Publications by authors named "Macpherson P"

With the decline in the morbidity and mortality associated with HIV infection, the majority of people living with HIV (PWHIV) experience a higher quality of life and longer life expectancy. Since this diagnosis no longer prevents an active lifestyle, many PWHIV are re-integrating into the workplace or are contemplating this possibility. Despite the multiple advantages associated with a return to work, research has identified barriers related to work and HIV infection.

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Objectives: For individuals not on antiretroviral therapy, the risk of heterosexual transmission of HIV appears negligible when blood plasma (BP) viral loads are <1500 HIV-1 RNA copies/mL. It is not clear whether this observation can be extrapolated to individuals on highly active antiretroviral therapy (HAART). Because of differential tissue penetration, antiretroviral drug concentrations may be sufficient to maintain an undetectable viral load in the BP yet not achieve adequate levels to suppress HIV in the genital tract.

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IL-7 signaling is essential for optimal CD8 T cell function, homeostasis and establishment of memory. We have previously shown decreased expression of the IL-7 receptor alpha-chain (CD127) on CD8 T cells from HIV-infected patients with active viral replication. We have also shown that soluble HIV Tat protein specifically down-regulates CD127 on the surface of CD8 T cells and impairs cell proliferation and cytolytic potential following stimulation with IL-7 in vitro.

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Muscle activity contributes to formation of the neuromuscular junction and affects muscle metabolism and contractile properties through regulated gene expression. However, the mechanisms coordinating these diverse activity-regulated processes remain poorly characterized. Recently, it was reported that histone deacetylase 4 (HDAC4) can mediate denervation-induced myogenin and nicotinic acetylcholine receptor gene expression.

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A retrospective cohort study of mortality rates and potential predictors of death was conducted in public-sector patients initiating highly active antiretroviral therapy (HAART) between October 2005 and September 2007 in a rural, under-resourced region of South Africa. The aims were to determine the relative contribution of death to cohort exit and the causes and predictors of mortality among HAART initiators. A community outreach programme traced non-attenders.

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Objectives: To describe the epidemiology of an outbreak of infectious syphilis in Ottawa.

Methods: A retrospective chart review of infectious syphilis cases in Ottawa from 2001-2006.

Results: Rates of syphilis have risen more than tenfold.

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This paper provides an overview of HIV viral loads in blood and genital fluids and how these relate to HIV transmission during sexual activity. Current knowledge around HIV viral loads and transmission are then discussed in relation to HIV disclosure laws in Canada. HIV counsellors and health care workers should ensure that their clients/patients are aware that blood viral load is not necessarily equivalent to genital tract viral load and that the development of drug resistance within the two compartments may be unrelated.

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The hippocampus is critical for memory formation. However, the contributions of the hippocampal commissure (HC) and the corpus callosum (CC) are less clear. To elucidate the role of the forebrain commissures in learning and memory, we performed a behavioural and electrophysiological characterization of an inbred mouse strain that displays agenesis of the CC and congenitally reduced HC (BTBR T+ tf/J; 'BTBR').

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We standardized an indirect ELISA for measurement of serum antibody levels to four individual treponemal recombinant proteins that have been commonly used in a number of commercial EIAs, mostly as a mixture of antigens. When tested with 127 syphilis-negative and 37 secondary syphilis sera, ELISA O.D.

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Accurate treatment knowledge is required for patients to successfully manage complex medical conditions. Existing HIV knowledge scales focus on disease transmission and risk factors. This is the first study to develop and validate a scale to measure HIV treatment knowledge about complex treatment issues such as adherence, side-effects and drug resistance.

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Excellent medication adherence (>95%) is required for optimal HIV treatment success. This study aimed to develop and validate a brief scale to assess psychological readiness for successfully starting and adhering to HIV medications. HIV-positive men and women (N = 142) from an HIV outpatient clinic completed the proposed HIV Medication Readiness Scale (HMRS) prior to starting HIV medications.

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Ultraviolet A (UVA) makes up more than 90% of incident terrestrial ultraviolet radiation. Unlike shorter wavelength UVB, which damages DNA directly, UVA is absorbed poorly by DNA and is therefore considered to be less hazardous. Organ transplant patients treated with the immunosuppressant azathioprine frequently develop skin cancer.

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2-Hydroxyadenine (2-OH-A), a product of DNA oxidation, is a potential source of mutations. We investigated how representative DNA polymerases from the A, B and Y families dealt with 2-OH-A in primer extension experiments. A template 2-OH-A reduced the rate of incorporation by DNA polymerase alpha (Pol alpha) and Klenow fragment (Kf(exo-)).

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The purpose of this study was to evaluate a novel psycho-educational intervention intended to increase patients' medication preparedness and treatment adherence skills before initiating highly active antiretroviral therapy (HAART). Sixty-three HIV-positive patients not currently on antiretroviral therapy participated in a randomized controlled trial of a standardized, four-session psycho-educational intervention (Supportive Therapy for Adherence to Antiretroviral Treatment; STAART). Session topics included learning techniques to increase medication adherence and learning effective strategies to cope with stress and depression.

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We have previously shown decreased expression of the interleukin (IL)-7 receptor alpha-chain (CD127) on CD8 T-cells in HIV-infected patients and an apparent recovery of this receptor in those receiving antiretroviral therapy with sustained viral suppression. Here, we demonstrate that the HIV Tat protein specifically downregulates cell surface expression of CD127 on human CD8 T-cells in a dose- and time-dependent manner. The effects of Tat on CD127 expression could be blocked with anti-Tat monoclonal antibodies or by preincubating Tat with heparin.

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Article Synopsis
  • During the development of the neuromuscular junction, agrin and laminin help cluster nicotinic acetylcholine receptors (nAChRs) through the activation of MuSK, a tyrosine kinase.
  • Myogenin is identified as a crucial muscle-specific transcription factor for not only myoblast differentiation but also for effective nAChR clustering.
  • The study reveals that myogenin expression is vital for robust nAChR clustering, and this function cannot be replaced by other muscle regulatory factors or by simply increasing levels of clustering molecules like MuSK, rapsyn, and nAChRs.
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The present review considers issues pertaining to the precision and variability of quantitative hepatitis C virus (HCV) measurement in general, outlines the characteristics of HCV RNA in HIV-HCV coinfection and evaluates those factors which may affect this measure. The clinical relevance of accurate HCV measurement in HIV-HCV coinfection is discussed.

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Using optical imaging assays, we investigated the dynamics of acetylcholine receptors (AChRs) at laminin-associated clusters on cultured myotubes in the absence or presence of the nerve-derived clustering factor, agrin. Using fluorescence recovery after photobleaching (FRAP) on fluorescent bungarotoxin-labeled receptors, we found that approximately 9% of original fluorescence was recovered after 8 h as surface AChRs were recruited into clusters. By quantifying the loss of labeled receptors and the recovery of fluorescence after photobleaching, we estimated that the half-life of clustered receptors was approximately 4.

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DNA 8-oxoguanine (8-oxoG) causes transversions and is also implicated in frameshifts. We previously identified the dNTP pool as a likely source of mutagenic DNA 8-oxoG and demonstrated that DNA mismatch repair prevented oxidation-related frameshifts in mononucleotide repeats. Here, we show that both Klenow fragment and DNA polymerase alpha can utilize 8-oxodGTP and incorporate the oxidized purine into model frameshift targets.

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Relations between adult anxiety and mood disorders and retrospective reports of excessive childhood shyness were investigated in the US National Comorbidity, Survey (n=5877). Results indicated that 26% of women and 19% of men described themselves as 'very shy' when they were growing up. Of these shy individuals, 53% of women and 40% of men met criteria for a lifetime diagnosis of one or more anxiety or mood disorders.

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Microsatellite instability (MSI) in tumors is diagnostic for inactive DNA mismatch repair. It is widespread among some tumor types, such as colorectal or endometrial carcinoma, but is rarely found in leukemia. Therapy-related acute myeloid leukemia/myelodysplastic syndrome (tAML/MDS) is an exception, and MSI is frequent in tAML/MDS following cancer chemotherapy or organ transplantation.

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Huntington disease presents many challenges for the anesthetist. Of primary importance is that these patients are at increased risk of pulmonary aspiration. The use of short-acting anesthetic drugs should, therefore, be advantageous in promoting the rapid return of protective airway reflexes.

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Nucleotide excision (NER) is generally considered to comprise two partially distinct subpathways. Global genomic repair (GGR) removes damage from the genome overall and transcription-coupled repair (TCR) selectively excises damage from transcribed DNA. Cells from individuals belonging to xeroderma pigmentosum (XP) complementation group C are defective in GGR but retain a functional TCR pathway.

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