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Biomedical subjects

S Harding

Publications and source records attributed to S Harding.

At least 19 recordsLinked to original sources
PubMed2001

Effects of ectopias and their cortical location on several measures of learning in BXSB mice.

About half of BXSB/MpJ-Yaa mice have ectopias, which are misplaced clusters of neurons located in layer I of cortex. This study replicated several previous findings showing that there are learning differences between mice with ectopias and those without. In addition, we had sufficient numbers of ectopic mice to investigate if ectopics learned differently depending on the cortical location of the ectopia(s). Mice with at least one ectopia located in prefrontal cortex were initially impaired in learning the Morris maze, as well as relearning the Lashley maze when it was inverted, but learned better in the radial-arm maze when compared to ectopic mice with ectopias located in nonprefrontal regions of cortex. Mice with at least one ectopia in motor cortex learned the Lashley maze better than mice with ectopias located outside motor cortex. In sum, the cortical location of the ectopia(s) affected learning performance in certain tasks within the ectopic group, but regardless of the cortical location of the ectopia(s), ectopics still learned differently than nonectopics in several tasks.

Animals↗
PubMed2001

Geographical distribution and host range of entomophthorales infecting the green spruce aphid Elatobium abietinum Walker in Iceland.

Entomophthora planchoniana and Neozygites fresenii caused infection in populations of the green spruce aphid, Elatobium abietinum, in Iceland. On this aphid species En. planchoniana was exclusively found in the western part of Iceland, while N. fresenii was exclusively found in the eastern part of Iceland. This discrete and nearly nonoverlapping geographical distribution correlates with the distribution of two different populations of El. abietinum found in Iceland. On other aphid species N. fresenii, En. planchoniana, Pandora neoaphidis, and Conidiobolus obscurus were documented throughout the country. Transmission experiments showed that Pa. neoaphidis and En. planchoniana could infect the eastern population of El. abietinum, although they have never been found on this population in nature. This strongly indicates that there is little or no interaction among El. abietinum, other aphids, and their respective entomophthoralean fungi in the field. Furthermore, this study is the first to record epizootics caused by N. fresenii and En. planchoniana in the subpolar region.

Animals↗
PubMed2001

Photodynamic therapy in the treatment of subfoveal choroidal neovascularisation.

Subfoveal choroidal neovascularisation (CNV) is a major cause of visual disability, with age-related macular degeneration (AMD) the commonest cause. Confluent laser to CNV significantly reduces severe visual loss but the profound visual loss after treatment of subfoveal lesions and the high recurrence rate has meant its restriction to extrafoveal lesions. Developed initially as a treatment for cancers, photodynamic therapy (PDT) has been shown to successfully close CNV in the eye. Large international randomised placebo-controlled studies of the safety and efficacy of PDT with verteporfin are under way. The Treatment of Age-related Macular Degeneration with Photodynamic Therapy (TAP) study has demonstrated a reduction of visual loss in treated patients with any classic CNV. Subgroup analysis showed a greater benefit in predominantly classic lesions (p < 0.001, NNT: 3.6), increasing further for lesions with no occult component, roughly equivalent to pure classic (p < 0.01, NNT: 2.2) A significant benefit at 12 months has been shown in patients with CNV secondary to myopia in the Verteporfin in AMD (VIP) trial, but no benefit in pure occult lesions. Further research is required to establish cost-effectiveness and appropriate referral patterns in the UK and optimise treatment strategies. Further data are awaited from TAP/VIP. At present verteporfin PDT is indicated in eyes with subfoveal predominantly classic CNV secondary to AMD with visual acuity of 6/60 or better and lesions < 5,400 microm in diameter. Juxtafoveal lesions meeting the above criteria and CNV secondary to pathological myopia should also be considered for treatment. The efficacy of treatment of larger lesions, juxtapapillary CNV, occult/no classic with high-risk characteristics (HRC) and CNV from other causes remains unclear. The treatment of minimally classic lesions and those with occult/no classic without HRC is not indicated.

Choroidal Neovascularization↗
PubMed2001

Longitudinal study of socio-economic differences in mortality among South Asian and West Indian migrants.

AIM: To examine socio-economic differences in mortality of South Asian and West Indian migrants. DESIGN: ONS Longitudinal Study, a 1% sample of the population of England and Wales. PARTICIPANTS: First generation South Asian and West Indian migrants present at the 1971 and 1981 censuses, aged under 65 years in 1981, were classified by occupational class, access to cars, housing, and a deprivation score. OUTCOME MEASURES: Relative risks of mortality, 1981-1997. RESULTS: There was considerable upward social mobility but most people remained socially stable, mainly relatively disadvantaged compared to all other study members. High levels of owner occupied housing among South Asians at both censuses were an exception. Socio-economic differentials in mortality were significant with car access in 1981 (relative risk 1.32, 95% confdence interval 1.03-1.70), and housing (rented vs owner occupied relative risk 1.50, 95% confidence interval 1.08-2.08) among South Asians and, among West Indians with car access in 1981 (relative risk 1.43, 95% confidence interval 1.05-1.94). Mortality was not significantly associated with socioeconomic circumstances in 1971. CONCLUSION: The disparity between those who remained advantaged or who moved up, and those who remained persistently disadvantaged, would have been a factor underlying the stronger differentials by later socio-economic circumstances. As these migrants age an increase in health inequalities could be expected.

Adult↗
PubMed2001

Genetic selection for high and low alcohol consumption in a limited-access paradigm.

BACKGROUND: Several rat lines have been bred for their differences in alcohol consumption based on a continuous-access paradigm in which alcohol solution is available 24 hr/day. The limited-access paradigm (LAP), in which access to alcohol solution is restricted to a short period per day, however, has been used extensively to investigate the neurochemical mechanisms underlying alcohol consumption. There is evidence of possible differences in genetic determination of alcohol drinking in a continuous- versus limited-access condition. For these reasons, selective breeding for high- and low-alcohol consumption (HARF and LARF, respectively) based on a LAP was conducted. METHODS: N/Nih rats were used as the breeding stock. A within-family breeding procedure was used to develop HARF and LARF lines with 10 families per line. Access to alcohol solution was restricted to 20 min/day. Alcohol was provided as 3%, 6% and 12% w/v solutions. Average intake of alcohol during the 12% phase was used as the selection criterion. Inbreeding began in the seventh generation. RESULTS: After the sixth generation of selection, rats from the HARF line consumed an average of 1.2 g/kg, whereas rats from the LARF line consumed an average of 0.6 g/kg of alcohol during the 20-min access period. Alcohol consumption remained stable over the next eight generations of inbreeding. In the continuous-access-drinking paradigm, the HARF and LARF rats consumed an average of 5.5 to 7.0 g/kg and 1.0 to 2.0 g/kg of alcohol per day respectively. An estimated heritability of 0.25 was obtained. CONCLUSIONS: These findings indicate that alcohol drinking in the LAP is influenced by genetic factors. Differences in alcohol drinking in the LAP also generalize to continuous access drinking. These rat lines will be very useful for investigations into the genetic and neurochemical mechanisms underlying alcohol drinking.

Alcohol Drinking↗
PubMed2001

Tumor necrosis factor-alpha inhibits store-mediated Ca2+ entry in the human hepatocellular carcinoma cell line HepG2.

Tumor necrosis factor-alpha (TNF-alpha) is an important component of the early signaling pathways leading to liver regeneration and proliferation, but it is also responsible for several hepatotoxic effects. We have investigated the effect of TNF-alpha on thapsigargin (TG)-induced store-mediated Ca2+ entry (SMCE) in the human hepatocellular carcinoma cell line HepG2. In these cells, short-term (10 min) exposure to TNF-alpha slightly increased SMCE. In contrast, long-term (12 h) exposure to TNF-alpha significantly reduced SMCE. This effect was reversed by coincubation with atrial natriuretic peptide (ANP), which itself had no effect on SMCE. Cytochalasin D and latrunculin A, inhibitors of actin polymerization, abolished SMCE. Long-term exposure of HepG2 cells to TNF-alpha abolished TG-induced actin polymerization and membrane association of Ras proteins. When TNF-alpha was added in combination with ANP, these effects were reduced. These findings suggest that in HepG2 cells, TNF-alpha inhibits SMCE by affecting reorganization of the actin cytoskeleton, probably by interfering with the activation of Ras proteins, and that ANP protects against these inhibitory effects of TNF-alpha.

Actins↗
PubMed2001

Vascular complications after hemostatic puncture closure device (Angio-Seal) are not higher in overweight patients.

BACKGROUND: Angio-Seal (Daig Corporation, Minnetonka, Minnesota) allows earlier discharge from the hospital after coronary angiography. Manual compression in overweight patients after percutaneous procedures is associated with a higher incidence of groin complications. The purpose of this study was to determine if a vascular closure device could be safely used without increasing the risk of vascular complications in overweight patients. METHODS: A total of 198 patients who received the 6 French Angio-Seal device after diagnostic coronary angiography were divided into 3 groups. Group A included patients with a body mass index (BMI) of < or = 25, group B with BMI between 25 and 30, and group C with BMI > or = 30. Patients were followed for groin complications during their hospital stay. RESULTS: Complication rates were comparable between the 3 groups. Groin complications occurred in 11% in group A, 5% in group B and 6% in group C. CONCLUSION: After diagnostic cardiac catheterization, a vascular closure device such as Angio-Seal can be safely used in overweight patients.

Aged↗
PubMed2000

NMR microscopy of the uptake, distribution and mobility of dissolution media in small, sub-millimetre drug delivery systems.

NMR techniques were used to study the drug release process from small (sub-mm) lipophilic matrix theophylline beads. NMR microscopy was used to follow the ingress of the dissolution medium into the beads. Pulsed gradient spin echo (PGSE) NMR and 3D NMR imaging were used to measure the mobility and distribution of liquid within fully liquid penetrated beads. These techniques were used to rationalise the increase in the drug release rate with increasing proportion of GMS (glycomonosaccharide):paraffin in the matrix composition. A well-defined penetrant front was seen to move towards the centre of the bead during the dissolution process and the rate of liquid uptake showed the same trend with increasing GMS content as the rate of drug release. The total concentration of absorbed liquid increased and its T(2) relaxation time decreased with increasing GMS content of the bead matrix. This combined with the interpretation of PGSE results suggested that liquid resides in the matrix material as well as in pores left by the dissolved drug, and that this tendency increases with increasing GMS content. Heterogeneities in liquid distribution within the beads were quantified using percolation analysis and were related to the lipid matrix composition and may be a contributory factor in determining the rate of drug release.

Algorithms↗
PubMed2000

The role of corticotrophin-releasing factor in stress-induced relapse to alcohol-seeking behavior in rats.

RATIONALE: Intermittent footshock stress reliably reinstates extinguished alcohol-taking behavior in drug-free rats, but the neurochemical events involved in this effect are not known. OBJECTIVE: We studied here whether two main modulators of stress responses, corticotropin-releasing factor (CRF) and corticosterone, are involved in reinstatement of alcohol seeking induced by the intermittent footshock stressor. METHDOS: Rats were given alcohol in a two-bottle choice procedure (water versus alcohol) for 30 days and were then trained for 60 min per day to press a lever for alcohol (12% w/v) for 24-30 days in operant conditioning chambers. After stable drug-taking behavior was obtained, lever pressing for alcohol was extinguished by terminating drug delivery for 5-8 days. Reinstatement of alcohol seeking was then determined after exposure to intermittent footshock (0.8 mA; 10 min) in different groups of rats that were pretreated with CRF receptor antagonists or underwent adrenalectomy (ADX) to remove endogenous corticosterone from the body. RESULTS: The CRF receptor antagonists, d-phe-CRF (0.3 or 1.0 microg; ICV) and CP-154,526 (15, 30 or 45 mg/kg; IP) attenuated footshock-induced reinstatement of alcohol seeking in a dose dependent manner. In contrast, the removal of circulating corticosterone by ADX had no effect on footshock stress-induced reinstatement of alcohol-taking behavior. In addition, the prevention of the footshock-induced rise in corticosterone while maintaining basal levels of the hormone by providing adrenalectomized rats with corticosterone pellets (50 mg/kg per day), had no effect on stress-induced reinstatement. CONCLUSIONS: These data suggest that CRF contributes to stress-induced relapse to alcohol seeking via its actions on extra-hypothalamic sites. The present data, and previous data with heroin- and cocaine-trained rats, point to a general role of CRF in relapse to drugs induced by stressors.

Adrenalectomy↗
PubMed2000

Effects of the non-pseudoautosomal region of the Y-chromosome on behavior in female offspring of two congenic strains of mice.

The learning behavior of female offspring of two strains of mice congenic for the Y-chromosome, BXSX/MpJ-Yaa and BXSB/MpJ-Yaa+, was examined. Significant differences were found in the Morris water maze and the Lashley III maze, demonstrating that the fathers' Y-chromosome can indirectly affect their daughters' behavior. Approximately half the mice had neocortical ectopias, and females from the two paternal groups reacted differently to the presence or absence of ectopias. Since females do not have a Y-chromosome, these effects must be through non-genetic mechanisms. Prenatal factors that could have played a role include possible differences in gonadal growth and the presence of different H-Y antigens. Postnatally, the sires and male siblings of the two strains may not have behaved the same toward the female offspring and/or the dams, creating differences in behavior. In summary, the behavior of female offspring of two groups of males, genetically the same except for their Y-chromosomes, was examined. Since females do not receive a Y-chromosome from their fathers, in theory their behavior should not differ. Significant differences were found, indicating that the Y-chromosome, through some indirect mechanism, can affect females of the next generation.

Animals↗
PubMed2000

Comparison of once- and twice-daily dosing of fluticasone propionate 200 micrograms per day administered by diskus device in patients with asthma treated with or without inhaled corticosteroids.

BACKGROUND: There are limited published data regarding the efficacy of once- versus twice-daily administration of flutica-sone propionate. OBJECTIVE: Our purpose was to evaluate the effectiveness of fluticasone propionate powder 200 microg/d administered as a once- or twice-daily dosage regimen in patients who were currently being treated with bronchodilators only (BD patients) and in patients who required inhaled corticosteroids for maintenance treatment of asthma (ICS patients). METHODS: Five hundred seventy patients were randomly assigned to receive one of the following inhaled treatments through the Diskus device (Glaxo Wellcome, Research Triangle Park, NC) for 12 weeks: fluticasone propionate 100 microg twice daily (FP100BID) or 200 microg once daily (FP200QD) or placebo. RESULTS: BD patients treated with FP100BID, FP200QD, and placebo had mean increases in FEV(1) from baseline to end point of 0. 49 L, 0.37 L, and 0.21 L, respectively (P <.001, FP100BID vs placebo; P =.05, FP200QD vs placebo). ICS patients treated with FP100BID and FP200QD had mean increases in FEV(1) of 0.27 L and 0.11 L, respectively, compared with a decrease in FEV(1) of -0.08 L with placebo (P <.001, FP100BID vs placebo; P =.023, FP200QD vs placebo). BD patients treated with FP100BID and FP200QD had mean increases in morning peak expiratory flow from baseline to end point of 31 L/min and 27 L/min, respectively, compared with a 1 L/min increase in patients treated with placebo. ICS patients treated with FP100BID had a mean increase in morning peak expiratory flow (from baseline to end point) of 18 L/min compared with mean decreases of -3 L/min and -12 L/min in the FP200QD and placebo groups, respectively. More patients were withdrawn from placebo (26% and 48%, in BD and ICS patients, respectively) than from fluticasone propionate (7%-9% [BID-QD] and 18%-32% [BID-QD], in BD and ICS patients, respectively) because of failure to meet predetermined asthma stability criteria. CONCLUSION: The efficacies of FP100BID and FP200QD were comparable with regard to improvement in pulmonary function and asthma stability in BD patients. In ICS patients, asthma control was maintained with FP200QD, whereas FP100BID provided greater improvements in pulmonary function and asthma stability.

Administration, Inhalation↗
PubMed2000

Limiting long-term illness among black Caribbeans, black Africans, Indians, Pakistanis, Bangladeshis and Chinese born in the UK.

AIM: To examine limiting long-term illness among ethnic groups born in the UK. DESIGN: Study members in the ONS Longitudinal Study, a representative 1% sample of England and Wales, present at the 1991 Census were examined. Socio-economic position was measured using housing tenure and access to cars. MAIN RESULTS: Black Caribbeans, Black Africans, Indians, Pakistanis and Bangladeshis reported more limiting long-term illness than whites, and the Chinese less. The level was higher among Black Africans than Black Caribbeans, even after adjustment for socio-economic position. Corresponding patterns were seen across the generations for all groups except Black Africans. Black Africans born in the UK reported more limiting long-term illness than did those born in Africa. Adjusting for socio-economic position lowered the risks in every group except Indians. The effect was strongest for Black Caribbeans, among whom adjustment removed the higher risks, and Bangladeshis, among whom the higher risks were no longer significant. CONCLUSION: For South Asians and Black Caribbeans poor health persisted across generations, and for Black Africans health worsened. There are over 1.5 million second- and third-generation migrants in these ethnic groups, but little is known about the consequences of having a multigenerational identity.

Africa↗
PubMed1999

Effects of naltrexone and fluoxetine on alcohol self-administration and reinstatement of alcohol seeking induced by priming injections of alcohol and exposure to stress.

We have recently shown that priming injections of alcohol and footshock stress reinstate alcohol seeking in drug-free rats. Here we tested whether naltrexone and fluoxetine, two drugs used in the treatment of alcohol dependence, would affect reinstatement of alcohol seeking induced by these events. We also determined the effects of these drugs on alcohol self-administration during the maintenance phase. Rats were trained to press a lever for a 12% w/v alcohol solution. After stable drug-taking behavior was obtained, lever pressing for alcohol was extinguished. Reinstatement of drug seeking was then determined after priming injections of alcohol (0.24-0.96 g/kg) or exposure to intermittent footshock (5 and 15 min). Rats were pretreated with naltrexone (0.2-0.4 mg/kg) or fluoxetine (2.5-5 mg/kg) during maintenance or during tests for reinstatement. Both naltrexone and fluoxetine decreased lever presses for alcohol during the maintenance phase. Naltrexone blocked alcohol-induced, but not stress-induced reinstatement. In contrast, fluoxetine blocked stress-induced reinstatement, while its effect on alcohol-induced reinstatement was less consistent. The implications of these data to the understanding of relapse to alcohol are discussed.

Alcohol Deterrents↗