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J Beech

Publications and source records attributed to J Beech.

At least 37 records · Page 2Linked to original sources
PubMed1995

Effect of phenytoin on skeletal muscle from quarter horses with hyperkalaemic periodic paralysis.

The contractile activity, the threshold for calcium-induced calcium release in fractions of sarcoplasmic reticulum and the potassium concentration were determined in preparations of semimembranosus muscle from normal quarter horses and quarter horses with hyperkalaemic periodic paralysis before and after they were treated with phenytoin. Before the treatment there was no difference in caffeine contracture or electrically elicited twitch response between the two groups. For one week after the treatment, the time to peak tension of caffeine contractures was significantly (P < 0.005) reduced in the horses with hyperkalaemic periodic paralysis but unchanged in the normal horses. The variance but not the mean values for the threshold for Ca(2+)-induced Ca2+ release from the sarcoplasmic reticulum was greater for the horses with hyperkalaemic period paralysis before but not after the treatment with phenytoin.

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PubMed1995

Sodium channel inactivation is impaired in equine hyperkalemic periodic paralysis.

1. Equine hyperkalemic periodic paralysis (E-HPP) is a dominantly inherited disorder of muscle that causes recurrent episodes of stiffness (myotonia) and weakness in association with elevated serum K+. Affected horses carry a mutant allele of the skeletal muscle isoform of the Na channel alpha-subunit. To understand how this mutation may cause the disease phenotype, the functional defect in Na channel behavior was defined physiologically by recording unitary currents from cell-attached patches on normal and affected equine myotubes. 2. The presence of the mutation was confirmed in our cell line by restriction digest of polymerase chain reaction (PCR)-amplified genomic DNA. Myotubes from the affected horse were heterozygous for the point mutation that codes for a Phe to Leu substitution in S3 of domain IV. This assay provides a rapid technique to screen for the mutation in horses at risk. 3. The primary physiological defect in mutant Na channels was an impairment of inactivation. This defect was manifest as bursts of persistent activity during which the channel closed and reopened throughout a maintained depolarization. Disrupted inactivation slowed the decay of the ensemble-averaged current and produced an eightfold increase in the steady-state open probability measured at the end of a 40-ms pulse. This point mutation identifies a new region of the alpha subunit that is important for rapid inactivation of the channel. 4. The persistent Na current was produced by a distinct mode of gating. Failure of a mutant channel to inactivate was infrequent and occurred in groups of consecutive trials.(ABSTRACT TRUNCATED AT 250 WORDS)

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PubMed1994

Myotoxin a reduces the threshold for calcium-induced calcium release in skeletal muscle.

Myotoxin a, isolated from the venom of the prairie rattlesnake Crotalus viridis viridis, induces necrosis in skeletal muscle. In isolated organelles, it has been reported that myotoxin a reduces Ca2+ uptake into the sarcoplasmic reticulum. The effects of the toxin on Ca2+ regulation were examined in heavy sarcoplasmic reticulum fractions from human and equine skeletal muscle. Ca2+ uptake and release (the threshold of Ca(2+)-induced Ca2+ release) were examined by dual wavelength spectrophotometry. The toxin lowered the threshold of Ca(2+)-induced Ca2+ release in a dose-dependent manner (1-10 microM) and this effect was antagonized by ruthenium red, a Ca2+ release channel blocker. Ca2+ uptake into equine heavy sarcoplasmic reticulum was not decreased by myotoxin a (10 microM) when Ca2+ release was blocked by ruthenium red. [3H]Ryanodine binding to equine heavy sarcoplasmic reticulum was converted from a relatively low affinity state to a higher affinity state by myotoxin a. These results suggest that the dominant effect of myotoxin a is to increase the Ca2+ sensitivity for the opening of the calcium release channel (ryanodine receptor). Myotoxin a may prove to be a useful tool to probe the modulation of calcium release in sarcoplasmic reticulum fractions.

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PubMed1994

Pathophysiology of sodium channelopathies: correlation of normal/mutant mRNA ratios with clinical phenotype in dominantly inherited periodic paralysis.

It is often suggested that polygenic or environmental factors are responsible for clinical variability between patients with identical mutations. However, most dominant diseases are caused by a change-of-function alteration in the mutant allele's protein product. All patients are heterozygous and presumably express both mutant and normal proteins from the corresponding genes. Thus, a possible molecular mechanism for clinical variability could be the difference in relative levels of mutant vs. normal mRNA in different patients with the same mutation. To investigate this hypothesis, it is necessary to have access to a series of tissue biopsies from many patients with the same mutation causing a clinically variable dominant disease. Human hyperkalemic periodic paralysis (HyperPP) has been shown to be a clinically variable disorder caused by change-of-function mutations of the skeletal muscle sodium channel protein. We recently identified a large (> 50,000) pedigree of affected Quarter Horses sharing the same causative amino acid alteration of the muscle sodium channel protein. The horses like humans show substantial clinical variability. In this report, we developed a fluorescent reverse transcription-polymerase chain reaction assay which quantifies the relative levels of normal and mutant mRNA expression of the horse adult skeletal muscle sodium channel gene in affected Quarter Horses. We found that asymptomatic horses showed more normal sodium channel mRNA, while moderately affected horses showed more mutant mRNA. The ratios of mutant/normal mRNA between these two groups are statistically different, suggesting that severity of HyperPP Quarter Horses may indeed be correlated to the ratio of mutant and normal sodium channel gene expression in skeletal muscle.

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PubMed1993

Disseminated Halicephalobus deletrix infection in a horse.

A 13-year-old Quarter Horse gelding was referred for evaluation of a draining tract and fracture of the right hemimandible of 4 weeks' duration. Two days prior to admission, the horse had developed pigmenturia. Radiography of the mandible revealed a fracture of the vertical ramus of the right hemimandible, loss of the right lower second premolar, and osteomyelitis involving an extensive portion of the hemimandible. Ultrasonography of the left kidney revealed loss of normal renal architecture. Histologic examination of tissue obtained from the right hemimandible revealed granulomatous osteomyelitis and multiple metazoan parasites identified as Halicephalobus deletrix. The horse was treated with antimicrobial and deworming agents, and the mandible was surgically debrided. The horse became atactic 8 days after surgery and was euthanatized. Necropsy identified parasitic migration in the right hemimandible, kidneys, and CNS.

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PubMed1993

Phenytoin increases specific triacylglycerol fatty esters in skeletal muscle from horses with hyperkalemic periodic paralysis.

Previous studies have demonstrated that phenytoin decreases the levels of triacylglycerols in several tissues other than skeletal muscle. Since phenytoin is clinically effective in several skeletal muscle disorders, triacylglycerol metabolism in skeletal muscle from four normal Quarter horses and four Quarter horses with hyperkalemic periodic paralysis was examined. The horses with hyperkalemic periodic paralysis had low levels of 18:3 in the phospholipids, low levels of 16:0, 16:1 and 18:3 in the free fatty acids and low levels of 20:4 in triacylglycerols. Triacylglycerol levels were increased in skeletal muscle from seven (three controls, four hyperkalemic periodic paralysis) of the eight horses on treatment with oral phenytoin for one week. Instead of an increase in all fatty ester types only 16:0, 16:1, 18:1 and 18:2 were significantly increased. Total lipid phosphorus and the distribution of phospholipid fatty esters and free fatty acids were not significantly altered by phenytoin treatment in most cases. An alteration in triacylglycerol metabolism by phenytoin was also observed in primary cultures of normal equine skeletal muscle radiolabeled with 18:1, but not in those radiolabeled with 18:2. These findings suggest that phenytoin does not just increase the levels of triacylglycerol in skeletal muscle, but alters the utilization and incorporation of fatty esters. These findings suggest a potential involvement of triacylglycerol metabolism in the clinical efficacy of phenytoin in hyperkalemic periodic paralysis.

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PubMed1993

Caffeine contractures, twitch characteristics and the threshold for Ca(2+)-induced Ca2+ release in skeletal muscle from horses with chronic intermittent rhabdomyolysis.

Muscle from horses with intermittent exercise associated rhabdomyolysis was examined to determine if calcium regulation was abnormal. In vitro studies on semimembranosus muscle fibre bundles showed the time to 50 per cent relaxation of caffeine-induced contractures was shorter and the electrically elicited twitch longer in horses with exercise associated rhabdomyolysis. Substitution of strontium for calcium eliminated the difference in caffeine contracture between the normal and rhabdomyolysis horses. The threshold of calcium-induced calcium release was lower than normal in terminal cisternae-containing fractions of muscle from horses with rhabdomyolysis. Thoroughbreds with rhabdomyolysis had a shorter time to peak twitch tension than standardbreds, and normal thoroughbreds had a shorter caffeine contracture than normal standardbreds. There was no difference in fibre typing between breeds or groups. Either no histological changes or low grade to moderate degenerative myopathy was seen in muscle from horses with rhabdomyolysis. These results suggest horses with intermittent exercise associated rhabdomyolysis have abnormal calcium regulation.

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PubMed1993

Potassium concentrations in muscle, plasma and erythrocytes and urinary fractional excretion in normal horses and those with chronic intermittent exercise-associated rhabdomyolysis.

Potassium concentrations were measured in semimembranosus muscle, plasma and erythrocytes, and the urinary fractional excretion determined in normal horses and those that had chronic intermittent exercise-associated rhabdomyolysis. Muscle from the rhabdomyolysis horses was also evaluated microscopically. The horses with rhabdomyolysis had a lower muscle potassium concentration on a dry weight basis. Although the wet weight potassium content was also lower, the difference was not significant. Urinary fractional excretion of potassium (and also sodium and chloride) did not differ significantly between the two groups although the rhabdomyolysis group had a lower percentage excretion of potassium. Erythrocyte potassium concentration was similar for both groups. Low grade to moderate degenerative myopathy or absence of lesions was seen on microscopic sections of muscle from horses with rhabdomyolysis; only one had a vacuolar myopathy and potassium content was not determined. These results suggest that altered muscle potassium content may be a factor in rhabdomyolysis.

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PubMed1993

Species difference in modulation of calcium release by Naja naja kaouthia snake venom cardiotoxin in terminal cisternae from human and equine skeletal muscle.

The modulation of Ca2+ release by a cardiotoxin (CTX) from Naja naja kaouthia snake venom was examined in terminal cisternae-containing fractions from equine and human skeletal muscle. Pretreatment with CTX (10 microM) decreased by 27% (human muscle), or had no effect on (equine muscle), the threshold of Ca(2+)-induced Ca2+ release. If terminal cisternae fractions were first preloaded with Ca2+ to greater than 65% of the threshold of Ca(2+)-induced Ca2+ release and then CTX added, an immediate and sustained release of Ca2+ occurred in preparations from both species. Addition of CTX after a Ca2+ preload of less than 60% of the threshold of Ca(2+)-induced Ca2+ release did not elicit Ca2+ release in preparations from either species. Ruthenium red (10 microM) antagonized CTX-induced Ca2+ release, whereas dantrolene (10 microM) did not. These findings suggest that the effects of CTX on the Ca2+ release channel are dependent on Ca2+ preload and that CTX may be an important probe of the Ca(2+)-modulated Ca2+ release process and in understanding regulation of Ca2+ release in skeletal muscle from different species.

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PubMed1993

Malignant hyperthermia: halothane- and calcium-induced calcium release in skeletal muscle.

The temperature dependence of oleic acid-enhanced halothane- induced Ca2+ release and the existence of a reduced threshold of Ca(2+)-induced Ca2+ release were examined to determine their roles in human malignant hyperthermia. Halothane (8-11 mM) induced Ca2+ release from terminal cisternae-containing preparations from skeletal muscle. Oleic acid (15 microM) markedly reduced the threshold of halothane-induced Ca2+ release to < 0.5 mM at 37 degrees C, but not at 25 degrees C, consistent with the temperature dependence of halothane action in intact muscle. Two states of the threshold of Ca(2+)-induced Ca2+ release were unrelated to malignant hyperthermia in humans, in contrast to pigs. Excess fatty acid production may be an important modulator of halothane action in malignant hyperthermia.

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PubMed1992

Effects of phenytoin in two myotonic horses with hyperkalemic periodic paralysis.

The effects of phenytoin treatment were evaluated in 2 myotonic horses with hyperkalemic periodic paralysis (HPP). Phenytoin treatment abolished the clinical signs of muscle fasciculations following oral potassium challenge and decreased or abolished repetitive firing and myotonic discharges found on electromyographic examination. In both horses, an abnormally low threshold for calcium-induced calcium release was measured in heavy sarcoplasmic reticulum fractions from skeletal muscle, and this threshold increased with phenytoin treatment. Results suggest phenytoin is useful in modifying disordered ion regulation in the sarcolemma and sarcoplasmic reticulum of skeletal muscle in equine hyperkalemic periodic paralysis.

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PubMed1992

Bee venom melittin is a potent toxin for reducing the threshold for calcium-induced calcium release in human and equine skeletal muscle.

The modulation of Ca2+ release by synthetic bee venom melittin was examined in equine and human terminal cisternae-containing fractions. Melittin (0.1 microM) decreased the threshold of Ca(2+)-induced Ca2+ release by 20% in equine muscle and by 36% in human muscle. If terminal cisternae fractions were first preloaded with Ca2+ to greater than about 75% of the threshold of Ca(2+)-induced Ca2+ release and then melittin added, an immediate and sustained release of Ca2+ occurred in preparations from both species. Addition of melittin after a Ca2+ preload of < 50% of the threshold of Ca(2+)-induced Ca2+ release did not elicit sustained Ca2+ release. Ruthenium red (10 microM) antagonized all effects of melittin on Ca2+ release. Melittin (0.1-10 microM) did not affect [3H]ryanodine binding. Melittin (0.1 microM) slightly (10%) inhibited the Ca2+ pump and this action was not antagonized by ruthenium red. These findings suggest that melittin may be an important new probe of the Ca(2+)-modulated Ca2+ release process that does not act at the ryanodine binding site.

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PubMed1991

Use of manual stimulation for collection of semen from an atactic stallion unable to mount.

A 9-year-old atactic breeding stallion was trained to ejaculate, with only manual stimulation, while standing on the ground. Ejaculates obtained yielded fertile semen with morphologic and motility characteristics within the range for normal stallions. This method extended the breeding life of a stallion unable to mount a live or dummy mare or to ejaculate into an artificial vagina while standing on the ground.

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PubMed1991

Azathioprine for treatment of immune-mediated thrombocytopenia in two horses.

Azathioprine, a thiopurine antimetabolite used in the treatment of immune-mediated thrombocytopenia in human beings and dogs, was used in 2 cases of immune-mediated thrombocytopenia in horses that failed to respond to corticosteroid therapy alone. Platelet counts were increased to acceptable values in both horses. One horse returned to a successful racing career, and the other was euthanatized after developing renal disease and mild laminitis.

Animals↗
PubMed1991

Aerobic and anaerobic bacterial isolates from horses with pneumonia or pleuropneumonia and antimicrobial susceptibility patterns of the aerobes.

Frequency of aerobic and anaerobic isolates in 327 aspirates and in 123 pleural fluid samples from 327 horses with pneumonia or pleuropneumonia and antimicrobial susceptibility patterns of the aerobes were reported. Of the 327 horses, 75% survived, 20% were euthanatized, and 5% died. Tracheobronchial aspirates or pleural fluid specimens from 25 of the horses did not yield growth. Of the remaining 302 horses, 221 had only aerobic organisms isolated, whereas only anaerobes were isolated from 6 of the 302 horses. The remaining 75 horses had mixed aerobic and anaerobic bacterial infections. The survival rates for horses with aerobic only isolates was twice that of horses with anaerobic isolates. The aerobic bacteria most frequently isolated were beta-Streptococcus spp, Pasteurella spp, Escherichia coli, and Enterobacter spp. The anaerobic species most frequently isolated were Bacteroides spp and Clostridium spp.

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