Publications by authors named "Peter P Doran"

Background: Classical Galactosaemia (CG) (OMIM #230400) is a rare inborn error of galactose metabolism caused by deficiency of the enzyme galactose-1-phosphate uridylyltransferase (GALT). Long-term complications persist in treated patients despite dietary galactose restriction with significant variations in outcomes suggesting epigenetic glycosylation influences. Primary Ovarian Insufficiency (POI) is a very significant complication affecting females with follicular depletion noted in early life.

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Among the long-term complications of Classic Galactosaemia (Gal) is premature ovarian insufficiency (POI) in female patients with subtle abnormalities of reproductive function also reported in male patients. Leptin is a circulating hormone which reflects body energy stores and which affects the neuroendocrine reproductive axis and pubertal development.We measured serum leptin in 28 children (10 girls, 18 boys; mean age 7.

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HIV infection is associated with metabolic bone disease resulting in bone demineralization and reduced bone mass. The molecular mechanisms driving this disease process have yet to be elucidated. Wnt/β-catenin signaling plays a key role in bone development and remodeling.

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People often feel unhappy in the morning but better later in the day, and this pattern may be amplified in the distressed. Past work suggests that one function of cortisol is to energize people in the morning. In a study of 174 students, we tested to see whether daily affect patterns, psychological distress, and awakening cortisol levels were interlinked.

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Background: NET1, a RhoA guanine exchange factor, is up-regulated in gastric cancer (GC) tissue and drives the invasive phenotype of this disease. In this study, we aimed to determine the role of NET1 in GC by monitoring the proliferation, motility and invasion of GC cells in which NET1 has been stably knocked down. Additionally, we aimed to determine NET1-dependent transcriptomic events that occur in GC.

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Background And Purpose: Metal ion toxicity both locally and systemically following MoM hip replacements remains a concern. Cobalt ions have been shown to induce secretion of proinflammatory chemokines locally; however, little is known about their effect systemically. We investigated the in vitro effect of cobalt ions on a variety of cell lines by measuring production of the proinflammatory chemokines IL-8 and MCP-1.

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The Wnt/β-catenin pathway is a major signaling cascade in bone biology, playing a key role in regulating bone development and remodeling, with aberrations in signaling resulting in disturbances in bone mass. The objectives of our study were to correlate serum Dkk1 expression with bone mineral density (BMD) and assess the potential role of Dkk1 as a serological marker of bone mass. Serum was collected from a cohort of patients (n = 36), 18 patients with a reduced BMD and 18 control patients.

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An increased incidence of bone and lipid toxicities is associated with HIV-1 infection and its treatment. Mesenchymal stem cells (MSCs) are multipotent cells that can differentiate into both osteoblasts (OB) and adipocytes (AC). We hypothesize that the interaction of MSC and HIV-1 underlie these toxicities.

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Background: The Wnt/β-catenin pathway is a major signaling cascade in bone biology, playing a key role in bone development and remodeling. The objectives of this study were firstly, to determine the effects of dexamethasone exposure on Wnt/β-catenin signaling at an intracellular and transcriptional level, and secondly, to assess the phenotypic effects of silencing the Wnt antagonist, Dickkopf-1 (Dkk1) in the setting of dexamethasone exposure.

Methods: Primary human osteoblasts were exposed in vitro to 10-8 M dexamethasone over a 72 h time course.

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Introduction: We have previously reported that Myeov (MYEloma OVerexpressed gene) expression is enhanced in colorectal cancer (CRC) and that it promotes CRC cell proliferation and invasion. The role of Myeov in CRC migration is unclear. ProstaglandinE2 (PGE 2) is a known factor in promoting CRC carcinogenesis.

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Background: Ischaemic preconditioning (IPC) has emerged as a method of reducing ischaemia-reperfusion injury. However, the complex mechanism through which IPC elicits this protection is not fully understood. The aim of this study was to investigate the genomic response induced by IPC in muscle biopsies taken from the operative leg of total knee arthroplasty patients in order to gain insight into the IPC mechanism.

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Objective: Prospective studies have linked negative affect with hypertension, cardiovascular disease, and mortality. This study aims to identify if cardiovascular activity in day-to-day settings is related to affect levels as assessed using the Day Reconstruction Method (Kahneman, Krueger, Schkade, Schwarz, & Stone, 2004).

Design: 186 people underwent baseline physiological testing and were monitored naturalistically for an entire day.

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Idiopathic pulmonary fibrosis (IPF) is a refractory and lethal interstitial lung disease characterized by alveolar epithelial cells apoptosis, fibroblast proliferation and extra-cellular matrix protein deposition. EBV, localised to alveolar epithelial cells of pulmonary fibrosis patients is associated with a poor prognosis. A strategy based on microarray-differential gene expression analysis to identify molecular drivers of EBV-associated lung fibrosis was utilized.

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Currently infection with the human immunodeficiency virus-1 (HIV-1) is in most instances a chronic disease that can be controlled by effective antiretroviral therapy (ART). However, chronic use of ART has been associated with a number of toxicities; including significant reductions in bone mineral density (BMD) and disorders of the fat metabolism. The peroxisome proliferator-activated receptor γ (PPARγ) transcription factor is vital for the development and maintenance of mature and developing adipocytes.

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EBV infection has been implicated in the pathogenesis of Idiopathic Pulmonary Fibrosis (IPF). Viral infection may occur from the early or late stage in IPF development. Whether alveolar epithelial cells, AECs, normally express EBV main receptor, CD21, remains uncertain.

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The quality of tissue studied impacts greatly on oligonucleotide microarray results, emphasizing the importance of harvesting techniques. The analyzed RNA extracted from human lung samples preserved via 4 different storage conditions (RNAlater, phosphate-buffered saline, TRIzol, liquid nitrogen). RNA was assessed by denaturing gel electrophoresis, Agilent bioanalysis, real-time polymerase chain reaction (PCR), and Test3 Affymetrix chip hybridization.

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Idiopathic pulmonary fibrosis (IPF) is a refractory and lethal interstitial lung disease characterized by alveolar epithelial cells apoptosis, fibroblast proliferation, and ECM protein deposition. Epstein-Barr virus (EBV) has previously been localized to alveolar epithelial cells of IPF patients and is associated with a poor prognosis. In this study, we utilized a microarray-based differential gene expression analysis strategy to identify molecular drivers of EBV-associated lung fibrosis.

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Background: A high incidence of decreased bone mineral density (BMD) has been associated with HIV infection. Normal skeletal homeostasis is controlled, at least in part, by the maturation and activity of mature osteoblasts. Previous studies by our group have demonstrated the ability of HIV proteins to perturb osteoblast function, and the degree of osteogenesis in differentiating mesenchymal stem cells (MSCs).

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A high incidence of decreased bone mineral density (BMD) has increasingly been associated with HIV infection. In this study mesenchymal stem cell (MSC) and human osteoblast (hOB) cell lines were treated with HIV tat, HIV rev, HIV p55-gag, HIV gp120 and HTLV env (100 ng/ml, 24 h). Cells were then analyzed for calcium deposition, alkaline phosphatase (ALP) activity, and lipid levels using established methods.

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Background: Idiopathic Pulmonary Fibrosis (IPF) is a progressive diffuse disease involving the lung parenchyma. Despite recent advances, the molecular mechanisms of the initiation and progression of this disease remain elusive. Previous studies have demonstrated TGFbeta1 as a key effector cytokine in the development of lung fibrosis.

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Purpose Of Review: Since the introduction of potent antiretroviral therapy, the emphasis in managing HIV patients has changed from treatment and prevention of opportunistic infections to dealing with toxicities of long-term antiretroviral therapy such as bone demineralization. To date, the pathogenic mechanisms underlying the initiation and progression of osteoporosis in HIV patients remain to be elucidated. This review focuses on recent advances in our understanding of the role of both HIV and antiretroviral therapy in driving bone disease and presents an update on current treatment options and new therapeutic agents targeting novel sites.

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HIV-infected patients are at increased risk of decreased bone mineral density. Some studies have implicated antiretroviral therapy as a contributor to the decreased bone mineral density seen in treated HIV-1 patients. In this study we explore the interactions between protease inhibitors (PI) and primary human osteoblast gene expression, highlighting a group of dysregulated genes that potentially are key factors in reducing bone formation.

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Background: Osteoporosis, a disease of decreased bone mineral density represents a significant and growing burden in the western world. Aging population structure and therapeutic use of glucocorticoids have contributed in no small way to the increase in the incidence of this disease. Despite substantial investigative efforts over the last number of years the exact molecular mechanism underpinning the initiation and progression of osteoporosis remain to be elucidated.

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HIV-infected patients are at increased risk of decreased bone mineral density. Several studies have implicated antiretroviral therapy as a contributor to the decreased bone mineral density seen in treated HIV-1 patients. Whilst the exact molecular mechanisms underlying decreased bone density remain to be elucidated, inflammation has been postulated to be an important pathogenomic mechanism.

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