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Biomedical subjects

M A Ferguson

Publications and source records attributed to M A Ferguson.

At least 19 recordsLinked to original sources
PubMed2006

Effect of resistance training on risk of coronary artery disease in women with multiple sclerosis.

The effects of a lower-extremity progressive resistance-training program (PRT) on risk factors for coronary artery disease (CAD) were determined in patients with multiple sclerosis (MS). Twelve ambulatory women with MS (47.3+/-4.7 years; Expanded Disability Status Score (EDSS), 4.00+/-1.37) completed twice weekly lower-body PRT for 8 weeks. Knee extensor and ankle flexor strength improved significantly (p<0.05) after training, and self-reported fatigue decreased (p<0.05). Serum triglyceride concentrations decreased (p<0.05) but body-weight and fatness, blood pressure, and serum glucose, total cholesterol and high-density lipoprotein cholesterol were unchanged. However, the number of CAD risk factors that reached the clinical threshold for each subject declined after PRT, suggesting that resistance training can promote CAD risk reduction in ambulatory female MS subjects.

Activities of Daily Living↗
PubMed2005

Lipid and lipoprotein changes in premenstrual women following step aerobic dance training.

Exercise training can improve lipid and lipoprotein concentrations and reduce the risk of heart disease. Little information is available concerning aerobic dance training and lipoprotein concentration changes in women. The purpose of this study was to compare the effects of two different methods of step bench training on cardiorespiratory fitness, body composition, and lipoprotein concentrations in college-aged females. Subjects were assigned to one of three groups: a traditional continuous step (CS), an interval step group (IS), or a non-exercise control group (C). The CS and the IS groups participated in three 50-minute sessions for 12 weeks. The CS session included a warm-up, 30-35 min of continuous bench stepping, 10-15 min of calisthenic exercises, and a 5-min cool-down. The IS sessions included a 5-7-min warm-up, 35-40 min of alternating intervals of bench stepping and non-step aerobic dance, and a 5-7-min cool-down. Target heart rates were maintained within 70 to 85% of maximal heart rate. Results showed increases in HDL-C concentrations in the IS group (p<0.05). Decreases in percent body fat were evident in both dance groups (p<0.05) and cardiovascular fitness increased in both groups (p<0.01). No changes were evident in the control group. In college-aged women, 12 weeks of IS or CS training improved cardiorespiratory fitness and body composition. In addition, IS training appears to have a greater effect on HDL-C concentrations than CS training.

Adolescent↗
PubMed2005

Effect of exercise duration on plasma endothelin-1 concentration.

AIM: Endothelin-1 (ET-1) is a potent vasoconstricting peptide released mostly from vascular endothelial cells. Isolated exercise sessions of relatively long duration (=or>30 min) have produced increases in plasma ET-1 concentration while shorter exercise sessions usually have not. The purpose of the present study was to verify an effect of exercise duration at a steady work rate on plasma ET-1 concentration. METHODS: Eleven endurance-trained males (age 27+/-6 years; maximal oxygen consumption--VO2max--56+/-7 mLxkg-1xmin-1, body fat 11+/-5%; mean+/-SD) exercised on a treadmill at 70% VO2max on 2 occasions separated by at least 2 weeks. During a short-duration session, subjects expended approximately 3,360 kJ (60+/-2 min). During a long-duration session, subjects expended approximately 6,300 kJ (112+/-4 min). Six of the subjects performed the 3,360 kJ session before the 6,300 kJ session while the other 5 subjects performed the 6,300 kJ session first. RESULTS: The short-duration session did not cause plasma ET-1 concentration to change immediately after exercise (0.23+/-0.01 pmolxL-1 before exercise, 0.22+/-0.02 pmolxL-1 after exercise, mean+/-SE). However, 10 of 11 subjects had increased ET-1 after the long-duration session (0.28+/-0.02 pmolxL-1 before exercise, 0.32+/-0.02 pmolxL-1 after exercise, P=0.0004). A treatment-by-time effect was present (P=0.003). CONCLUSION: These results demonstrate an effect of exercise duration on plasma ET-1 concentration. Exercise duration is, therefore, an essential consideration when investigating exercise's effect on ET-1.

Adult↗
PubMed2005

Exercise in a hot environment: comparison of two different fluid intake patterns.

AIM: Extensive research has been undertaken in the area of exercise and hydration. Most work has focused on prehydration. Less is known about different fluid intake patterns during exercise and its effect in thermoregulatory variables in hot environments. This study attempted to determine if ingesting fluid either in a single bolus or intermittently during exercise had different results in thermoregulatory parameters and thirst in a hot environment. METHODS: Six moderately trained men and women (n=6, 5 male, 1 female; mean+/-SD: age 28.5+/-2.5 y; weight 74.4+/-3.3 kg, VO2max 45.9+/-3.7 ml.kg.min-1) completed 2 exercise sessions in a randomized, counterbalanced order. Treatment 1 (bolus) consisted of 60 minutes of bicycling at 50% of VO2max in a climatic chamber (dry bulb temperature, 35 degrees C, 45% relative humidity). Subjects consumed 1 000 ml of plain cool (22 degrees C) water immediately before exercise. During treatment 2 (intermittent) the same environmental conditions were present, but subjects consumed 250 ml of water immediately before exercise. During the bicycle ride, subjects consumed 250 ml of cool water at minutes 15, 30, and 45 of exercise for a total trial volume of 1,000 ml. Tympanic ear temperatures, heart rates, rating of perceived exertion (RPE), and thirst scale data were collected immediately before exercise and at minutes 10, 20, 30, 40, 50, and 60 of exercise. RESULTS: No statistical differences were noted in temperature between treatments (P>0.05). Lower heart rates and thirst scores were noted for the bolus treatment at various time points (P<0.05). Little differences were noted between treatments for RPE during exercise. CONCLUSIONS: These results suggest that consumption of water in a single bolus is more beneficial for some aspects of thermoregulatory control and delaying thirst during exercise in the heat. Additional mechanistic studies with larger sample sizes are warranted.

Adult↗
PubMed2003

Plasma lipid and lipoprotein responses during exercise.

The purpose of this study was to examine the effect of prolonged exercise on plasma lipid and lipoprotein concentrations and to identify caloric time-points where changes occurred. Eleven active male subjects ran on a treadmill at 70% of maximal fitness (VO2max) and expended 6278.7 kilojoules (Kj) energy (1500 kcal). Blood samples were obtained at the 4185.8 Kj (1000 kcal) timepoint during exercise and at each additional 418.6 Kj (100 kcal) expenditure until 6278.7 Kj was expended. After correcting for plasma volume changes, decreases in low-density lipoprotein cholesterol (LDL-C) were observed during exercise at time-points corresponding to 4604.4 and 5441.5 Kj (1100 and 1300 kcal) of energy expenditure, and immediately after exercise. Total cholesterol concentrations decreased significantly at exercise kilojoule expenditures of 4604.4, 5441.5 and 5860.1 (1100, 1300 and 1400 kcal). There were also exercise induced increases in high-density lipoprotein cholesterol (HDL-C) and HDL2-C concentrations immediately after exercise. Although acute lipid and lipoprotein changes are typically reported in the days following exercise, the current data indicate that some lipoprotein concentrations change during acute exercise. Our data suggest that a threshold of exercise may be necessary to change lipoproteins during exercise. Future work should identify potential mechanisms (lipoprotein lipase, cholesterol ester transport protein, LDL uptake) that alter lipoprotein concentrations during prolonged exercise.

Adult↗
PubMed2001

Purification, cloning and characterization of a GPI inositol deacylase from Trypanosoma brucei.

Inositol acylation is an obligatory step in glycosylphosphatidylinositol (GPI) biosynthesis whereas mature GPI anchors often lack this modification. The GPI anchors of Trypanosoma brucei variant surface glycoproteins (VSGs) undergo rounds of inositol acylation and deacylation during GPI biosynthesis and the deacylation reactions are inhibited by diisopropylfluorophosphate (DFP). Inositol deacylase was affinity labelled with [3H]DFP and purified. Peptide sequencing was used to clone GPIdeAc, which encodes a protein with significant sequence and hydropathy similarity to mammalian acyloxyacyl hydrolase, an enzyme that removes fatty acids from bacterial lipopolysaccharide. Both contain a signal sequence followed by a saposin domain and a GDSL-lipase domain. GPIdeAc(-/-) trypanosomes were viable in vitro and in animals. Affinity-purified HA-tagged GPIdeAc was shown to have inositol deacylase activity. However, total inositol deacylase activity was only reduced in GPIdeAc(-/-) trypanosomes and the VSG GPI anchor was indistinguishable from wild type. These results suggest that there is redundancy in T.brucei inositol deacylase activity and that there is another enzyme whose sequence is not recognizably related to GPIdeAc.

3' Untranslated Regions↗
PubMed2001

Specificity of GlcNAc-PI de-N-acetylase of GPI biosynthesis and synthesis of parasite-specific suicide substrate inhibitors.

The substrate specificities of Trypanosoma brucei and human (HeLa) GlcNAc-PI de-N-acetylases were determined using 24 substrate analogues. The results show the following. (i) The de-N-acetylases show little specificity for the lipid moiety of GlcNAc-PI. (ii) The 3'-OH group of the GlcNAc residue is essential for substrate recognition whereas the 6'-OH group is dispensable and the 4'-OH, while not required for recognition, cannot be epimerized or substituted. (iii) The parasite enzyme can act on analogues containing betaGlcNAc or aromatic N-acyl groups, whereas the human enzyme cannot. (iv) Three GlcNR-PI analogues are de-N-acetylase inhibitors, one of which is a suicide inhibitor. (v) The suicide inhibitor most likely forms a carbamate or thiocarbamate ester to an active site hydroxy-amino acid or Cys or residue such that inhibition is reversed by certain nucleophiles. These and previous results were used to design two potent (IC50 = 8 nM) parasite-specific suicide substrate inhibitors. These are potential lead compounds for the development of anti-protozoan parasite drugs.

Acetates↗
PubMed2001

Binding site differences revealed by crystal structures of Plasmodium falciparum and bovine acyl-CoA binding protein.

Acyl-CoA binding protein (ACBP) maintains a pool of fatty acyl-CoA molecules in the cell and plays a role in fatty acid metabolism. The biochemical properties of Plasmodium falciparum ACBP are described together with the 2.0 A resolution crystal structures of a P. falciparum ACBP-acyl-CoA complex and of bovine ACBP in two crystal forms. Overall, the bovine ACBP crystal structures are similar to the NMR structures published previously; however, the bovine and parasite ACBP structures are less similar. The parasite ACBP is shown to have a different ligand-binding pocket, leading to an acyl-CoA binding specificity different from that of bovine ACBP. Several non-conservative differences in residues that interact with the ligand were identified between the mammalian and parasite ACBPs. These, together with measured binding-specificity differences, suggest that there is a potential for the design of molecules that might selectively block the acyl-CoA binding site.

Amino Acid Sequence↗
PubMed2001

Requirement of mitogen-activated protein kinases and I kappa B phosphorylation for induction of proinflammatory cytokines synthesis by macrophages indicates functional similarity of receptors triggered by glycosylphosphatidylinositol anchors from parasitic protozoa and bacterial lipopolysaccharide.

In the present study, we evaluated the ability of GPI-anchored mucin-like glycoproteins purified from Trypanosoma cruzi trypomastigotes (tGPI-mucin) to trigger phosphorylation of different mitogen-activated protein kinases (MAPKs) and related transcription factors in inflammatory macrophages. Kinetic experiments show that the peak of extracellular signal-related kinase (ERK)-1/ERK-2, stress-activated protein kinase (SAPK) kinase-1/mitogen-activated protein kinase (MAPK) kinase-4, and p38/SAPK-2, phosphorylation occurs between 15 and 30 min after macrophage stimulation with tGPI-mucin or GPI anchors highly purified from tGPI-mucins (tGPI). The use of the specific inhibitors of ERK-1/ERK-2 (PD 98059) and p38/SAPK-2 (SB 203580) phosphorylation also indicates the role of MAPKs, with possible involvement of cAMP response element binding protein, in triggering TNF-alpha and IL-12 synthesis by IFN-gamma-primed-macrophages exposed to tGPI or tGPI-mucin. In addition, tGPI-mucin and tGPI were able to induce phosphorylation of I kappa B, and the use of SN50 peptide, an inhibitor of NF-kappa B translocation, resulted in 70% of TNF-alpha synthesis by macrophages exposed to tGPI-mucin. Finally, the similarity of patterns of MAPK and I kappa B phosphorylation, the concentration of drugs required to inhibit cytokine synthesis, as well as cross-tolerization exhibited by macrophages exposed to tGPI, tGPI-mucin, or bacterial LPS, suggest that receptors with the same functional properties are triggered by these different microbial glycoconjugates.

Activating Transcription Factor 2↗
PubMed2001

Effects of mental stress on coronary epicardial vasomotion and flow velocity in coronary artery disease: relationship with hemodynamic stress responses.

OBJECTIVES: This study examines the prevalence and hemodynamic determinants of mental stress-induced coronary vasoconstriction in patients undergoing diagnostic coronary angiography. BACKGROUND: Decreased myocardial supply is involved in myocardial ischemia triggered by mental stress, but the determinants of stress-induced coronary constriction and flow velocity responses are not well understood. METHODS: Coronary vasomotion was assessed in 76 patients (average age 59.9 +/- 10.4 years; eight women). Coronary flow velocity responses were assessed in 20 of the 76 patients using intracoronary Doppler flow. Repeated angiograms were obtained after a baseline control period, a 3-min mental arithmetic task and administration of 200 microg intracoronary nitroglycerin. Arterial blood pressure (BP) and heart rate assessments were made throughout the procedure. RESULTS: Mental stress resulted in significant BP and heart rate increases (p < 0.001). Coronary constriction (>0.15 mm) was observed in 11 of 59 patients with coronary artery disease (CAD) (18.6%). Higher mental stress pressor responses were associated with more constriction in diseased segments (rdeltaSBP = -0.26, rdeltaDBP = -0.30, rdeltaMAP = -0.29; p's < 0.05) but not with responses in nonstenotic segments. The overall constriction of diseased segments was not significant (p > 0.10), whereas a small but significant constriction occurred in nonstenotic segments (p = 0.04). Coronary flow velocity increased in patients without CAD (32.2%; p = 0.008), but not in patients with CAD (6.4%; p = ns). Cardiovascular risk factors were not predictive of stress-induced vasomotion in patients with CAD. CONCLUSIONS: Coronary vasoconstriction in angiographically diseased arteries varies with hemodynamic responses to mental arousal. Coronary flow responses are attenuated in CAD patients. Thus, combined increases in cardiac demand and concomitant reduced myocardial blood supply may contribute to myocardial ischemia with mental stress.

Aged↗
PubMed2001

Contralateral suppression of transient evoked otoacoustic emissions in patients with cerebello-pontine angle tumor.

OBJECTIVE: During measurement of transient evoked otoacoustic emissions (TEOAEs), acoustic stimulation of the contralateral ear reduces or suppresses TEOAE amplitude. This is thought to be due to the inhibitory control that the medial efferent auditory nerve exerts on outer hair cell (OHC) function. The main aim of this study was to investigate the effect of cerebello-pontine angle (CPA) tumor on the medial efferent nerve pathways to both tumor and non-tumor ears by examining alterations in TEOAE amplitude that result from contralateral acoustic stimulation. DESIGN: Contralateral suppression of TEOAEs using broadband noise was measured preoperatively in 17 patients with unilateral CPA tumor and 17 normally hearing controls, matched for age and gender. RESULTS: The control ears demonstrated significantly more suppression than the tumor and non-tumor ears in the patient group. There was, however, no significant difference in suppression between the tumor and non-tumor ears, and the statistical correlation for suppression between them was high. There was no effect of gender, hearing threshold levels, or size and type of tumor on suppression, although there was an effect of age on suppression in both the control and patient groups where suppression reduced as age increased. Four of the 17 patients had TEOAEs, which were clearly present in the tumor ear despite substantial hearing loss, three of which had no measurable hearing. CONCLUSIONS: It is hypothesized that neural compression by CPA tumor disrupts the medial efferent nerve control mechanism to the OHCs of tumor ears. It also is hypothesized that neural compression reduces transmission of afferent nerve impulses from the tumor ear, which cross over to the medial olivo-cochlear complex and reduce the inhibitory control of OHC function in the non-tumor cochlea.

Acoustic Impedance Tests↗
PubMed2001

Effects of short-duration and long-duration exercise on lipoprotein(a).

PURPOSE: Most studies that use either a single exercise session, exercise training, or a cross-sectional design have failed to find a relationship between exercise and plasma lipoprotein(a) [Lp(a)] concentrations. However, a few studies investigating the effects of longer and/or more strenuous exercise have shown elevated Lp(a) concentrations, possibly as an acute-phase reactant to muscle damage. Based on the assumption that greater muscle damage would occur with exercise of longer duration, the purpose of the present study was to determine whether exercise of longer duration would increase Lp(a) concentration and creatine kinase (CK) activity more than exercise of shorter duration. METHODS: Ten endurance-trained men (mean +/- SD: age, 27 +/- 6 yr; maximal oxygen consumption [VO(2max)], 57 +/- 7 mL x kg(-1) x min(-1)) completed two separate exercise sessions at 70% VO(2max). One session required 800 kcal of energy expenditure (60 +/- 6 min), and the other required 1500 kcal (112 +/- 12 min). Fasted blood samples were taken immediately before (0-pre), immediately after (0-post), 1 d after (1-post), and 2 d after (2-post) each exercise session. RESULTS: CK activity increased after both exercise sessions (mean +/- SE; 800 kcal: 0-pre 55 +/- 11, 1-post 168 +/- 64 U x L(-1) x min(-1); 1500 kcal: 0-pre 51 +/- 5, 1-post 187 +/- 30, 2-post 123 +/- 19 U x L(-1) x min(-1); P < 0.05). However, median Lp(a) concentrations were not altered by either exercise session (800 kcal: 0-pre 5.0 mg x dL(-1), 0-post 3.2 mg x dL(-1), 1-post 4.0 mg x dL(-1), 2-post 3.4 mg x dL(-1); 1500 kcal: 0-pre 5.8 mg x dL(-1), 0-post 4.3 mg x dL(-1), 1-post 3.2 mg x dL(-1), 2-post 5.3 mg x dL(-1)). In addition, no relationship existed between exercise-induced changes in CK activity and Lp(a) concentration (800 kcal: r = -0.26; 1500 kcal: r = -0.02). CONCLUSION: These results suggest that plasma Lp(a) concentration will not increase in response to minor exercise-induced muscle damage in endurance-trained runners.

Adult↗
PubMed2001

Blood lipid and lipoprotein adaptations to exercise: a quantitative analysis.

Dose-response relationships between exercise training volume and blood lipid changes suggest that exercise can favourably alter blood lipids at low training volumes, although the effects may not be observable until certain exercise thresholds are met. The thresholds established from cross-sectional literature occur at training volumes of 24 to 32 km (15 to 20 miles) per week of brisk walking or jogging and elicit between 1200 to 2200 kcal/wk. This range of weekly energy expenditure is associated with 2 to 3 mg/dl increases in high-density lipoprotein-cholesterol (HDL-C) and triglyceride (TG) reductions of 8 to 20 mg/dl. Evidence from cross-sectional studies indicates that greater changes in HDL-C levels can be expected with additional increases in exercise training volume. HDL-C and TG changes are often observed after training regimens requiring energy expenditures similar to those characterised from cross-sectional data. Training programmes that elicit 1200 to 2200 kcal/wk in exercise are often effective at elevating HDL-C levels from 2 to 8 mg/dl, and lowering TG levels by 5 to 38 mg/dl. Exercise training seldom alters total cholesterol (TC) and low-density lipoprotein-cholesterol (LDL-C). However, this range of weekly exercise energy expenditure is also associated with TC and LDL-C reductions when they are reported. The frequency and extent to which most of these lipid changes are reported are similar in both genders, with the exception of TG. Thus, for most individuals, the positive effects of regular exercise are exerted on blood lipids at low training volumes and accrue so that noticeable differences frequently occur with weekly energy expenditures of 1200 to 2200 kcal/wk. It appears that weekly exercise caloric expenditures that meet or exceed the higher end of this range are more likely to produce the desired lipid changes. This amount of physical activity, performed at moderate intensities, is reasonable and attainable for most individuals and is within the American College of Sports Medicine's currently recommended range for healthy adults.

Adult↗
PubMed2000

Parasite-specific inhibition of the glycosylphosphatidylinositol biosynthetic pathway by stereoisomeric substrate analogues.

The natural substrate for the first alpha-D-mannosyltransferase of glycosylphosphatidylinositol biosynthesis in the protozoan parasite Trypanosoma brucei is D-GlcNalpha1-6-D-myo-inositol-1-P-sn-1, 2-diacylglycerol. Here we show that a diastereoisomer, D-GlcNalpha1-6-L-myo-inositol-1-P-sn-1,2-diacylglycerol, is an inhibitor of this enzyme in a trypanosomal cell-free system. Tests with other L-myo-inositol-containing compounds revealed that L-myo-inositol-1-phosphate is the principal inhibitory component and that methylation of the 2-OH group of the L-myo-inositol residue abolishes any inhibition. Comparisons between the natural substrate and the inhibitors suggested that the inhibitors bind to the first alpha-D-mannosyltransferase by means of charge interactions with the 1-phosphate group and/or hydrogen bonds involving the 3-, 4-, and 5-OH groups of the L-myo-inositol residue, which are predicted to occupy orientations identical to those of the 1-phosphate and 5-, 4-, and 3-OH groups, respectively, of the D-myo-inositol residue of the natural substrate. However, additional experiments indicated that the 4-OH group of the D-myo-inositol residue is unlikely to be involved in substrate recognition. None of the L-myo-inositol-containing compounds that inhibited glycosylphosphatidylinositol (GPI) biosynthesis in a parasite cell-free system had any effect on GPI biosynthesis in a comparable human (HeLa) cell-free system, suggesting that other related parasite-specific inhibitors of this essential pathway might be developed.

Animals↗
PubMed2000

Characterization of the elongating alpha-D-mannosyl phosphate transferase from three species of Leishmania using synthetic acceptor substrate analogues.

Leishmania express lipophosphoglycans and proteophosphoglycans that contain Galbeta1-4Manalpha1-P phosphosaccharide repeat structures assembled by the sequential addition of Manalpha1-P and betaGal. The synthetic acceptor substrate Galbeta1-4Manalpha1-P-decenyl and a series of analogues were used to probe Leishmania alpha-D-mannosyl phosphate transferase activity. We show that the activity detected with Galbeta1-4Manalpha1-P-decenyl is the elongating alpha-D-mannosyl phosphate transferase associated with lipophosphoglycan biosynthesis (eMPT(LPG)). Differences in the apparent K(m) values for the donor and acceptor substrates were found using L. major, L. mexicana, and L. donovani promastigote membranes, but total activity correlated with the number of lipophosphoglycan repeats. Further comparisons showed that lesion-derived L. mexicana amastigotes, that do not express lipophosphoglycan, lack eMPT(LPG) and that nondividing L. major metacyclic promastigotes contain 5-fold less eMPT(LPG) activity than dividing procyclic promastigotes. The fine specificity of promastigote eMPT(LPG) activity was determined using 24 synthetic analogues of Galbeta1-4Manalpha1-P-decenyl. The three species gave similar results: the negative charge of the phosphodiester and the C-6 hydroxyl of the alphaMan residue are essential for substrate recognition, the latter most likely acting as a hydrogen bond acceptor. The C-6' hydroxyl of the betaGal residue is required for substrate recognition as well as for catalysis. The rate of Manalpha1-P transfer declines with increasing acceptor substrate chain length. The presence of a monosaccharide substituent at the C-3 position of the terminal betaGal residue abrogates Man-P transfer, showing that chain elongation must precede side chain modification during lipophosphoglycan biosynthesis. In contrast, substitution of the penultimate phosphosaccharide repeat does not abrogate transfer but is slightly stimulatory in L. mexicana and inhibitory in L. major.

Amino Acid Sequence↗