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Biomedical subjects

M Burnett

Publications and source records attributed to M Burnett.

18 recordsLinked to original sources
PubMed2000

Analysis of 'natural' and vaccine-induced haemophilus influenzae type B capsular polysaccharide serum antibodies for 3H1, a V3-23-associated idiotope.

The variable (V-) region repertoire of antibodies (Abs) to Haemophilus influenzae capsular polysaccharide (Hib PS) has been extensively studied in individuals vaccinated against the microbe, but to a lesser extent in subjects who generated such Abs in response to a 'natural' encounter with this microbe or its antigenic mimics. To gain an insight into the repertoire of Hib PS-reactive Abs in vaccinated and non-vaccinated individuals, we used a monoclonal Ab, 3H1, which detects an idiotypic marker associated with an Ab V-region gene, V3-23. We show here that Hib PS-reactive Abs with detectable 3H1 idiotope can be quantified by an indirect inimunoezymatic assay in serum samples of non-vaccinated healthy adults as well as of recently vaccinated healthy infants. The percentage of Abs that was simultaneously Hib PS-reactive and 3H1-positive ranged widely (from 0 to 68%) among individual serum samples from both groups of subjects. No dramatic differences in the expression of 3H1 idiotope on Hib PS-reactive Abs were found between vaccinated and non-vaccinated individuals. Our results are consistent with the hypothesis that the utilization of V-region genes in Hib PS-reactive Abs that individuals generate after a 'natural' encounter with Hib PS or its mimics is similar to that in these Abs elicited by Hib PS conjugate vaccines.

Adult↗
PubMed2000

Adaptations in skeletal muscle exercise metabolism to a sustained session of heavy intermittent exercise.

The purpose of this study was to investigate the hypothesis that a single, extended session of heavy exercise would be effective in inducing adaptations in energy metabolism during exercise in the absence of increases in oxidative potential. Ten healthy males [maximal aerobic power (VO(2 peak)) = 43.4 +/- 2.2 (SE) ml x kg(-1) x min(-1)] participated in a 16-h training session involving cycling for 6 min each hour at approximately 90% of maximal oxygen consumption. Measurements of metabolic changes were made on tissue extracted from the vastus lateralis during a two-stage standardized submaximal cycle protocol before (Pre) and 36-48 h after (Post) the training session. At Pre, creatine phosphate (PCr) declined (P < 0.05) by 32% from 0 to 3 min and then remained stable until 20 min of exercise at 60% VO(2 peak) before declining (P < 0.05) by a further 35% during 20 min of exercise at 75% VO(2 peak). Muscle lactate (mmol/kg dry wt) progressively increased (P < 0.05) from 4.59 +/- 0.64 at 0 min to 17.8 +/- 2.7 and 30.9 +/- 5.3 at 3 and 40 min, respectively, whereas muscle glycogen (mmol glucosyl units/kg dry wt) declined (P < 0.05) from a rest value of 360 +/- 24 to 276 +/- 31 and 178 +/- 36 at similar time points. During exercise after the training session, PCr and glycogen were not as depressed (P < 0.05), and increases in muscle lactate were blunted (P < 0.05). All of these changes occurred in the absence of increases in oxidative potential as measured by the maximal activities of citrate synthase and malate dehydrogenase. These findings are consistent with other studies, namely, that muscle metabolic adaptations to regular exercise are an early adaptive event that occurs before increases in oxidative potential.

Adaptation, Physiological↗
PubMed2000

Postcontractile force depression in humans is associated with an impairment in SR Ca(2+) pump function.

To investigate the hypothesis that intrinsic changes in sarcoplasmic reticulum (SR) Ca(2+)-sequestration function can be implicated in postcontractile depression (PCD) of force in humans, muscle tissue was obtained from the vastus lateralis and determinations of maximal Ca(2+) uptake and maximal Ca(2+)-ATPase activity were made on homogenates obtained before and after the induction of PCD. Eight untrained females, age 20.6+/-0.75 yr (mean +/- SE), performed a protocol consisting of 30 min of isometric exercise at 60% maximal voluntary contraction and at 50% duty cycle (5-s contraction and 5-s relaxation) to induce PCD. Muscle mechanical performance determined by evoked activation was measured before (0 min), during (15 and 30 min), and after (60 min) exercise. The fatiguing protocol resulted in a progressive reduction (P<0.05) in evoked force, which by 30 min amounted to 52% for low frequency (10 Hz) and 20% for high frequency (100 Hz). No force restoration occurred at either 10 or 100 Hz during a 60-min recovery period. Maximal SR Ca(2+)-ATPase activity (nmol x mg protein(-1) x min(-1)) and maximal SR Ca(2+) uptake (nmol. mg protein(-1) x min(-1)) were depressed (P<0.05) by 15 min of exercise [192+/-45 vs. 114+/-8.7 and 310+/-59 vs. 205+/-47, respectively; mean +/- SE] and remained depressed at 30 min of exercise. No recovery in either measure was observed during the 60-min recovery period. The coupling ratio between Ca(2+)-ATPase and Ca(2+) uptake was preserved throughout exercise and during recovery. These results illustrate that during PCD, Ca(2+) uptake is depressed and that the reduction in Ca(2+) uptake is due to intrinsic alterations in the Ca(2+) pump. The role of altered Ca(2+) sequestration in Ca(2) release, cytosolic-free calcium, and PCD remains to be determined.

Adult↗
PubMed2000

Downregulation in muscle Na(+)-K(+)-ATPase following a 21-day expedition to 6,194 m.

To investigate the hypothesis that acclimatization to altitude would result in a downregulation in muscle Na(+)-K(+)-ATPase pump concentration, tissue samples were obtained from the vastus lateralis muscle of six volunteers (5 males and 1 female), ranging in age from 24 to 35 yr, both before and within 3 days after a 21-day expedition to the summit of Mount Denali, Alaska (6,194 m). Na(+)-K(+)-ATPase, measured by the [(3)H]ouabain-binding technique, decreased by 13.8% [348 +/- 12 vs. 300 +/- 7.6 (SE) pmol/g wet wt; P < 0.05]. No changes were found in the maximal activities (mol. kg protein(-1). h(-1)) of the mitochondrial enzymes, succinic dehydrogenase (3.63 +/- 0.20 vs. 3.25 +/- 0.23), citrate synthase (4. 76 +/- 0.44 vs. 4.94 +/- 0.44), and malate dehydrogenase (12.6 +/- 1. 8 vs. 12.7 +/- 1.2). Similarly, the expedition had no effect on any of the histochemical properties examined, namely fiber-type distribution (types I, IIA, IIB, IC, IIC, IIAB), area, capillarization, and succinic dehydrogenase activity. Peak aerobic power (52.3 +/- 2.1 vs. 50.6 +/- 1.9 ml. kg(-1). min(-1)) and body mass (76.9 +/- 3.7 vs. 75.5 +/- 2.9 kg) were also unaffected. We concluded that acclimatization to altitude results in a downregulation in muscle Na(+)-K(+)-ATPase pump concentration, which occurs without changes in oxidative potential and other fiber-type histochemical properties.

3-Hydroxyacyl CoA Dehydrogenases↗
PubMed2000

Increases in submaximal cycling efficiency mediated by altitude acclimatization.

To investigate the hypothesis that respiratory gas exchange and, in particular, the O(2) consumption (VO(2)) response to exercise is altered after a 21-day expedition to 6,194 m, five male climbers (age 28.2 +/- 2 yr; weight 76.9 +/- 4.3 kg; means +/- SE) performed a progressive and prolonged two-step cycle test both before and 3-4 days after return to sea level. During both exercise tests, a depression (P < 0.05) in VO(2) (l/min) and an increase (P < 0.05) in minute ventilation (VE BTPS; l/min) and respiratory exchange ratio were observed after the expedition. These changes occurred in the absence of changes in CO(2) production (l/min). During steady-state submaximal exercise, net efficiency, calculated from the rates of the mechanical power output to the energy expended (VO(2)) above that measured at rest, increased (P < 0.05) from 25.9 +/- 1.6 to 31. 3 +/- 1.3% at the lighter power output and from 24.4 +/- 1.3 to 29.5 +/- 1.5% at the heavy power output. These changes were accompanied by a 4.5% reduction (P < 0.05) in peak VO(2) (3.99 +/- 0.17 vs. 3.81 +/- 0.18 l/min). After the expedition, an increase (P < 0.05) in hemoglobin concentration (15.0 +/- 0.49 vs. 15.8 +/- 0.41 g/100 ml) was found. It is concluded that, because resting VO(2) was unchanged, net efficiency is enhanced during submaximal exercise after a mountaineering expedition when the exercise is performed soon after return to sea level conditions.

Acclimatization↗
PubMed1999

Alterations in sarcoplasmic reticulum function in female vastus lateralis with eccentric exercise.

This study examined the alterations in sarcoplasmic reticulum (SR) Ca2+ sequestration function in homogenates during eccentric exercise and recovery and following additional eccentric exercise, and correlated these alterations with changes in force output. Eight healthy, untrained females, aged 20-25 years, cycled for a total of 60 min on an eccentric cycle ergometer (30 min at 66+/-3% VO2 peak and 30 min at 76+/-3% VO2 peak, determined during concentric exercise). Biopsies (extracted from the vastus lateralis) were taken before and after the exercise as well as on days 2, 6 and prior to and following identical exercise on day 14. Ca2+-uptake (nmol/min/mg protein) was unaffected (p > 0.05) following the first session of eccentric exercise; however, by day 2 a depression in uptake (p < 0.05) was observed which persisted throughout the remainder of the experiment. Maximal Ca2+-ATPase activity (nmol/min/mg protein) was elevated (p < 0.05) immediately following the first exercise session, remained elevated through day 2 and returned to pre-exercise levels by day 6 of recovery and increased again by day 14. No changes in either Ca2+-ATPase activity or Ca2+-uptake were observed with exercise on day 14. Both eccentric sessions, performed on days 0 and 14, resulted in similar depressions in force (p < 0.05) immediately following exercise. By day 2 force had recovered to pre-exercise levels. The results demonstrate that a prolonged alteration in SR Ca2+-uptake occurs following eccentric work that is unaccompanied by parallel changes in either SR Ca2+-ATPase activity or mechanical performance.

Adult↗
PubMed1997

Does persistent postmenopausal bleeding justify hysterectomy?

Postmenopausal vaginal bleeding is an early sign of endometrial cancer. persistent postmenopausal bleeding refers to uterine bleeding for which no malignant cause can be demonstrated by endometrial sampling. Hysterectomy has routinely been performed in this group of patients because of a perceived risk of endometrial cancer. The objective of this study was to quantify the risk of endometrial cancer in patients undergoing hysterectomy for postmenopausal bleeding after benign histology on endometrial sampling. One thousand four hundred and sixty-three patients underwent a hysterectomy during the study period. Forty hysterectomies (2.7%) were performed for persistent postmenopausal bleeding. The final pathology of the 40 hysterectomy specimens demonstrated hyperplasia with atypia in four patients (10%), hyperplasia without atypia in 14 (35%), and other non malignant pathology in 22 (55%). There were no cases of carcinoma of the endometrium. We conclude that persistent postmenopausal bleeding with non malignant pathology on endometrial sampling is not an indication for hysterectomy.

Aged↗
PubMed1996

Gait of a deafferented subject without large myelinated sensory fibers below the neck.

We evaluated the gait pattern of a deafferented subject who suffered a permanent loss of large sensory myelinated fibers below the neck following an acute episode of purely sensory neuropathy 21 years ago. The subject has developed several strategies to achieve a secure gait, namely: (1) a reduction of the degrees of freedom by freezing the knee articulations during the stance phase, (2) a preservation of body balance by enlarging his base of support, and (3) visual monitoring of his step by stabilizing the head-trunk linkage together with a characteristic forward tilt. As a result, the gait of the deafferented subject lacks the fluidity of normal gait. Compared with normal subjects, the gait pattern of the deafferented subjects is characterized by a shorter cycle length, a longer cycle duration, a slower speed, and a lower cadence. Using a dual-task paradigm, the attentional demands for walking were particularly important (as indexed by longer probe reaction times) during the double-support phase, suggesting that the deafferented subject uses the double-support phase as a transitory stable phase to update cognitively the postural features necessary for generating his next step.

Denervation↗
PubMed1996

Inter- and intraindividual variability of the response to intravenous glucose tolerance testing in cats.

OBJECTIVE: To evaluate inter- and intraindividual variation in results of the intravenous glucose tolerance test in cats. ANIMALS: 19 healthy specific-pathogen-free-derived cats were allotted to group A (n = 13), which was accustomed, and group B (n = 6), which was unaccustomed to having blood drawn. PROCEDURE: Blood samples were collected for glucose and insulin assays before and 5, 10, 15, 30, 45 and 60 minutes after i.v. administration of 500 mg of dextrose/kg of body weight. Glucose half-life (t1/2) and disappearance co-efficient (K), and the acute-phase insulin response (Ins0-10) were calculated. Inter- and intraindividual variability was assessed by calculating the coefficient of variation for test variables. RESULTS: Comparing the 2 tests, there were no significant differences in glucose and insulin concentrations prior to dextrose administration or in t1/2, K, or Ins0-10. However, compared with group-A cats, cats in group B had significantly (P < 0.05) longer t1/7 and lower K and Ins0-10 values, which was attributed to increased stress in these cats. Overall, the interindividual variability was 62.8% for K, 54.6% for t1/2, and 76.0% for Ins0-10. Mean intraindividual variability was 32.0 (range, 0.1 to 72.0)% for K and t1/2, and 45.8 (range, 4.0 to 179.5)% for Ins0-10. There was only a moderate correlation in results between the 2 tests (rs = 0.59 for t1/2 and K, rs = 0.58 for Ins0-10). CONCLUSION: The variability in results of intravenous glucose tolerance tests in cats suggests caution is necessary in interpreting results of a single test in individuals.

Animals↗
PubMed1992

Immunoradiometric assay of insulin, intact proinsulin and 32-33 split proinsulin and radioimmunoassay of insulin in diet-treated type 2 (non-insulin-dependent) diabetic subjects.

Plasma insulin, intact proinsulin and 32-33 split proinsulin measured by specific immunoradiometric assays and insulin and C-peptide measured by radioimmunoassay were measured during a constant infusion of glucose test in ten diet-treated subjects with a history of Type 2 (non-insulin-dependent) diabetes (termed diabetic subjects), mean fasting plasma glucose 6.0 +/- 1.0 mmol/l (mean +/- SD), and 12 non-diabetic control subjects. Immunoreactive insulin concentrations measured by radioimmunoassay were 33% higher than insulin and 16% higher than the sum of insulin and its precursors by immunoradiometric assay. The diabetic and non-diabetic subjects had similar fasting concentrations of insulin, intact proinsulin and 32-33 split proinsulin. The ratio of fasting intact proinsulin to total insulin was greater in the diabetic than the non-diabetic group 12.0% (6.8-21.0%, 1 SD range) and 6.3% (4.0-9.8%), respectively, p less than 0.01), though the groups overlapped substantially. After glucose infusion, diabetic and non-diabetic subjects had similar intact proinsulin concentrations (geometric mean 4.9 and 5.2 pmol/l, respectively), but the diabetic group had impaired insulin secretion by immunoradiometric assay (geometric means 55 and 101 pmol/l, p less than 0.05) or by radioimmunoassay C-peptide (geometric means 935 and 1410 pmol/l, p less than 0.05), though not by radioimmunoassay insulin (87 and 144 pmol/l, p = 0.12), respectively. Individual immunoradiometric assay insulin responses to glucose expressed in terms of obesity were subnormal in nine of ten diabetic subjects. Radioimmunoassay insulin and C-peptide gave less complete discrimination (subnormal responses in six of ten and eight of ten, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Glucose↗
PubMed1991

Ethnic differences in fasting plasma C-peptide and insulin in relation to glucose tolerance and blood pressure.

The frequency of non-insulin-dependent diabetes mellitus (NIDDM) and of high blood pressure (or hypertension) is higher in some ethnic groups than in others for reasons that remain unclear. To investigate the mechanisms leading to these ethnic differences, plasma C-peptide and insulin concentrations were measured after overnight fast and during an oral glucose tolerance test in subjects aged 45-74 years sampled from the practice lists of two north west London health centres. Ethnic group was defined by grandparental origin as Afro-Caribbean in 106, Gujerati Indian in 107, and white European in 101. The total age-adjusted prevalence of NIDDM was 29% in the Afro-Caribbean, 30% in the Gujerati, and 3% in the white groups, respectively. Fasting C-peptide and insulin concentrations increased from the subgroup with normal glucose tolerance, through impaired glucose tolerance, to new NIDDM, and were lower again in subjects with known NIDDM. The odds ratio for new NIDDM was 1.87 (95% confidence interval 1.26-2.77) per 1 SD increase in fasting C-peptide, which was the most powerful independent indicator of new NIDDM (p = 0.0005) and accounted for the effect of ethnic group. Fasting insulin had a similarly strong effect. There was no relation between any index of insulin secretion and blood pressure or hypertension. There were differences among the ethnic groups in the C-peptide response relative to the insulin response. These results suggest that factors determining insulin secretion and its hepatic clearance, possibly including dietary fat, are the main causes of ethnic variation in rates of new NIDDM.

Aged↗
PubMed1991

Simple empirical assessment of beta-cell function by a constant infusion of glucose test in normal and type 2 (non-insulin-dependent) diabetic subjects.

The plasma insulin or C-peptide response to a 90-min constant glucose infusion 5 mg.kg ideal body weight-1.min-1 provides Beta-cell assessment comparable to more intensive methods. In 14 diet-treated Type 2 (non-insulin-dependent) diabetic subjects and 12 non-diabetic subjects, plasma insulin and C-peptide concentrations gave near linear plots against simultaneous glucose values. The 'glucose-insulin and glucose-C-peptide vectors' (G-I and G-C vectors), could be extrapolated to predict insulin and C-peptide levels during a 12 mmol/l hyperglycaemic clamp. Predicted concentrations correlated with clamp concentrations, r = 0.94 and r = 0.98 respectively, p less than 0.001, validating the vectors as empirical glucose dose-response curves. The vector slopes correlated highly with %Beta, a mathematical model-derived measure of Beta-cell function using constant infusion of glucose model assessment, Spearman r = 0.95 and 0.93 for insulin and C-peptide, respectively. G-I vector slopes in 21 diet-treated Type 2 diabetic subjects with fasting glucose (mean + 1 SD) 7.5 +/- 2.3 mmol/l, were lower than in 28 non-diabetic subjects, (geometric mean, 1 SD range, 8.4 pmol/mmol (3.3-21.0) and 25.1 pmol/mmol (14.3-44.1), p less than 0.001, respectively), indicating an impaired Beta-cell response. The G-I vector slopes correlated with obesity in both groups (r = 0.54 p less than 0.02 and 0.72, p less than 0.001 respectively), and, in 15 non-diabetic subjects, correlated inversely with insulin sensitivity as measured by a euglycaemic clamp (r = -0.66, p less than 0.01). Thus, Beta-cell function needs to be interpreted in relation to obesity/insulin resistance and, taking obesity into account, only 4 of 21 diabetic patients had Beta-cell function (G-I vector slope) in the non-diabetic range. The fasting plasma glucose in the diabetic subjects correlated inversely with the obesity-corrected G-I and G-C vector slopes (partial r = -0.57, p less than 0.01 and -0.86, p less than 0.001, respectively). The insulin or C-peptide response to the glucose infusion provides a direct empirical measure of the Beta-cell function, which can be interpreted in relation to obesity or to insulin resistance to assess underlying pancreatic responsiveness.

Blood Glucose↗
PubMed1989

Metabolic function of intraportal and intrasplenic islet autografts in cynomolgus monkeys.

Intraportal islet autografting can restore near-normal glucose homeostasis in large diabetic animals, but the long-term failure rate of such grafts remains high. To assess the effect of the site of transplantation, we compared the hormonal responses to glucose (500 mg/kg i.v.) of intraportal (IP) and intrasplenic (IS) islet autografts in the cynomolgus monkey previously rendered diabetic by total pancreatectomy. Intravenous glucose tolerance tests (IVGTTs) 6 wk after IP grafting (n = 10) demonstrated nearly normal plasma glucose changes, with qualitatively normal but quantitatively reduced insulin and glucagon responses; only two animals have maintained these responses for greater than 2 yr. IVGTTs 6 wk after IS grafting (n = 4) demonstrated more abnormal plasma glucose changes, with qualitatively normal but weak insulin responses and glucagon levels that did not fall in response to hyperglycemia; only one animal has maintained fasting normoglycemia for greater than 9 mo. These results suggest that IS transplantation confers no benefit over IP transplantation in this model.

Animals↗
PubMed1982

Pulsatile, synchronous basal insulin and glucagon secretion in man.

The basal plasma insulin, glucagon, and glucose concentrations of 28 normal subjects were measured at 1-min intervals for periods of 45-120 min. Regular plasma insulin and/or glucagon cycles were detected in 11 subjects by autocorrelation (mean periods 13.1 and 13.7 min, respectively). Individual plasma insulin cycles were defined in all subjects (mean period 10.7 min, amplitude 1.1 mU/L), and were associated, after averaging, with plasma glucagon (amplitude 5.5 pg/ml) and plasma glucose (0.02 mmol/L) cycles. There was a significant correlation between the amplitudes of simultaneous plasma insulin and glucagon cycles (r = 0.23, P = less than 0.05, N = 124). Cross-correlation demonstrated a delay of 2 min between the changes in plasma insulin and glucagon. No comparable oscillations in plasma pancreatic polypeptide were detected. The synchronous pulsatile secretion of glucagon and insulin may be a mechanism by which insulin's hepatic effects are limited, thereby maintaining hepatic glucose production but allowing sufficient peripheral insulin concentrations to inhibit excessive catabolism. The simultaneous pulses of insulin and glucagon may be stimulated by a pacemaker, with the A-B intercellular connections producing insulin and glucagon synchrony.

Adult↗
PubMed1981

Brief, irregular oscillations of basal plasma insulin and glucose concentrations in diabetic man.

The basal plasma insulin and glucose concentrations of 12 diet-treated maturity-onset diabetics were measured at minute intervals for 2 h. Brief, irregular oscillations (mean period 8.8 min) in plasma insulin were superimposed on longer term fluctuations (greater than 30 min). Time series analysis demonstrated a synchronous plasma glucose oscillation (mean amplitude 0.03 mmol/L) associated with short insulin cycles. The glucose changes seen in diabetic subjects were similar to the short plasma insulin cycles (less than 10 min) observed in normal subjects. In contrast, the longer plasma insulin cycles (greater than 10 min) of normal subjects were associated with a plasma glucose oscillation that rose before the end of the cycle. The demonstration of insulin oscillations independent of preceding plasma glucose changes in both normal and diabetic subjects suggests a pancreatic oscillating mechanism of "pacemaker". The associated glucose changes may reflect the entrainment, by the insulin cycles, of glucose production or utilization.

Blood Glucose↗
PubMed1980

The effect of sodium removal on the contractile response of the guinea-pig taenia coli to carbachol.

1. The effects of Na-free solutions (using Li, Tris, sucrose or Mg as Na substitutes) on the contractile responses, membrane depolarization and 42K efflux produced by carbachol in the smooth muscle of the guinea-pig taenia coli have been investigated. The effect of these Na-free solutions on intracellular ion content of the muscle has also been studied. 2. Na removal induced a pattern of changes in the tone of the muscle characteristic of the substitute used, probably reflecting changes in transmembrane Ca fluxes involving Na. 3. Contractile responses to 10 sec application of 5 x 10(-5) M-carbachol were greatly reduced in Na-free solutions with all the Na substitutes used. This did not correlate with reduction in membrane depolarization or 42K efflux produced by the drug in the various Na-free medial used. 4. Intracellular Na seems important for maintaining the contractile response, since in Na-free solutions cellular Na levels and contractile responses were better maintained at 13 degrees than 34 degrees C and in tissues stimulated with carbachol every 10 min the final magnitude of the response was related to cellular Na content. If, however, the tissues was left unstimulated in Na-free Mg or sucrose solution a large response could still be obtained when cellular Na content was very low. A model is described which could account for these results in terms of an intracellular Ca store released by carbachol and requiring intracellular Na. 5. In tissues continuously exposed to 10(-4) M-carbachol Na removal, even for only 10 sec, produced rapid relaxation, probably secondary to changes in electrical properties of the membrane caused by removal of external Na.

Animals↗