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Biomedical subjects

M C Evans

Publications and source records attributed to M C Evans.

At least 55 records · Page 3Linked to original sources
PubMed1995

The effect of the anti-estrogen tamoxifen on cardiovascular risk factors in normal postmenopausal women.

There is growing interest in the use of anti-estrogens as agents of disease prevention. Studies of women with breast cancer suggest that the synthetic anti-estrogen tamoxifen may reduce the incidence of cardiovascular disease, but the effects of this agent on cardiovascular risk factors in healthy women have not been studied. We have performed a two-year, randomized, placebo-controlled trial to assess the effects of tamoxifen 20 mg/day on serum lipids, fibrinogen, and body composition in 57 normal postmenopausal women. Tamoxifen treatment lowered levels of serum cholesterol by (mean +/- SE) 12 +/- 2%, low density lipoprotein cholesterol by 19 +/- 3%, and fibrinogen by 18 +/- 4% (P < 0.0001 vs. placebo for each). Levels of high density lipoprotein cholesterol were not altered by tamoxifen, but the ratio of total cholesterol to HDL-cholesterol decreased by 11 +/- 4% (P < 0.001 vs. placebo). Tamoxifen did not affect levels of triglycerides, high density lipoprotein cholesterol subfractions, apolipoprotein A1, or glucose, and did not change body weight, body mass index, or body fat distribution. We conclude that tamoxifen significantly reduces the levels of atherogenic lipids and fibrinogen in normal postmenopausal women. The results suggest that the anti-estrogens may substantially reduce the risk of cardiovascular disease, which remains the most common cause of death among postmenopausal women.

Adipose Tissue↗
PubMed1995

Regular exercise dissociates fat mass and bone density in premenopausal women.

Body weight is one of the principal determinants of bone density and fracture frequency, but there is significant disagreement in the literature regarding the relative contributions of the lean and fat components of body weight to this relationship. As previous studies have not considered the possible role of exercise in soft tissue-bone density interrelationships, we measured areal bone mineral density (BMD), fat mass, and lean mass in eumenorrheic premenopausal women and determined whether the interrelationships of these variables are influenced by the subject's exercise status. Subjects with mean activity levels of more than 140 kilojoules/kg.day (equivalent to undertaking vigorous physical activity for > 1.5 h/week) were classified as exercisers. In the nonexercising subjects (n = 36; age, 36 +/- 8 yr), BMD was markedly weight dependent (0.45 < r < 0.62), and this was contributed to by both fat and lean tissue. Because this finding may have arisen from the mutual dependence of soft tissue mass and areal BMD on body size, fat and lean masses were reexpressed as a percentage of body weight. The percent fat tended to be positively related to areal BMD (0.23 < r < 0.35), whereas the percent lean was inversely related to this index. A second way of obviating the mutual dependence of soft tissue mass and areal BMD on body size is to derive BMD/height as an index of volumetric bone density. This parameter was only related to lean mass in the femur, whereas the correlations with fat mass were little changed. The percent fat was positively (0.29 < r < 0.43) and the percent lean was negatively (-0.43 < r < -0.29) related to BMD/height throughout the skeleton, including the femur. In the exercising subjects (n = 63; age, 33 +/- 8 yr), fat mass and lean mass were unrelated to BMD/height (r < 0.23). However, the percent lean was positively correlated with BMD and BMD/height in the femoral neck (r = 0.28 and r = 0.31, respectively). It is concluded that bone density is only associated with fat mass in sedentary women. In exercisers, femoral neck density is related to lean mass, possibly through the effects of weight-bearing exercise on both of these variables.

Adipose Tissue↗
PubMed1994

Investigation of the ammonium chloride and ammonium acetate inhibition of oxygen evolution by Photosystem II.

Using EPR and EXAFS spectroscopies we show that high concentrations of ammonium cations at alkaline pH are required for (1) inhibition of oxygen evolution: (2) an alteration of the EPR properties of the oxygen evolving complex: (3) the ability to detect YZ; and (4) the slow reduction of the Mn complex leading to the appearance of EPR detectable Mn2+. The inhibition of S state cycling, slowing of YZ reduction, appearance of Mn2+ and the yield of a Hpp < 10 mT S3 type EPR signal are decreased by calcium addition. This indicates that these effects were probably associated with calcium depletion arising from the high concentration of ammonium cation. The ammonia-induced changes to the S2 multiline EPR signal are not affected by calcium addition. The appearance of Mn2+ is shown to be reversible on illumination, suggesting that the Mn reduced from the native state is located at or near the native site. Simulations of the interaction which give rise to the S3 EPR signal are also presented and discussed. These indicate that lineshape differences occur through small changes in the exchange component of the interaction between the manganese complex and organic radical, probably through minor structural changes between the variously treated samples.

Acetates↗
PubMed1994

Body weight and bone mineral density in postmenopausal women with primary hyperparathyroidism.

OBJECTIVE: To assess bone mineral density and body composition in postmenopausal women with primary hyperparathyroidism. DESIGN: Cross-sectional study with an age-matched control group. SETTING: University teaching hospital. PATIENTS: 41 postmenopausal women with mild primary hyperparathyroidism and 43 eucalcemic, age-matched controls. MEASUREMENTS: Total body, lumbar spine, and proximal femoral (femoral neck, Ward's triangle, and trochanter) bone mineral density; body composition; and fat distribution were measured using dual-energy x-ray absorptiometry. RESULTS: Women with primary hyperparathyroidism were heavier (75.5 kg compared with 66.3 kg; difference, 9.2 kg [95% CI, 3.7 to 14.7 kg]; P = 0.002), had a higher fat mass (33.3 kg compared with 26.1 kg; difference, 7.2 kg [CI, 3.0 to 11.4 kg]; P = 0.001), and had a more android pattern of fat distribution (android-to-gynoid fat ratio, 1.05 compared with 0.84; difference, 0.21 [CI, 0.1 to 0.32]; P = 0.0004) than the controls. Unadjusted bone mineral density was similar in patients and controls at all sites: total body, 0.990 compared with 1.023 g/cm2 (difference, 0.033; CI, -0.004 to 0.070); posteroanterior lumbar spine, 1.032 compared with 1.018 g/cm2 (difference, 0.014; CI, -0.031 to 0.059); lateral lumbar spine, 0.569 compared with 0.528 g/cm2 (difference, 0.041; CI, -0.022 to 0.104); femoral neck, 0.799 compared with 0.825 g/cm2 (difference, 0.026; CI, -0.072 to 0.124); Ward's triangle, 0.653 compared with 0.677 g/cm2 (difference, 0.024; CI, -0.035 to 0.089); trochanter, 0.734 compared with 0.733 g/cm2 (difference, 0.001; CI, -0.024 to 0.026); and arms, 0.720 compared with 0.739 g/cm2 (difference, 0.019; CI, -0.015 to 0.053). After adjustment for body weight, bone mineral density in women with primary hyperparathyroidism was lower than that in controls for total body (P = 0.0004), femoral neck (P = 0.001), Ward's triangle (P = 0.01), trochanter (P = 0.02), and arms (P = 0.0006). Spinal bone mineral density did not differ between groups. CONCLUSIONS: Body weight, total body fat mass, and proportion of android fat are increased in postmenopausal women with primary hyperparathyroidism; these unexplained factors may be relevant to the increased incidence of cardiovascular disease in this condition. Unadjusted bone mineral density values are similar in patients with primary hyperparathyroidism and in controls, suggesting that this condition is not associated with an increased risk for fracture.

Adipose Tissue↗
PubMed1994

Path of electron transfer in photosystem 1: direct evidence of forward electron transfer from A1 to Fe-Sx.

Pulsed EPR spectroscopy and selective removal of the iron-sulfur centers in photosystem 1 have been used to study forward electron transfer from the secondary electron acceptor A1. At cryogenic temperatures where forward electron transfer is inhibited, we have observed a g = 2.003 electron spin-echo signal presenting a characteristic phase shift. This out-of-phase signal is attributed to the electron spin-polarized pair P700+/A1-, it decays with t1/e = 23 microseconds, reflecting the recombination reaction. At room temperature the out-of-phase signal is also observed, but it decays with t1/c = 200 ns in untreated photosystem 1, due to forward electron transfer from A1- to one of the iron-sulfur centers. This rate is unchanged in Fe-SA/B-depleted PS1 but is lost when the iron-sulfur center Fe-Sx is removed. In the preparations depleted of all iron-sulfur centers the out-of-phase signal decays with t1/c = 1.3 microseconds, reflecting either the back reaction or the decay of polarization. These results demonstrate that the electron transfer pathway in photosystem 1 is P700-->A1-->Fe-SX-->Fe-SA/B.

Chlorophyll↗
PubMed1994

The electronic structure of P840+. The primary donor of the Chlorobium limicola f. sp. thiosulphatophilum photosynthetic reaction centre.

The radical cation P840+. was studied in frozen suspensions of Chlorobium limicola f. sp. thiosulphatophilum membranes using ENDOR and Special TRIPLE spectroscopies. The spectra show that P840+. arises from a bacteriochlorophyll a 'special' pair with a highly symmetrical distribution of electron spin density between the constituent bacteriochlorophylls. Special TRIPLE spectroscopy has resolved the separate contributions of the two halves of the pair and revealed small deviations from a 1:1 electron spin density distribution. Nevertheless P840+. appears to come the closest yet to the symmetrical 'dimer' originally proposed for the structure of the primary donor radical cation (P870+.) in purple non-sulphur photosynthetic bacteria.

Bacteria↗
PubMed1994

Volumetric bone density of the lumbar spine is related to fat mass but not lean mass in normal postmenopausal women.

We have previously found that fat mass but not lean body mass is related to bone mineral density (BMD) in women. In these and most other studies of the dependence of BMD on body composition, areal rather than volumetric bone density was measured. It is possible that the dependence of this variable on body size introduced a scale artifact that contributed to the previous findings. The present study addresses this issue by measuring the volumetric density of the third lumbar vertebra from simultaneous anteroposterior (AP) and lateral scans using dual-energy X-ray absorptiometry in 119 normal postmenopausal women. Whole body fat and lean body mass were also measured using this technique. In the AP projection, BMD was similarly related to body weight and to fat mass (r = 0.44, p < 0.0001 for both) but not to lean body mass (r = 0.17, NS). BMD in the lateral projection was less closely related to body composition than was AP BMD, but the greater impact of fat (r = 0.25, p < 0.01) than lean body mass (r = 0.09, NS) was still evident. When AP or lateral BMDs were divided by height, arm span or the square root of the scan area to produce an index with the dimensions of volumetric density, the dependence of BMD on body weight and fat mass was not affected but the relationship to lean body mass was eliminated (-0.02 < r < 0.09). Similarly, the volumetric density of the third lumbar vertebra was related to fat mass (r = 0.21, p = 0.02) but not to lean body mass (r = 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Absorptiometry, Photon↗
PubMed1994

Determinants of the rate of bone loss in normal postmenopausal women.

Despite a large number of studies assessing relationships between putative risk factors and bone density, it is not known which factors influence the rate of axial bone loss in normal postmenopausal women. We have examined the relationships between the rate of bone loss (delta BMD) and variables related to calcium metabolism, lifestyle, diet (calcium, sodium, caffeine, and protein), body composition, muscle strength, sex hormones, and spinal osteophytosis in 122 normal postmenopausal women participating in a 2-yr prospective randomized placebo-controlled trial of calcium supplementation. Univariate correlation coefficients indicated that delta BMD at most sites was inversely related to baseline BMD and positively related to rate of change in body weight (0.10 < r < 0.36) and fat mass (0.11 < r < 0.42) during the study. Lean mass and its rate of change showed no consistent relationship to delta BMD. There was no correlation between delta BMD and any of the lifestyle, muscle strength, dietary, or hormonal indices or with the severity of spinal osteophytosis. Multiple regression analysis indicated that delta BMD in the total body was directly related to fat mass (P < 0.0001), the rate of change in fat mass (P < 0.0001), the renal tubular reabsorption of calcium (P < 0.01), and calcium treatment (P < 0.01) and inversely to the initial BMD (P < 0.0001; r2 = 0.42; P < 0.0001). Similar effects were seen throughout the skeleton, although the fraction of the variance accounted for was less in the subregions, consistent with the lower precision of measurement of regional bone density. It is concluded that baseline bone density, fat mass, and renal calcium handling are important factors influencing bone loss in normal postmenopausal women.

Body Composition↗
PubMed1994

Continuous therapy with pamidronate, a potent bisphosphonate, in postmenopausal osteoporosis.

There is a need for effective and acceptable therapies for postmenopausal osteoporosis. The bisphosphonates show promise in this role, but the effects of the potent bisphosphonates in established osteoporosis have not yet been reported. We performed a 2-yr, randomized, double blind, placebo-controlled trial of pamidronate (150 mg/day) in 48 postmenopausal osteoporotic women. Bone mineral density of the total body, lumbar spine, and proximal femur was measured every 6 months by dual energy x-ray absorptiometry. Bone mineral density increased progressively in the total body (1.9 +/- 0.7%; P < 0.01), lumbar spine (7.0 +/- 1.0%; P < 0.0001), and femoral trochanter (5.4 +/- 1.3%; P < 0.001) in subjects receiving pamidronate, but did not change significantly in those receiving placebo. There were significant decreases in bone density at both the femoral neck (P < 0.02) and Ward's triangle (P < 0.01) in subjects taking placebo, which did not occur in the pamidronate group. The differences between the treatment groups were significant at all sites (0.0001 < P < 0.05) except Ward's triangle. Vertebral fracture rates were 13/100 patient yr in the pamidronate group and 24/100 patient yr in those receiving placebo (P = 0.07), and there was a nonsignificant trend toward height loss being less in those receiving pamidronate (P = 0.16). It is concluded that pamidronate is an effective therapy in postmenopausal osteoporosis.

Aged↗
PubMed1993

The synthetic substrate succinyl(carbadethia)-CoA generates cob(II)alamin on adenosylcobalamin-dependent methylmalonyl-CoA mutase.

Succinyl(carbadethia)-coenzyme A, a synthetic substrate for adenosylcobalamin-dependent methylmalonyl-CoA mutase, has been prepared by a simplified procedure. When recombinant mutase was mixed with the synthetic substrate, the u.v./visible absorption spectrum of the bound cofactor changed rapidly to resemble that of cob(II)alamin, with an absorption maximum at 467 nm. Addition of the natural substrates, in contrast, produced only minor changes in the u.v./visible spectrum. The recent report of the generation of a complex e.p.r. spectrum on addition of substrate to the holo-methylmalonyl-CoA mutase was confirmed with the recombinant enzyme. The signals observed were stronger when the succinyl(carbadethia) analogue was used. Cobalt K-edge X-ray absorption spectroscopy confirmed that the addition of this analogue to holoenzyme leads to the generation of a cob(II)alamin-like species. These results strongly support the generation of cob(II)alamin during the 1,2-skeletal rearrangement catalysed by methylmalonyl-CoA mutase, as required if this enzyme follows the reaction pathway involving radical intermediates previously proposed for other adenosylcobalamin-dependent enzymes.

Acyl Coenzyme A↗
PubMed1993

Effect of calcium supplementation on bone loss in postmenopausal women.

BACKGROUND: The use of calcium supplements slows bone loss in the forearm and has a beneficial effect on the axial bone density of women in late menopause whose calcium intake is less than 400 mg per day. However, the effect of a calcium supplement of 1000 mg per day on the axial bone density of postmenopausal women with higher calcium intakes is not known. METHODS: We studied 122 normal women at least three years after they had reached menopause who had a mean dietary calcium intake of 750 mg per day. The women were randomly assigned to treatment with either calcium (1000 mg per day) or placebo for two years. The bone mineral density of the total body, lumbar spine, and proximal femur was measured every six months by dual-energy x-ray absorptiometry. Serum and urine indexes of calcium metabolism were measured at base line and after 3, 12, and 24 months. RESULTS: The mean (+/- SE) rate of loss of total-body bone mineral density was reduced by 43 percent in the calcium group (-0.0055 +/- 0.0010 g per square centimeter per year) as compared with the placebo group (-0.0097 +/- 0.0010 g per square centimeter per year, P = 0.005). The rate of loss of bone mineral density was reduced by 35 percent in the legs (P = 0.02), and loss was eliminated in the trunk (P = 0.04). Calcium use was of significant benefit in the lumbar spine (P = 0.04), and in Ward's triangle the rate of loss was reduced by 67 percent (P = 0.04). Calcium supplementation had a similar effect whether dietary calcium intake was above or below the mean value for the group. Serum parathyroid hormone concentrations tended to be lower in the calcium group, as were urinary hydroxyproline excretion and serum alkaline phosphatase concentrations. CONCLUSIONS: Calcium supplementation significantly slowed axial and appendicular bone loss in normal post-menopausal women.

Alkaline Phosphatase↗
PubMed1993

Heat stress attenuates free radical release in the isolated perfused rat heart.

Prior heat stress leads to an enhancement of postischemic mechanical function and improvement in biochemical indices of injury in the rat heart, associated with an elevation in endogenous catalase activity. We have examined the effect of heat stress on free radical release during reperfusion in the isolated rat heart using electron spin resonance (ESR). Twenty four hours after heat stress or sham treatment, hearts were perfused in the Langendorff mode and subjected to 10 min of no-flow global ischemia followed by 10 min of reperfusion. Coronary effluent was collected at specific time points in PBN for ESR measurement. A PBN adduct was identified with characteristics consistent with an alkoxyl radical: PBN-LO. In sham hearts there was a rapid rise in adduct release to a maximum (228 +/- 15% of stabilization values, p < .05) occurring 1 min into reperfusion. In heat stress hearts there was no significant rise in adduct release during the reperfusion period. Pretreatment of hearts with 3-amino triazole, an inhibitor of catalase, failed to clarify whether the protection seen in heat stress hearts was a result of the elevation in catalase activity. These results suggest that heat stress protects the myocardium against the oxidative stress of ischemia-reperfusion.

Animals↗
PubMed1993

Circulating insulin levels are related to bone density in normal postmenopausal women.

We recently established that the dependence of bone mineral density (BMD) on body weight in women is mainly attributable to a close relationship between total body fat mass and BMD. The present study assesses whether this latter relationship might be contributed to by the hormones insulin or amylin, both of which may influence fat mass and calcium metabolism. Fifty-three normal postmenopausal women underwent a 75-g glucose tolerance test with measurement of plasma insulin and amylin concentrations every 30 min for 2 h. Body composition and BMD/height (to provide a quantity with the dimensions of volumetric density that is independent of body size) were measured by dual-energy X-ray absorptiometry, and volumetric density of the third lumbar vertebral body was calculated. Circulating insulin concentrations correlated with BMD/height and volumetric density of the third lumbar vertebral body (r = 0.28-0.52). They also were related to body weight (r = 0.34-0.56) and fat mass (r = 0.38-0.56) but were not independently related to lean mass on multiple regression. There were no consistent relationships between amylin levels and these variables. Multiple-regression analyses with fat mass and insulin levels as independent variables indicated that BMD/height of total body and femoral trochanter were primarily related to fat mass, whereas, in femoral neck, the significant relationship was with insulin. Volumetric density of the third lumbar vertebral body was related to insulin levels alone on this analysis.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1992

An e.x.a.f.s. study of the manganese O2-evolving complex in purified Photosystem II membrane fractions. The S1 and S2 states.

Manganese K-edge X-ray spectra have been obtained for Photosystem II samples isolated using Triton X-100 detergent and samples further purified by n-heptyl beta-D-thioglucoside detergent treatment to remove light-harvesting polypeptides and low-affinity calcium. The structure of the manganese complex is very similar for the two detergent preparations used. Analysis of the e.x.a.f.s. spectra for samples in the S1 and S2 states indicate changes in bond lengths for the shells of oxygen/nitrogen atoms. For the S1 state, oxygen shells at 0.181 and 0.193 nm (1.81 and 1.93 A) were observed and one manganese shell at 0.270 nm (2.70A). In the S2 state the oxygen bond lengths are longer at 0.184 and 0.200 nm (1.84 and 2.00 A). Additionally a shell of scatterers at 0.37 nm (3.7 A) was observed in both states which could be fitted to models with calcium scatterers at this distance.

Cell Membrane↗