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Biomedical subjects

M Brown

Publications and source records attributed to M Brown.

At least 19 recordsLinked to original sources
PubMed2006

Chlamydia trachomatis and Neisseria gonorrhoeae infection and the sexual behaviour of men who have sex with men.

BACKGROUND: Rates of bacterial sexually transmitted infections (STIs) continue to rise among men who have sex with men (MSM) in the UK. OBJECTIVE: To evaluate factors associated with Chlamydia trachomatis and Neisseria gonorrhoeae among MSM attending a genitourinary medicine clinic in inner London. STUDY DESIGN: 599 MSM undergoing testing for STIs were recruited. Specimens for ligase chain reaction (LCR), strand displacement amplification (SDA) assay and culture were collected from the pharynx, urethra and rectum for the detection of C trachomatis and N gonorrhoeae. Details regarding demographics, symptoms, signs and sexual behaviour were recorded. Associations of these factors with each infection were tested, adjusting for other risk factors. RESULTS: The prevalence of C trachomatis and N gonorrhoeae was 11.0% and 16.0%, respectively. LCR and SDA performed well for the detection of C trachomatis and N gonorrhoeae from urethra and rectum. Using either method, compared with our current testing policy, over 18% of those with C trachomatis and N gonorrhoeae would not have had their infection diagnosed or treated. Age, sexual behaviour, urethral and rectal symptoms and signs were strongly associated with both infections. A total of 33.7% of men reported at least one episode of unprotected anal intercourse in the previous month. Men reporting multiple episodes were markedly more likely to be HIV positive. CONCLUSION: The prevalence of infection, rates of partner acquisition and unprotected anal intercourse reported among these MSM are alarming. Improved detection of C trachomatis and N gonorrhoeae using nucleic acid amplification tests has major public health implications for STI and possibly HIV transmission in this population.

Adolescent↗
PubMed2006

Application of SSH and a macroarray to investigate altered gene expression in Mytilus edulis in response to exposure to benzo[a]pyrene.

The lack of genomic resources for aquatic invertebrates restricts their use as sentinel species in coastal environments. It is known that where genomic data are not available, suppression subtractive hybridisation (SSH) can generate cDNA libraries representative of pollutant-responsive gene transcription in aquatic vertebrates. To assess whether the approach was equally suited to aquatic invertebrates, altered gene expression in digestive gland of the mussel, Mytilus edulis, in response to exposure to benzo[a]pyrene (BaP) (1 mg/l) was investigated with SSH and a nylon macroarray. Screening of the subtracted libraries showed 112/250 up-regulated and 25/55 down-regulated clones were positive for differential expression and characterisation of these identified 87 with unique sequence suitable for array on a nylon membrane. The transcripts isolated were from a diverse range of genes involved in general stress, oxidative stress, cell adhesion, transcriptional and translational regulation, transport mechanisms, energy metabolism, cell metabolism, lipid metabolism, protein turnover and activation, lysosomal activity and 22 cryptic clones. Subsequent use of the clones in macroarray format to analyse expression of BaP-responsive genes (0 vs 4 day exposed) showed 0-100-fold increased levels of the forward-subtracted probes and between 0 and 0.1-fold down-regulation of the reverse-subtracted probes. Only 15% of the clones showed less than 2-fold change in expression. The gene ontology of the transcripts isolated demonstrates that BaP elicits a multitude of responses with a major feature being disruption of cellular redox status. The results indicate that the use of SSH and a macroarray is a robust method to discover novel pollutant-responsive genes in aquatic invertebrates.

Animals↗
PubMed2006

Domains of a TBI minimal data set: community reintegration phase.

Efforts to establish a minimal data set for the period of community integration after traumatic brain injury (TBI) have been the focus of a working group of leading researchers, clinicians and advocates attending the Galveston Brain Injury Symposium in 2001 and 2002. The purpose of the data set is to increase the consistency and interpretability of TBI research and programme evaluation by providing a common set of measures to document key aspects of community integration. It is intended to be sensitive to intervention, comprehensive, reflect satisfaction and outcome and promote future treatment/therapy. In deciding on the components of a minimal data set, the tri-partite model of outcomes was adopted (initially employed in psychotherapy, adapted to TBI) which focuses on the needs of the individual, society and the health provider. Scales are recommended for the respective components of the model.

Age Factors↗
PubMed2006

Cognitive behaviour therapy and people with learning disabilities: implications for developing nursing practice.

People with learning disabilities are an ageing and increasing population and have been the subject of policy initiatives by the four countries of the UK, detailing the range of supports that need to be in place for this group. The evidence base of their mental health needs is growing and with it the need to ensure the full range of psychotherapies available to the general population are made available to people with learning disabilities. Cognitive Behaviour Therapy (CBT) is now a widely accepted and effective form of psychotherapy for many mental health problems and the evidence base is growing on the effectiveness with the learning disability population; however, the model needs to be applied differently for this group to take account of their cognitive impairment and support needs. Registered Nurses in Learning Disabilities are well placed to apply this approach within their clinical practice; however, there is an absence of leadership and direction in the development of CBT for this group of clinicians. There is a need to support education and practice development to contribute to addressing the emotional needs of people with learning disabilities. Action is required to support education to prepare Registered Nurses in Learning Disabilities to practice CBT and to contribute to the ongoing development of research in this area of clinical practice.

Adult↗
PubMed2006

Helminths and HIV infection: epidemiological observations on immunological hypotheses.

Parasitic helminths have co-evolved with the mammalian immune system. Current hypotheses suggest that immunological stimulation in the presence of helminths is balanced by immuno-regulation and by the broad spectrum of mechanisms possessed by helminths for countering the host immune response. The degree to which this balance is perfected, and the mechanisms by which this is achieved, vary between helminth species; we suggest that this is reflected not only in the degree of pathology induced by helminths but also in a variety of relationships with HIV infection and HIV disease. Available epidemiological data regarding interactions between helminths and HIV are largely observational; results are variable and generally inconclusive. Well designed, controlled intervention studies are required to provide definitive information on the species-specific nature of these interactions and on the advantages, disadvantages and optimal timing of de-worming in relation to HIV infection.

Animals↗
PubMed2006

Diagnosis of American foulbrood in honey bees: a synthesis and proposed analytical protocols.

Worldwide, American foulbrood (AFB) is the most devastating bacterial disease of the honey bee (Apis mellifera). Because the distinction between AFB and powdery scale disease is no longer considered valid, the pathogenic agent has recently been reclassified as one species Paenibacillus larvae, eliminating the subspecies designations Paenibacillus larvae subsp. larvae and Paenibacillus larvae subsp. pulvifaciens. The creamy or dark brown, glue-like larval remains of infected larvae continue to provide the most obvious clinical symptom of AFB, although it is not conclusive. Several sensitive and selective culture media are available for isolation of this spore-forming bacterium, with the type of samples that may be utilized for detection of the organism being further expanded. PCR methods for identification and genotyping of the pathogen have now been extensively developed. Nevertheless, biochemical profiling, bacteriophage sensitivity, immunotechniques and microscopy of suspect bacterial strains are entirely adequate for routine identification purposes.

Animals↗
PubMed2006

Blunt traumatic dissection of the proximal left anterior descending artery.

Coronary artery dissection secondary to blunt chest trauma is a rare occurrence recently reported in the Emergency Medicine Journal. The case here is reported of a left anterior descending artery dissection after blunt chest trauma to illustrate a different, more precipitous presentation of this condition after severe trauma. This case report highlights how clinical history can alert to the presence of this complication and how electrocardiography is fundamental to risk stratification after trauma, and discusses management alternatives for this condition in the setting of multi-trauma.

Accidents, Traffic↗
PubMed2006

Dissemination of Strongyloides stercoralis as an immune restoration phenomenon in an HIV-1-infected man on antiretroviral therapy.

We present a case of Strongyloides stercoralis infection in an HIV-infected man, resulting in Escherichia coli meningitis after initiation of antiretroviral therapy. Recent evidence from studies of strongyloides development supports the concept that strongyloides dissemination in this case is an example of an immune reconstitution inflammatory syndrome.

Adult↗
PubMed2006

Central line pump infusion and large volume mediastinal contrast extravasation in CT.

The use of multidetector CT scanners for CT angiography requires rapid injection of radiographic contrast media. Central venous catheters are now widely used for this purpose. Several complications may occur while using central venous access for rapid, large volume contrast injection such as catheter rupture and contrast extravasation. We describe a case in which inadvertent malposition of a central venous catheter led to a high volume extravasation of contrast in the mediastinum in a trauma patient.

Adult↗
PubMed2005

A scientific note on the detection of honeybee viruses using real-time PCR (TaqMan) in Varroa mites collected from a Thai honeybee (Apis mellifera) apiary.

Bee parasitic mite syndrome is a disease complex of colonies simultaneously infested with Varroa destructor mites and infected with viruses and accompanied by high mortality. By using real-time PCR (TaqMan), five out of seven bee viruses were detected in mite samples (V. destructor) collected from Thailand. Moreover, the results of this study provide an evidence for the co-existence of several bee viruses in a single mite. This is also the first report of bee viruses in mites from Thailand.

Animals↗
PubMed2005

Preservation of thoracic spine microarchitecture by alendronate: comparison of histology and microCT.

The effect of bisphosphonates on trabecular microarchitecture may contribute to the reduced risk of vertebral fracture with treatment independent of the bone volume. Trabecular structure was examined at the twelfth thoracic vertebra after 2 years of treatment of two groups of ovariectomized baboons on high and low doses of alendronate, compared with ovariectomized and non-ovariectomized controls. Standard 2D histological measurements showed that alendronate treatment of ovariectomized animals resulted in significantly higher total trabecular length and a lower marrow star volume in comparison with ovariectomized controls indicating preservation of connectivity. Similarly when the vertebrae were examined using a novel thick slice technique that combines 2D and 3D information, ovariectomy produced a significantly higher number of "real" trabecular termini in comparison with normal. When ovariectomized animals were treated with increasing doses of alendronate, fewer "real" termini were seen. MicroCT analysis (2D and 3D) correlated well with the histological measurements, although more variability and less discrimination between groups was seen, with no statistically significant differences with alendronate treatment. Reduced vertebral fracture risk with alendronate may be due to a combination of factors including the increased bone volume, reduced turnover and greater mineralization reported by others. Added to this is now suggested the preservation of several aspects of vertebral cancellous architecture, with microscopy the most sensitive method of analysis.

Alendronate↗
PubMed2005

Correlation between mouse potency and in vitro relative potency for human papillomavirus Type 16 virus-like particles and Gardasil vaccine samples.

An in vitro relative potency (IVRP) assay has been developed as an alternative to the mouse potency assay used to release Merck's human papillomavirus (HPV) vaccine, Gardasil, for early phase clinical trials. The mouse potency assay is a classical, in vivo assay, which requires 4-6 weeks to complete and exhibits variability on the order of 40% relative standard deviation (RSD). The IVRP assay is a sandwich-type immunoassay that is used to measure relative antigenicity of the vaccine product. The IVRP assay can be completed in three days, has a variability of approximately 10% RSD and does not require the sacrifice of live animals. Because antigen detection is achieved using H16.V5, a neutralizing monoclonal antibody, which binds to a clinically-relevant epitope, the relative antigenicity measured by the IVRP assay is believed to be a good predictor of in vivo potency. In this study, the relationship between immunogenicity, as measured by the mouse potency assay and antigenicity as measured by the IVRP assay, is demonstrated. Freshly manufactured and aged samples produced using two different manufacturing processes were tested using both methods. The results demonstrate that there is an inverse correlation between the IVRP and mouse potency assays. Additionally, clinical results indicate IVRP is predictive of human immunogenicity. Thus, antigenicity, as defined by the H16.V5 epitope, can be used as a surrogate for immunogenicity and the IVRP assay is suitable for use as the sole potency test for Gardasil samples.

Animal Testing Alternatives↗
PubMed2005

Allosteric activation of protein phosphatase 2C by D-chiro-inositol-galactosamine, a putative mediator mimetic of insulin action.

Insulin-stimulated glucose disposal in skeletal muscle proceeds predominantly through a nonoxidative pathway with glycogen synthase as a rate-limiting enzyme, yet the mechanisms for insulin activation of glycogen synthase are not understood despite years of investigation. Isolation of putative insulin second messengers from beef liver yielded a pseudo-disaccharide consisting of pinitol (3-O-methyl-d-chiro-inositol) beta-1,4 linked to galactosamine chelated with Mn(2+) (called INS2). Here we show that chemically synthesized INS2 has biological activity that significantly enhances insulin reduction of hyperglycemia in streptozotocin diabetic rats. We used computer modeling to dock INS2 onto the known three-dimensional crystal structure of protein phosphatase 2C (PP2C). Modeling and FlexX/CScore energy minimization predicted a unique favorable site on PP2C for INS2 in a surface cleft adjacent to the catalytic center. Binding of INS2 is predicted to involve formation of multiple H-bonds, including one with residue Asp163. Wild-type PP2C activity assayed with a phosphopeptide substrate was potently stimulated in a dose-dependent manner by INS2. In contrast, the D163A mutant of PP2C was not activated by INS2. The D163A mutant and wild-type PP2C in the absence of INS2 had the same Mn(2+)-dependent phosphatase activity with p-nitrophenyl phosphate as a substrate, showing that this mutation did not disrupt the catalytic site. We propose that INS2 allosterically activates PP2C, fulfilling the role of a putative mediator mimetic of insulin signaling to promote protein dephosphorylation and metabolic responses.

Amino Acid Substitution↗
PubMed2005

X-ray specular reflectivity study of a critical binary fluid mixture.

We have used direct inversion of x-ray reflectivity data to extract the liquid-vapor interface composition profile and the related critical scaling function of a binary mixture of dodecane and tetrabromoethane. The mixture was in the one-phase region above its critical point. The results indicate the formation of a monolayer of the lower surface tension component followed by an abrupt change to a mixed composition which gradually relaxes to the bulk composition deep within the fluid.

Journal Article↗
PubMed2005

Invasive characteristics of human prostatic epithelial cells: understanding the metastatic process.

Prostate cancer has a predilection to metastasise to the bone marrow stroma (BMS) by an as yet uncharacterised mechanism. We have defined a series of coculture models of invasion, which simulate the blood/BMS boundary and allow the elucidation of the signalling and mechanics of trans-endothelial migration within the complex bone marrow environment. Confocal microscopy shows that prostate epithelial cells bind specifically to bone marrow endothelial-to-endothelial cell junctions and initiate endothelial cell retraction. Trans-endothelial migration proceeds via an epithelial cell pseudopodial process, with complete epithelial migration occurring after 232+/-43 min. Stromal-derived factor-1 (SDF-1)/CXCR4 signalling induced PC-3 to invade across a basement membrane although the level of invasion was 3.5-fold less than invasion towards BMS (P=0.0007) or bone marrow endothelial cells (P=0.004). Maximal SDF-1 signalling of invasion was completely inhibited by 10 microM of the SDF-1 inhibitor T140. However, 10 microM T140 only reduced invasion towards BMS and bone marrow endothelial cells by 59% (P=0.001) and 29% (P=0.011), respectively. This study highlights the need to examine the potential roles of signalling molecules and/or inhibitors, not just in single-cell models but in coculture models that mimic the complex environment of the bone marrow.

Bone Marrow Cells↗
PubMed2005

Fixation protocols for subcellular imaging by synchrotron-based Fourier transform infrared microspectroscopy.

Synchrotron-based Fourier transform infrared (SR-FTIR) microspectroscopy is a powerful bioanalytical technique for the simultaneous analysis of lipids, proteins, carbohydrates, and a variety of phosphorylated molecules within intact cells. SR-FTIR microspectroscopy can be used in the imaging mode to generate biospectroscopic maps of the distribution and intensity profiles of subcellular biomolecular domains at diffraction-limited spatial resolution. However, the acquisition of highly spatially resolved IR images of cells is not only a function of instrumental parameters (source brightness, sampling aperture size) but also the cell preparation method employed. Additionally, for the IR data to be biochemically relevant the cells must be preserved in a life-like state without introducing artefacts. In the present study we demonstrate, for the first time, the differences in biomolecular localizations observed in SR-FTIR images of cells fixed by formalin, formalin-critical point drying (CPD), and glutaraldehyde-osmium tetroxide-CPD, using the PC-3 prostate cancer cell line. We compare these SR-FTIR images of fixed cells to unfixed cells. The influence of chemical fixatives on the IR spectrum is discussed in addition to the biological significance of the observed localizations. Our experiments reveal that formalin fixation at low concentration preserves lipid, phosphate, and protein components without significantly influencing the IR spectrum of the cell.

Animals↗