Publications by authors named "Leach L"

The outer blood-retinal barrier is composed of a monolayer of retinal pigment epithelium, Bruch's membrane and the choriocapillaris which is fenestrated. Endothelial proliferation and breaching of Bruch's membrane leads to the neovascular form of age-related macula degeneration (ARMD). The aim of this study was to generate an in vitro model that mimics more faithfully the phenotype of the choriocapillaris and the trilayer architecture in vitro.

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Apolipoprotein E (APOE) is the major genetic risk factor for late-onset Alzheimer's disease (AD) and has also been implicated in cardiovascular disease, cognitive decline and cognitive changes in healthy ageing. The aim of this paper is to systematically review and critically assess the association between the APOE genotype and structural/functional cerebral changes as evidenced by brain imaging studies. A second aim is to determine whether these observed associations between APOE and the brain reflect changes which are consistent with the progression of AD neurodegenerative changes described in Braak stages.

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Purpose: To develop a method to screen for serum biomarkers of early hepatic metastasis from uveal melanoma.

Methods: Cytokeratin 18 (TPS) was identified from gene expression profiles as protein generated by highly invasive uveal melanoma cells. Sera were collected from two groups of 15 SCID mice 2 weeks after injection of either tissue culture medium or MUM2B human metastatic uveal melanoma cells into the mouse liver.

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Expression divergence of duplicate genes is widely believed to be important for their retention and evolution of new function, although the mechanism that determines their expression divergence remains unclear. We use a genetical genomics approach to explore divergence in genetical control of yeast duplicate genes created by a whole-genome duplication that occurred about 100 MYA and those with a younger duplication age. The analysis reveals that duplicate genes have a significantly higher probability of sharing common genetic control than pairs of singleton genes.

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Background: Caring for a terminally ill family member can be extremely stressful, and stress is known to have a negative influence on aspects of cognition. In contrast to the well-known physical and mental health risks associated with caregiving, little is known about its impact on cognitive functioning.

Objective: The primary objective of this study was to explore cognition among caregivers of palliative family members with a battery of neuropsychological tests.

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Purpose: To model the behavior of uveal melanoma in the liver.

Methods: A 15-muL suspension of metastatic MUM2B or either primary OCM1 or M619 uveal melanoma cells was injected into the liver parenchyma of 105 CB17 SCID mice through a 1-cm abdominal incision. Animals were killed at 2, 4, 6, or 8 weeks after injection.

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We previously described techniques to generate 3-dimensional reconstructions of the tumor microcirculation using immunofluorescence histochemistry and laser scanning confocal microscopy on serial sections from archival formalin-fixed, paraffin-embedded tissues. By aligning sequential z-stacks in an immersive visualization environment (ImmersaDesk), the need to insert fiduciary markers into tissue was eliminated. In this study, we developed methods to stitch overlapping confocal z-series together to extend the surface area of interest well beyond that captured by the confocal microscope objective and developed methods to quantify the distribution of markers of interest in 3 dimensions.

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Primary Objective: To assess the utility of the Mini-Mental Status Examination (MMSE) among the older TBI population.

Methods And Procedures: The MMSE and a number of other neuropsychological tests were administered to forty-three adults aged 50 and over one year following mild to moderate TBI. The sensitivity, specificity, and predictive value of the MMSE were evaluated in relation to these tests.

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People know thousands of words in their native language, and each of these words must be learned at some time in the person's lifetime. A large number of these words will be learned when the person is an adult, reflecting the fact that the mental lexicon is continuously changing. We explore how new words get added to the mental lexicon, and provide empirical support for a theoretical distinction between what we call lexical configuration and lexical engagement.

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Uncovering genetic control of variation in ethanol tolerance in natural populations of yeast Saccharomyces cerevisiae is essential for understanding the evolution of fermentation, the dominant lifestyle of the species, and for improving efficiency of selection for strains with high ethanol tolerance, a character of great economic value for the brewing and biofuel industries. To date, as many as 251 genes have been predicted to be involved in influencing this character. Candidacy of these genes was determined from a tested phenotypic effect following gene knockout, from an induced change in gene function under an ethanol stress condition, or by mutagenesis.

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Background: Many people with a mental disorder do not access help from mental health services. Internet websites may be a useful tool for disseminating mental health information to those who remain untreated, however little is known about people's perceptions of websites as mental health information sources. The current study examined characteristics that may influence belief in the helpfulness of websites as modes of delivering information about mental health.

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Previous work had suggested that in addition to serving the function of a siderophore, pyridine-2,6-bis(thiocarboxylic acid) (PDTC) may also provide producing organisms with the ability to assimilate other divalent transition metals. This was tested further by examining regulation of siderophore production, expression of pdt genes, and growth in response to added zinc. In media containing 10-50 microM ZnCl2, the production of PDTC was found to be differentially repressed, as compared with the production of pyoverdine.

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The compound pyridine-2,6-bis(thiocarboxylic acid) (PDTC) is known to be produced and excreted by three strains of Pseudomonas. Its reactivity includes the complete dechlorination of the environmental contaminant carbon tetrachloride. PDTC functions as a siderophore; however, roles as a ferric reductant and antimicrobial agent have also been proposed.

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The histological detection of laminin-rich vasculogenic mimicry patterns in human primary uveal melanomas is associated with death from metastases. We therefore hypothesized that highly invasive uveal melanoma cells forming vasculogenic mimicry patterns after exposure to a laminin-rich three-dimensional microenvironment would differentially express genes associated with invasive and metastatic behavior. However, we discovered that genes associated with differentiation (GDF15 and ATF3) and suppression of proliferation (CDKNa1/p21) were up-regulated in highly invasive uveal melanoma cells forming vasculogenic mimicry patterns, and genes associated with promotion of invasive and metastatic behavior such as CD44, CCNE2 (cyclin E2), THBS1 (thrombospondin 1), and CSPG2 (chondroitin sulfate proteoglycan; versican) were down-regulated.

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Maternal undernutrition is thought to result in smaller offspring and programme disease in later life. It is not known whether gestational nutrition affects development and functioning of placental vessels. The aim of this study was to ascertain if disturbed angiogenesis and junctional integrity were features of the labyrinthine vessels of placenta taken from transgenic Tie2-GFP mice fed either 18% (control) or 9% (low protein; MLP) casein diet.

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Increased difficulty with response inhibition occurs with age, although there is some controversy as to whether increased interference on Stroop tasks reflects difficulties with response inhibition or simply reflects generalized cognitive slowing. The Victoria Stroop Test (VST) is a brief, easily administered, psychometrically sound version of Stroop's original task. Performance on the VST by adults across a wide age span was examined to determine the association between age and various measures of interference.

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Background: The cadherin-catenin complex is the key component of the adherens junction in epithelial cells, and changes in this complex are implicated in gastric adenocarcinoma. Germline mutations in E-cadherin have been described in diffuse-type gastric adenocarcinoma. Helicobacter pylori infection is the first stage in gastric carcinogenesis.

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To assess the effectiveness of telephone-based interventions for mental illness, a systematic search of the literature was conducted using the databases PsycINFO and PubMed, and the search engine Google Scholar. The search identified 14 studies evaluating telephone-based interventions in the areas of depression (n = 6), anxiety (n = 3), eating disorders (n = 3), substance use (n = 1) and schizophrenia (n = 1). Although these studies provide evidence that telephone interventions can be effective, the few studies conducted, small sample sizes and lack of randomized controlled trial methodology prevent firm conclusions from being drawn.

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Background: To date, there has been very little work investigating behaviour changes induced by interventions that are designed to increase help seeking. The present paper examines the effects of two Internet depression websites on help seeking.

Methods: 414 individuals with elevated scores on a depression assessment scale were randomly allocated to a depression information website, a cognitive-behavioural skills training website (CBT) or an attention control condition.

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Purpose: This was a pilot study conducted to examine the expression of osteopontin in uveal melanoma and to determine whether serum osteopontin can be used in detecting metastatic uveal melanoma.

Methods: Osteopontin mRNA was measured in three uveal melanoma cell lines of various invasive potential by real-time PCR. Tissue sections of primary and metastatic uveal melanomas were stained for osteopontin.

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