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Biomedical subjects

D J Bell

Publications and source records attributed to D J Bell.

At least 19 recordsLinked to original sources
PubMed2007

Avian blood parasites in an endangered columbid: Leucocytozoon marchouxi in the Mauritian Pink Pigeon Columba mayeri.

There is increasing evidence that pathogens can play a significant role in species decline. This study of a complete free-living species reveals a cost of blood parasitism to an endangered host, the Pink Pigeon Columba mayeri, endemic to Mauritius. We investigated the prevalence and effect of infection of the blood parasite, Leucocytozoon marchouxi, in the free-living Pink Pigeon population. Overall, L. marchouxi infection prevalence detected was 18.3%. Juveniles were more likely to be infected than older birds and there was geographical variation in infection prevalence. Survival of birds infected with L. marchouxi was lower than that of uninfected birds to 90 days post-sampling. This study suggests that while common haematozoa are well tolerated in healthy adults, these parasites may have greater pathogenic potential in susceptible juveniles. The study is unusual given its completeness of species sampling (96%) within a short time-period, the accurate host age data, and its focus on blood parasites in a threatened bird species. Species for which long-term life-history data are available for every individual serve as valuable models for dissecting the contribution of particular pathogens to species decline.

Animals↗
PubMed2006

Practical HPLC methods for the quantitative determination of common antimalarials in Africa.

This article describes high-performance liquid chromatographic assays for the quantification of sulfadoxine (SDX), pyrimethamine (PYM), chloroquine (CQ), amodiaquine (AQ) and desethylamodiaquine (AQM) from whole blood. All four assays were set up and validated in Malawi using a common high-performance liquid chromatography platform and column and involved the use of simple mobile phase and extraction reagents. Calibration curves were linear (r(2)>0.95) in the ranges 5-100microg/ml, 50-1000, 150-1500, 100-1000 and 100-1000ng/ml for SDX, PYM, CQ, AQ and AQM, respectively. Intra-assay and inter-assay coefficients of variation were <15% at 3 points spanning the concentration range and <20% at the lower limit of quantification. The assays were specific with no interference from the other antimalarials described in this report. All four assays use liquid-liquid extraction, reversed-phase chromatography and UV detection and require between 50 and 200microl of blood. Because the assays share common instruments and reagents, they are cost-efficient and could be used to optimise antimalarial drug therapies in other resource poor settings.

Africa↗
PubMed2006

Avian influenza H5N1 in viverrids: implications for wildlife health and conservation.

The Asian countries chronically infected with avian influenza A H5N1 are 'global hotspots' for biodiversity conservation in terms of species diversity, endemism and levels of threat. Since 2003, avian influenza A H5N1 viruses have naturally infected and killed a range of wild bird species, four felid species and a mustelid. Here, we report fatal disseminated H5N1 infection in a globally threatened viverrid, the Owston's civet, in Vietnam, highlighting the risk that avian influenza H5N1 poses to mammalian and avian biodiversity across its expanding geographic range.

Animals↗
PubMed2006

Low levels of pyrazinamide and ethambutol in children with tuberculosis and impact of age, nutritional status, and human immunodeficiency virus infection.

Recent pharmacokinetic studies that included children found that serum drug levels were low compared to those of adults for whom the same dosages were used. This study aimed to characterize the pharmacokinetics of pyrazinamide and ethambutol in Malawian children and to examine the impact of age, nutritional status, and human immunodeficiency virus (HIV) infection. We conducted a pharmacokinetic study of children treated for tuberculosis with thrice-weekly pyrazinamide (n = 27; mean age, 5.7 years) and of a separate group of children treated with thrice-weekly ethambutol (n = 18; mean age, 5.5 years) as portions of tablets according to national guidelines. Malnutrition and HIV infection were common in both groups. Blood samples were taken just prior to oral administration of the first dose, and subsequent samples were taken at intervals of 2, 3, 4, 7, 24, and 48 h after drug administration. Serum drug levels were low in all children for both drugs; in almost all cases, the maximum concentration of the drug in serum (Cmax) failed to reach the MIC for Mycobacterium tuberculosis. The Cmax of pyrazinamide was significantly lower in younger children (<5 years) than in older children. The Cmax of pyrazinamide was also lower for HIV-infected children and children with severe malnutrition, but these differences did not reach statistical significance. No differences were found for ethambutol in relation to age, HIV infection, or malnutrition, but the Cmax was <2 mg/liter in all cases. Studies of pharmacokinetic parameters and clinical outcomes obtained by using higher dosages of drugs for treatment of childhood tuberculosis are needed, and recommended dosages may need to be increased.

Adolescent↗
PubMed2005

Ultrasound-guided core biopsy for the diagnosis of lumps in the neck: results in 82 patients.

Ultrasound-guided core biopsy of nodes (n = 78) and other lumps (n = 4) in the neck allowed a firm histological diagnosis in 76 of 82 patients (93%). Of the remaining six patients, histological examination was equivocal in four and valueless in two. Of 18 patients with a diagnosis of lymphoma only 3 required excision of the node to provide additional information for the planning of treatment.

Adult↗
PubMed2003

Apoptosis in HIV-1 infection.

Apoptosis is a key event in biologic homeostasis with particular importance to the immune system. It is an active energy-dependent process that is tightly regulated and controlled by a variety of signal transduction pathways. Apoptosis modulation plays a part in the pathogenesis of many human diseases, including HIV infection. Although multiple mechanisms may contribute to the decline in CD4 T-lymphocyte numbers observed, apoptosis is a significant factor. Alterations in levels of apoptosis are observed in both directly infected and uninfected bystander cells and a variety of pathways of apoptosis induction have been implicated. Apoptosis induction is related to death receptor and mitochondrial-induced pathways in specific circumstances. These events have been linked to individual HIV proteins and have been demonstrated to be altered by antiretroviral therapy.

Apoptosis↗
PubMed2001

Effect of MAO-A inhibition on the pharmacokinetics of almotriptan, an antimigraine agent in humans.

AIMS: To assess the effect of a reversible MAO-A inhibitor, moclobemide, on the single-dose pharmacokinetics of almotriptan and assess the clinical consequences of any interaction. METHODS: Twelve healthy volunteers received the following treatments in a randomized, open-label, two-way crossover design (with a 1 week washout between treatments): (A) one 150 mg moclobemide tablet every 12 h for 8 days and one 12.5 mg almotriptan tablet on the morning of day 8; and (B) one 12.5 mg almotriptan tablet on day 8. Plasma almotriptan was quantified by h.p.l.c.-MS-MS, while urinary concentrations were measured by h.p.l.c.-u.v. Vital signs, ECGs, and adverse events were evaluated after almotriptan administration. Treatment effects on pharmacokinetics and vital signs were assessed by analysis of variance. RESULTS: Mean almotriptan AUC was higher (483 +/- 99.9 vs 352 +/- 75.4 ng ml-1 h, P = 0.0001) and oral clearance was lower (26.6 +/- 4.00 vs 36.6 +/- 5.89 l h-1, P = 0.0001) when almotriptan was administered with moclobemide. Mean half-life was longer (4.22 +/- 0.78 vs 3.41 +/- 0.45 h, P = 0.0002) after coadministration with moclobemide. Renal clearance of almotriptan was unaffected by moclobemide. No serious adverse events occurred and no clinically significant vital sign changes were observed. CONCLUSIONS: Moclobemide increased plasma concentrations of almotriptan on average by 37%, but the combined administration of these two compounds was well tolerated. The degree of interaction was much less than that seen previously for sumatriptan or zolmitriptan given with moclobemide.

Adolescent↗
PubMed2000

One or more labile proteins regulate the stability of chimeric mRNAs containing the 3'-untranslated region of cholesterol-7alpha -hydroxylase mRNA.

Multiple AUUUA elements similar to those that regulate the degradation of several different mRNAs are conserved in the 3'-untranslated region (3'-UTR) of cholesterol-7alpha-hydroxylase (CYP7A1) mRNAs from several species. We examined if stabilization of mRNA decay could account for the >20-fold increase in the expression of CYP7A1 mRNA without a detectable change in transcription following dexamethasone treatment of rat hepatoma cells (L35 cells). Following RNA polymerase II-dependent transcription block or protein synthesis block, the decay of CYP7A1 mRNA displayed a short half-life ( approximately 30 min). Control experiments showed that in cells pre-treated with a RNA polymerase II inhibitor, dexamethasone had no detectable effect on CYP7A1 mRNA decay. Stable expression of luciferase reporter mRNAs in L35 cells showed that the CYP7A1 3'-UTR was required to observe a dexamethasone induction. To examine the hypothesis that a labile protein is required for dexamethasone-induced mRNA stabilization, cells were stably transfected with a tetracycline-repressible promoter that drives the expression of a green fluorescent protein analogue (ECFP) with or without the 3'-UTR of CYP7A1. Cells expressing ECFP with the 3'-UTR of CYP7A1 displayed a 3-fold dexamethasone induction of ECFP mRNA, whereas cells expressing ECFP without the 3'-UTR did not. Moreover, specific block of the transcription of ECFP containing the 3'-UTR by adding the tetracycline analogue doxycycline clearly displayed dexamethasone-induced stabilization of mRNA decay. These data provide compelling evidence that a putative labile protein and the 3'-UTR of CYP7A1 act together to decrease the rate of CYP7A1 mRNA degradation.

3' Untranslated Regions↗
PubMed2000

SB-219383, a novel tyrosyl tRNA synthetase inhibitor from a Micromonospora sp. II. Structure determination.

A novel tyrosyl tRNA synthetase inhibitor, SB-219383, has been isolated from a Micromonospora sp. The structure of SB-219383 has been elucidated by a combination of derivatisation, spectroscopic and other analytical techniques and found to be N-(L-tyrosyl)-2-amino[1(S*),3(S*),4(S*),5(R*),8(R*)-2,4,5,8-tetrahydroxy -7-oxa-2-azabicyclo[3.2.1]oct-3-y1]acetic acid (1).

Bridged Bicyclo Compounds, Heterocyclic↗
PubMed1999

An integrated proteomic approach to studying glomerular nephrotoxicity.

A single dose of puromycin aminonucleoside (PAN) given parenterally to rats induces ultrastructural glomerular changes and a nephrotic syndrome similar in many respects to human minimal change nephropathy. The exact aetiologies of both the human and the experimental syndromes are unknown, and are probably multifactorial. However, among the observed consequences in humans and rats is increased plasma protein excretion in urine, beginning in the latter typically 3-6 days after PAN administration. In view of this, two-dimensional polyacrylamide gel electrophoresis (2-D PAGE) has been used to profile urinary proteins during PAN-induced nephrotoxicity and subsequent recovery in the rat. In addition, urinary high performance liquid chromatography (HPLC) profiles and high resolution proton nuclear magnetic resonance (NMR) spectroscopy has been utilised to simultaneously detect toxin-induced changes in the relative concentrations of a number of metabolites. The proteomic approach, in conjunction with these other techniques, has the potential to provide significantly more mechanistic information than is provided readily by traditional clinical chemistry.

Animals↗
PubMed1999

Fine-scale genetic structuring in a natural population of European wild rabbits (Oryctolagus cuniculus).

The genetic structure of a free-living tagged population of European wild rabbits (Oryctolagus cuniculus) was investigated for two consecutive years (1990 and 1991) using 10 polymorphic microsatellite loci. A specific social behaviour, the formation of stable breeding groups, influenced the genetic structure of the population. These breeding groups were shown to constitute genetically differentiated units with low levels of gene flow between them. The average relatedness among members of a social group was higher than within the population as a whole. As a result of female philopatry coupled with male-biased natal dispersal, the relatedness of females was higher than that of males, both within social groups and in the whole population. Furthermore, the average relatedness of females within groups was twice the relatedness of females between groups. This study reveals marked fine-scale, intrapopulation genetic structure, which is attributable to the social behaviour of the European wild rabbit.

Age Factors↗
PubMed1998

Comparative effects of early weaning or once-daily suckling on occurrence of postpartum estrus in primiparous beef cows.

We concurrently evaluated early weaning and once-daily suckling as options for shortening postpartum interval to estrus in primiparous cows calving in good body condition. Over 2 consecutive years, a total of 77 primiparous cows were assigned to 1 of 3 treatments: control (ad libitum suckling); once-daily suckling (for 30 d prior to start of breeding); or early weaning (calves weaned 30 d prior to start of breeding). All cows had a body condition score (BCS) of > or = 5 at parturition and were maintained in good condition throughout the breeding season. Cows were observed for estrus twice daily and blood samples for subsequent measurement of progesterone were collected at 48-h intervals. For data analysis, cows were divided into early- (> or = 85 d post partum) and late-calving (< 85 d post partum) groups at the onset of the breeding season. All calves were weighed at birth, at the onset of treatment, at weekly intervals until the start of the breeding season, and within 45 d of 205 d of age. Early weaning or once-daily suckling shortened the postpartum interval to first estrus of late-calving primiparous cows by 17 (P < 0.01) and 12 d (P < 0.08), respectively, compared with control group cows. However, among early-calving cows, neither early weaning nor once-daily suckling influenced the postpartum interval. Postpartum intervals of once-daily suckled cows and early-weaned cows were similar (P > 0.10).

Animals↗
PubMed1997

Polymorphic microsatellite loci in the European rabbit (Oryctolagus cuniculus) are also amplified in other lagomorph species.

Six polymorphic microsatellite markers developed for the European wild rabbit (Oryctolagus cuniculus) were amplified with 20 other species of lagomorphs, representing both commercially important species and species important from a conservation perspective. Successful amplification of a number of these loci has provided an important set of new molecular markers for this mammalian order.

Alleles↗
PubMed1997

Chronic mild stress-induced reductions in saccharin intake depend upon feeding status.

The consumption of a weak saccharin solution was examined in rats subjected to chronic mild stress (CMS). Intake of saccharin was reduced in stressed animals compared to isolated and group control animals but saccharin preference was not affected. Removal of water deprivation from the CMS schedule did not alter the effects of CMS upon saccharin intake. However, when food deprivation was omitted entirely from the CMS schedule the reduction in saccharin intake was eliminated. Similarly, in animals habituated to the full CMS procedure, reduction in saccharin intake was abolished by omitting food deprivation or by delaying the intake test for 24 h. Both CMS and food deprivation reduced water intake but had no effect on food consumed during the fluid-intake test. The presence of food deprivation during CMS appears to be a key factor affecting saccharin intake. Our data suggest that saccharin intake is not an appropriate measure of stress and anhedonia.

Animals↗
PubMed1996

Methodology for adjusting scrotal circumference to 365 or 452 days of age and correlations of scrotal circumference with growth traits in beef bulls.

A retrospective analysis was conducted on data collected from 1983 through 1991, where weight and hip height were measured at start of test and every 28 d on 604 bulls completing a 224-d forage-based gain test. Scrotal circumference (SC) was measured at start of test, and at either end of test or end of the weigh period after individual bulls reached 365 d of age. Over 3 yr of this study, SC was additionally measured every 28 d. Bulls were representatives of 5 breed groups: Angus, Santa Gertrudis, Simmental, Continental (predominantly Charolais), and Zebu (predominantly Simbrah). Adjusted 365-d SC and adjusted 452-d SC were calculated by regression analysis and from formulas based on SC growth of individuals to 140 and 224 d on test, respectively. Breed group differences were observed for age of dam, birth weight, hip height, weight per day of age, average daily gain and SC at start of test, 140 d, and end of test (224 d). Scrotal circumference was positively correlated with all growth traits. Scrotal circumference was related to breed group, age, weight, hip height, average daily gain, weight per day of age, age by year, and age-by-breed group (P<0.05), as determined by regression analysis. However, omitting weight, hip height, average daily gain, and weight per day of age from the regression model did not significantly affect R2 value. Scrotal circumference growth was linear to 140 d on test; however, SC growth to 224 d on test was curvilinear. The 365-d SC predicted from the formula and from regression analysis differed for Simmental and Zebu by 0.3 and 0.4 cm, respectively (P<0.05). The 452-d SC differed for Santa Gertrudis and Zebu by 0.5 and 0.6 cm, respectively (P<0.05). Formulas based on SC growth of individuals are reasonably accurate predictors of SC at 365 and 452 d of age, when compared with more complex regression analysis. Basing SC adjustments on individual growth appears to account for variables known to affect yearling SC.

Journal Article↗
PubMed1995

Natal dispersal and genetic structure in a population of the European wild rabbit (Oryctolagus cuniculus).

A combination of behavioural observation, DNA fingerprinting, and allozyme analysis were used to examine natal dispersal in a wild rabbit population. Rabbits lived in territorial, warren based social groups. Over a 6-year period, significantly more male than female rabbits moved to a new social group before the start of their first breeding season. This pattern of female philopatry and male dispersal was reflected in the genetic structure of the population. DNA fingerprint band-sharing coefficients were significantly higher for females within the same group than for females between groups, while this was not the case for males. Wright's inbreeding coefficients were calculated from fingerprint band-sharing values and compared to those obtained from allozyme data. There was little correlation between the relative magnitudes of the F-statistics calculated using the two techniques for comparisons between different social groups. In contrast, two alternative methods for calculating FST from DNA fingerprints gave reasonably concordant values although those based on band-sharing were consistently lower than those calculated by an 'allele' frequency approach. A negative FIS value was obtained from allozyme data. Such excess heterozygosity within social groups is expected even under random mating given the social structure and sex-biased dispersal but it is argued that the possibility of behavioural avoidance of inbreeding should not be discounted in this species. Estimates of genetic differentiation obtained from allozyme and DNA fingerprint data agreed closely with reported estimates for the yellow-bellied marmot, a species with a very similar social structure to the European rabbit.

Analysis of Variance↗
PubMed1994

Immunocytochemical detection of extracellular annexin II in cultured human skin keratinocytes and isolation of annexin II isoforms enriched in the extracellular pool.

Monoclonal antibodies were raised against trypsinized human skin epidermal cells and selected for their staining of the epidermal cells in a cell periphery pattern. One antibody, CP-1, immunoprecipitated a 36 kDa protein that was identified as annexin II heavy chain by microsequencing of a CNBr-generated peptide fragment from the antigen and by cross-identification with another anti-annexin II antibody. In addition to staining a broad cell periphery band in keratinocytes, CP-1 also detected annexin II outside and in between the top layer cells before cell permeabilization. Double-labeling of annexin II and F-actin revealed a distinct topographical relationship between the two, with intercellular annexin II flanked by the submembranously located actin of the juxta-positioned cells. Annexin II was isolated from cultured keratinocytes via immunoaffinity column chromatography in one step, using the same monoclonal antibody CP-1 and was found to be resolved into multiple isoforms when analyzed by two-dimensional gel electrophoresis. The predominant components of annexin II were basic, with pI of 6.5-8.5, and some of them formed disulfide-linked monomeric multimers under non-reducing conditions. Acidic annexin II isoforms with pI 5.4-5.8 were barely detectable among the total annexin II isolated but were selectively enriched in an extracellular pool created by 0.05% ethylenediaminetetraacetic acid (EDTA) dispersion of the cultured cells into single cell suspensions. Furthermore, they can be separated from the rest of annexin II by using a different elution condition. A 46 kDa protein, the identity of which is unclear, co-eluted with the acidic isoforms in the EDTA washes. These acidic isoforms, which co-eluted with the 46 kDa protein, are suspected of corresponding to the extracellular annexin II detected immunocytochemically.

Amino Acid Sequence↗