Search PubMed⌕ Search

Biomedical subjects

M J Jackson

Publications and source records attributed to M J Jackson.

At least 181 records · Page 10Linked to original sources
PubMed1987

Isolation and characterization of brush border membrane vesicles from pig small intestine.

1. Brush border membrane vesicles (BBMV) were isolated from swine mid-intestine by a MgCl2 precipitation and sucrose density gradient centrifugation. 2. Transport of D-glucose and L-alanine were Na+-stimulated and into an osmotically sensitive space. 3. Estimates of kinetic parameters for Na+-dependent D-glucose transport were: apparent Kt = 1.8 mM and Jmax = 16.8 nmol/mg protein/min. 4. Results of experiments with the delta pH sensitive fluorescent probe 9-aminoacridine indicated independent mechanisms for Na+-dependent glucose transport and Na+/H+ exchange. 5. This study demonstrates that pig BBMV provide a useful model for investigating intestinal membrane transport.

Alanine↗
PubMed1987

Development of changes in cation content of muscles from the 129 ReJ dystrophic mouse.

1. Muscle cation levels have been measured in severely affected and relatively unaffected muscles of dystrophic mice (129 ReJ strain) compared to control animals at various ages. 2. Muscle calcium levels were found to be elevated in the severely affected gastrocnemius muscles only at a late stage of the disease, calcium levels in mildly affected triceps muscles were unaffected. 3. Muscle sodium levels were elevated in both triceps and gastrocnemius muscles at all ages studied. 4. Muscle magnesium and potassium contents showed similar changes, being significantly reduced in the gastrocnemius from the time of development of the first signs of weakness (i.e. 3-5 weeks of age), this decrease becoming more marked with increasing age and showing a less marked, but significant, change in the triceps muscle at a later stage of the disease.

Aging↗
PubMed1987

Indices of free radical activity in the cerebrospinal fluid in motor neuron disease.

Indices of free-radical activity and lipid peroxidation were studied in cerebrospinal fluid samples obtained from 11 patients with motor neuron disease and 11 reference subjects. No differences were found between the two groups. The significance of this finding is discussed in relation to current views of the possible pathogenesis of this disease.

Adult↗
PubMed1987

Different mechanisms mediate structural changes and intracellular enzyme efflux following damage to skeletal muscle.

Cellular damage, induced by either A23187 (2 X 10(-5)M) or 2,4-dinitrophenol (DNP) (10(-3)M), has been studied in incubated mouse soleus muscle and has been monitored by electron microscopy and measurement of creatine kinase (CK) efflux. CK efflux induced by DNP was dependent on extracellular Ca, whereas the characteristic myofilament breakdown was not. Chlorpromazine (2 X 10(-4)M; an inhibitor of phospholipase A (PLA2] or 5 X 10(-6)M-nordihydroguaiaretic acid (NDGA) (a lipoxygenase inhibitor) almost completely inhibited CK efflux, following treatment with either A23187 or DNP, but did not affect myofilament damage. It is concluded that there are at least two separate pathways in cellular damage: (1) PLA2 activation and lipoxygenase activity culminating in sarcolemma damage and (2) a system that produces characteristic destruction of the myofilament apparatus.

2,4-Dinitrophenol↗
PubMed1986

Physiological zinc-binding proteins of medium molecular weight in the rat gut.

1. Gel filtration on Sephadex G 75 was used to separate the medium-molecular-weight zinc-binding proteins from the soluble fractions from the duodenal and jejuno-ileal segments of the rat gut at 30 min after the intragastric administration of a tracer dose of 65Zn. These proteins were resolved by ion-exchange chromatography on DEAE cellulose. 2. In both the duodenum and jejuno-ileal segment an appreciable fraction of the total soluble Zn was bound in a protein fraction that resembled metallothionein (MT) in its behaviour on gel filtration. These fractions, however, were not homogeneous, but contained several medium-molecular-weight Zn-binding proteins. In the duodenum, but not in the jejuno-ileal segment, two of these proteins appeared to be the isometallothioneins, ZnMT-I and ZnMT-II. 3. These results suggest a possible role for MT in the binding of newly-absorbed Zn in the duodenal mucosal cells. They also show that gel filtration alone is insufficient for the identification of MT in the intestine.

Animals↗
PubMed1986

Iron chelation using subcutaneous infusions of diethylene triamine penta-acetic acid (DTPA).

The iron chelating ability and potential toxicity of subcutaneous infusions of the calcium and zinc salts of diethylene triamine penta-acetic acid (DTPA) have been assessed in metabolic balance studies in 2 iron-loaded thalassaemic patients. Infusions of calcium DTPA were locally well tolerated and the drug was as effective as desferrioxamine in mobilising iron. However, daily infusions in the 1st patient also produced symptomatic zinc depletion which could not be controlled by simultaneous oral zinc supplements. Zinc DTPA proved ineffective as an iron chelator, but zinc balance could be maintained in the 2nd patient by combining intermittent (every 4 d) use of calcium DTPA with oral zinc supplements. Combined studies with desferrioxamine and calcium DTPA showed the drugs to have additive effects, probably as a result of the chelation of iron from different body sites.

Administration, Oral↗
PubMed1986

Arginine-mediated regulation of an argininosuccinate synthetase minigene in normal and canavanine-resistant human cells.

Regulation of argininosuccinate synthetase (AS) was studied by using minigenes containing 3 kilobases of DNA upstream from the TATAA box and 9 kilobases downstream (including the first four exons of the AS gene) ligated to either the cDNA for AS or to the chloramphenicol acetyltransferase (CAT) gene. Unlike the endogenous AS gene, expression of the CAT minigene was not elevated in Canr1 cells, which overproduce AS compared with parental RPMI-2650 cells. Expression of the CAT minigene in both stable and transient analyses was four- to five-fold higher in RPMI-2650 cells grown in citrulline medium than in cells grown in arginine medium. Although endogenous AS activity is not subject to metabolite regulation in Canr1 cells and expression of the CAT minigene in Canr1 cells was not increased when cells were grown in citrulline medium, expression of the CAT minigene was 10- to 22-fold greater when intracellular arginine pools were depleted by transient starvation for arginine and citrulline.

Arginine↗
PubMed1986

Substrate metabolism of isolated jejunal epithelium: conservation of three-carbon units.

This study characterizes the substrate metabolism of isolated jejunal epithelial cells. Utilization of substrates was assessed by spectrophotometric assay. Significant quantities of glucose, glutamine, and ketone bodies were consumed in a 1-h period; lactate and ammonia were produced. [U-14C]glucose was metabolized in this medium to approximately three moles of lactate per mole of CO2. The pattern of tricarboxylic acid (TCA) cycle metabolism was analyzed utilizing media containing different concentrations of potential metabolic substrates and trace quantities of [14C]- succinate. O2 consumption rates indicated that glutamine can serve as an energy source in the absence of other substrates. Relative 14CO2 production from [1,4-14C]succinate versus [2,3-14C]succinate, which estimates flux of TCA cycle intermediates to products other than CO2, was increased more than twofold when glutamine was the only major substrate available. Alanine was produced from TCA cycle intermediates. Analysis of the citrate labeling pattern in the presence of [2,3-14C] succinate suggested that carbon from the TCA cycle does not form a significant fraction of acetyl-CoA used for citrate synthesis and that glutamine carbon was not completely oxidized to CO2. These findings suggest that glucose and glutamine are converted to three-carbon compounds by the jejunal epithelium.

Animals↗
PubMed1986

Jejunal epithelial glucose metabolism: effects of Na+ replacement.

The objective of this study was to characterize the effects of replacement of extracellular Na+ with a nontransportable cation, N-methyl-D-glucamine (NMDG+) on jejunal epithelial glucose metabolism. Jejunal epithelium isolated from male Sprague-Dawley rats was incubated in media containing 5 mM glucose, 0.5 mM glutamine, 0.5 mM beta-hydroxybutyrate, and 0.3 mM acetoacetate as the principal carbon sources. O2 consumption and total glucose utilization were reduced 30 and 50%, respectively, when Na+ was replaced with NMDG+. In both media, approximately 75% of utilized glucose carbon was converted to lactate. The rate of glucose metabolism via the hexose monophosphate shunt, as evaluated using specific 14CO2 yields from [1-14C]glucose and [6-14C]glucose, was not appreciably altered by Na+ replacement. Tricarboxylic acid (TCA) cycle flux was evaluated using 14CO2 production from [14C]glucose and [14C]pyruvate radioisotopes. Approximately 50% of TCA cycle flux was shunted into products other than CO2 in both media. The majority of the acetyl-CoA oxidized in the TCA cycle was derived from cytosolic pyruvate. It is concluded that removal of Na+ from the bathing medium substantially reduced glucose utilization via the Embden-Meyerhof pathway and TCA cycle in the jejunal epithelium.

Animals↗
PubMed1986

In vitro screening of iron chelators using models of free radical damage.

The effect of chelators on free radical damage to deoxyribose induced by iron, on IgG by UV irradiation, and on mouse muscle by homogenisation has been studied using the Thiobarbituric acid method and the increase in fluorescence in IgG mixtures. Although there were some variations on the effects of the chelators in the three models, it was shown that most of the chelators could inhibit the noxious effects of the free radicals and some which are orally effective in increasing iron excretion in animals could be potentially useful in preventing iron toxicity in related pathogenic diseases.

Animals↗
PubMed1985

Electron spin resonance studies of intact mammalian skeletal muscle.

Samples of skeletal muscle from mice, rats and man have been examined by conventional electron spin resonance techniques. One major free-radical signal with g value 2.0036-2.004 was detected in all intact muscle samples and homogenates at 77 K whereas this signal was not seen at room temperature. Other less prominant signals were also detected. Thirty minutes of excessive contractile activity of rat hind limb muscles was found to result in a leakage of intracellular creatine kinase enzyme into the blood plasma and also produced an average 70% increase in the amplitude of the major electron spin resonance signal. These data support the hypothesis that increased free-radical activity may play some role in muscle damage caused by extensive muscular activity.

Animals↗
PubMed1985

Measurements of calcium and other elements in muscle biopsy samples from patients with Duchenne muscular dystrophy.

The calcium, magnesium, sodium and potassium content of needle biopsy samples of human muscle from control subjects and patients with various neuromuscular disorders has been analysed by atomic absorption spectrometry. The calcium content of muscle from both patients with Duchenne Muscular Dystrophy and other myopathies was significantly elevated compared to both normal and patient control subjects. Muscle sodium content was not significantly altered in any group compared to control subjects. Decreased magnesium and potassium levels were found in muscle from patients with Duchenne Muscular Dystrophy, although the muscle magnesium/potassium ratio was unchanged, the most likely explanation for this being non-specific loss of intracellular components from the cell.

Biopsy, Needle↗
PubMed1985

Vitamin E and muscle diseases.

Studies of the basic biochemical mechanisms underlying muscle damage aimed at finding agents which might reduce the amount of damage occurring in muscular dystrophy and other severe myopathies have been performed. These have suggested three types of agent which might be useful for this purpose, namely calcium antagonists, phospholipase inhibitors, and antioxidants or scavengers of reactive-free radicals. Vitamin E falls into the latter of these three categories and has been shown to reduce the amount of damage which occurs in isolated skeletal muscles following a given stress. It is suggested that, in the absence of calcium antagonists having relatively specific and effective actions on skeletal muscle or suitable inhibitors of muscle phospholipases in man, therapy with vitamin E or other antioxidants may reduce the amount of muscle damage occurring in patients with severe myopathies.

Calcium↗