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Biomedical subjects

G J Kemp

Publications and source records attributed to G J Kemp.

At least 19 recordsLinked to original sources
PubMed1992

Skeletal muscle Pi transport and cellular [Pi] studied in L6 myoblasts and rabbit muscle-membrane vesicles.

In the rat skeletal myoblast line L6 and in a rabbit skeletal muscle sarcolemma/t-tubule vesicle preparation, [32P]Pi uptake was largely dependent on the transmembrane Na gradient. Na-dependent [32P]Pi uptake had a hyperbolic relationship to [Pi] and [Na], being half-maximal at 0.2-0.3 mM [Pi] and at 25-40 mM [Na]. In vesicles the Na-dependence suggests that approx. two Na are transported with each Pi, but the inhibition of [32P]Pi uptake at high pH suggests that the Pi monoanion is the transported form. Together these imply electrogenic transport and this is confirmed by the results of manipulating the vesicle membrane potential. Thus, electrogenic Na-Pi co-transport exploits both the sodium gradient and the cell membrane potential to maintain muscle cellular [Pi] against an unfavourable electrochemical gradient. The low [Pi] for half-maximal flux may partly explain the small effect of altered extracellular [Pi] on cellular [Pi]. In L6 myoblasts most 32P was first detectable in an organic phosphate pool rather than cellular Pi, while the specific activity of cell Pi rapidly reached 40% of that of extracellular Pi and was stable for at least 3 h. These results are discussed in terms of the organisation of cellular phosphate metabolism.

Animals↗
PubMed1992

Proton efflux from rat skeletal muscle in vivo: changes in hypertension.

1. An analysis of the recovery kinetics of intracellular pH and phosphocreatine concentration after exercise in skeletal muscle was developed to calculate the rate of proton efflux in vivo. 2. Recovery of rat leg muscle pH after sciatic nerve stimulation was faster in spontaneously hypertensive rats than in Wistar-Kyoto controls (both n = 5). 3. Analysis of these data showed that the rate of proton efflux depends on intracellular pH, being greater at lower pH. 4. The early rate of proton efflux was greater in spontaneously hypertensive rats [measured over the first 0.8 min, 12.5 mmol min-1 kg-1 (SEM 1.8) in spontaneously hypertensive rats compared with 7.6 mmol min-1 kg-1 (SEM 0.4) in Wistar-Kyoto rats, P less than 0.05], even though pH at the start of recovery was higher [6.30 (SEM 0.03) in spontaneously hypertensive rats compared with 6.17 (SEM 0.01) in Wistar-Kyoto rats, P less than 0.01]. 5. This novel analysis provides a quantitative estimate of the rate of proton efflux in vivo, and demonstrates directly that this is increased in spontaneously hypertensive rats, as has previously been inferred from pH changes during exercise and studies of cultured muscle cells in vitro.

Animals↗
PubMed1992

Bio-energetic changes in human gastrocnemius muscle 1-2 days after strenuous exercise.

[31P]magnetic resonance spectroscopy was used to study the metabolic sequelae of intense muscular activity in gastrocnemius of seven subjects 1-2 days after a 67-mile bicycle ride. The muscle was examined at rest, during a test exercise and during recovery from test exercise. Post-ride and pre-ride results were compared. At rest, the ratio of phosphocreatine to ATP (PCr/ATP) was increased post-ride; during test exercise PCr/(PCr+Pi) was lower post-ride; and the recoveries of PCr, Pi and PCr/(PCr+Pi) after test exercise were delayed, with decreased 'overshoot' of PCr/(PCr+Pi) (which is due to recovery of Pi to below its resting value). Mild mitochondrial damage (perhaps due to exposure to high cytosolic [Pi] during the bicycle ride) may explain some of these results. In contrast to reports of largely eccentric exercise there was no increase in resting Pi/ATP. We have thus demonstrated perturbations of muscle bio-energetics 1-2 days after strenuous exercise, in the absence of convincing enzymological evidence of muscle damage.

Adult↗
PubMed1992

Changes in high-energy phosphates in rat skeletal muscle during acute respiratory acidosis.

We used 31P magnetic resonance spectroscopy to study changes in phosphorus metabolite concentrations in rat skeletal muscle during respiratory acidosis (14 and 20% inspired CO2) and recovery. As intracellular pH fell (from 7.05 to 6.75 after 20 min of 20% CO2), intracellular [P(i)] increased by up to 50% while phosphocreatine concentration decreased by up to 8%. The sum of all intracellular phosphates remained constant. [ADP] decreased by up to 40% in accordance with the creatine kinase equilibrium but the phosphorylation potential [ATP]/([ADP][P(i)]) was preserved as a result of increased [P(i)]. This adjustment may be a mechanism for maintaining mitochondrial ATP synthesis despite low pH. Eventually this increase in cellular [P(i)] could lead to slow efflux of P(i) from the skeletal muscle cell contributing to the hyperphosphataemia of acute respiratory acidosis.

Acidosis, Respiratory↗
PubMed1992

Residual bone-mineral density and muscle strength after fractures of the tibia or femur in children.

This study compared the bone-mineral density in the proximal part of the femur and the flexion and extension strength of the knee in the fractured and the non-fractured limbs after an uncomplicated fracture of the tibia or femur in children. Thirty-eight children, whose ages ranged from two to fifteen years at the time of the injury, were evaluated at an average of 2.3 years after the injury. The mean difference in bone-mineral density between the fractured and non-fractured limbs was 3.3 per cent (p = 0.004). There was no significant difference between the bone-mineral density of the limbs that had been immobilized for less than four weeks and that of the contralateral, non-fractured limbs. However, the mean difference between the bone-mineral density of the limbs that had been immobilized for more than eight weeks and that of the contralateral limbs was 4.3 per cent (p = 0.006). There was little or no relationship between the time since the injury and the difference in bone-mineral density between the two limbs of the patient at the intervals of follow-up that were studied. No residual weakness in flexion and extension of the knee was detected, and no relationship was established between the limb-to-limb differences in strength and the limb-to-limb differences in bone-mineral density. The residual bone-mineral deficit was found to be minimum after an uncomplicated fracture. This difference, while statistically significant, is unlikely to be clinically important in the long term. However, the fact that there was a deficit raises a potential concern for children who have more severe or repeated injuries.

Adolescent↗
PubMed1992

Circadian changes in plasma phosphate concentration, urinary phosphate excretion, and cellular phosphate shifts.

The concentration of phosphate (Pi) in plasma, Pi excretion, and the tubular threshold of Pi resorption (TmP/GFR) all increase throughout the day from about 1100 to 0300 h. For plasma [Pi], cosinor analysis yielded the following estimates of the parameters of this pattern (with 95% confidence limits): amplitude = 0.17 (0.07-0.26) mmol/L, phase = peak at 0201 (1127-0342) h, and MESOR = 1.14 (1.11-1.18) mmol/L. The increase in TmP/GFR reflects an underlying change in renal Pi handling, which is not attributable to changes in parathyrin concentrations. The changes in Pi excretion work both for and against the changes in plasma [Pi], at different times. The calculated net nonrenal flux of Pi into the extracellular fluid increases in the morning and remains high until 0300 h, and neither it nor Pi excretion nor plasma [Pi] shows any relation to meals. This illustrates the importance of transient net fluxes of Pi between intracellular and extracellular spaces in the control of hour-to-hour changes of plasma [Pi].

Adult↗
PubMed1992

Adolescent tibia vara: alternatives for operative treatment.

We reviewed the cases of fifteen obese patients (twenty-one extremities) who had had adolescent tibia vara and had been followed for at least two years. Of the nine patients (eleven extremities) who had been initially managed with lateral tibial hemiepiphyseodesis, eight (ten extremities) were skeletally mature at the time of the review (mean duration of follow-up, five years). The mechanical alignment was judged to be excellent in three of these ten extremities, fair in three, and poor in four. Excellent mechanical alignment was defined as a value within the reported normal range of 5 degrees of varus to 2 degrees of valgus. A poor result was defined as alignment that was more than 5 degrees outside the normal range. After secondary operative procedures, three of the extremities for which the result had been poor and one for which it had been fair had excellent alignment. Five of the nine patients had bilateral involvement. Two of them were managed with bilateral tibial hemiepiphyseodesis; two, with contralateral proximal tibial osteotomy; and one had a mild deformity on the contralateral side that was not treated. Six extremities in six patients (two of whom had a contralateral hemiepiphyseodesis) were managed primarily with proximal tibial osteotomy and were evaluated an average of seven years postoperatively. Two additional patients were managed with proximal tibial osteotomy because of residual varus deformity after the hemiepiphyseodesis.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1991

Effect of insulin on intracellular pH and phosphate metabolism in human skeletal muscle in vivo.

1. 31P nuclear magnetic resonance spectroscopy and the hyperinsulinaemic-euglycaemic clamp were used simultaneously to assess the effect of insulin on intracellular pH and the major phosphorus-containing metabolites of normal human skeletal muscle in vivo in four normal subjects. 2. Insulin and glucose were infused for 120 min. Plasma insulin increased approximately 10-fold over preclamp levels (5.6 +/- 0.9 m-units/l pre-clamp and 54 +/- 5 m-units/l over the last hour of infusion; mean +/- SEM, n = 4). Plasma glucose concentration did not change significantly (5.4 +/- 0.2 mmol/l pre-clamp and 5.5 +/- 0.1 mmol/l over the last hour of infusion). 3. Insulin and glucose infusion resulted in a decline in the intracellular pH of forearm muscle of 0.027 +/- 0.007 unit/h (P less than 0.01), whereas in control studies of the same subjects, pH rose by 0.046 +/- 0.005 unit/h (P less than 0.001). 4. In the clamp studies, intracellular inorganic phosphate concentration rose by 18%/h, whereas ATP, phosphocreatine and phosphomonoester concentrations did not change. In plasma, inorganic phosphate concentration was 1.16 +/- 0.05 mmol/l before infusion, and this decreased by a mean rate of 0.14 mmol h-1 l-1. No change was observed in any of these intracellular metabolites in the control studies. 5. The results show that, under physiological conditions, insulin does not raise intracellular pH in human muscle, and thus cannot influence muscle metabolism by this mechanism. The results also suggest that insulin causes a primary increase in the next flux of inorganic phosphate across the muscle cell membrane.

Adult↗
PubMed1991

Assessment of the mechanical axis in adolescent tibia vara.

To assess precision of measurement, the mechanical axis was determined by two independent observers on 52 radiographs of 15 obese patients with adolescent tibia vara. Special, but simple, modifications in radiographic technique are described that allow simultaneous exposure of the hip, knee, and ankle joints. Even in this challenging population, assessment of the alignment of the lower extremity is possible with excellent precision using the mechanical axis. In 42 of the 52 radiographs, the two independent observers differed by less than or equal to 1 degree. The mechanical axis is superior to measurement of the tibial-femoral shaft angle for evaluation of lower extremity alignment.

Adolescent↗
PubMed1990

Calcium and orthophosphate deposits in vitro do not imply osteoblast-mediated mineralization: mineralization by betaglycerophosphate in the absence of osteoblasts.

It has been shown in several laboratories that addition of beta-glycerophosphate (beta GP), a substrate for alkaline phosphatase (AP), to cultured osteoblast-like cells induces deposition of orthophosphate (Pi) and Ca within seven days. Even though this effect is regarded as an in vitro model of bone mineralization, it is not known whether it is specific for osteoblasts. We have, therefore, studied the amounts of Pi and Ca deposited after seven days with 10 mM beta GP in culture wells containing confluent cultures of osteoblast-like cells (OB) derived from human trabecular bone explants, human skin fibroblasts (SF), or culture medium alone (MED). Ox liver AP at an activity considerably greater than the endogenous AP activity of the cells, but comparable with that of other osteoblast models, was added to ensure a similar rate of Pi generation from beta GP in all wells. beta GP was converted quantitatively to Pi within seven days, leading to a nonphysiological 10-fold increase in the Pi concentration in the culture medium. After thorough rinsing on day seven, the OB and SF wells contained deposits of Pi and Ca, but the amounts were comparable for the two cell types. Smaller, but significant, amounts of Pi and Ca were also detectable even in rinsed MED wells. This suggests that the detection of such deposits in beta GP experiments cannot necessarily be interpreted as a specific property of osteoblast cultures in vitro, and may simply reflect the presence of AP.(ABSTRACT TRUNCATED AT 250 WORDS)

Alkaline Phosphatase↗
PubMed1990

Evidence for abnormal Na+/H+ antiport activity detected by phosphorus nuclear magnetic resonance spectroscopy in exercising skeletal muscle of patients with essential hypertension.

1. Exercise-induced pH changes in skeletal muscle were studied in a group of eight subjects with essential hypertension by using 31P n.m.r. spectroscopy. 2. Leucocyte Na+/H+ antiport activity was measured in vitro in the same subjects using a pH-sensitive fluorescent dye. 3. Resting skeletal muscle pH and unstimulated leucocyte pH values were similar to those in control subjects, but increased Na+/H+ antiport activity was demonstrated in the leucocytes from hypertensive subjects by acid loading in vitro. Decreased skeletal muscle acidification and an increased rate of pH recovery was also demonstrated in vivo in these same patients during an acid load induced by isotonic exercise. 4. These findings suggest that the increased cellular Na+/H+ antiport activity, which has been demonstrated in vitro in essential hypertension, also affects the biochemical response of skeletal muscle to physiological levels of exercise. This strengthens the argument that increased Na+/H+ antiport activity in hypertension is a generalized and physiologically relevant cellular abnormality.

Biological Transport, Active↗
PubMed1990

Fructose-induced aberration of metabolism in familial gout identified by 31P magnetic resonance spectroscopy.

The hyperuricemia responsible for the development of gouty arthritis results from a wide range of environmental factors and underlying genetically determined aberrations of metabolism. 31P magnetic resonance spectroscopy studies of children with hereditary fructose intolerance revealed a readily detectable rise in phosphomonoesters with a marked fall in inorganic phosphate in their liver in vivo and a rise in serum urate in response to very low doses of oral fructose. Parents and some family members heterozygous for this enzyme deficiency showed a similar pattern when given a substantially larger dose of fructose. Three of the nine heterozygotes thus identified also had clinical gout, suggesting the possibility of this defect being a fairly common cause of gout. In the present study this same noninvasive technology was used to identify the same spectral pattern in 2 of the 11 families studied with hereditary gout. In one family, the index patient's three brothers and his mother all showed the fructose-induced abnormality of metabolism, in agreement with the maternal inheritance of the gout in this family group. The test dose of fructose used produced a significantly larger increment in the concentration of serum urate in the patients showing the changes in 31P magnetic resonance spectra than in the other patients with familial gout or in nonaffected members, thus suggesting a simpler method for initial screening for the defect.

Diet↗
PubMed1990

Finding hydrophobic microdomains using an object-oriented database.

A procedure for finding clusters of adjacent residues in protein hydrophobic cores--hydrophobic microdomains--has been proposed by Plochocka et al. A program is presented that finds hydrophobic microdomains, making use of protein structure data stored in an object-oriented database and the list-processing features of Prolog. Alternative definitions for hydrophobic microdomains are explored. Results are presented for haemoglobin.

Algorithms↗