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Search Results: 1 - 10 of 132143 matches for " V Hugh Perry "
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Mouse maternal systemic inflammation at the zygote stage causes blunted cytokine responsiveness in lipopolysaccharide-challenged adult offspring
Charlotte L Williams, Jessica L Teeling, V Hugh Perry, Tom P Fleming
BMC Biology , 2011, DOI: 10.1186/1741-7007-9-49
Abstract: In the short term, maternal LPS challenge induced a transient and typical maternal sickness response (elevated serum proinflammatory cytokines and hypoactive behaviour). Maternal LPS challenge altered preimplantation embryo morphogenesis and cell lineage allocation, resulting in reduced blastocyst inner cell mass (ICM) cell number and a reduced ICM:trophectoderm cell ratio. In the long term, diverse aspects of offspring physiology were affected by maternal LPS treatment. Whilst birthweight, growth and adult blood pressure were unaltered, reduced activity in an open-field behaviour test, increased fat pad:body weight ratio and increased body mass index were observed in male, but not female, offspring. Most importantly, the maternal LPS challenge caused corticosterone-independent blunting of the serum proinflammatory cytokine response to innate immune challenge in both male and female offspring. The suppressed state of innate immunity in challenged offspring was dose-dependent with respect to the maternal LPS concentration administered.These results demonstrate for the first time that the preimplantation embryo in vivo is sensitive to maternal systemic inflammation, with effects on blastocyst cell lineage allocation and consequences for behaviour, adiposity and innate immune response in adult offspring. Critically, we identify a novel mechanism mediated through maternal-embryonic interactions that confers plasticity in the development of the innate immune system, which is potentially important in setting postnatal tolerance to environmental pathogens. Our study extends the concept of developmental programming of health and disease to include maternal health at the time of conception.Substantial evidence supports the concept that adult health and physiology are influenced by environmental factors during the gestational and infant stages of development [1-3]. The developmental origins of health and disease (DOHaD) hypothesis proposes that such programming may be contrib
Long-term impact of systemic bacterial infection on the cerebral vasculature and microglia
Ursula Puentener, Steven G Booth, V Hugh Perry, Jessica L Teeling
Journal of Neuroinflammation , 2012, DOI: 10.1186/1742-2094-9-146
Abstract: Mice were given repeated doses of lipopolysaccharide (LPS) or a single injection of live Salmonella typhimurium. Inflammatory cytokines were measured in serum, spleen and brain, and microglial phenotype studied by immunohistochemistry. To assess priming of the innate immune response in the brain, mice were infected with Salmonella typhimurium and subsequently challenged with a focal unilateral intracerebral injection of LPS.Repeated systemic LPS challenges resulted in increased brain IL-1β, TNF-α and IL-12 levels, despite attenuated systemic cytokine production. Each LPS challenge induced significant changes in burrowing behaviour. In contrast, brain IL-1β and IL-12 levels in Salmonella typhimurium-infected mice increased over three weeks, with high interferon-γ levels in the circulation. Behavioural changes were only observed during the acute phase of the infection. Microglia and cerebral vasculature display an activated phenotype, and focal intracerebral injection of LPS four weeks after infection results in an exaggerated local inflammatory response when compared to non-infected mice.These studies reveal that the innate immune cells in the brain do not become tolerant to systemic infection, but are primed instead. This may lead to prolonged and damaging cytokine production that may have a profound effect on the onset and/or progression of pre-existing neurodegenerative disease.
Early Hippocampal Synaptic Loss Precedes Neuronal Loss and Associates with Early Behavioural Deficits in Three Distinct Strains of Prion Disease
Kathryn J. Hilton, Colm Cunningham, Richard A. Reynolds, V. Hugh Perry
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0068062
Abstract: Prion diseases are fatal neurodegenerative diseases of the CNS that are associated with the accumulation of misfolded cellular prion protein. There are several different strains of prion disease defined by different patterns of tissue vacuolation in the brain and disease time course, but features of neurodegeneration in these strains have not been extensively studied. Our previous studies using the prion strains ME7, 79A and 22L showed that infected mice developed behavioural deficits in the same sequence and temporal pattern despite divergent end-stage neuropathology. Here the objective was to address the hypothesis that synaptic loss would occur early in the disease in all three strains, would precede neuronal death and would be associated with the early behavioural deficits. C57BL/6 mice inoculated with ME7, 79A, or 22L-infected brain homogenates were behaviourally assessed on species typical behaviours previously shown to change during progression and euthanised when all three strains showed statistically significant impairment on these tasks. A decrease in labelling with the presynaptic marker synaptophysin was observed in the stratum radiatum of the hippocampus in all three strains, when compared to control animals. Negligible cell death was seen by TUNEL at this time point. Astrocyte and microglial activation and protease resistant prion protein (PrPSc) deposition were assessed in multiple brain regions and showed some strain specificity but also strongly overlapping patterns. This study shows that despite distinct pathology, multiple strains lead to early synaptic degeneration in the hippocampus, associated with similar behavioural deficits and supports the idea that the initiation of synaptic loss is a primary target of the misfolded prion agent.
Brain Region Specific Pre-Synaptic and Post-Synaptic Degeneration Are Early Components of Neuropathology in Prion Disease
Zuzana ?i?ková, Richard A. Reynolds, Vincent O’Connor, V. Hugh Perry
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0055004
Abstract: Synaptic abnormalities, one of the key features of prion disease pathogenesis, gives rise to functional deficits and contributes to the devastating clinical outcome. The synaptic compartment is the first to succumb in several neurodegenerative diseases linked with protein misfolding but the mechanisms underpinning this are poorly defined. In our current study we document that a focal intrahippocampal injection of the mouse-adapted 22L scrapie strain produces a complex, region-specific pathology in the brain. Our findings reveal that early synaptic changes in the stratum radiatum of the hippocampus, identical to those observed with the ME7 strain, occur when 22L strain is introduced into the hippocampus. The pathology was defined by degenerating Type I pre-synaptic elements progressively enveloped by the post-synaptic density of the dendritic spine. In contrast, the pathology in the cerebellum suggested that dendritic disintegration rather than pre-synaptic abnormalities dominate the early degenerative changes associated with the Purkinje cells. Indeed, both of the major synaptic inputs into the cerebellum, which arise from the parallel and climbing fibers, remained intact even at late stage disease. Immunolabeling with pathway selective antibodies reinforced these findings. These observations demonstrate that neuronal vulnerability to pathological protein misfolding is strongly dependent on the structure and function of the target neurons.
Soluble Axoplasm Enriched from Injured CNS Axons Reveals the Early Modulation of the Actin Cytoskeleton
Patrick Garland, Lucy J. Broom, Shmma Quraishe, Paul D. Dalton, Paul Skipp, Tracey A. Newman, V. Hugh Perry
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0047552
Abstract: Axon injury and degeneration is a common consequence of diverse neurological conditions including multiple sclerosis, traumatic brain injury and spinal cord injury. The molecular events underlying axon degeneration are poorly understood. We have developed a novel method to enrich for axoplasm from rodent optic nerve and characterised the early events in Wallerian degeneration using an unbiased proteomics screen. Our detergent-free method draws axoplasm into a dehydrated hydrogel of the polymer poly(2-hydroxyethyl methacrylate), which is then recovered using centrifugation. This technique is able to recover axonal proteins and significantly deplete glial contamination as confirmed by immunoblotting. We have used iTRAQ to compare axoplasm-enriched samples from na?ve vs injured optic nerves, which has revealed a pronounced modulation of proteins associated with the actin cytoskeleton. To confirm the modulation of the actin cytoskeleton in injured axons we focused on the RhoA pathway. Western blotting revealed an augmentation of RhoA and phosphorylated cofilin in axoplasm-enriched samples from injured optic nerve. To investigate the localisation of these components of the RhoA pathway in injured axons we transected axons of primary hippocampal neurons in vitro. We observed an early modulation of filamentous actin with a concomitant redistribution of phosphorylated cofilin in injured axons. At later time-points, RhoA is found to accumulate in axonal swellings and also colocalises with filamentous actin. The actin cytoskeleton is a known sensor of cell viability across multiple eukaryotes, and our results suggest a similar role for the actin cytoskeleton following axon injury. In agreement with other reports, our data also highlights the role of the RhoA pathway in axon degeneration. These findings highlight a previously unexplored area of axon biology, which may open novel avenues to prevent axon degeneration. Our method for isolating CNS axoplasm also represents a new tool to study axon biology.
The Role of Activity in Synaptic Degeneration in a Protein Misfolding Disease, Prion Disease
Matteo Caleo, Laura Restani, Eleonora Vannini, Zuzana Siskova, Hussain Al-Malki, Ruth Morgan, Vincent O'Connor, V. Hugh Perry
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0041182
Abstract: In chronic neurodegenerative diseases associated with aggregates of misfolded proteins (such as Alzheimer's, Parkinson's and prion disease), there is an early degeneration of presynaptic terminals prior to the loss of the neuronal somata. Identifying the mechanisms that govern synapse degeneration is of paramount importance, as cognitive decline is strongly correlated with loss of presynaptic terminals in these disorders. However, very little is known about the processes that link the presence of a misfolded protein to the degeneration of synapses. It has been suggested that the process follows a simple linear sequence in which terminals that become dysfunctional are targeted for death, but there is also evidence that high levels of activity can speed up degeneration. To dissect the role of activity in synapse degeneration, we infused the synaptic blocker botulinum neurotoxin A (BoNT/A) into the hippocampus of mice with prion disease and assessed synapse loss at the electron microscopy level. We found that injection of BoNT/A in na?ve mice caused a significant enlargement of excitatory presynaptic terminals in the hippocampus, indicating transmission impairment. Long-lasting blockade of activity by BoNT/A caused only minimal synaptic pathology and no significant activation of microglia. In mice with prion disease infused with BoNT/A, rates of synaptic degeneration were indistinguishable from those observed in control diseased mice. We conclude that silencing synaptic activity neither prevents nor enhances the degree of synapse degeneration in prion disease. These results challenge the idea that dysfunction of synaptic terminals dictates their elimination during prion-induced neurodegeneration.
Mucinous carcinoma in Crohn’s disease originating in a fistulous tract
Hugh J Freeman,Tom Perry,Douglas L Webber,Silvia D Chang
World Journal of Gastrointestinal Oncology , 2010,
Abstract: Malignant disease, including mucinous carcinomas of the colorectum, may complicate long-standing Crohn’s disease. An 18-year-old male with extensive small and large bowel involvement with Crohn’s disease developed recurrent peri-rectal fistulous disease that persisted for more than a decade despite pharmacological and surgical therapy as well as later therapy with biological agents. Eventually, an extensive and difficult-to-detect mucinous carcinoma developed in the fistulous tract. Although fistula cancer is rarely described in Crohn’s disease, use of immunosuppressant and biological agents may play an initiating or exacerbating role in its development or progression. As potent biological agents are frequently used, often to avoid surgical treatment, clinicians should have an increasingly high index of suspicion for this potential complication, especially if fistulous drainage persists and remains refractory to medical therapy.
HEIs-Regions Engagement Using Knowledge Management Strategy  [PDF]
Milly Perry
Modern Economy (ME) , 2014, DOI: 10.4236/me.2014.57068

Historically, the higher education system was the first knowledge industry. Today however, it no longer stands alone, but is one knowledge industry among many. Now, more than ever before, there is a stronger cooperation between the academia and industry, due to interdisciplinary activities, and because R & D activities are not limited to universities, but performed by industry too. Thus, new knowledge is created not only in universities and research institutes, but also in industry. Also, the implementation of knowledge develops not only in industry, but also within the academia. This means that the boundaries between industrial and academic research have been blurred. However, in spite of this fact, we still have not witnessed the breakthrough that we have been anticipating so keenly. It is highly important that policy leaders and decision makers in both the academia and industry should use “knowledge tools” for better communication between them. In industry, the tremendous value of knowledge strategy for business sustainability has already been realized. But while knowledge management tools that are suited to the current knowledge world have been implemented in industry for some time now, universities have not yet done so.

Solution Focused Brief Therapy Applied to Diverse Classroom Settings in a Four-Year University  [PDF]
Charity Perry
Creative Education (CE) , 2014, DOI: 10.4236/ce.2014.522218
Abstract: Solution Focused Brief Therapy was developed during the late 1970s and 1980s by Steve de Shazer and his colleagues. The purpose of this paper was to examine the application of Solution Focused Brief Therapy’s parallels with the author’s classroom experiences in a higher education setting that gave special considerations to the author’s disciplines of sociology, critical thinking, and marriage and family therapy. More specifically, the unique experiences are brought to a classroom by students much in the same manner that individuals bring experiences to a therapist who practices Solution Focused Brief Therapy. The author concludes that the perception of what constitutes a problem can be expressed as a limitation, not just merely defined as a problem.
Family Systems Perspective and Diabetes Type I: Reflective Analysis  [PDF]
Charity Perry
Advances in Applied Sociology (AASoci) , 2015, DOI: 10.4236/aasoci.2015.511025
Abstract: The purpose of this paper is to reflectively explore diabetes from a family systems perspective. Specific discussion will involve current understanding of Type I Diabetes and Family Systems, understanding suffering of illness experience, and will provide comparison and contrast of effective behavioral interventions for families under the care of a marriage and family therapist. While moving expectations toward systemic understanding of Type I Diabetes will be explored, and a brief account of the researchers’ personal and present familial history within the discipline of marriage and family therapy will also be discussed.
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