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Biomedical subjects

T Wilson

Publications and source records attributed to T Wilson.

At least 37 records · Page 2Linked to original sources

Synthesis and anti-inflammatory activities of N-benzoylamino-1,2,3,6-tetrahydropyridine analogs.

The anti-inflammatory activity of N-benzoylamino-1,2,3,6-tetrahydropyridine (Fig. 1) has been previously described. Further structural modification of 1 indicated that anti-inflammatory activities were greatly influenced by the position and nature of substituents on the tetrahydropyridine ring moiety. Analogs of 1 with benzyl group at position 4 of the tetrahydropyridine ring moiety and substituents on the benzene moiety were synthesized (9a-90). The effect of these substituents on pharmacological activity was screened in vivo using the carrageenan-induced paw edema assay in male Sprague-Dawley rats. Analogs with electron-donating substituents at position 4 and 2 of the benzene moiety 9f, 90 and 9d exhibited significant anti-inflammatory activities, similar to that observed for the reference compound, indomethacin. In summary, at an early stage of efforts to establish structure-activity relationship within this series, we found that 9f is a promising lead compound chosen for further investigation.

Animals↗

Bmp15 mutations and ovarian function.

BMP15, also known as growth and differentiation factor 9B (GDF9B), is a member of the transforming growth factor beta superfamily (TGFbeta) which in humans, rodents and sheep is expressed exclusively in the oocyte. BMP15 is closely related to GDF9, another oocyte-specific member of this superfamily which has been shown to be essential for early ovarian folliculogenesis. Inactivation of the BMP15 gene in mice has shown only minor effects on fertility. However, Inverdale and Hanna lines of sheep carry naturally occurring mutations in BMP15 which highlight differences in the action of this gene between mice and other mammals. Sheep which are heterozygous show an increase in ovulation rate whereas homozygotes are infertile. The granulosa cell receptor which mediates the BMP15 response has not yet been identified, but the discovery that a point mutation in the BMP1B receptor in Booroola sheep is responsible for increased ovulation rate highlights the importance of the TGFbeta signalling molecules in early folliculogenesis.

Animals↗

Optimisation of one-tube PCR-ELISA to detect femtogram amounts of genomic DNA.

A simple, high-throughput, low-cost polymerase chain reaction-enzyme linked immunosorbent assay (PCR-ELISA) protocol that detects the presence of 4 fg of DNA from four bacterial fish pathogens Yersinia ruckeri, Tenacibaculum maritimum (formerly Flexibacter maritimus), Lactococcus garvieae and Aeromonas salmonicida was developed. DNA amplification was undertaken in a biphasic system with free and bound PCR that are achieved in the one NucleoLink tube. Solid-phase amplicons were detected using biotin labelled hybridization probes and visualised colourimetrically with streptavidin-alkaline phosphatase and p-nitrophenylphosphate as substrate. PCR and hybridization took less than 8 h to perform with maximum signal output for femtogram amounts of template DNA achieved within 24 h. Implementation and optimization of the protocol is discussed.

Animals↗

New imaging modes for lenslet-array tandem scanning microscopes.

The tandem scanning microscope permits confocal images to be obtained in real time and viewed directly by eye. The light budget of these instruments may be increased from a few percent to a few tens of percent by incorporating an array of microlenses so as to increase the amount of illumination light that reaches the specimen. These instruments are configured for fluorescence imaging together with laser illumination. We describe how the versatility of the instrument may be enhanced to permit the use of incoherent light sources as well as extending the imaging modes to include bright-field reflection.

Dentin↗

Video-rate confocal endoscopy.

Rigid endoscopes provide high quality optical images of reasonably accessible regions of the inner body, especially regions such as the aero-digestive and genital tracts. In order to enhance the versatility of these instruments we describe a development that permits confocal endoscopic images to be obtained - along with traditional endoscopic images - in real-time, from within the living patient. The system is based around a host lenslet-array tandem scanning microscope, which is capable of producing images viewed directly by eye. These types of confocal microscope are configured for fluorescence imaging together with laser illumination. Hard and soft tissues in the mouth were imaged using this combined system.

Endoscopy↗

Linkage disequilibrium in domestic sheep.

The last decade has seen a dramatic increase in the number of livestock QTL mapping studies. The next challenge awaiting livestock geneticists is to determine the actual genes responsible for variation of economically important traits. With the advent of high density single nucleotide polymorphism (SNP) maps, it may be possible to fine map genes by exploiting linkage disequilibrium between genes of interest and adjacent markers. However, the extent of linkage disequilibrium (LD) is generally unknown for livestock populations. In this article microsatellite genotype data are used to assess the extent of LD in two populations of domestic sheep. High levels of LD were found to extend for tens of centimorgans and declined as a function of marker distance. However, LD was also frequently observed between unlinked markers. The prospects for LD mapping in livestock appear encouraging provided that type I error can be minimized. Properties of the multiallelic LD coefficient D' were also explored. D' was found to be significantly related to marker heterozygosity, although the relationship did not appear to unduly influence the overall conclusions. Of potentially greater concern was the observation that D' may be skewed when rare alleles are present. It is recommended that the statistical significance of LD is used in conjunction with coefficients such as D' to determine the true extent of LD.

Animals↗

Production of avirulent mutants of Mycobacterium bovis with vaccine properties by the use of illegitimate recombination and screening of stationary-phase cultures.

A better tuberculosis vaccine is urgently required to control the continuing epidemic. Molecular techniques are now available to produce a better live vaccine than BCG by producing avirulent strains of the Mycobacterium tuberculosis complex with known gene deletions. In this study, 1000 illegitimate recombinants of Mycobacterium bovis were produced by illegitimate recombination with fragments of mycobacterial DNA containing a kanamycin resistance gene. Eight recombinant strains were selected on the basis of their inability to grow when stationary-phase cultures were inoculated into minimal medium. Five of these recombinants were found to be avirulent when inoculated into guinea pigs. Two of the avirulent recombinants produced vaccine efficacy comparable to BCG against an aerosol challenge in guinea pigs with M. bovis. One of these recombinants had an inactivated glnA2 gene encoding a putative glutamine synthetase. Transcriptional analysis showed that inactivation of glnA2 did not affect expression of the downstream glnE gene. The other recombinant had a block of 12 genes deleted, including the sigma factor gene sigG. Two avirulent recombinants with an inactivated pckA gene, encoding phosphoenolpyruvate carboxykinase which catalyses the first step of gluconeogenesis, induced poor protection against tuberculosis. It is clear that live avirulent strains of the M. tuberculosis complex vary widely in their ability as vaccines to protect against tuberculosis. Improved models may be required to more clearly determine the difference in protective effect between BCG and potential new tuberculosis vaccines.

Animals↗

Quality collaboratives: lessons from research.

Quality improvement collaboratives are increasingly being used in many countries to achieve rapid improvements in health care. However, there is little independent evidence that they are more cost effective than other methods, and little knowledge about how they could be made more effective. A number of systematic evaluations are being performed by researchers in North America, the UK, and Sweden. This paper presents the shared ideas from two meetings of these researchers. The evidence to date is that some collaboratives have stimulated improvements in patient care and organisational performance, but there are significant differences between collaboratives and teams. The researchers agreed on the possible reasons why some were less successful than others, and identified 10 challenges which organisers and teams need to address to achieve improvement. In the absence of more conclusive evidence, these guidelines are likely to be useful for collaborative organisers, teams and their managers and may also contribute to further research into collaboratives and the spread of innovations in health care.

Cooperative Behavior↗

The social construction of sexually transmitted infections (STIs) in South African communities.

Since the medical link between sexually transmitted infections (STIs) and HIV/AIDS was established, there has been an increased focus on the spread of STIs in South Africa. The aim of this study was to provide an in-depth picture of the dynamics involved in sexuality and the spread of STIs and HIV/AIDS. The authors present the findings of a focus group study, which was a part of a larger, national project addressing the broad question of health-care seeking behavior for STIs. A discourse analysis carried out on 10 focus groups reveals complex and rich narratives on the way in which STIs are constructed in South African communities. The dominant discourses focused on the continuing stigmatization of STIs, causal explanations, and prevention strategies. The analysis raises important recommendations for both educational interventions and health services toward the challenge of halting the spread of STIs and HIV/AIDS.

Attitude to Health↗

Adenosine nucleotide modulates the physical interaction between hMSH2 and BRCA1.

We have identified the physical interaction between the Breast Cancer susceptibility gene product BRCA1 and the Hereditary Non-Polyposis Colorectal Cancer (HNPCC) and DNA mismatch repair (MMR) gene product hMSH2, both in vitro and in vivo. The BRCA1-hMSH2 association involved several well-defined regions of both proteins which include the adenosine nucleotide binding domain of hMSH2. Moreover, the interaction of BRCA1 with purified hMSH2-hMSH6 appears to be modulated by adenosine nucleotide much like G protein downstream interaction/signaling is modulated by guanosine nucleotide. BARD1, another BRCA1-interacting protein, was also found to interact with hMSH2. In addition, BRCA1 was found to associate with both hMSH3 and hMSH6, the heterodimeric partners of hMSH2. These observations implicate BRCA1/BARD1 as downstream effectors of the adenosine nucleotide-activated hMSH2-hMSH6 signaling complex, and suggest a global role for BRCA1 in DNA damage processing. The functional interaction between BRCA1 and hMSH2 may provide a partial explanation for the background of gynecological and colorectal cancer in both HNPCC and BRCA1 kindreds, respectively.

Adenosine Diphosphate↗

Identification of a cadmium-induced gene in Mycobacterium bovis and Mycobacterium tuberculosis.

A 17-kDa protein (CadI) was induced by cadmium in Mycobacterium bovis and Mycobacterium tuberculosis. Comparison of the N-terminal sequence from M. bovis CadI with the annotated M. tuberculosis genome database identified Rv2641 as the encoding gene. Long and short promoter fragments from M. bovis cadI were fused to the lacZ reporter gene in pYUB76. Only the long fragment directed cadmium-inducible activity when electroporated into M. bovis. The cadI promoter has potential for both constitutive and inducible expression studies in M. bovis and M. tuberculosis.

Amino Acid Sequence↗