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Biomedical subjects

T E Nelson

Publications and source records attributed to T E Nelson.

At least 91 records · Page 5Linked to original sources
PubMed1979

Does prior dantrolene affect the in vitro diagnosis of malignant hyperthermia susceptibility?

A therapeutic and prophylactic dose of dantrolene administered to malignant hyperthermia-susceptible pigs had no effect on the abnormal in vitro contracture response of subsequent muscle biopsies. The in vitro contracture response of MHS pig muscle to halothane and to caffeine was not altered by prior dantrolene treatment. It is concluded that prior dantrolene administration has no effect on the discrimination of porcine MSH by in vitro pharmacological testing.

Animals↗
PubMed1979

Rationale for dantrolene vs. procainamide for treatment of malignant hyperthermia.

The use of procainamide or procaine for treatment of malignant hyperthermia is commonly recommended. The skeletal muscle relaxant dantrolene has also been indicated for treatment of this complication during anesthesia. In the present study, effects of procainamide and dantrolene were compared in malignant hyperthemia-susceptible (MHS) pigs in vivo and on MHS muscle from human patients in vitro. The ED50 for dantrolene block of indirectly evoked twitch tension was 0.85 mg/kg in MHS pigs. A final cumulative dose of 2 mg/kg resulted in 68 per cent block of the twitch response. In contrast, procainamide at a final cumulative dose of 14 mg/kg had no effect on twitch response of the MHS pigs. Dantrolene, 3 micrometer, in vitro (approximately 0.8 mg/kg in vivo) was effective in preventing or reversing the abnormal halothane-induced contracture response of human MHS muscle strips. Procainamide, 0.11 mM, a dose approximating clinical levels (about 22 mg/kg), had no effect on basal twitch response or on the abnormal halothan-induced contracture of MHS human muscle. These results confirm the effectiveness of dantrolene and the lack of effectiveness of procainamide in the treatment of malignant hyperthemia.

Animals↗
PubMed1979

Temperature perturbation studies of sarcoplasmic reticulum from malignant hyperthermia pig muscle.

The effects of varying temperatures from 25 degrees to 37 degrees C on calcium binding characteristics of sarcoplasmic reticulum from malignant hyperthermia-susceptible (MHS) and control pig muscle were examined. Two groups of MHS pigs were included: those with high susceptibility to malignant hyperthermia (MHS group) and a cross-bred, less susceptible group (MHX). At 25 degrees C, calcium binding was lower for MHS than for controls and MHX. As temperature was increased by 2 degrees C jumps, calcium binding decreased in all sarcoplasmic reticulum fractions. At 35 degrees C a sharp decrease in calcium binding occurred in the MHS and MHX fractions. The sharp decrease in calcium binding at 35 degrees C differentiated the MHS and MHX fractions from controls. The initial velocity (Vi) for calcium binding was lower in MHS fractions between 25 degrees and 35 degrees C when compared with MHX and controls. All fractions had increased Vi values as temperature increased from 25 degrees to 35 degrees C. From 35 degrees to 39 degrees Vi for controls increased markedly. In contrast, Vi for the MHX fraction decreased as temperature exceeded 35 degrees C. These temperature effects on calcium binding characteristics of sarcoplasmic reticulum from MHS and MHX muscle may be indicative of a membrane transition that impairs calcium binding.

Animals↗
PubMed1979

Malignant hyperthermia: diagnosis, treatment and investigations of a skeletal muscle lesion.

A center for the diagnosis and research for malignant hyperthermia is established within the Research Division of the Department of Anesthesiology at the University of Texas Medical Branch, Galveston, Texas. In this Research Conference we define malignant hyperthermia, present its brief history, and describe the diagnostic procedures and directions of research in our laboratory. Although rare in occurrence, malignant hyperthermia is a significant disease entity because it (a) has a high morbidity and mortality; (b) is of genetic basis; and (c) for lack of a simple diagnostic test, it's occurrence is unexpected. The primary defect appears to occur in skeletal muscle, thus the diagnostic test and research efforts center upon abnormal pharmacologic and biochemical responses of skeletal muscle from affected subjects.

Anesthetics↗
PubMed1978

Cystic fibrosis: isolation and physical properties of a salivary cystic fibrosis factor.

A ciliostatic factor has been isolated from cystic fibrosis (CF) saliva by dialyzing it from purified alpha-amylase prepared by a glycogen-complex method. This method of isolating the CF factor is an improvement over the previously employed heparin procedure. The activity of the isolated factor is proportional with concentration using the oyster gill ciliostatic assay and in its inhibition of mammalian glycogen debranching enzyme. The ciliostatic action of the factor can be reversed by heparin under certain conditions. The type of inhibition of the debranching enzyme by the isolated CF factor indicates that its chemical structure is similar to that observed with hydroxyalkylamines and polyamine metabolites. Physical properties of the isolated factor indicate that it is of low molecular weight and is labile as a function of pH and temperature. At neutral pH the conditions under which it is maintained have a direct effect on the length of time that it is stable.

Animals↗
PubMed1977

Screening for malignant hyperpyrexia.

Skeletal muscle from normal human subjects produced linear contracture responses in vitro to caffeine at concentrations of between 4 and 32 mmol/litre. In the presence of 0.4% halothane, caffeine contractures were greater but the magnitude of halothane potentiation decreased as the caffeine concentration was increased. The contractures produced by caffeine 4 and 8 mmol/litre at 37 degrees C were significantly reduced by decreasing the temperature of the incubation solution to 25 degrees C. Among 57 normal subjects, 18% had fibres which responded to halothane treatment with contracture. On the basis of these findings, it is suggested that screening for malignant hyperpyrexia by in vitro pharmacological testing of skeletal muscle should be carried out at 37 degrees C, and should include exposure of the sample to halothane, caffeine, suxamethonium and potassium rather than to halothane alone.

Caffeine↗
PubMed1977

Estrogen and prothrombin synthesis: effect of estrogen on absorption of vitamin K1.

Intact male and female albino rats fed a vitamin K-deficient diet develop a plasma prothrombin-proconvertin deficiency. Male rats respond with a precipitous drop to approximately 20-30% of normal plasma levels within 2-5 days, whereas female rats respond at a slower rate. Ethynylestradiol, 5-10 mug/day, or castration, reduces the progressive decline of plasma prothrombin-proconvertin seen in nonsupplemented intact male rats. The response of castrate females differs little from the response of intact females. Ethynylestradiol, 5-10 mug/day, affects both castrate males and females similarly, limiting the prothrombin-proconvertin decrease to about 13% below control value after 14 days. Intestinal absorption of vitamin K1 measured in the thoracic duct lymph of pentobarbital-anesthetized castrate male and female rats was shown to increase significantly after estrogen treatment. Estrogen-treated castrate male and female rats absorbed 25.8 mug and 11.8 mug vitamin K1, respectively. Nontreated control castrate male and female rats absorbed 0.0 mug and 1.2 mug, respectively, during a 240-min collection period. Use of radioactive vitamin K1 in similar experiments confirmed these results. Estrogen-treated castrate males absorbed vitamin K1 at the rate of 30-40 mug/g lymph whereas nontreated control males absorbed only about 6 mug/g lymph.

Animals↗
PubMed1976

Association of gylcogenolysis with cardiac sarcoplasmic reticulum.

Sarcoplasmic reticulum fragments isolated from dog cardiac muscle possess a calcium-accumulating system associated with a series of enzymes linked to glycogenolysis. These enzymes include: adenylate cyclase, cyclic AMP-dependent protein kinase, phosphorylase b kinase, phosphorylase (b/a, 30/1),"debrancher" enzyme, and glycogen (0.3 to 0.7 mg/mg of protein). The sarcoplasmic reticulum preparation produced glucose 1-phosphate and glucose from either endogenous or exogenous glycogen. Both the calcium-accumulating and glycogenolytic enzymes sediment in a single peak at 33% sucrose on a linear continous sucrose density gradient, and the complex remains intact throughout repeated washing. Glycogen particles appear to be associated with the sarcoplasmic reticulum in situ as well as in the isolated microsomal fraction. The sarcoplasmic reticulum-glycogenolytic complex, monitored by a linked enzyme spectrophotometric assay, shows several features: (a) activation of phosphorylase activity to peak rate occurs over a very rapid time course which cannot be duplicated using combinations of purified enzymes; (b) activation is inhibited by protein kinase inhibitor; (c) phosphorylase b functions as in the purified form with respect to AMP (Km, 0.3 mM); (d) in the presence of limiting amounts of glycogen, optimal phosphorylase b activity in the sarcoplasmic reticulum requires the presence of debrancher, and the activity is sensitive to inhibitors of that enzyme such as Tris, which suggests the possiblity that the enzymes bear a specific structual relationship to the glycogen present. Phosphorylase b leads to a activation in the sarcoplasmic reticulum was completely resistant to ethylene glycol bis(beta-aminoethyl either)-N,N'-tetraacetic acid (EGTA). Inhibition of calcium accumulation by or release of bound calcium from sarcoplasmic reticulum by X537A (RO 2-2985) did not alter the EGTA resistance. These results suggest that cardiac sarcoplasmic reticulum is a complex organelle containing functions that may be related to excitation-contraction coupling and intermediary metabolism.

Adenosine Monophosphate↗
PubMed1976

Cystic fibrosis: enzymatic detection of a ciliostatic factor.

The ciliostatic cystic fibrosis (CF) factor has been investigated in order to develop an enzymatic assay for its detection. In saliva, this factor is associated with alpha-amylase. Removal or addition of the factor by dialysis does not affect the alpha-amylase catalytic activity of CF or control (normal) saliva. Crude preparations of the dialyzable factor from CF saliva are ciliostatic. Alpha-Amylase-catalyzed starch hydrolysis from both CF and control saliva was found to be insensitive to hydroxyalkylamine inhibitors so this method could not be used to detect differences in CF and control amylase. Since another carbohydrase, mammalian debranching enzyme, is much more sensitive to inhibition, the effect of the isolated crude factor on this enzyme was determined. The mean values for percentage of inhibition of debranching enzyme activity by fractions obtained from saliva of CF patients, obligate heterozygotes, and control subjects are: 32% (27 samples), 13% (21 samples), and 6% (11 samples), respectively. Fifteen of the CF values exceed the maximum 13% inhibition observed for controls. Indeed, five samples almost completely inhibited debranching enzyme. This inhibitory action provides the basis of an enzymatic assay for the detection of the ciliostatic CF factor.

Amylases↗
PubMed1975

Analytical gel chromatography of rabbit muscle amylo-1,6-glucosidase/4-alpha-glucanotransferase under denaturing and non-denaturing conditions.

Rabbit muscle amylo-1,6-glucosidase/4-alpha-glucanotransferase has a molecular weight of 160 000-170 000 as determined by analytical gel chromatography under denaturing and non-denaturing conditions. Three different data analyses of the results of gel chromatography in the presence of 6 M guanidine-HCl on 4% agarose give values of 159 000, 161 000, and 165 000 for amylo-1,6-glucosidase/4-alpha-glucanotransferase from rabbit muscle. Analytical gel chromatography under non-denaturing conditions gives a value of 170 000 for the molecular weight and a value of 4.8 nm for the Stokes'' radius. A calculation based on the Stokes radius using the Svedberg equation gives a value of 160 000 for the molecular weight. This verifies by two independent methods the previously reported molecular weight for the protein using sodium dodecyl sulphate-polyacrylamide gel electrophoresis. The results establish that the mammalian debranching enzyme is a single polypeptide chain containing two enzymatic activities.

Animals↗
PubMed1975

The attack mechanism of an exo-1,3-beta-glucosidase from Basidiomycete sp. QM 806.

The attack mechanism of a purified exo-1,3-beta glucosidase (1,3-beta-D-glucan glucohydrolase, EC 3.2.1.58) was investigated by using as a substrate a mixture of two structurally characterized periodate-oxidized and reduced unbranched 1,3-beta-D-glucans which differed only at the reducing terminal. The substrates, derivatives of laminarin, were altered only at the terminals due to resistance of the internal (1 leads to 3)-linked glucosyl residues to periodate oxidation. Each glucan has only a single and identical altered non-reducing terminal per molecule. Upon enzymatic hydrolysis, one molar equivalent of glycerol was produced from the altered non-reducing terminal of each substrate molecule attacked. Using glycerol as an indication of the number of chains acted upon, the quantity of D-glucose produced from the internal residues was used to determine the extent to which a chain was initially attacked. The glucose to glycerol ratio during the course of the hydrolysis indicates that the enzyme proceeds by a multiple-attack mechanism where four glucosyl residues are successively removed per encounter from the non-reducing terminal of each substrate molecule.

Basidiomycota↗
PubMed1975

Porcine malignant hyperthermia: effects of temperature and extracellular calcium concentration on halothane-induced contracture of susceptible skeletal muscle.

Skeletal muscle from malignant hyperthermic (MH) pigs incubated at 37 C in 2.3 mM calcium-Krebs-Ringer solution contracts spontaneously when exposed to halothane. In contrast, halothane did not induce contracture in MH muscle incubated in 2.3 mM calcium-Krebs-Ringer solution at 25 C or in calcium-free Krebs-Ringer's solution at 37 C. Halothane did not induce contracture in normal control muscle in 2.3 mM Krebs-Ringer solution at 25 or 37 C. In the presence of halothane, addition of caffeine produced greater contracture in MH muscle than in normal controls. Halothane-caffeine-induced contractures of MH and control muscles at 25 and 37 C were similar. Elucidation that under certain experimental conditions halothane induces contracture in MH muscle, but not in normal muscle 1) may aid in development of a diagnostic test; 2) establishes further evidence for skeletal muscle as the target tissue for anesthetic-induced MH; 3) suggests that halothane may affect systems that regulate sarcoplasmic calcium concentration below contracture threshold in MH muscle. (Key words: Hyperthermia, malignant; Anesthetics, volatile, halothane; Ions, calcium; Muscle, skeletal, malignant hyperthermia.).

Animals↗