Search PubMed⌕ Search

Biomedical subjects

M C Stuart

Publications and source records attributed to M C Stuart.

At least 19 recordsLinked to original sources
PubMed1998

Binding of annexin V to bilayers with various phospholipid compositions using glass beads in a flow cytometer.

Annexin V belongs to the family of calcium-dependent phospholipid binding proteins and binds almost solely to phosphatidylserine (PS). When annexin V is used to detect loss of membrane asymmetry in cellular systems, the binding properties under physiological conditions are of importance. Most biochemical studies use optimized binding conditions, conditions that are often far from physiological. For the interpretation of flow cytometric studies that use fluorescent annexin V to probe PS exposure, it is important to know what mixture of lipid species exposed in the outer leaflet of a membrane can evoke a positive annexin V signal. The lipid species is important in this respect as well as the concentration that just evokes a positive signal (detection level). Furthermore, the influence of the composition of the lipid matrix (cholesterol content, other phospholipid species) was investigated, as well as the influence of the calcium concentration on annexin V binding. In this study, we report on the binding of annexin V to phospholipid bilayers (adsorbed to glass beads) as measured by flow cytometry at physiological conditions. Annexin V binding was found to increase rapidly, with increasing PS concentrations up to a certain level (attained at 6 mol% PS). Further increase of the PS concentration resulted only in a slight increase of annexin V binding. Calcium concentrations below 3 mM were found to reduce the sensitivity of the binding assay. Phosphatidylethanolamine incorporated in the phospholipid bilayer resulted in a lower threshold for the binding assay, whereas sphingomyelin had no influence on the binding of annexin V and cholesterol reduces binding of annexin V to lipid bilayers. These data may help in the interpretation of results obtained from binding of annexin V to cell membranes (e.g., involved in apoptosis).

Annexin A5↗
PubMed1998

Surface exposure of phosphatidylserine during apoptosis of rat thymocytes precedes nuclear changes.

Cell surface exposure of phosphatidylserine (PS) during apoptosis serves recognition and removal of the dying cell by phagocytes. Loss of phospholipid asymmetry and PS exposure is investigated by immunocytochemistry and related to morphological changes. Loss of membrane asymmetry was determined on dexamethasone-treated rat thymocytes using the PS specific probe annexin V. Thymocytes incubated in the presence of dexamethasone were studied in time series during the execution of the apoptotic program. Thymocytes first start to expose PS at their cell surface. At this initial stage the barrier function of the plasma membrane remains intact. At a later stage the plasma membrane becomes leaky for compounds like propidium iodide and subsequently the cell disintegrates into apoptotic bodies. Microscopical evaluation of dexamethasone-treated thymocytes showed that the cells with an apoptotic morphology all bound annexin V. The cells with a normal viable morphology lacked annexin V binding except for those cells that started to shed small vesicles. These vesicles were positive for annexin V, indicating a local disturbance of the phospholipid asymmetry. The local exposure of PS is considered to be a very early event of apoptosis, preceding the full sequence of morphological changes at the ultrastructural level.

Animals↗
PubMed1997

Reevaluation of the effect of lysoyzme on Escherichia coli employing ultrarapid freezing followed by cryoelectronmicroscopy or freeze substitution.

Lysozyme is able to lyse Gram-positive bacteria acting as muramidase on the peptidoglycan polymer. Gram-negative bacteria in vitro are not lysed by lysozyme. It was assumed that the peptido-glycan is protected by the outer membrane and thus that Gram-negative bacteria are not affected by lysozyme without the aid of other factors such as EDTA or complement which enable lysozyme to penetrate the outer membrane. Accidentally, Pellegrini et al. [(1992) J. Appl. Bacteriol., 72:180-187] found that lysozyme per se is able to kill some Gram-negative bacteria. On the basis of morphological and immunocytochemical findings obtained from chemically fixed bacteria, it was concluded that lysozyme does not lyse Gram-negative bacteria but affects the cytoplasm of for example, Escherichia coli, leading to its disintegration, whilst the membranes do not break down. In an attempt to clarify the action of lysozyme on E. coli, we employed cryotechniques including ultrarapid freezing, cryomicroscopy and freeze substitution, and immunolabeling. Bacteria that were immediately frozen after exposure to lysozyme remained morphologically intact. Individual bacteria plated on agar after exposure to lysozyme were mostly intact when frozen within a few seconds. However, inner and outer membranes of 80% of the bacteria were disrupted, whereas the cytoplasm of only a few bacteria showed signs of disintegration when bacteria were frozen with a delay of only 5 min of plating onto pure agar or agar containing growth medium. After a period of time of 15 min between plating onto agar and freezing, about 97% of the bacteria showed changes of disintegration of various extent. Immunolabeling showed that lysozyme binds to the outer cell membrane and may penetrate the membrane, reaching the periplasmic space and possibly the inner cell membrane. The ultrastructural findings and the results of antibacterial assays suggest that lysozyme is bactericidal for E. coli but is not able to induce disintegration. Disintegration is accomplished by changes of the environment starting at the cell membranes. The mechanism by which lysozyme penetrates the membrane, the way it acts to be bactericidal, and the way disintegration is initiated remain to be clarified.

Escherichia coli↗
PubMed1995

Transmembrane gradient driven phase transitions within vesicles: lessons for drug delivery.

Phase transitions in closed vesicles, i.e., microenvironments defined by the size of the vesicle, its contents, and permeability of its membrane are becoming increasingly important in several scientific disciplines including catalysis, growth of small crystals, cell function studies, and drug delivery. The membrane composed from lipid bilayer is in general impermeable to ions and larger hydrophilic ions. Ion transport can be regulated by ionophores while permeation of neutral and weakly hydrophobic molecules can be controlled by concentration gradients. Some weak acids or bases, however, can be transported through the membrane due to various gradients, such as electrical, ionic (pH) or specific salt (chemical potential) gradients. Upon permeation of appropriate species and reaction with the encapsulated species precipitation may occur in the vesicle interior. Alternatively, these molecules can also associate with the leaflets of the bilayer according to the transmembrane potential. Efficient liposomal therapeutics require high drug to lipid ratios and drug molecules should have, especially when associated with long circulating liposomes, low leakage rates. In this article we present very efficient encapsulation of two drugs via their intraliposomal precipitation, characterize the state of encapsulated drug within the liposome and try to fit the experimental data with a recently developed theoretical model. Nice agreement between a model which is based on chemical potential equilibration of membrane permeable species with experimental data was observed. The high loading efficiencies, however are only necessary but not sufficient condition for effective therapies. If adequate drug retention within liposomes, especially in the case of long-circulating ones, is not achieved, the therapeutic index decreases substantially. Anticancer drug doxorubicin precipitates in the liposome interior in a form of gel with low solubility product and practically does not leak out in blood circulation in the scale of days. With an antibiotic, ciprofloxacin, the high loading efficacy and test tube stability is not reproduced in in vitro plasma leakage assays and in vivo. We believe that the reasons are higher solubility product of precipitated drug in the liposome, larger fraction of neutral molecules due closer pK values of the drug with the pH conditions in the solutions and high membrane permeability of this molecule. High resolution cryoEM shows that encapsulated anticancer agent doxorubicin is precipitated in the form of bundles of parallel fibers while antibiotic ciprofloxacin shows globular precipitate. Doxorubicin gelatin also causes the change of vesicle shape.

Animals↗
PubMed1995

Allergy to laboratory animals among animal handlers.

OBJECTIVE: To determine the prevalence among laboratory animal handlers of allergy to laboratory animals and of asthma and the factors associated with their development. DESIGN: A cross-sectional survey. SETTING: Teaching and research institutions in Sydney, between January 1989 and December 1992. PARTICIPANTS: Laboratory animal handlers (teaching and research staff, animal house workers and animal husbandry students and teachers). MAIN OUTCOME MEASURES: Duration of exposure to laboratory animals, allergic symptoms on contact, skin reactivity to laboratory and domestic animal allergens and evidence of current asthma. RESULTS: 228 subjects were surveyed. Allergy symptoms occurred in 73 (56%) of the subjects exposed to laboratory animals for three months or more. This group also had significantly higher prevalences of skin reactivity to laboratory animal allergens (62%) and bronchial hyperresponsiveness (21%) than those with shorter exposure (14% and 8%, respectively). Atopic subjects exposed to laboratory animals (particularly those sensitised to domestic animals) and animal attendants (with a high intensity of exposure to laboratory animals) had significantly higher frequencies of skin reactivity to laboratory animals and asthma than other subjects (77% and 30%, respectively, among exposed atopic subjects and 84% and 33%, respectively, among animal attendants). CONCLUSIONS: Allergy to laboratory animals is an occupational hazard among laboratory animal handlers, especially for those who are atopic and sensitised to domestic animals, and may lead to the development of asthma. Screening for atopy and skin reactivity to laboratory animals before and during employment would enable those at risk to take precautions.

Adult↗
PubMed1995

Ultrastructural detection of surface exposed phosphatidylserine on activated blood platelets.

Phosphatidylserine (PS) is normally restricted to the inner leaflet of the plasma membrane of cells (including blood platelets). Upon cell activation PS may become exposed to the outer surface of the cell. Cell membranes with surface exposed PS at the outside form a catalytic surface for coagulation reactions. When platelets are activated with ionophore or with thrombin in combination with thapsigargin, calcium induced scrambling of phospholipids takes place, resulting in PS exposure. Concomitant with PS exposition structural changes take place. On resting and activated platelets we combined the immunocytochemical detection of surface exposed PS with (ultra)structural information. Blood platelets were activated in the presence of annexin V, a protein which binds to PS in the presence of Ca2+. Annexin V was found to bind to lipid bilayers containing more than 5 mole % PS as estimated by binding of fluorescent-labelled annexin V to liposomes with varying PS concentrations. After vitrification, freeze-substitution and embedding of the platelets, annexin V was located on ultra thin sections, as detected by an anti-annexin V antibody and gold labelled protein A. Upon activation, the platelets show two different forms; irregular platelets with unchanged cytoplasm and round cells with apparently diluted cytoplasm. Activation with ionophore initially resulted in both forms, but after ten minutes only round platelets with diluted cytoplasm were observed. Both forms of these platelets as well as the microvesicles were found to be annexin V positive. However upon activation with thrombin in combination with thapsigargin, only the round cells with diluted cytoplasm and microvesicles were annexin V positive, whereas platelets with unchanged cytoplasm, even when microvesicles are present, are negative for annexin V.

Annexin A5↗
PubMed1993

Aggregation of phospholipid vesicles by a chimeric protein with the N-terminus of annexin I and the core of annexin V.

A chimeric protein was produced with the N-terminal domain (amino acids 1-45) of annexin I and the core of annexin V (amino acids 19-320). This protein, annexin IN-VC, has a similar Ca2+ requirement for binding to phospholipid bilayers of 20% phosphatidylserine (PS)/80% phosphatidylcholine (PC) as annexin V. In contrast to annexin V, this protein has a strong potency to aggregate phospholipid vesicles as is shown by turbidimetric measurements and cryo-electron microscopy. Ellipsometry was employed to study quantitatively the phenomenon of phospholipid vesicle adhesion to annexin IN-VC bound to a planar phospholipid bilayer. The amount of phospholipid vesicles bound by annexin IN-VC on the planar bilayer is proportional to its surface coverage and can be inhibited by coadsorption of annexin V on the planar bilayer or by shielding the phospholipid surface of the vesicles with blood coagulation factor Va. Annexin IN-VC, like annexin V, does not bind to pure PC bilayers, but its adsorption on anionic phospholipid bilayers brings about the capacity to bind pure PC vesicles. This suggests that annexin IN-VC generates or exposes after binding to anionic phospholipids another phospholipid binding site, that differs from the annexin V phospholipid binding site. Collectively, the data suggest that two-dimensional cluster formation of annexin IN-VC on a bilayer with anionic phospholipids is involved in vesicle adherence.

Adsorption↗
PubMed1993

Monitoring of unbound protein in vesicle suspensions with off-null ellipsometry.

In studies on the binding of proteins to small unilamellar phospholipid vesicles (SUV), the concentration of unbound protein usually remains unknown, because the vesicles cannot be separated from the bulk solution. In the present study, this limitation was overcome by addition of a supported planar phospholipid bilayer to the cuvette containing a vesicle suspension. Ellipsometric measurement of the protein adsorption velocities on this bilayer allowed determination of the concentrations of unbound protein. At high protein concentrations the adsorption is rapidly completed and the usual null-ellipsometry is too slow to obtain well-defined initial adsorption rates. Therefore, an off-null technique was developed, allowing measurement of the adsorbed protein mass at time intervals of 20 ms. Binding of prothrombin and coagulation factor Xa was measured in SUV suspensions prepared from a 20% dioleoylphosphatidylserine (DOPS) and 80% dioleoylphosphatidylcholine (DOPC) phospholipid mixture. For prothrombin, a dissociation constant Kd = 140 +/- 27 nM (mean +/- S.E.) and maximal surface concentration gamma max = (8.9 +/- 0.8) x 10(-3) mole of protein per mole of lipid, were obtained. For factor Xa, these values were Kd = 49.6 +/- 6.3 nM and gamma max = (23.0 +/- 1.4) x 10(-3) mole of protein per mole of lipid. These binding parameters are similar to those obtained earlier for planar bilayers. Apparently, the binding of factor Xa and prothrombin is not dependent on surface curvature.

Adsorption↗
PubMed1993

Isoelectric charge of recombinant human follicle-stimulating hormone isoforms determines receptor affinity and in vitro bioactivity.

Recombinant human FSH (rhFSH) was obtained by expressing the human FSH alpha- and beta-subunit complementary DNAs in the chinese hamster ovary cell line. Isoforms of rhFSH were resolved into specific isoelectric (pI) fractions by chromatofocusing. rhFSH isoforms ranged from pI 3.0-5.5 with a modal value of pI 4.2. Analysis of the biological activity of specific pI isoforms of rhFSH was undertaken using both the rat granulosa cell aromatase (in vitro) bioassay and a RRA. More acidic isoforms (e.g. pI 3.5) showed significantly lower affinity (P < 0.05) for rat testicular FSH receptors than did the less acidic isoforms (e.g. pI 4.8). Consistent with the receptor binding affinity data, the more acidic fractions resulted in significantly less activation (P < 0.05) of rat granulosa cell aromatase activity, as measured by estrogen production, than did the less acidic isoforms. The observed bioactivities and their correlation with the pI values of the rhFSH isoforms are consistent with observations of differing bioactivities seen in both pituitary and urinary FSH isoforms. These results demonstrate that rhFSH, made in the chinese hamster ovary cell line, is both biologically active and has isoform profiles, and presumably carbohydrate structures, that closely resemble those seen in natural hFSH.

Animals↗
PubMed1992

Gelation of liposome interior. A novel method for drug encapsulation.

Liposomes can be loaded with weak acids and bases, which exist in solutions in equilibrium with membrane permeable uncharged form, using various gradients across their membranes. Because in some cases the estimated drug concentration in the loaded liposomes exceeds their aqueous solubility we investigated the physical state of the liposome encapsulated anticancer drug Doxorubicin. X-Ray diffraction, electron microscopy, and test tube solubility experiments have shown that upon encapsulation the drug molecules form a gel-like phase.

Doxorubicin↗
PubMed1992

Clustering of lipid-bound annexin V may explain its anticoagulant effect.

In 1985 we isolated a new vascular anticoagulant protein VAC alpha, now called annexin V, with a high binding affinity (Kd less than 10(-10) M) for phospholipids. Its anticoagulant effect was attributed to displacement of coagulation factors from the phospholipid membrane. The present study demonstrates that the inhibition of prothrombinase activity by annexin V strongly depends on the curvature of the membrane surface and on the calcium concentration. Half-maximal inhibition of prothrombinase on and binding of annexin V to small vesicles, composed of 20% phosphatidylserine and 80% phosphatidylcholine, requires 2-3 mM calcium. With large vesicles and planar bilayers considerably less calcium is required for inhibition of prothrombinase and for lipid binding. Half-maximal binding of annexin V to large vesicles and to planar bilayers occurs at 0.7 and 0.2 mM calcium, respectively. This seemingly confirms the displacement model. The displacement of coagulation factors, however, proved to be incomplete, with residual surface concentrations of factors Xa, Va, and prothrombin sufficient for effective production of thrombin. Cryoelectron microscopy revealed that annexin V binding to large vesicles caused planar facets, indicating the formation of large sheets of clustered annexin V. Apparently, the formation of these two-dimensional arrays is promoted by calcium and hampered by high surface curvature. It is speculated that the complete inhibition (greater than 99%) of prothrombinase activity by annexin V is caused by the reduced lateral mobility of prothrombin and factor Xa in rigid sheets of annexin V covering the membrane.

Annexin A5↗
PubMed1991

Lipid polymorphism as observed by cryo-electron microscopy.

Lipid polymorphism was studied with the aim to gain more insight in bilayer to non-bilayer phase transitions, with particular emphasis on the development of cubic structures on one hand and inverted hexagonal structures on the other hand. Thin vitrified films prepared from aqueous lipid suspensions were used in this study. The entire hydrated contents of these films can be visualized in their two-dimensional projection by cryo-electron microscopy. As the starting material, unilamellar vesicles were prepared from mixtures of dioleoylphosphatidylethanolamine, dioleoylphosphatidylcholine and cholesterol. By heating of the suspension, vesicle fusion (Frederik et al. (1989) Biochim. Biophys. Acta 979, 275-278) and lipid polymorphism was induced. From these suspensions thin films were prepared at various temperatures, and vitrified for low temperature observation. In a parallel series of experiments samples were fast-frozen for freeze-fracture analysis. In vitrified thin films bilayer structures were often observed in coexistence with an inverted hexagonal structure. The bilayer areas were frequently of a complex structure because multiple contacts between stacked membranes were found. These contact points were variable in size and shape and usually had the form of a diabolo (when viewed side-on) giving the impression of a bilayer contact with an aqueous channel. This structure is compatible with the interlamellar attachment site (ILA) proposed by Siegel ((1986) Biophys. J. 49, 1155-1170). In some specimens ILA's seemed to merge into arrays. After thermal cycling of the suspension, arrays of packed globules were observed, which are likely the result of close packing of ILA's. The arrays probably represent a cubic structure. A comparison of freeze-fracture replicas and vitrified thin films indicated that both techniques may provide valuable structural information on lipid polymorphism. Most of the lipidic particles observed by freeze-fracturing probably correspond to the ILA's (fractured around their waist region) as observed in vitrified thin films. The results obtained with vitrified thin films were interpreted in relation to the principles of thin-film formation. Finally, we speculate that lipid structures occurring close to each other in space may represent a developmental series of structures occurring successively in time.

Cholesterol↗
PubMed1991

Perspective and limitations of cryo-electron microscopy. From model systems to biological specimens.

We investigated the possibility of vitrifying temperature-sensitive lipid phases as well as (small) biological specimens. From a suspension of unilamellar vesicles, prepared from dipalmitoyl-phosphatidylcholine (DPPC), thin aqueous films were formed at various temperatures. With cryo-electron microscopy vesicles were found to be smooth, rippled and faceted or faceted only, depending on the temperature of thin-film formation (318, 312 and 296 K respectively). The morphology and the electron diffraction patterns indicate that membranes can by physically fixed by vitrification in their high-temperature configuration and studied at low temperature by cryo-electron microscopy. This finding suggests that it may also be possible to preserve, in their original state, the more complex membrane systems found in living organisms by initiating rapid-cooling at a physiological temperature. This was explored by vitrification of thin films formed on specimen grids with (human) blood platelets adhering to collagen fibres. Low-temperature observation with an acceleration voltage of 120 kV revealed subcellular details, More details were observed when using higher accelerating voltages (200 and 300 kV) of the electron beam. The results presented in this paper illustrate the great potential of cryo-electron microscopy in the study of membrane dynamics, both in relatively simple model membrane systems and in more complex biological membrane systems.

Blood Platelets↗
PubMed1991

Influence of nutritional status on growth hormone-dependent circulating somatomedin-C activity in mature sheep.

The effect of daily administration of ovine GH for a period of 4 weeks on somatomedin-C biological activity in plasma was investigated in mature Merino sheep fed a maintenance energy intake (low plane; LP) or 1.6 times this amount (high plane; HP). The GH treatment resulted in a significant (P less than 0.05) increase in plasma GH levels in blood samples collected 23.5 h after each daily injection in both LP and HP groups. Plasma concentrations of somatomedin-C activity and insulin were significantly stimulated to a maximum level by the third GH injection and remained at this level for 7 days. Subsequently, circulating levels of both hormones fell to 40-50% of the peak response to GH and returned to basal levels within 48 h of the cessation of GH injections. In the HP group the response of plasma insulin and somatomedin-C activity to GH injection was greater than in the LP group.

Animals↗
PubMed1991

The ultrastructure of cryo-sections and intact vitrified cells--the effects of cryoprotectants and acceleration voltage on beam induced bubbling.

Chemically fixed pancreas was infiltrated with various cryoprotectants to obtain homogeneously vitrified samples upon cooling. The suitability of these samples for cryoultramicrotomy was tested. Contrast was hardly detectable initially in thin cryo-sections but increased upon irradiation, irrespective of the cryoprotectant (glycerol, propylene glycol, methanol) used. Contrast and beam damage were analyzed in vitrified thin films from collagen, phospholipid vesicles and various concentrations of glycerol. Glycerol increased the beam sensitivity of both collagen and phospholipid vesicles, but diminished the contrast between matrix and lipid vesicles or collagen fibers. The effects of glycerol as observed in thin films explain some of the effects of cryoprotectants in thin cryo-sections. To reduce beam damage in vitrified specimens two approaches are proposed. Firstly, when vitrified films are prepared, dilute suspensions should be used without cryoprotectant. In some cases, such as (thin) intact cells, the composition of the suspended material can only be marginally influenced. Then a second approach can be used involving the application of higher accelerating voltages (e.g. 300 kV). This has two advantages; the increase in mean free path-length of the electrons causes less beam damage on one hand and allows better resolution of thick specimens on the other hand. Micrographs from E. coli bacteria vitrified from suspension illustrate some of the potentials of "intermediate voltage" cryo-electron microscopy.

Animals↗
PubMed1990

Effect of biosynthetic human growth hormone on insulin action in individual tissues of the rat in vivo.

Excessive endogenous production or exogenous administration of human growth hormone (hGH) causes insulin resistance at both the hepatic and extrahepatic levels. However, which extrahepatic tissues are involved have not been defined. We have examined the diabetogenic action of authentic biosynthetic hGH on whole body glucose disposal, hepatic glucose output, and glucose metabolism in individual peripheral tissues. The use of a highly purified preparation of the hormone allowed us to examine the isolated effects of 22K hGH. The euglycemic hyperinsulinemic (approximately 100 mU/L) clamp plus 3H-2-deoxyglucose technique was used to quantitate the effects of hGH on insulin action in vivo. Administration of biosynthetic hGH at a dose of 10 IU/kg/24 h for 48 hours in male Wistar rats (approximately 340 g) produced a highly significant decrease in the steady state clamp glucose infusion rate (GIR) when compared with controls (8.1 +/- 0.6 v 18.7 +/- 0.7 mg/kg/min, P less than .001), reduced insulin-mediated suppression of hepatic glucose output (Ra) (3.9 +/- 0.6 v 0.7 +/- 0.3 mg/kg/min, P less than .05) and a decreased clamp glucose disposal rate (Rd) (12.0 +/- 0.4 v 18.10 +/- 1.1 mg/kg/min, P less than .001). There was a significant decrease in insulin-mediated glucose uptake as indicated by tissue accumulation of [3H]-2-deoxyglucose phosphorylation in diaphragm and hindlimb muscles. Insulin action was more substantially reduced in muscles (approximately 50%) than in adipose tissues (approximately 20%). These studies confirm that the diabetogenic action of hGH in the rat is due to a combination of inhibition of insulin suppression of hepatic glucose output and inhibition of the uptake and subsequent utilization of glucose in skeletal muscles.

Adipose Tissue↗
PubMed1990

Somatomedin-C, physical fitness, and bone density.

Somatomedin-C (Sm-C) or insulin-like growth factor-I, GH and physical fitness decline with age. Physical fitness and muscle strength are important determinants of bone density, and the age-related decline in bone density may be related in part to a decline in fitness and muscle strength. Also, Sm-C has been shown to stimulate osteoblasts in vitro and may effect skeletal muscle mass. We postulated that the age-related decline in GH and Sm-C levels may be related to an age-related decline in physical fitness and/or muscle strength, and the effect of physical fitness and muscle strength on bone may be mediated by Sm-C. We, therefore, examined the relationship between circulating GH and Sm-C levels and physical fitness, as determined by predicted maximal oxygen uptake (VO2max) in 134 normal women, 34 of whom were postmenopausal. In a subgroup of 62 women overall muscle strength was estimated as the sum of the Z-sores for biceps, quadriceps, and grip strength. Overall muscle strength correlated with GH levels (r = 0.28; P less than 0.02), but not with Sm-C levels. There was a significant positive relationship between plasma Sm-C levels and VO2max in all women (r = 0.47; P less than 0.001) and in the postmenopausal group alone (r = 0.05; P less than 0.01). Although there was a significant negative relationship between Sm-C and age (r = -0.36; P = 0.001), VO2max was a better independent predictor than age (r = 0.47; P = 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗