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Biomedical subjects

R J Edwards

Publications and source records attributed to R J Edwards.

At least 145 records · Page 8Linked to original sources
PubMed1985

Evaluation of carrier detection of Duchenne muscular dystrophy using carbonic anhydrase III and creatine kinase.

Carbonic anhydrase III (CAIII) and creatine kinase (CK) were measured in plasma samples from a series of females at-risk as carriers of Duchenne muscular dystrophy and compared with control groups. Both plasma CAIII and CK levels were raised in a proportion of carriers. Although measurement of CAIII and CK was no more successful in identifying carriers than CK alone, CAIII could fulfill a useful confirmatory role, particularly for cases with a marginally elevated CK or where the sample is poorly preserved. The difference between the CK and CAIII results could indicate biochemical heterogeneity in the expression of Duchenne muscular dystrophy.

Carbonic Anhydrases↗
PubMed1984

Human 'creatine kinase conversion factor' identified as a carboxypeptidase.

The effect of partially purified 'creatine kinase conversion factor' on rabbit muscle creatine kinase is shown to be that of a carboxypeptidase, removing the C-terminal lysine residue from both subunits. These changes fully explain the three-banded electrophoretic patterns of the partially and the fully modified rabbit and human enzymes. The factor also produces a similar electrophoretic pattern with haemoglobin A; comparison with the effects of carboxypeptidases A and B permits the inference that the C-terminal residues of both alpha- and beta-subunits are removed. Small synthetic peptides are poor or non-substrates. A low activity with hippuryl-L-lysine may be due to contamination of the preparation with carboxypeptidase N. The possibility has been excluded that the action of conversion factor on creatine kinase involves modification of the protein thiol groups. Mr, substrate-specificity, pH-activity profile and the effects of metal ions distinguish creatine kinase conversion factor from carboxypeptidases A, B and N. On the basis of this evidence it is proposed to give the conversion factor the provisional name of carboxypeptidase K.

Animals↗
PubMed1984

Pyruvate kinase in fetal plasma and amniotic fluid unsuccessful for the prenatal diagnosis of Duchenne muscular dystrophy.

A specific spectrophotometric assay of muscle-pyruvate kinase (M-PK) was used to measure the activity of this isozyme in fetal muscle, fetal plasma and amniotic fluid at about 17-24 wk of gestational age to assess its predictive value for the prenatal diagnosis of Duchenne muscular dystrophy (DMD). Fetal muscle obtained after termination was found to contain a high M-PK specific activity. No significant activity was detected in amniotic fluid from normal or at-risk fetuses. Pure fetal blood was obtained in utero by fetoscopy; significant plasma levels of M-PK activity were measured in a series of control samples, but at-risk fetal plasma contained no higher levels. We conclude that M-PK is of no use for the prenatal diagnosis of DMD.

Amniotic Fluid↗
PubMed1984

The diagnostic value of plasma myoglobin levels in the adult and fetus at-risk for Duchenne muscular dystrophy.

In boys with Duchenne muscular dystrophy (DMD) plasma myoglobin levels remained approximately constant with age while creatine kinase (CK) activity progressively decreased. For carrier detection, plasma myoglobin level was found to be less reliable than CK activity. The myoglobin level was raised only in some of those subjects who also showed a raised CK activity and was normal in those with a normal CK activity. The myoglobin level in fetal muscle at 18-22 weeks gestational age was found to be low compared with adult skeletal muscle levels and, consequently, the myoglobin level in fetal plasma and in amniotic fluid was found to be negligible. It is concluded that measurement of myoglobin offers no advantage over CK for the investigation of any aspect of DMD.

Adolescent↗
PubMed1984

Intravascular volume and protein responses to running exercise.

The roles of posture and mean skin temperature (Tsk) in determining intravascular volume and protein responses to running exercise were examined in 12 male subjects. Moving from a sitting to a standing position before exercise was always accompanied by a decrease in blood volume (BV), as indicated by increases in the hematocrit and hemoglobin concentration. Although neither the onset of running nor alterations in Tsk during running caused any further consistent change in BV, there was an acceleration of the rate at which protein entered the intravascular space. At the end of exercise and in recovery this led to an augmentation of intravascular protein. It is concluded that intravascular volume responses to running exercise are determined by the accompanying postural hemoconcentration, and that running per se and any imposed thermal stress have minimal effects on BV thereafter. A hypothesis is presented which accounts for the reportedly diverse effects of different forms of exercise on BV in terms of the posture-dependent BV being obtained immediately before exercise begins.

Adult↗
PubMed1983

Tetrathionate-blocked creatine kinase as a substrate for human plasma 'creatine kinase conversion factor'.

'Creatine kinase conversion factor' has been partially purified from whole plasma. The preparation has the ability to convert slowly migrating, native CK-MM into a faster electrophoretic form through a form of intermediate mobility. These changes are accompanied by a loss in CK activity. The rates of both electrophoretic conversion and loss of enzyme activity are reduced or prevented by the presence of 2-mercaptoethanol, EDTA, or by formation of the creatine-MgADP-nitrate dead-end complex. When the thiol group essential for enzyme activity found at the CK active site is first blocked by treatment with potassium tetrathionate, full activity may be retained under conditions that fully convert CK to the faster electrophoretic forms. The conversion factor activity was not inhibited by a pre-incubation with the protease inhibitor, PMSF and the converted form of CK showed no evidence of proteolytic cleavage. The molecular basis of the chemical alteration caused by the conversion is discussed.

Creatine Kinase↗
PubMed1983

Plasma creatine kinase and myoglobin levels, before and after abortion, in human fetuses at risk for Duchenne muscular dystrophy.

Plasma levels of creatine kinase (CK) were measured in 14 abortuses, nine of which were at risk for Duchenne muscular dystrophy (DMD). The plasma CK level was found to be increased in all abortuses, compared with the value obtained by fetoscopy before the termination. The causes of the increase in CK level were found to be 1) method of termination, 2) physical state of the abortus at delivery, 3) delay between delivery of the abortus and taking the blood sample, and 4) site of blood sampling. It is concluded that even under optimum conditions of termination the plasma creatine kinase level of the abortus is significantly raised above the true level; hence, this measurement is not reliable as a guide to the genetic status of the fetus. Cardiac leakage was the main source of the raised plasma CK level in the abortus and this was corroborated by measurement of myoglobin levels.

Abortion, Therapeutic↗
PubMed1983

Blood volume and protein responses to skin cooling and warming during cycling exercise.

The effects of alterations in mean skin temperature (Tsk) on intravascular volume and protein responses to 90 min of bicycle ergometer exercise have been studied in six male subjects. The onset of exercise was accompanied by an initial rapid haemoconcentration, followed by a slower, progressive haemoconcentration as core and skin temperatures increased. Cooling the skin after 30 min of exercise abolished the slow haemoconcentration, and thereafter, even when Tsk was raised to the pre-exercise level during the final 30 min of exercise, little further change in blood volume was observed. During skin warming, and during recovery from exercise, there was an increase in the total intravascular protein content compared with before exercise. It is concluded that the progressive haemoconcentration often described during cycling exercise may be attributed to an increase in skin blood flow occurring as a result of rises in core and skin temperature, the associated increase in filtration through the cutaneous capillaries causing a progressive loss of plasma volume. The mechanism of the augmentation of intravascular protein remains unclear.

Adult↗
PubMed1983

Blood volume and protein responses to skin heating and cooling in resting subjects.

The effects of alterations in skin temperature on intravascular volume and protein content have been investigated in resting subjects. With a normal core temperature (Tac) both skin cooling and skin heating caused hemoconcentration, and heating was associated with an increased rate of protein loss from the intravascular space. Raising of the skin temperature after cooling, with Tac depressed, and cooling of the skin after heating, with Tac raised, were associated with an immediate reversal of the hemoconcentration, and gain of protein by the intravascular space. It is concluded that intravascular volume responses to thermal stress are dependent on the skin and core temperatures obtaining immediately prior to imposition of the stress and that, in particular, a low skin temperature predisposes toward hemodilution on subsequent exposure to heat; sweating per se does not necessarily result in hemoconcentration. The association of hemodilution with augmentation of intravascular protein, and the rapidity with which extravascular protein can apparently gain entry to the intravascular space, is taken as indicating a possible direct return of protein through capillary walls.

Adult↗
PubMed1981

Blood volume and plasma protein responses to heat acclimatization in humans.

The effects of heat acclimatization on intravascular volume and protein responses to acute heat stress and exercise were studied in six male subjects. Absolute values for hematocrit and hemoglobin concentration were lower after, than before, acclimatization, indicating hemodilution. Also, after acclimatization, the magnitude of the hemoconcentration response to exercise in the heat was significantly increased. There ws no change in the concentration of plasma protein during or after acclimatization compared with before acclimatization, but there was a net increase in the total intravascular protein content. It is suggested that the hemodilution associated with heat acclimatization may be explained in terms of an increase in the intravascular oncotic pressure following an exercise-induced augmentation of protein, occurring at the expense of the interstitial compartment. It is concluded that this hemodilution is unlikely to be primarily responsible for the cardiovascular adjustment accompanying heat acclimatization and that it should be regarded as a secondary feature of adaptation to heat.

Acclimatization↗
PubMed1981

Effect of saline loading during heat acclimatization on adrenocortical hormone levels.

Six male subjects were acclimatized to heat; once they were given sufficient 1% saline to prevent the occurrence of a salt deficit during acclimatization, and another time they were given no saline. Plasma aldosterone (PA), plasma cortisol (PC), plasma renin activity (PRA), and plasma electrolytes were measured before, during, and after and sweat electrolytes before and after the 11-day acclimatization program. PRA and PA were significantly increased by the acute stress of heat and exercise but were unaffected by acclimatization. These increases were attenuated, but not prevented, by drinking saline, whereas sweat [Na] and PC were reduced by acclimatization but were unaffected by saline. Thus adrenocortical activity has been shown not to be increased after heat acclimatization, and mineralocorticoid activity, although potentiated by a Na deficit, appears to be determined primarily by the acute stress of heat and of exercise. Hence, the increased Na conservation with acclimatization is likely to be a normal response to heat and exercise even in the absence of a negative Na balance.

Acclimatization↗
PubMed1981

Specific spectrophotometric assay for the M isoenzymes of pyruvate kinase in plasma samples containing mixtures of the muscle (M) and liver (L) isoenzymes.

Plasma pyruvate kinase (EC 2.7.1.40) activity contains two major isoenzymes. The "L" type originates from liver (erythrocytes contain a similar isoenzyme), the "M" type predominantly from skeletal muscle. The diagnostic use of pyruvate kinase as an index of muscle leakage requires an assay of only the M type. An M-type-selective assay for mixtures of the two isoenzymes was devised, based on the differences that the L form has a higher Km for phosphoenolpyruvate and is inhibited by about 95% by a high concentration of ADP. All relevant conditions of the assay have been examined and the reaction system has been optimized at 30 degrees C. The assay yields the expected Km values for M type pyruvate kinase. An apparent increase in activity in hemolysed plasma samples was found to be derived from leukocytes.

Blood Specimen Collection↗
PubMed1979

Plasma assay of fetal factors VIIIC and IX for prenatal diagnosis of haemophilia.

Fetal blood unmixed with maternal blood or amniotic fluid was obtained by direct-vision fetoscopy in 22 consecutive cases at 15--22 weeks' gestation; the investigation was done either for prenatal diagnosis or before therapeutic abortion. Fetal plasma factors VIIIC and IX averaged 50 I.U./dl (S.D. 12.8) and 12.5 I.U./dl (S.D. 2.4), respectively. Two male fetuses at risk of haemophilia had normal factor VIIIC levels by these criteria, and both pregnancies ended in the birth of a normal boy. Five others gave 3 normal and 2 haemophilic results, which were confirmed in two of the three terminated pregnancies.

Amniocentesis↗
PubMed1978

Intravascular volume and tonicity as factors in the regulation of body temperature.

The effect of alterations in intravascular volume and tonicity on thermoregulatory and cardiovascular responses to heat and exercise have been compared in four subjects. Core temperatures were found to be significantly higher during dehydration, and when dehydration was prevented by administration of 1% saline, than when dehydration was prevented by water administration. These higher temperatures were associated with elevated levels of plasma [Na] and osmolarity, but no consistent relationship between temperature and changes in intravascular volume could be demonstrated. Relationships observed between core temperature and plasma tonicity were consistent with the hypothesis that the adverse effects of dehydration on thermoregulation can be attributed to an inhibition of sweating mediated by an increase in either plasma osmotic pressure or plasma [Na]. In separate experiments the heart rate response to exercise was shown to be reduced by saline, compared with water and dehydration, and this may be explained by the smaller reduction in intravascular volume which occurs during exercise following administration of hypertonic saline. It is concluded that the effects of reduced intravascular volume, and increased intravascular tonicity on physical work capacity may be distinguished by the adverse effect on the cardiovascular system of the former, and on the thermoregulatory system of the latter.

Adult↗
PubMed1978

Core temperature measurement in man.

Transient changes in core temperature were induced in 12 subjects--passively by immersion in a hot bath, and actively by light intermittent exercise. Measurements of core temperature were made at four sites--the auditory canal, mouth, rectum, and oesophagus--and, by using the measurements from the first three of these sites, a mathematical model was derived which permits the calculation of a predicted value for oesophageal temperature (Toe). This model--which takes the general form Toe = ATx + BdTx/dt + C where Tx = amplitude of the temperature change at a specific site, dTx/dt = rate of change of temperature at that site, and A, B, and C = site constants (different for passive and active heating)--provides an accurate prediction of Toe (to within 0.1 degrees C) from both auditory canal and mouth temperature. For prediction of Toe from rectal temperature, however, two models appear to be necessary--one to predict Toe when core temperature is rising, and another to predict Toe during the return to equilibrium when core temperature is declining.

Adult↗