult MHS showed faster GFR, higher renal perfusion flow and urine flow, yet similar tubular Na+ reabsorption when compared to MNS. Moreover a faster decay in kidney function was observed in the experiments with MHS. The existence of an extrarenal factor(s) correcting the intrinsic MHS kidney abnormality in vivo is suggested, as no differences were reported in kidney function of intact adult animals.
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PMID:Renal function of isolated perfused kidneys from hypertensive (MHS) and normotensive (MNS) rats of the Milan strain at different ages. 659 80

Body temperature at a variety of sites (external auditory meatus, rectum, thigh, chest wall, pad of thumb), blood cortisol, lactate and free fatty acid levels and urinary adrenaline, noradrenaline and dopamine excretion were measured in five human subjects susceptible to malignant hyperpyrexia (MHS) and five normal subjects during a period of progressively severe exercise, starting at rest and going up to an exercise intensity producing heart rates in excess of 180 beats/min. In addition, results are reported of a further study of rectal temperature measurements made during a period of mild exercise in a different group of nine MH susceptible and nine nonsusceptible subjects. The results of the progressive exercise study indicated that as the exercise increased in severity, central (external auditory meatal) temperature rose more in the MHS subjects than it did in the controls. Thumb temperature in both groups rose with exercise but in the MHS subjects this rise was significantly delayed compared with the control subjects. It was thought that this was due to a delay in the onset of vasodilatation which usually accompanies high intensities of exercise. Serum free fatty acids and cortisol levels rose more in the MHS subjects than the controls and during the early stages of exercise blood lactate concentrations in the MHS subjects were higher than in the controls group. During mild exercise, rectal temperature in the MHS subjects was lower than in the controls. It was concluded that the pattern of temperature change was evidence of an abnormality of the heat dissipation mechanisms in the MHS subjects.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Studies of body temperatures, blood lactate, cortisol and free fatty acid levels during exercise in human subjects susceptible to malignant hyperpyrexia. 663 62

A two-colour fluorescence microcytotoxicity test was used to screen antisera for antibodies specific for bovine B lymphocytes. A total of 114 cattle alloantisera were screened against peripheral blood lymphocytes from 100 unrelated individuals. Anti-B lymphocyte activity was detected in 47 antisera. Cytotoxic antibodies to antigens other than B lymphocyte specific antigens were removed by absorbing the antisera with buffy coat cells or platelets isolated from whole blood. Selected antisera were used to type paternal half-sib families. The presence of a polymorphic, MHS-linked antigen system on B lymphocytes was demonstrated. The tissue distribution and MHS linkage of these antigens suggests this system is analogous to the class II or Ia antigens of other species.
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PMID:Serological and genetic identification of a bovine B lymphocyte alloantigen system. 675 15

An increase in external K+ can generate contractile force in muscle, and K+ contractures are an established means to determine the effect of an agent on the relation between membrane potential and mechanical activity [8]. We have used K+-contractures to further test our hypothesis [5] that abnormal cell membrane potential responses are intrinsic to skeletal muscle of Poland China pigs susceptible to malignant hyperthermia (MHS), and a nervous system is not required to initiate malignant hyperthermia (MH). Recently it has been shown that K+-induced contractures in certain skeletal and cardiac muscles might not be determined only by cellular membrane potential changes predicted by the tendency for K+ to move in accord with its electrical and concentration gradients [3, 12]. We report here that normal and diseased skeletal muscles respond differently to raised external K+, which supports the idea that the onset of the MH syndrome is determined by a defect associated with a site in muscle cells superficial to the cytoplasm rather than, as has been suggested, within the cell or in the nervous system [7]. In addition, we find that porcine skeletal muscles, like certain other muscles, produce much less force in K+ than expected from our measurements of the relationship between membrane potential and external K+.
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PMID:Cellular membrane potentials and contractile threshold in mammalian skeletal muscle susceptible to malignant hyperthermia. 707 Jul 7

Height, weight, and skinfold thickness were measured on 82 patients prior to muscle biopsy which was performed to determine their susceptibility to malignant hyperpyrexia. Percentage body fat was calculated from the skinfold measurements. Using AP photographs six coronal diameters of the left thigh, equally spaced between the lower border of the patella and the perineum, were measured on another group of 90 patients referred for biopsy. The subjects were then divided into those who were susceptible to malignant hyperpyrexia (MHS) and those who were normal and acted as controls. Each group was separated into males and females. There was no significant difference in age between the MHS and the control groups. There was no difference between MHS and controls in height or weight but the percentage body fat in the MHS males was significantly lower than in the controls (P less than 0.02). The upper three thigh diameters in the MHS females were significantly greater than in the control group (P less than 0.05). There appears to be a difference in the leanness/fatness relationship and in the development of the thigh in MHS subjects compared with controls, but these differences are subtle and appear to vary with sex.
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PMID:Anthropometric studies of human subjects susceptible to malignant hyperpyrexia. 712 14

Resting metabolic rate and the energy cost of performing a specific (light work load on a bicycle ergometer were measured in nine subjects susceptible to malignant hyperpyrexia (MHS) and nine control subjects, both fasting and following a 600-kcal meal. Blood glucose, lactate, pyruvate and serum triglycerides, thyroxine, cortisol, creatine kinase, growth hormone, and calcium and potassium levels at rest and immediately following exercise, after fasting and eating, were measured. There was no evidence of increased heat production in the MHS subjects compared with controls. The MHS subjects, however, showed a complete absence of dietary-induced thermogenesis with exercise. Compared with the controls, MHS subjects had higher insulin levels for essentially the same blood glucose values. Triglycerides in the MHS group rose steadily over the course of the experiment, whereas in the controls they did not vary from the initial value. Lactate did not rise as much with exercise in the MHS group but did nor fall with rest, and pyruvate did not change from resting fasting values, whereas in the controls it rose steadily. Differences were also found in thyroxine and cortisol levels between the MHS and control groups. The shunting of blood away from thermogenic tissue is suggested as a mechanism for the absence of diet-induced thermogenesis with exercise in the MHS group and the possibility of an underlying abnormality of cardiovascular (sympathetic) control mechanisms in these subjects is discussed. The biochemical abnormalities are discussed in relation to previous biochemical data from MHS humans and pigs and in relation to the abolition of dietary-induced thermogenesis.
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PMID:Metabolic rate and blood hormone and metabolite levels of individuals susceptible to malignant hyperpyrexia at rest and in response to food and mild exercise. 724 57

1. Blood pressure was measured and plasma levels of noradrenaline and adrenaline were determined radioenzymatically under basal conditions and after 10% blood volume reduction in blood drawn through catheters previously implanted in young and adult rats of two different genetically hypertensive strains: the Kyoto strain (SHR) and the Milan strain (MHS), and in their respective controls: Wistar--Kyoto strain (WKY) and Milan normotensive strain (MNS). 2. Under basal conditions no differences were observed between plasma noradrenaline and adrenaline levels in SHR and MHS rats and in the controls, at any age. Haemorrhage produced a greater fall in the blood pressure (P less than 0.01) of young and adult hypertensive strains (SHR-MHS) than in WKY and MNS rats, and a greater rise in plasma adrenaline (P less than 0.01). 3. These results suggest that: (a) there may be differences in involvement of the sympathetic nervous system in the pathogenesis of hypertension in SHR and MHS rats but not such as to cause differences in plasma catecholamine levels in either young or adult rats; (b) haemorrhage activates the sympatho--adrenal systems more in SHR and MHS rats, than in controls, and the greater percentage fall in blood pressure is probably due to a difference in reflex venoconstriction.
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PMID:Plasma concentrations of catecholamines in two strains of spontaneously hypertensive rats at different ages. 731 24

The authors examined the thesis that a dose of dantrolene producing 95 per cent of maximal muscle relaxation (ED95) would effectively prevent or treat malignant hyperthermia (MH). In one group of four pigs sensitive to malignant hyperthermia (MHS) a dose response to intravenous dantrolene was determined by quantitation of toe twitch tension. From these data, the ED95 relaxant dose (3.5 mg/kg) was derived. In a second group of four MHS pigs, the ED95 dantrolene dose was administered prior to MH challenge with succinylcholine, 2 mg/kg, and halothane, 1.5 per cent. MH was prevented in each animal, while measurements of arterial pressure, arterial blood-gas, pH and lactate values, rectal temperature, and heart rate were done. Later, MH rapidly developed in the same four animals when they were again challenged. When treated with the ED95 dose, each animal survived. Finally, each pig was challenged without dantrolene prophylaxis or therapeusis, and all succumbed from MH. Previous studies have shown the efficacious use of dantrolene in prevention or treatment of porcine MH, but doses used have varied, without rationale. The present study shows that in MHS pigs the ED95 muscle relaxant dose of dantrolene (3.5 mg/kg) successfully prevents and treats MH.
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PMID:Dantrolene dose response in malignant hyperthermia-susceptible (MHS) swine: method to obtain prophylaxis and therapeusis. 736 49


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