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)

Rats of the Milan Normotensive Strain (MNS) develop a dyslipoproteinemia that is associated with a spontaneous, age-dependent and slowly progressive nephropathy characterized by proteinuria and hypoalbuminemia (nephrotic syndrome). We assumed that the MNS strain might be a suitable model for studying the features of nephrotic dyslipoproteinemia and its relationship with proteinuria, hypoalbuminemia, and hepatic apolipoprotein production. Plasma lipoproteins were investigated in MNS rats at various ages (4-48 weeks) and in another rat strain (Milan Hypertensive Strain, MHS), genetically related to MNS but free of nephropathy, that was used as control. In MNS rats, abnormal proteinuria was detectable at 20 weeks and increased 2-fold up to 34 weeks with no reduction of plasma albumin (compensated stage). During this stage we found increased levels of plasma cholesterol (+ 34%), high density lipoprotein-1 (HDL1) (+ 73%), and HDL2 (+ 31%) that were positively correlated with proteinuria but not with plasma albumin. The later stage (34-48 weeks) (nephrotic stage) was characterized by a further increase of proteinuria, moderate hypoalbuminemia (- 25%), a 2-fold increase of plasma cholesterol, triacylglycerols, low density lipoprotein (LDL), and HDL1, and a 1.2-fold increase of HDL2. In this stage the levels of LDL, HDL1, and HDL2 were positively correlated with proteinuria, and negatively correlated with plasma albumin. The most striking change in apolipoproteins was a progressive increase of the relative content of apoA-I in HDL (in 48-week-old MNS rats the A-I/E ratio was 3-fold that found in MHS rats) that was associated with a similar increase of plasma apoA-I. None of these lipoprotein changes were observed in age-matched MHS rats. At the end of the compensated stage, the hepatic levels of A-I, B, A-II, and albumin mRNA were 5.3-, 3.5-, 1.3-, and 2.0-fold, respectively, those found in age-matched MHS rats. During the nephrotic stage, albumin mRNA continued to increase, whereas A-I, B, and A-II mRNAs decreased toward the levels found in age-matched MHS rats. Thus, nephrotic dyslipoproteinemia in MNS rats starts to develop in the compensated stage before the onset of hypoalbuminemia, is characterized by an early elevation of HDL1 + HDL2, and is associated with an increased content of hepatic mRNAs of some apolipoproteins, especially apoA-I. The slow progression of nephrotic syndrome with the long-standing proteinuria and no reduction in plasma albumin renders the MNS strain the most suitable animal model for the study of the effect of proteinuria on plasma lipoprotein metabolism.
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PMID:Dyslipoproteinemia in an inbred rat strain with spontaneous chronic progressive nephrotic syndrome. 179 47

The distribution of the sperm protein SP-10 was investigated in plastic-embedded samples of human testes by light and electron microscopy. An immunogold and silver enhancement technique, in conjunction with a monoclonal antibody (MHS-10) raised against SP-10, was used to localize the protein. SP-10 was detected in spermatids at each of the six stages of the cycle of the seminiferous epithelium. Light microscopy showed immunoreactive material at the circumference of developing acrosomes in the early steps of spermiogenesis. As differentiation proceeded and cell shape changed from round to elongated, immunoreactive material appeared in an arc, which gradually became a V shape bordering the spermatid nucleus. The area of the immunoreactive material and its shape corresponded to that of the developing acrosome. At the electron microscopic level, gold particles indicative of the presence of SP-10 were detected on electron-dense material found within the developing acrosomal vesicle in early steps of spermiogenesis. As the electron density of the acrosome increased, a high concentration of gold particles was seen in the vesicle matrix. The gold particles gradually became associated with the inner and outer acrosomal membranes of the most mature spermatids.
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PMID:Localization of sperm antigen SP-10 during the six stages of the cycle of the seminiferous epithelium in man. 186 40

Central core disease of muscle (CCD; MIM 117000) is a rare inheritable myopathy that is frequently found in association with susceptibility to malignant hyperthermia (MHS). This observation has prompted us to perform a linkage study in CCD families using various chromosome 19q probes that are linked to the MHS locus and map close to the ryanodine receptor gene (RYR1), a strong MHS candidate gene. Our genetic linkage data support a location of the CCD gene on proximal 19q13.1 and thus suggest that CCD and MHS may be allelic.
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PMID:Evidence for linkage of the central core disease locus to the proximal long arm of human chromosome 19. 188 18

The intra- and postoperative course of 30 general and 3 regional anesthetics in 27 MH-carriers verified by in vitro contracture tests is reported. None of the patients received dantrolene prophylactically. Disposable tubings were used for ventilation, vaporizers and soda lime were removed. ECG, esophageal temperature, blood pressure, oxygen saturation, and end tidal pCO2 were monitored. Minor tranquilizers were offered for premedication. Fentanyl, thiopentone, nitrous oxide, non depolarizing relaxants, neuromuscular antagonists and naloxone were used. In three patients, surgery was performed during epidural or spinal anesthesia with the use of amide local anesthetics. Neither MH-related changes in perioperative heart rates, body temperatures, and CK levels nor any other symptoms of MH were observed in any patient. The anesthetic techniques used seem to be safe and reliable; the anesthetic management of known MHS patients is discussed in detail.
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PMID:Anesthesia in malignant hyperthermia susceptible patients. 197 53

Six subjects susceptible to malignant hyperthermia (MHS) and seven control subjects exercised for 4 min at 120% of their calculated maximal oxygen uptake on a bicycle ergometer. Mean (SEM) muscle pH, measured with a needle-tipped electrode in the vastus lateralis muscle, decreased from a resting value of 7.16 (0.04) to 6.78 (0.04) after exercise in the control group, and from 7.15 (0.05) to 6.56 (0.05) in the MHS group (P less than 0.01 compared with control group). A further decrease in muscle pH to 6.68 (0.06) by 5 min after exercise occurred in the control group, followed by incomplete recovery to 7.06 (0.04) 30 min after exercise. In the MHS group, however, muscle pH decreased to 6.45 (0.05) 5 min after exercise before recovering slowly to only 6.64 (0.07) after 30 min (P less than 0.01 compared with control group). There was no difference in muscle temperature, venous pH or venous lactate concentrations between the two groups. The results show that there is abnormal recovery of muscle pH after short-duration, high-intensity exercise in MHS subjects.
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PMID:Delayed recovery of muscle pH after short duration, high intensity exercise in malignant hyperthermia susceptible subjects. 203 10

Differences genetically associated with the development of hypertension in a strain of genetically hypertensive rat (MHS) were described in ion transport across erythrocyte membranes compared to normotensive control (MNS). Antibodies against the MNS ghost proteins were raised in the MHS, producing an immunoreaction against a 105 KDa protein later identified as adducin. A clone coding for a portion of mouse adducin was isolated with these antibodies. Using this clone, overlapping cDNA clones coding for a 63 KDa adducin-like protein were isolated. A family of related mRNAs of about 3500, 3800, 4200 nt, was found to be present in spleen, kidney and heart tissues. Similar mRNAs and an additional tissue specific 8000 nt mRNA are present in brain. All mRNAs seem to be generated by alternative splicing from the transcript of a single gene. An interesting polymorphism, a Gln to Arg substitution, was detected in the carboxiterminal area of rat adducin 63.
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PMID:Molecular cloning of an adducin-like protein: evidence of a polymorphism in the normotensive and hypertensive rats of the Milan strain. 205 21

The region of intron A of the rat renin gene containing a unique tandemly repeated sequence was analysed in the Milan and Lyon hypertensive rat strains and their controls, and in several Sprague-Dawley rats, using an oligonucleotide probe complementary to the tandemly repeated sequence and a renin complementary DNA probe. In the Milan rats, the size of the Bgl II DNA fragment encompassing the tandem repeat region was the same in the hypertensive (MHS) and normotensive (MNS) strains. In the Lyon model, a difference of 1.1 kilobase (equivalent to about 28 copies of the 38 basepair tandem repeat sequence) was observed in the size of the Bgl II fragment of the hypertensive (LH) and normotensive (LN) strains. However, the finding that the size of the fragment in the Lyon low-blood-pressure (LL) strain was the same as that in the LH strain rather than the LN strain suggests that the difference between the two latter strains is not by itself a major cause of the blood pressure difference between them in the intron A tandem region. An analysis of Sprague-Dawley rats, from which the Lyon strains are derived, showed that at least three different renin gene alleles, two with Bgl II fragments of the same size as those seen in the Lyon strains, are randomly segregating in this population.
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PMID:Analysis of the renin gene intron A tandem repeat region of Milan and Lyon hypertensive rat strains. 217 69

In this review, constituting the 1990 International Lecture of the Biophysical Society, research is described in two areas in which molecular genetic techniques were used to dissect problems related to sarcoplasmic reticulum proteins: the use of site-directed mutagenesis to gain insight into the mechanism of Ca2+ transport by the Ca2(+)-ATPase; and the use of cloning and genetic linkage analysis to identify the Ca2+ release channel (RYR1) gene as a candidate gene for the predisposition to malignant hyperthermia, a neuromuscular disease of humans and domestic animals.
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PMID:Molecular tools to elucidate problems in excitation-contraction coupling. 217 55

Normotensive rats of the Milan strain (MNS) spontaneously develop focal glomerulosclerosis. In order to explore the contribution of glomerular thromboxane (TX) A2 synthesis to the development of the disease, we have characterized the time course of renal functional and biochemical changes, and their modification by long-term treatment with a TX-synthase inhibitor. Oral administration (150 mg.kg-1 from 1 to 14 months of age) of FCE 22178 suppressed enhanced glomerular TXB2 production at all experimental times (mean inhibition 80%) and proteinuria (varying between 27.1 and 73.0%) while preserving renal blood flow and glomerular filtration rate. These effects of TX-synthase inhibition were seen in the absence of any statistically significant changes in systemic blood pressure. Moreover, FCE 22178 had no antihypertensive effects in hypertensive rats of the Milan strain (MHS) nor in spontaneously hypertensive rats (SHR). Treatment also prevented the age-related hypoalbuminemia and hyperlipidemia observed in control MNS and significantly (P less than 0.01) reduced glomerular histologic damage, as demonstrated by light microscopy studies and measurement of sclerotic area. We conclude that: 1) MNS rats provide an animal model of long-lasting proteinuria characterized by an age-related increase in glomerular TXB2 production paralleled by progressive loss of renal structural integrity and function and by a secondary dyslipidemia; 2) pharmacological inhibition of glomerular TX-synthase attenuates the structural as well as the functional expression of kidney disease, without a primary effect on systemic blood pressure. These data are suggestive of an important modulating role of TXA2 in the progression of MNS renal disease.
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PMID:Role of enhanced glomerular synthesis of thromboxane A2 in progressive kidney disease. 223 87

It is generally assumed that the brain is not primarily involved in the development of a malignant hyperthermia syndrome (MH). However, spontaneous brain electrical activity (EEG) has not been related temporally to the development of haemodynamic, respiratory and metabolic changes during a fulminant MH crisis. In the present study cerebral blood flow (CBF) and spontaneous electroencephalogram (EEG) were recorded in 8 pigs susceptible (MHS) for the development of malignant hyperthermia and 8 non-susceptible pigs (nMHS) after exposure to 1% halothane. Power densities in selected frequency bands were calculated from the EEG. Additionally, body temperature and haemodynamic and blood gas parameters were studied over a period of 60 min. MH was triggered in all MHS animals. Following exposure to halothane initial EEG changes were noted after 20 to 30 min. They consisted of a decrease in total power and a shift to lower frequencies (delta-theta activity). At this time, CBF was significantly increased compared to control. In 4 animals an isoelectric EEG was noted at a PaO2 of 65-78 mmHg and PaCO2 of 52 to 64 mmHg. Characteristic changes for the development of an MH syndrome in haemodynamic and respiratory parameters as well as a rise in body temperature occurred after first EEG changes were seen. Our results do not support the hypothesis that early EEG changes during MH occur as a result of systemic hypotension, hypoxaemia, hypercapnia or cerebral ischaemia. Our data indicate that EEG monitoring in combination with monitoring of haemodynamic, respiratory and metabolic parameters may be of value for an early detection of an MH-crisis.
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PMID:[Characteristics of cerebral blood flow and the electroencephalogram during experimental malignant hyperthermia]. 225 75


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