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Biomedical subjects

M Barnard

Publications and source records attributed to M Barnard.

At least 19 recordsLinked to original sources
PubMed1999

Angiotensin-converting-enzyme gene insertion/deletion polymorphism and response to physical training.

BACKGROUND: The function of local renin-angiotensin systems in skeletal muscle and adipose tissue remains largely unknown. A polymorphism of the human angiotensin converting enzyme (ACE) gene has been identified in which the insertion (I) rather than deletion (D) allele is associated with lower ACE activity in body tissues and increased response to some aspects of physical training. We studied the association between the ACE gene insertion or deletion polymorphism and changes in body composition related to an intensive exercise programme, to investigate the metabolic effects of local human renin-angiotensin systems. METHODS: We used three independent methods (bioimpedance, multiple skinfold-thickness assessment of whole-body composition, magnetic resonance imaging of the mid-thigh) to study changes in body composition in young male army recruits over 10 weeks of intensive physical training. FINDINGS: Participants with the II genotype had a greater anabolic response than those with one or more D alleles for fat mass (0.55 vs -0.20 kg, p=0.04 by bioimpedance) and non-fat mass (1.31 vs -0.15 kg, p=0.01 by bioimpedance). Changes in body morphology with training measured by the other methods were also dependent on genotype. INTERPRETATION: II genotype, as a marker of low ACE activity in body tissues, may conserve a positive energy balance during rigorous training, which suggests enhanced metabolic efficiency. This finding may explain some of the survival and functional benefits of therapy with ACE inhibitors.

Adipose Tissue↗
PubMed1999

Esophageal-directed pressure support ventilation in normal volunteers.

STUDY OBJECTIVES: To ascertain whether inspiratory pressure support (IPS) can be triggered reliably from and targeted at esophageal pressures (Pes), and to compare the work of breathing and time delay to initiation of inspiratory flow between conventional pressure support and esophageal-directed pressure support (EDPS). DESIGN: Prospective laboratory study. SETTING: University medical school. PATIENTS OR PARTICIPANTS: Five normal volunteers. INTERVENTIONS: IPS at a level to achieve tidal volume of 10 mL/kg, and EDPS with a target Pes of 0 cm H2O via full facemask. MEASUREMENTS AND RESULTS: Pes, airway pressure, and inspiratory flow were measured during spontaneous breathing. Peak Pes and pressure time product (PTP) of Pes were calculated during spontaneous breathing and through linear resistances. Measurements were repeated during IPS and EDPS ventilation. At rest, PTP was 7.56 (+/- 3.6) and peak Pes was -5.8 cm H2O (+/- 1.44). When subjects were breathing through the resistors, PTP increased to 12.4 (+/- 8.1) and 30.3 (+/- 8.9) and peak Pes decreased to -7.2 and -15.3 cm H2O respectively. With facemask IPS, unloaded PTP fell to 1.7 (+/- 1.3) and peak Pes fell to -3.3 cm H2O (+/- 1.3). When ventilated through the highest resistance with IPS, mean PTP increased to 21.9 and peak Pes increased to -11.9 (+/- 4.2) cm H2O relative to baseline. During EDPS with the resistor, PTP fell to 1.5+/-1.1 (p < 0.007) and peak Pes fell to -1.9+/-1.1 cm H2O (p < 0.0001). CONCLUSIONS: It was possible to initiate supported breathing from Pes values. The work performed, as measured by PTP, was lower during EDPS than during either unsupported breathing or conventional IPS.

Feasibility Studies↗
PubMed1998

Augmentation of lung liquid clearance via adenovirus-mediated transfer of a Na,K-ATPase beta1 subunit gene.

Previous studies have suggested that alveolar Na,K-ATPases play an important role in active Na+ transport and lung edema clearance. We reasoned that overexpression of Na,K-ATPase subunit genes could increase Na,K-ATPase function in lung epithelial cells and edema clearance in rat lungs. To test this hypothesis we produced replication deficient human type 5 adenoviruses containing cDNAs for the rat alpha1 and beta1 Na,K-ATPase subunits (adMRCMValpha1 and adMRCMVbeta1, respectively). As compared to controls, adMRCMVbeta1 increased beta1 subunit expression and Na,K-ATPase function by 2. 5-fold in alveolar type 2 epithelial cells and rat airway epithelial cell monolayers. No change in Na,K-ATPase function was noted after infection with adMRCMValpha1. Rat lungs infected with adMRCMVbeta1, but not adMRCMValpha1, had increased beta1 protein levels and lung liquid clearance 7 d after tracheal instillation. Alveolar epithelial permeability to Na+ and mannitol was mildly increased in animals infected with adMRCMVbeta1 and a similar Escherichia coli lacZ-expressing virus. Our data shows, for the first time, that transfer of the beta1 Na,K-ATPase subunit gene augments Na,K-ATPase function in epithelial cells and liquid clearance in rat lungs. Conceivably, overexpression of Na,K-ATPases could be used as a strategy to augment lung liquid clearance in patients with pulmonary edema.

Adenoviruses, Human↗
PubMed1998

Cutaneous malakoplakia in a patient with acquired immunodeficiency syndrome (AIDS).

Malakoplakia is an uncommon granulomatous lesion that afflicts predominantly immunocompromised individuals but is extremely rare in acquired immunodeficiency syndrome (AIDS). We report a case of cutaneous malakoplakia in an AIDS patient that presented as a banal right axillary abscess which resolved after excision and drainage. The rarity of malakoplakia in AIDS may be due to a relative or selective preservation of antimicrobial function of monocytes. Malakoplakia is distinguished from other inflammatory or neoplastic lesions by the presence of Michaelis-Gutmann bodies. A correct diagnosis is usually made only after biopsy and is an indication to use antimicrobial agents with adequate cellular penetration and concentration.

Acquired Immunodeficiency Syndrome↗
PubMed1998

Syncope recurrence in children: relation to tilt-test results.

OBJECTIVES: To examine the intermediate-term outcome of children with syncope and its relationship to tilt test. DESIGN: This was a retrospective study of 45 children. In 20, the tilt test was negative. Follow-up with respect to the recurrence of syncope was obtained via chart review, a mailed questionnaire, or telephone interview. RESULTS: Follow-up data were available on 15 children whose tilt test was negative and on all 25 tilt-test positive children. Recurrent syncope was significantly greater in the positive-tilt children (13 of 25) than the negative-tilt children (2 of 15). There was no difference between the syncope-free group and the recurrent syncope group or between the tilt-positive and tilt-negative groups with respect to age at initial syncope, duration of symptoms, age at tilt test, and duration of follow-up. Children with a positive tilt test and those with recurrent syncope had more syncopal episodes before their evaluation than either the group with a negative tilt test or the group with no recurrent syncope, respectively. CONCLUSIONS: Syncope may recur after either a negative or a positive tilt test. The recurrence rate, however, is higher for the tilt-positive children.

Adolescent↗
PubMed1997

Molecular characterization of two mammalian bHLH-PAS domain proteins selectively expressed in the central nervous system.

Here we describe two mammalian transcription factors selectively expressed in the central nervous system. Both proteins, neuronal PAS domain protein (NPAS) 1 and NPAS2, are members of the basic helix-loop-helix-PAS family of transcription factors. cDNAs encoding mouse and human forms of NPAS1 and NPAS2 have been isolated and sequenced. RNA blotting assays demonstrated the selective presence of NPAS1 and NPAS2 mRNAs in brain and spinal cord tissues of adult mice. NPAS1 mRNA was first detected at embryonic day 15 of mouse development, shortly after early organogenesis of the brain. NPAS2 mRNA was first detected during early postnatal development of the mouse brain. In situ hybridization assays using brain tissue of postnatal mice revealed an exclusively neuronal pattern of expression for NPAS1 and NPAS2 mRNAs. The human NPAS1 gene was mapped to chromosome 19q13.2-q13.3, and the mouse Npas1 gene to chromosome 7 at 2 centimorgans. Similarly, the human NPAS2 gene was assigned to chromosome 2p11.2-2q13, and the mouse Npas2 gene to chromosome 1 at 21-22 centimorgans. The chromosomal regions to which human NPAS1 and NPAS2 map are syntenic with those containing the mouse Npas1 and Npas2 genes, indicating that the mouse and human genes are true homologs.

Amino Acid Sequence↗
PubMed1997

Musical preference as an indicator of adolescent drug use.

AIMS: This paper aims to demonstrate whether a relationship exists between adolescent drug use and identification with styles of music linked to specific youth culture. DESIGN: Survey data were collected by researchers, under exam conditions, from two contrasting samples of Scottish secondary schoolchildren. SETTING: Fieldwork was conducted in five comprehensive schools in the city of Dundee in 1994 and five comprehensive schools in the rural area of Perth and Kinross District in 1996. PARTICIPANTS: Questionnaires were administered to two randomly selected mixed ability classes in each of the four compulsory school years (S1 to S4), at each participating school. The eventual sample (n = 1523) was approximately 10% of all children in these school years from the geographical areas surveyed. MEASUREMENTS: Comparisons were made between life-time measures of legal and illegal drug use and current favourite style of music. FINDINGS: Although few children in this study had ever taken the drug ecstasy (MDMA), 'fans' of rave music were more likely to have used drugs than those who preferred other styles of music. This relationship held true across a range of drugs used, across two geographical areas, over time and controlling for age, gender and parental social class. CONCLUSIONS: The paper is one of the first to quantify a possible relationship between drug use and music style. On the basis of the evidence presented, a significant relationship was found between identification with rave music and life-time drug use.

Adolescent↗
PubMed1996

Circadian variation of ambulatory myocardial ischemia. Triggering by daily activities and evidence for an endogenous circadian component.

BACKGROUND: The morning peak in myocardial ischemia has been related to diurnal variations in physical and mental activities and to postural changes upon awakening. This study assesses (1) the effects of exogenous activity triggers at different times of the day and (2) the contribution of an endogenous (ie, activity- and posture-independent) circadian vulnerability for ambulatory ischemia. METHODS AND RESULTS: Sixty-three stable coronary artery disease patients underwent ambulatory ECG monitoring and completed a structured diary assessing physical and mental activities. During 2519 hours of observation, a morning increase in ischemia coincided with increases in physical and mental activities, and an evening decrease in ischemia coincided with a decline in activities. During the morning, ischemic versus ischemia-free periods were more likely to occur with high levels of physical activity (P < .001). High physical activity triggered ischemia to a lesser but still significant extent (P < .05) in the afternoon but not in the evening (P = NS). High levels of mental activity triggered ischemia significantly during the morning (P < .04) and evening (P < .04) but not in the afternoon. When a residualized score procedure was used to correct ischemic time for each patient's simultaneously measured activities, for hourly heart rates, or for activity-related heart rate fluctuations, the circadian variation in ischemia was still observed (P < .001), with a peak at 6 AM. A significant increase in ischemia occurred immediately after awakening (P < .05), but activity-adjusted increases in morning ischemia persisted (P < .05) for 2 hours after awakening. CONCLUSIONS: Exogenous factors (physical and mental activities) are most potent as triggers of ischemia during the morning hours, and the postural change after awakening contributes to the morning increase in ischemia. There is also evidence for an endogenous, activity-independent circadian influence on ischemic susceptibility that is independent of exogenous factors and that sustains the increase in ischemia upon awakening.

Activities of Daily Living↗
PubMed1996

Gene structure of murine Gna11 and Gna15: tandemly duplicated Gq class G protein alpha subunit genes.

G protein alpha subunits are encoded by a multigene family of 16 genes that can be grouped into four classes, Gq, Gs, Gi, and G12. The Gq class is composed of four genes in mouse and human, and two of these genes, Gna11 and Gna15, cosegregate on mouse chromosome 10. We have characterized the gene structures of murine Gna11 and Gna15. The two genes are tandemly duplicated in a head-to-tail array. The upstream gene, Gna11, is ubiquitously expressed, whereas expression of the downstream gene, Gna15, is restricted to hematopoietic cells. The coding sequence of each gene is contained within seven exons, and the two genes together span 43 kb, separated by 6 kb of intergenic region. We have found no evidence for alternative splicing within the coding sequence of either gene. Sequence alignments show that the positions of the six intervening sequences are conserved in the two genes, consistent with Gna11 and Gna15 arising by tandem duplication from a common progenitor gene in vertebrates. Phylogenetic trees reveal unequal evolutionary rates among alpha subunits of the Gq class. The rate of change is approximately six fold higher in Gna15 than in Gna11.

Alternative Splicing↗
PubMed1996

Fibrinolytic abnormalities in two different cutaneous manifestations of venous disease.

BACKGROUND: Chronic venous insufficiency may be associated with lipodermatosclerosis or atrophie blanche. Coagulation abnormalities may be related to these cutaneous disorders. OBJECTIVE: Our purpose was to determine whether fibrinolytic abnormalities exist in patients with lipodermatosclerosis or atrophie blanche. METHODS: A case control study of patients with venous disease and atrophie blanche or lipodermatosclerosis was performed. Plasma levels of tissue plasminogen activator (t-PA) and plasminogen activator inhibitor-1 (PAI-1) in a resting and venous occluded state were measured. RESULTS: Plasma levels of PAI-1 were different between the two groups of patients. The lipodermatosclerosis group had significantly higher levels of PAI-1 in both the resting and venous occluded states (p < 0.001). Patients with atrophie blanche had milder elevations of PAI-1 in the resting and venous occluded state (p = 0.06). CONCLUSION: Fibrinolytic abnormalities are present in patients with venous disease. These abnormalities are different between patients with lipodermatosclerosis and patients with atrophie blanche.

Aged↗
PubMed1995

Peroxynitrite-dependent chemiluminescence of amino acids, proteins, and intact cells.

Exposure of proteins to ONOO- (fatty acid-free bovine serum albumin (BSA) and histones, 10 mg/ml) was accompanied by light emission which could be detected using a photon counter. Light emission upon addition of ONOO- to either histones or BSA increased linearly with ONOO- concentration at a rate of 50 +/- 4 and 66 +/- 4 cps/(mg protein.mM ONOO-), respectively (averages+SE). Bicarbonate (25 mM) increased ONOO(-)-dependent BSA chemiluminescence approximately 3-fold above baseline (221 +/- 6 cps/(mg protein.mM ONOO-)). The peak of peroxynitrite-dependent light emission was around 40-fold higher than when 1 mM tert-butyl-hydroperoxide (t-BOOH) and 1.6 microM hemin were used as oxidants. Fatty acid-containing BSA (0.04-0.08%) emitted 3.4-fold more light than pure BSA. Chemiluminescence increased with pH, being 4.5-fold higher at pH 8.8 than at pH 6.0. However, the half-life of emissive species did not change with pH, suggesting that the process leading to the formation of electronically excited states is the same at all pHs. Tryptophan or N-acetyltyrosine oxidation by ONOO- was accompanied by chemiluminescence (130 +/- 10 and 14 +/- 3 cps/(mg amino acid.mM ONOO-), respectively). Exposure of DNA or isolated nucleotides to either t-BOOH/hemin or ONOO- was not accompanied by light emission. Leptomonas seymouri (an insect parasite used as a model of intact cells) exposed to ONOO- emitted 3700 +/- 400 cps/(mg protein.mM ONOO-), compared to 55 +/- 3 cps/(mg protein.mM peroxide) when t-BOOH was used as oxidant. While chemiluminescence of L. seymouri exposed to ONOO- increased measured at concentrations as low as 30 microM, carbonyl formation (from protein oxidation) and thiobarbituric acid-reactive substances (lipid peroxidation) could be measured only if cells were exposed to initial ONOO- larger than 700 microM. Spectral analysis suggests that excited carbonyls (emission wavelength 340-450 nm) are not produced in high proportions. A substantial amount of light is generated above 500 nm, part of which could come from triplet states of tryptophan and tyrosine.

Amino Acids↗
PubMed1995

Psychosocial adjustment and the role of functional status for children with asthma.

This study examined the psychosocial adjustment of children with asthma compared to children with diabetes, with cancer, and healthy children and the role of functional status in psychosocial adjustment. The total sample included 100 children, aged 8-16 years, (mean = 11.5 years), consisting of 48 boys and 52 girls. Children with asthma scored significantly higher on measures of affective adjustment (depression and internalizing behavior), significantly lower on self-esteem, and evidenced significantly greater functional impairment. Children with cancer missed significantly more school days. After controlling for functional status, no significant differences remained in affective adjustment but absences remained significantly higher for the children with cancer.

Adaptation, Psychological↗
PubMed1993

Regulation of intracellular pH in subpopulations of cells derived from spheroids and solid tumours.

Solid tumours are known to develop regions of extracellular acidity and survival of tumour cells in such regions depends on membrane-based mechanisms which regulate intracellular pH (pHi). We have therefore developed a method, based on dual staining of cells and flow cytometry, to study the regulation of pHi in subpopulations of tumours and spheroids. The activity of membrane-based pHi regulating transporters was studied in EMT-6 and MGH U1 cells grown in monolayer culture, spheroids, and tumours. pHi was measured with the fluorescent pH probe 2'7'-bis-(2-carboxyethyl)-5-(and-6)carboxyfluorescein, and Hoechst 33342 was used to identify cells from different regions of tumours and spheroids. In monolayer culture, incubation of cells for 18 h at pHe 6.6 led to a 1.3-1.5-fold enhancement in the activity of both the Na+/H+ exchanger and the Na(+)-dependent Cl-@HCO3- exchanger. This effect was prevented by the protein synthesis inhibitor cycloheximide. Cells from the centre of EMT-6 spheroids had increased activity of the Na+/H+ exchanger compared to cells from the periphery, when spheroids were grown in medium at pH 6.6, but not at 7.4. By contrast, in MGH U1 spheroids, cells from the centre had increased activity of the Na+/H+ antiport under both sets of conditions. There was no significant difference in the activity of the Na+/H+ exchanger in cells derived from different subpopulations of EMT-6 tumours or MGH U1 xenografts in nude mice. Although upregulation of Na+/H+ exchange occurs after exposure to acidic conditions in vitro, the microenvironmental conditions found within solid tumours do not appear to cause this effect. Our results suggest the feasibility of pharmacological inhibition of Na+/H+ exchange activity as an approach to therapy directed against nutrient-deprived tumour cells.

Animals↗
PubMed1993

Skin testing with food, codeine, and histamine in exercise-induced anaphylaxis.

A 33-year-old Chinese woman with exercise-induced anaphylaxis after ingesting Chinese seafood noodle soup, was studied for skin test reactivity to food, histamine, and codeine. Prick skin tests were negative for shrimp, wheat, and chicken soup base, but were positive at 5 to 6 mm (wheal diameter) to the whole broth after it had been combined with the other ingredients. No significant (> 3 mm) wheals were observed in eight controls who were simultaneously tested with the broth. To assess the role of exercise, three series of skin tests were performed with histamine, codeine, and whole broth before and after aerobic exercise on two occasions. Codeine elicited consistent increases in wheal size after exercise compared with pre-exercise skin tests. Histamine and whole broth wheal sizes did not increase significantly. Three control subjects also had codeine and histamine skin tests before and after exercise, No exercise-associated increases were noted for codeine. Potential insights into mast cell abnormalities in exercise-induced anaphylaxis may be gained by skin testing patterns with codeine and other mast cell degranulating agents.

Adult↗
PubMed1992

Female streetworking prostitution and HIV infection in Glasgow.

OBJECTIVES: To identify the extent of HIV infection and injecting drug use among female streetworking prostitutes in Glasgow; to estimate the size of the female streetworking prostitute population in the city; and to estimate the number of HIV positive women working as prostitutes on the streets in Glasgow. DESIGN: Observation and interviewing of female prostitutes over seven months in red light district; analysis of saliva samples for presence of antibodies to HIV; capture-recapture approach to estimating the size of the female streetworking prostitute population. SETTING: Glasgow. SUBJECTS: 206 female streetworking prostitutes. MAIN OUTCOME MEASURES: Number of women with antibodies to HIV, self reported use of injecting drugs, history of contact with 206 women. RESULTS: Saliva samples were requested from 197 women; 159 (81%) provided samples. Four (2.5%, 95% confidence interval 0.7%-6.3%) of the samples were positive for HIV, all of which had been provided by women who injected drugs. Of the 206 streetworking women contacted 147 (71%) were injecting drug users. About 1150 women are estimated to work on the streets in Glasgow over a 12 month period. CONCLUSIONS: HIV is not as widespread among female prostitutes as many reports in the tabloid press suggest. A greater proportion of female streetworking prostitutes in Glasgow are injecting drugs than has been reported for other British cities.

Female↗
PubMed1992

Selling sex: female street prostitution and HIV risk behaviour in Glasgow.

Female prostitutes have often been seen as a major source of HIV infection. In this paper we report on a study of HIV-related risk behaviour among street prostitutes in Glasgow. This paper is based on street interviews using a standardized schedule with 68 women. We focus on the extent of HIV testing amongst the women, travel, the sexual services provided, the use of condoms with clients and private partners, and the extent of drug injecting and equipment sharing by the women. It is shown that female street prostitution within Glasgow is, at present, unlikely to be associated with significant heterosexual spread of HIV as most commercial sex is with a condom. However, some risk activities are continuing. Additionally, prostitutes report worrying rates of condom failure with clients. It is suggested that attention should switch away from an exclusive focus on women selling sexual services to target the men who purchase sex. These data indicate that much of the pressure for these women to provide unprotected sex comes from their clients.

AIDS Serodiagnosis↗