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Biomedical subjects

M J Jackson

Publications and source records attributed to M J Jackson.

At least 163 records · Page 9Linked to original sources
PubMed1989

Proton efflux from rat intestinal basal-lateral membrane vesicles is stimulated by ATP and Na+.

1. ATP-stimulated 22Na uptake and 14C-methylamine efflux were studied in inside-out rat intestinal basal-lateral membrane vesicles (BLMV). 2. Uptake of 22Na by basal-lateral membrane vesicles was stimulated by addition of ATP and by an acidic vesicle interior. 3. Efflux of 14C-methylamine was stimulated by ATP and Na+. 4. 14C-methylamine efflux was not influenced by vanadate or amiloride by themselves but was inhibited by the presence of both agents. 5. These data are consistent with a basal-lateral proton translocation mechanism which may be responsible for alkalinization of the lateral intercellular space and implicates the Na+-pump in this mechanism.

Adenosine Triphosphate↗
PubMed1989

Effect of mazindol on dystrophic mice and on growth in young rats.

1. Mazindol, which has been proposed as a therapy for muscular dystrophy because of a suppression of growth hormone release was administered orally (0.1 mg/kg body wt/day) for approximately six weeks to healthy young rats and dystrophic mice. 2. Mazindol had no effect on the dystrophic mice. 3. Mazindol treated rats had reduced wt gain, but this effect was due to appetite suppression not growth hormone inhibition. 4. No effect of mazindol was seen on rat muscle, but there were significant increases in liver, heart and kidney wts compared to controls.

Animals↗
PubMed1989

Isoforms of creatine kinase: MM in the study of skeletal muscle damage.

Isoforms of creatine kinase (CK) MM have been analysed in plasma from normal subjects and patients with muscular dystrophy using isoelectric focusing techniques. Most plasma samples analysed contained three isoforms of CK-MM of isoelectric points 7.26 (MMI), 6.85 (MMII) and 6.45 (MMIII) although in some plasma samples two additional isoforms of isoelectric points 7.12 and 6.65 were seen. Patients with muscular dystrophy were found to have a generally higher proportion of CK-MMI in their plasma than normal subjects and this was relatively unaffected by large variations in the total creatine kinase activity. By comparison eccentric exercise in normal subjects was found to result in a large increase in total plasma CK activity which then declined to normal over a period of approximately 6 days. CK-MMI was found to increase initially followed by CK-MMII and CK-MMIII. Analysis of the isoforms in biopsy samples of human muscle revealed the presence of two of the bands found in plasma (CK-MMI and MMII) and a third muscle specific isoform, while incubation of muscle homogenates in plasma induced the formation of CK-MMIII and the two isoforms of pI 7.12 and 6.65. It is concluded that analyses of CK-MM isoforms in human plasma can provide useful information on the extent and relative time course following an episode of muscle damage but that in patients with muscular dystrophy the large variations in plasma CK activity are not reflected in the proportion of CK found in each isoform.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

A double-blind controlled trial of long chain n-3 polyunsaturated fatty acids in the treatment of multiple sclerosis.

A trial of n-3 polyunsaturated fatty acids in the treatment of multiple sclerosis has been conducted over a 5 year period. Ambulant patients (312) with acute remitting disease were randomly allocated to treatment or placebo. Both groups were given dietary advice to increase the intake of n-6 polyunsaturated fatty acids and the treatment group in addition received capsules containing n-3 polyunsaturated fatty acids. Analysis of clinical outcome at the end of 2 years of treatment was made in terms of the duration, frequency and severity of relapses and the number of patients who had improved or remained unchanged. The results showed no significant difference at the usual 95% confidence limits but there was a trend in favour of the group treated with n-3 polyunsaturated fatty acids in all parameters examined.

Adipose Tissue↗
PubMed1989

Selenium metabolism and supplementation in patients with muscular dystrophy.

We studied selenium metabolism in patients with Duchenne muscular dystrophy and in contrast to previous reports found no significant abnormalities in these patients. Supplementation of muscular dystrophy patients and control subjects with sodium selenite (1 mg selenium/day) induced a variable rise in the activity of the selenium-dependent enzyme glutathione peroxidase in plasma and red cells, but no significant change in muscle glutathione peroxidase activities. There was no effect of selenium supplementation on disease activity in the patients with muscular dystrophy. Thiobarbituric acid-reacting substances (an index of free radical-mediated lipid peroxidation) were elevated in the muscle of patients with Duchenne muscular dystrophy in contrast to patients with other forms of muscular dystrophy and control subjects. This elevation was unaffected by selenium supplementation.

Clinical Trials as Topic↗
PubMed1989

Analysis of deletions at the human argininosuccinate synthetase locus.

Heritable deficiency of the enzyme argininosuccinate synthetase results in the autosomal recessive disease citrullinemia. RNA was isolated from cultured fibroblasts from citrullinemic patients for synthesis of complementary DNA (cDNA). The mutant mRNAs were reverse transcribed, amplified and cloned for sequencing. The cDNA sequence from one mutant allele revealed the absence of exon 5 sequences, while the sequence from a second mutant allele revealed the absence of exon 6. Genomic DNA from 25 citrullinemic patients was analyzed using intron probes derived from the argininosuccinate synthetase gene. One polymorphic probe located between exons 5 and 6 identified two novel alleles amongst 48 citrullinemia chromosomes examined. Each of these alleles appears to involve deletion of genomic DNA from this region. These two mutations, which were detected as alterations of the gene structure, are the same two mutations that result in deletion of exon 5 or 6, respectively, from the mRNA. These two mutations account for approximately 10% of the chromosomes carrying mutations that cause citrullinemia.

Argininosuccinate Synthase↗
PubMed1988

Metabolite regulation of argininosuccinate synthetase in cultured human cells.

We have studied the transcription of the argininosuccinate synthetase gene in cultured RPMI 2650 cells under conditions where the enzyme is subject to metabolite regulation and in canavanine-resistant variants (Canr1 cells) which overproduce the enzyme greater than 200-fold. When grown continuously in medium with citrulline substituted for arginine, the argininosuccinate synthetase activity of RPMI 2650 cells increases 5- to 10-fold. In these cells, expression of a transfected minigene containing the 5'-flanking region of the argininosuccinate synthetase gene was increased 20-fold by short term starvation for arginine and 10-fold by short term starvation for leucine. Levels of nuclear RNA from the first intron of the gene correlated with enzyme activity; i.e. RPMI 2650 cells cultured in arginine medium less than RPMI 2650 cells cultured in citrulline medium less than Canr1 cells. Run-off transcription experiments showed that the transcription of argininosuccinate synthetase increased in RPMI 2650 cells starved for either arginine or leucine. While expression of the minigene and the transcription rate for argininosuccinate synthetase were increased during 48 to 72 h of starvation, the endogenous enzyme activity did not increase in RPMI 2650 cells. Amino acid starvation did not affect the rate of transcription of argininosuccinate synthetase in Canr1 cells. The results indicate that the steady state levels of argininosuccinate synthetase expression in Canr1 cells and in citrulline-adapted RPMI 2650 cells are largely determined by the rate of transcription. The failure of increased transcription rate to correlate with increased enzyme activity during acute starvation for arginine or leucine may suggest the involvement of post-transcriptional regulatory mechanisms for argininosuccinate synthetase or may merely be due to amino acid deprivation. The finding that leucine starvation has effects similar to arginine starvation raises the question of whether mammalian cells have general control mechanisms which are similar to the general control of amino acid biosynthesis in Saccharomyces cerevisiae.

Amino Acids↗
PubMed1988

Calcium ionophore enhances the electron spin resonance signal from isolated skeletal muscle.

Electron spin resonance studies of the free radical signal from isolated skeletal muscle during experimental damage have shown that elevation of muscle intracellular calcium with the calcium ionophore A23187 induced an average 61% increase in the amplitude of the signal of g value 2.0047 compared to paired, untreated control muscles, accompanied by a large efflux of intracellular creatine kinase to the external medium. Inhibitors of the calcium-induced loss of cell viability leading to enzyme efflux, i.e., chlorpromazine, phenidone and nordihydroguaiaretic acid had variable effects on the signal, suggesting that the free radical signal obtained from skeletal muscle by electron spin resonance techniques is stimulated by intracellular calcium overload, but is not directly related to the mechanisms by which calcium overload leads to a loss of cell viability leading to intracellular enzyme efflux.

Animals↗
PubMed1988

Failure to detect changes in sarcolemma permeability in amphibian muscle following severe cellular damage.

1. Isolated amphibian hearts and pectoris cutaneous muscles were exposed either to DNP or to caffeine, thereby producing severe myofilament damage. 2. No accompanying change in sarcolemma permeability was detected by monitoring either CK or LDH release or Procion yellow entry in the heart, or by Procion entry in amphibian skeletal muscle. 3. The findings are in contrast with mammalian cardiac and skeletal muscles, and confirm that the pathways leading to myofilament degradation and to the breakdown in sarcolemma organization are separate.

Animals↗
PubMed1988

Stable isotope metabolic studies of zinc nutrition in slum-dwelling lactating women in the Amazon valley.

1. Zinc metabolism has been studied in a group of undernourished, slum-dwelling, lactating women in Manaus, Brazil, by means of modified metabolic balance techniques and the stable isotope 67Zn. 2. The subjects were found to be consuming a diet which provided an average of 34% of the recommended dietary allowance for lactating women, but six of the seven appeared to achieve Zn balance. In five of the subjects use of 67Zn in a stable isotope dilution manner demonstrated that they were absorbing a high proportion of the dietary Zn (proportional absorption ranged from 0.59 to 0.84), suggesting an adaptation to the chronically low intake. 3. Two subjects had marginally low plasma Zn concentrations, although hair, urine and milk Zn contents were all within accepted normal values. 4. Preliminary findings on the rate of plasma Zn turnover and the size of the exchangeable body Zn pool obtained using 67Zn suggest that these subjects may have a reduction in both.

Brazil↗
PubMed1988

Effects of dietary-fish-oil feeding on muscle growth and damage in the rat.

1. Giving diets containing 100 g fully-refined, non-hydrogenated fish oil/kg to rats caused substantial modification of skeletal-muscle-membrane fatty acid composition compared with control animals fed on an equivalent diet containing 100 g maize oil/kg. 2. Total muscle arachidonic acid (20:4 omega 6) was reduced from 138 (SD 25) mg/g total fatty acids to 15 (SD 2) mg/g and phospholipid arachidonic acid content showed equivalent changes. 3. Reduction in muscle arachidonic acid content had no influence on the growth of individual muscles. 4. Variation in muscle fatty acid composition exacerbated the response of muscle to calcium-induced damage assessed by efflux of intracellular creatine kinase (EC 2.7.3.2). 5. It is concluded that metabolites of arachidonic acid are unlikely to be primary controlling factors of muscle growth or specific mediators of muscle sarcolemmal damage leading to enzyme efflux.

Aging↗
PubMed1988

Effect of Na+ on intestinal succinate transport and metabolism in vitro.

The effect of Na+ on 14CO2 production from [14C]succinate was studied in isolated rat enterocytes, and Na+-dependent succinate transport was characterized in pig intestinal brush-border membrane vesicles. The production of 14CO2 from [14C]succinate by enterocytes was decreased 12-fold when Na+ was replaced by N-methyl-D-glucamine in the absence of glutamine and 20-fold in the presence of 0.2 or 0.5 mM glutamine. The ratio of 14CO2 produced from [1,4-14C]succinate to that produced by [2,3-14C]succinate was not affected by Na+ replacement, indicating that the pattern of tricarboxylic acid cycle metabolism was not altered. The uptake of [14C]succinate by brush-border membrane vesicles was stimulated 10-fold in the presence of 100 mM NaCl compared with 100 mM KCl. When succinate uptake was corrected to transport into an osmotically sensitive space, the magnitude of the Na+ stimulation was 20-fold. Succinate transport into brush-border membrane vesicles was Na+ dependent, electroneutral, nonconcentrative, with an apparent Na+-succinate coupling ratio of 2:1. Results of this study indicate that Na+-stimulated CO2 production by enterocytes can be explained by the effect of Na+ on succinate transport across the brush-border membrane.

Amiloride↗
PubMed1988

Weak base binding and transport in pig brush border membrane vesicles.

Uptake of the weak bases, benzylamine and amphetamine, were characterized with pig intestinal brush border membrane vesicles. The absence of osmotic sensitivity indicated weak base binding and little or no transport into the brush border membrane vesicles at pH 7.4. Benzylamine binding was increased 30-fold when medium pH was increased from 7.0 to 9.0, which indicated binding of the nonionized form of benzylamine. Uptake of benzylamine into an osmotically sensitive space was observed at pH 9.0 in the presence of NaCl and no osmotic sensitivity was observed in the presence of KCl. The apparent energy of activation of benzylamine binding was 8.4 kCal/mol which is higher than values normally associated with a simple physical process such as diffusion or partition into the membrane. Benzylamine binding was saturable and two binding sites (KD = 25 microM, KD = 2.5 mM) were discriminated. Inhibition experiments with structurally related compounds indicated a high degree of structural selectivity for the binding sites. Analysis of inhibition patterns indicated that the amine nitrogen may act as a hydrogen acceptor for hydrogen bond formation. These results indicate binding of nonionized primary amines to specific sites on intestinal brush border membranes. The binding of primary amines may be important as a step in translocation and/or membrane discrimination between ionized and nonionized weak bases.

Amphetamine↗
PubMed1987

Effect of inhibitors of arachidonic acid metabolism on efflux of intracellular enzymes from skeletal muscle following experimental damage.

The role of arachidonic acid metabolism in the efflux of intracellular enzymes from damaged skeletal muscle has been examined in vitro using inhibitors of cyclo-oxygenase and lipoxygenase enzymes. Damage to skeletal muscle induced by either calcium ionophore A23187 (25 microM) or dinitrophenol (1 mM) caused an increase in the efflux of prostaglandins E2 and F2 alpha together with a large efflux of intracellular creatine kinase. Use of a cyclo-oxygenase inhibitor completely prevented the efflux of prostaglandins, but had no effect on creatine kinase efflux. However, several agents having the ability to inhibit lipoxygenase enzymes dramatically reduced creatine kinase efflux following damage. These data suggest that a product or products of lipoxygenase enzymes may be mediators of the changes in plasma membrane integrity which permit efflux of intracellular enzymes as a consequence of skeletal muscle damage.

2,4-Dinitrophenol↗
PubMed1987

An examination of some factors influencing creatine kinase in the blood of patients with muscular dystrophy.

The natural variability of plasma creatine kinase activity has been examined in patients suffering from muscular dystrophy and in normal subjects. The coefficient of variation of the plasma creatine kinase activities was found to be large (approximately 35%) in both patients with Duchenne muscular dystrophy and normal control subjects. A comparison of the plasma activities of creatine kinase with other muscle-derived enzymes suggests that the cause of this variability is changes in the release of enzymes from muscle. Data obtained concerning the effect of physical activity on plasma creatine kinase activity are contradictory, but several young patients with Duchenne muscular dystrophy and a very high creatine kinase activity (greater than 5000 IU/liter) showed a decreased activity following admission to hospital. An estimate of the rate of efflux of certain kinase from muscle has been made, indicating that young ambulant patients with Duchenne muscular dystrophy have a grossly elevated muscle creatine kinase efflux (495.0 +/- 61.3 IU/kg muscle/hr) compared to control subjects (1.4 +/- 0.5 IU/kg muscle/hr).

Adolescent↗