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Biomedical subjects

C Wilson

Publications and source records attributed to C Wilson.

At least 145 records · Page 8Linked to original sources
PubMed1998

Pharmacology of sensory stimulation-evoked increases in frontal cortical acetylcholine release.

Recent research has demonstrated that a variety of sensory stimuli can increase acetylcholine release in the frontal cortex of rats. The aim of the present experiments was to investigate the pharmacological regulation of sensory stimulation-induced increases in the activity of basal forebrain cholinergic neurons. To this end, the effects of agonists and antagonists at a variety of neurotransmitter receptors on basal and tactile stimulation-evoked increases in frontal cortical acetylcholine release were studied using in vivo brain microdialysis. Tactile stimulation, produced by gently stroking the rat's neck with a nylon brush for 20 min, significantly increased frontal cortical acetylcholine release by more than 100% above baseline. The noradrenergic alpha2 agonist clonidine (0.1 or 0.2 mg/kg) and alpha1 antagonist prazosin (1 mg/kg) failed to affect basal cortical acetylcholine release; however, both compounds significantly reduced the increases evoked by sensory stimulation. In contrast, the alpha2 antagonist yohimbine (3 mg/kg) increased basal cortical acetylcholine release, thereby preventing meaningful investigation of its effects on tactile stimulation-evoked increases. The benzodiazepine agonist diazepam (5 mg/kg) reduced, and the GABA(A) receptor antagonist picrotoxin (2 mg/kg) increased basal cortical acetylcholine release; in addition, diazepam attenuated the increases in cortical acetylcholine release evoked by tactile stimulation. While dopaminergic D1 (SCH 23390, 0.15 mg/kg) and D2 (raclopride, 1 mg/kg) receptor antagonists did not by themselves significantly influence the increases evoked by tactile stimulation, their co-administration produced a significant reduction. The opioid receptor antagonist naltrexone (1.5 mg/kg) failed to affect either basal or tactile stimulation-evoked increases in acetylcholine overflow. Finally, the non-competitive N-methyl-D-aspartate receptor antagonist, dizocilpine maleate (MK-801; 0.025 and 0.05 mg/kg) increased basal cortical acetylcholine release. These results confirm that cortically projecting cholinergic neurons are activated by sensory stimuli, and indicate that the increases in cortical acetylcholine release produced by tactile stimulation are inhibited by stimulation of alpha2 or blockade of alpha1 noradrenergic receptors, and by enhanced GABAergic transmission. In addition, simultaneous blockade of dopamine D1 and D2 receptors appears necessary to achieve a significant reduction of sensory stimulation-evoked acetylcholine release in the frontal cortex. The results are consistent with the hypothesis that cortical acetylcholine release is a component of the neurochemistry of arousal and/or attention and indicate that this is modulated by GABAergic, noradrenergic and dopaminergic systems. In contrast, endogenous opioid actions do not appear to be involved.

Acetylcholine↗
PubMed1998

Isolation of a fluorophore-specific DNA aptamer with weak redox activity.

BACKGROUND: In vitro selection experiments with pools of random-sequence nucleic acids have been used extensively to isolate molecules capable of binding specific ligands and catalyzing self-modification reactions. RESULTS: In vitro selection from a random pool of single-stranded DNAs has been used to isolate molecules capable of recognizing the fluorophore sulforhodamine B with high affinity. When assayed for the ability to promote an oxidation reaction using the reduced form of a related fluorophore, dihydrotetramethylrosamine, a number of selected clones show low levels of catalytic activity. Chemical modification and site-directed mutagenesis experiments have been used to probe the structural requirements for fluorophore binding. The aptamer recognizes its ligand with relatively high affinity and is also capable of binding related molecules that share extended aromatic rings and negatively charged functional groups. CONCLUSIONS: A guanosine-rich single-stranded DNA is capable of binding fluorophores with relatively high affinity and of weakly promoting a multiple-turnover reaction. A simple motif consisting of a three-tiered G-quartet stacked upon a standard Watson-Crick duplex appears to be responsible for this activity. The corresponding sequence might provide a useful starting point for the evolution of novel, improved deoxyribozymes that generate fluorescent signals by promoting multiple-turnover reactions.

Base Sequence↗
PubMed1998

Isolation and characterization of fluorophore-binding RNA aptamers.

BACKGROUND: In vitro selection has been shown previously to be a powerful method for isolating nucleic acids with specific ligand-binding functions ('aptamers'). Given this capacity, we have sought to isolate RNA motifs that can confer fluorescent labeling to tagged RNA transcripts, potentially allowing in vivo detection and in vitro spectroscopic analysis of RNAs. RESULTS: Two aptamers that recognize the fluorophore sulforhodamine B were isolated by the in vitro selection process. An unusually large motif of approximately 60 nucleotides is responsible for binding in one RNA (SRB-2). This motif consists of a three-way helical junction with two large, highly conserved unpaired regions. Phosphorothioate mapping with an iodoacetamide-tagged form of the ligand shows that these two regions make close contacts with the fluorophore, suggesting that the two loops combine to form separate halves of a binding pocket. The aptamer binds the fluorophore with high affinity, recognizing both the planar aromatic ring system and a negatively charged sulfonate, a rare example of anion recognition by RNA. An aptamer (FB-1) that specifically binds fluorescein has also been isolated by mutagenesis of a sulforhodamine aptamer followed by re-selection. In a simple in vitro test, SRB-2 and FB-1 have been shown to discriminate between sulforhodamine and fluorescein, specifically localizing each fluorophore to beads tagged with the corresponding aptamer. CONCLUSIONS: In addition to serving as a model system for understanding the basis of RNA folding and function, these experiments demonstrate potential applications for the aptamers in transcript double labeling or fluorescence resonance energy transfer studies.

Animals↗
PubMed1998

The contexts for managing depression and its stigma among black West Indian Canadian women.

There is a paucity of literature available to assist nurses and other care providers in knowing how to meet the needs of depressed women from non-dominant cultural backgrounds. To begin to address this need, we conducted a grounded theory study on black West Indian Canadian Women's strategies for managing depression. We discovered a basic social process, Being Strong, that the women used to manage or ameliorate depression. Being strong occurs within the overlapping areas of three social contexts: the cultural stigma of depression, male-female roles and relationships, and belief in Christian doctrine. These contexts are located against a backdrop of visible minority status within a eurocentric society. This socio-cultural contextual material provides the setting within which black West Indian Canadian women live and make decisions. In this article, we present findings related to the social and cultural aspects of the women's situation.

Adaptation, Psychological↗
PubMed1998

Effects of atropine on measures of behavioral arousal in rats.

Forty-day-old rats were given varying doses (0.0, 7.5, or 15.0 mg/kg/5 ml) of atropine sulfate or atropine methylnitrate and then were tested for levels of behavioral arousal-inhibition. Behavioral measures included transport response intensity, vertical cling catalepsy duration, and dorsal immobility duration. Atropine sulfate produced large increments in transport response intensities, and atropine methylnitrate produced intermediate effects, compared with saline-treated control rats. No drug effect was reported for the measures of vertical cling catalepsy or dorsal immobility. Intraclass correlations among the various behavioral measures in this study revealed a reliable relationship between dorsal immobility duration and transport response intensity in the saline group. Administration of either the methylnitrate or sulfate solution negated this relationship. Results are discussed with respect to (a) possible mechanisms relating dorsal immobility and transport response and (b) reasons for the loss of relationship between the two measures with administration of atropine solutions.

Animals↗
PubMed1998

Attitudes towards routine human immunodeficiency virus (HIV) screening and fertility treatment in HIV positive patients--a UK survey.

Of 70 fertility units licensed by the Human Fertilisation and Embryology Authority in the UK, 58 responded to a questionnaire regarding attitudes towards human immunodeficiency virus (HIV) screening and fertility treatment in HIV positive patients in November 1995. Of these 58 centres, 23 only performed routine screening for HIV for both partners, 24 for hepatitis B and eight for hepatitis C. In the event of a positive result in the male, fertility treatment would be offered in the form of donor insemination (n = 21), intrauterine insemination (IUI) after sperm washing (n = 21), and in-vitro fertilization (IVF) (n = 1). If the woman was HIV positive, two centres would offer IUI and three centres IVF. Nine centres had already provided treatment for couples in whom the male partner was HIV positive and two centres to HIV positive women.

Attitude to Health↗
PubMed1998

Effect of smoking on ovarian reserve and ovarian stimulation in in-vitro fertilization and embryo transfer.

The effect of cigarette smoking on ovarian reserve as measured by basal serum follicle stimulating hormone (FSH) concentrations, and by the response to a standard ovarian stimulation protocol, was examined retrospectively in 173 consecutive women (108 non-smokers and 65 smokers) undergoing in-vitro fertilization (IVF) and embryo transfer treatment. Women who smoked had a higher mean basal serum FSH concentration (P < or = 0.0001), in particular younger (<36 years) women, and required a statistically significantly higher mean dosage of gonadotrophins for ovarian stimulation than the non-smokers (48.1 +/- 15.6 versus 38.9 +/- 13.6 ampoules, 75 IU/ampoule; P < 0.0001). A lower mean number of oocytes was obtained in smokers than non-smokers (6.2 +/- 3.4 versus 11.1 +/- 6.3, oocytes P < or = 0.0001) and the rate of abandoned cycles (18.5 versus 8.5%) and total fertilization failure (18.5 versus 8.5%) was higher. The clinical pregnancy rate per cycle in smokers was 16.9% versus 21.3% in non-smokers but this was not statistically significant. In conclusion, cigarette smoking in women appears to significantly reduce their ovarian reserve and lead to poor response to ovarian stimulation at an earlier age.

Adult↗
PubMed1998

Antibodies to Klebsiella pneumoniae lipopolysaccharide in patients with ankylosing spondylitis.

The role of microbial lipopolysaccharides (LPS) in the aetiopathogenesis of ankylosing spondylitis (AS) is a matter of continuing debate. In this study, class-specific IgG, IgA and IgM antibodies against Klebsiella pneumoniae, Escherichia coli, Salmonella typhimurium and Salmonella enteritidis LPS were measured by enzyme-linked immunosorbent assay (ELISA) in 100 AS patients, 50 rheumatoid arthritis (RA) patients and 50 healthy control subjects. The AS patients had significantly elevated levels of IgG and IgA antibodies against K. pneumoniae LPS (P < 0.001) and IgA antibodies against E. coli LPS (P < 0.05) compared to healthy controls. There were no significant elevations of antibody levels against S. typhimurium and S. enteritidis in the three study groups. In addition, there was a correlation between IgG and IgA anti-K. pneumoniae LPS antibody levels and the acute-phase reactant C-reactive protein (P < 0.001).

Adult↗
PubMed1998

Characterization of the humoral immune response to Klebsiella species in inflammatory bowel disease and ankylosing spondylitis.

This study was carried out to characterize the antibody class response by ELISA to seven Klebsiella pneumoniae serotypes (K2, K3, K17, K21, K26, K36, K50) in five different groups, 40 HLA-B27-positive ankylosing spondylitis (AS) patients, 46 patients with Crohn's disease (CD), 38 patients with ulcerative colitis (UC), 50 patients with active anti-endomysial antibody-positive coeliac disease and 40 healthy controls, using whole bacteria and capsular polysaccharide. IgG antibody levels were significantly elevated in AS patients to K17, K36, K50; IgA to K2, K3, K21, K26, K36 and K50; and IgM to serotype K21 when compared to normal controls. Furthermore, IgG antibody levels were significantly elevated in CD patients to K2, K17, K21, K26, K36 and K50; IgA to K2, K3, K21, K26, K36 and K50; and IgM to K2, K3, K17, K21 and K50. Increased IgG antibody levels in the UC group were limited only to K17, K36 and K50. No antibody class was increased to any of the K. pneumoniae serotypes in the coeliac disease group. The immune responses in AS patients also involve Klebsiella bacteria having capsular serotypes other than K26, K36 and K50. The similarity in the immune responses between CD and AS groups suggests that many AS patients may have occult bowel inflammation.

Adolescent↗
PubMed1998

Predictors of lean body mass and total adipose mass in community-dwelling elderly men and women.

As part of an ongoing longitudinal study, we analyzed cross-sectional data to identify the predictors of lean body mass (LBM) and total adipose mass (TAM) in community-dwelling elderly men and women. Body composition analysis was done using dual energy x-ray absorptiometry. A total 262 subjects (118 women and 144 men), 60 to 80 years of age, from the urban and suburban communities of southeastern Wisconsin were studied. In women, the age (r = -.18), body mass index (BMI) (r = .43), and waist-to-hip ratio (WHR) (r = .30), and in men, BMI (r = .45) and insulin-like growth factor-1 (IGF-1) (r = .32) were identified as predictors (P < .05) of LBM. In women, the BMI (r = .87), WHR (r = .21), and functional work capacity (VO2 max) (r = -.47), and in men, the BMI (r = .83), WHR (r = .52), dehydroepiandrosterone sulfate (DHEAS) (r = -.27), total testosterone (TT) (r = -.35), free testosterone (FT) (r = -.23), physical activity (LTE) (r = -.32), and VO2 peak (r = -.59) were identified as predictors of TAM. After partialling out age in addition to the predictors identified earlier, the VO2 peak was identified as a predictor (P < .05) of LBM in both women and men, and TT, FT, and LTE as predictors (P < .05) of LBM in men. We conclude that the BMI, WHR, and VO2 peak influences LBM and TAM in both women and men. Additionally, in men LBM and TAM is influenced by hormone profile.

Absorptiometry, Photon↗
PubMed1998

A role for noradrenaline in pre-eclampsia: towards a unifying hypothesis for the pathophysiology.

OBJECTIVE: To compare plasma catecholamine (noradrenaline and adrenaline) levels in pre-eclamptic to normotensive pregnancy, and to study the activity of synthetic enzymes for catecholamines in placental and trophoblastic cell cultures. We postulated that catecholamines might be an important signal secreted by the fetoplacental unit in pre-eclampsia. METHODS: We recruited 12 women with pre-eclampsia and 12 pregnant women with nonproteinuric hypertension undergoing delivery by caesarean section, 23 normotensive women undergoing elective caesarean section at term, and 26 normotensive primigravid women with ongoing pregnancies at gestations equivalent to those women with pre-eclampsia. We measured venous blood concentrations of catecholamines. Following delivery, we studied tyrosine hydroxylase (the rate limiting enzyme for catecholamine synthesis) activity in placental tissue of these women as well as from four eclamptic women not in the observer study. We used Northern blot analysis to quantify mRNA for tyrosine hydroxylase and dopamine-beta-hydroxylase (D-beta-H, a non-rate-limiting synthetic enzyme for catecholamine) in placental tissue, as well as in trophoblast cells in primary culture and trophoblast cell lines. RESULTS: Venous blood concentrations of noradrenaline were significantly higher in pre-eclamptic women compared with normotensive women. Tyrosine hydroxylase activity was greater in placental tissue from pre-eclamptic and eclamptic compared with normotensive pregnancies, as were mRNA levels for this enzyme. The mRNA levels for the non-rate-limiting D-beta-H in women with pre-eclampsia were similar to those in normotensive pregnancies. First trimester trophoblast cells in primary culture and trophoblast cell lines transcript mRNA for tyrosine hydroxylase and D-beta-H. CONCLUSIONS: Trophoblasts have the capacity to secrete catecholamines, and we found increased activity of the rate-limiting synthetic enzyme in placental tissue from pre-eclamptic pregnancies. We postulate that the higher levels of catecholamines we found in the plasma of women with pre-eclampsia might be of placental origin. We hypothesise that in pre-eclampsia ischaemic trophoblast tissue secretes catecholamines as a physiological signal to increase maternal blood flow to the fetoplacental unit, which itself is spared the vasoconstrictor effects of catecholamines (placental vessels are known to be unresponsive to catecholamines). However, since the basic pathology--defective trophoblast invasion--is not corrected, the increased blood flow fails to resolve the ischaemia, and the secretion of catecholamines is therefore sustained or even enhanced. Noradrenaline is known to cause lipolysis. This results in breakdown of triglycerides to free fatty acids, which are oxidized to lipid peroxides. The latter are cytotoxic and cause widespread endothelial cell damage and dysfunction, culminating in the clinical syndrome of pre-eclampsia.

Adult↗
PubMed1998

Association of dehydroepiandrosterone sulfate, body composition, and physical fitness in independent community-dwelling older men and women.

OBJECTIVES: To determine the association of dehydroepiandrosterone sulfate (DHEAS), body composition, and physical fitness in independent community-dwelling men and women aged 60 to 80 years. DESIGN: Cross sectional analysis. PARTICIPANTS: Independent men and women, 60 years of age and older, living in urban and suburban communities of Southeastern Wisconsin. MEASUREMENTS: History, physical examination, physical activity level, and anthropometrics were measured for every subject. Total adipose mass (TAM) and lean body mass were measured using dual energy X-ray absorptiometry. Dehydroepiandrosterone sulfate, insulin-like growth factor-1 (IGF-1), total testosterone (TT), and free testosterone (FT) were measured using radioimmunoassay. Physical fitness was measured as VO2max using exercise stress tests. Blood for lipids was analyzed using standard assays. RESULTS: In men, the DHEAS was significantly correlated to age (r = -.32), TAM (r = -.27), percent fat (r = -.30), HDL cholesterol (r = .34), TT (r = .30), VO2max (r = .23), and percent lean body mass (% LBM) (r = .33). In women, the DHEAS was not significantly correlated to any of the variables examined except body mass index (BMI) (r = .23). In men, after partialling out age, DHEAS was significantly correlated to HDL, % fat, TAM, % LBM, and TT. Multivariate analysis for men revealed that high density lipoprotein cholesterol (HDL) was the strongest predictor of serum DHEAS level, followed by % LBM, BMI, and age. The men in the highest quartile of serum DHEAS levels were different from those in the lowest quartile in terms of age, TT, FT, % fat, TAM, % LBM, HDL, and low density lipoprotein (LDL) cholesterol level. No such differences were found in the two groups of women. CONCLUSION: In this group of independent community-dwelling older men, several factors were found to be associated with the serum DHEAS concentration, whereas in a group of older women, no such associations were identified with the exception of BMI. Men in the highest quartile of serum DHEAS level, compared with those with a serum DHEAS level in the lowest quartile, were younger, leaner, more fit, had higher TT and FT levels, and had a favorable lipid profile. No such differences were identified between the women in the highest and the lowest quartiles of serum DHEAS level.

Absorptiometry, Photon↗
PubMed1998

Inhibition of NF-kappaB activation in combination with bcl-2 expression allows for persistence of first-generation adenovirus vectors in the mouse liver.

NF-kappaB is a key regulator of the innate antiviral immune response, due in part to its transcriptional activation of cytokines and adhesion molecules, which, in turn, function in chemotaxis and activation of inflammatory cells. We reported earlier that viral gene expression in hepatocytes transduced with first-generation (E1-deleted) adenoviruses induced NF-kappaB activation, elevation of serum cytokines, and hepatocellular apoptosis during the first days postinfusion. These events did not occur in mice infused with an adenovirus vector deleted for E1, E2, E3, and late gene expression. In the present study, we used an adenovirus expressing an IkappaBalpha supersuppressor (Ad.IkappaBM) and bcl-2 transgenic mice to unravel the role of virus-induced NF-kappaB activation and apoptosis in the clearance of recombinant adenovirus vectors from the liver. The combined action of IkappaBM and Bcl-2 allowed for vector persistence in livers of C57BL/6 x C3H mice. In the absence of Bcl-2, IkappaBM expression in mouse livers significantly reduced NF-kappaB activation, cytokine expression, leukocyte infiltration, and the humoral immune response against the transgene product; however, this was not sufficient to prevent the decline of vector DNA in transduced cells. Infusion of Ad.IkappaBM caused extended apoptosis predominantly in periportal liver regions, indicating that NF-kappaB activation may protect transduced hepatocytes from apoptosis induced by adenovirus gene products. To confer vector persistence, bcl-2 transgene expression was required to block virus-induced apoptosis if NF-kappaB protection was inactivated by IkappaBM. Expression of gene products involved in early stages of apoptotic pathways was up-regulated in response to virus infusion in bcl-2 transgenic mice, which may represent a compensatory effect. Our study supports the idea that the suppression of innate defense mechanisms improves vector persistence.

Adenoviridae↗