A5018576704- Neonatal and fetal brain pathology
- Inflammatory Bowel Disease
- Acute Lymphoblastic Leukemia research
- Traumatic Brain Injury and Neurovascular Disturbances
- Autophagy in Disease and Therapy
- Gout, Hyperuricemia, Uric Acid
- Hepatitis C virus research
- Anesthesia and Neurotoxicity Research
- Autoimmune and Inflammatory Disorders Research
- Neuroinflammation and Neurodegeneration Mechanisms
- Eosinophilic Esophagitis
- IL-33, ST2, and ILC Pathways
- S100 Proteins and Annexins
- Microscopic Colitis
- Adolescent and Pediatric Healthcare
- Helicobacter pylori-related gastroenterology studies
- Drug-Induced Hepatotoxicity and Protection
- Pharmacogenetics and Drug Metabolism
- Cardiac Ischemia and Reperfusion
- Spondyloarthritis Studies and Treatments
- Immune Response and Inflammation
- Treatment of Major Depression
- Immunodeficiency and Autoimmune Disorders
- Mitochondrial Function and Pathology
- Liver Disease Diagnosis and Treatment
Sunderland Royal Hospital
2023
Ursinus College
2023
Oxford University Hospitals NHS Trust
2023
University of Otago
2010-2021
Monash Health
2021
University of Arizona
2020
PharmacoGenetics (China)
2015
GTx (United States)
2015
Dunedin Public Hospital
2012-2015
University of Sheffield
2014
The clinical course and eventual outcome, or prognosis, of complex diseases varies enormously between affected individuals. This variability critically determines the impact a disease has on patient's life but is very poorly understood. Here, we exploit existing genome-wide association study data to gain insight into role genetics in prognosis. We identify noncoding polymorphism FOXO3A (rs12212067: T > G) at which minor (G) allele, despite not being associated with susceptibility, milder...
Iron catalyzes the formation of damaging reactive species during cerebral reperfusion. Brain iron concentration is highest at birth, so brain asphyxiated newborn may be increased risk iron-dependent injury. We investigated whether ferric chelator deferoxamine could reduce hypoxic-ischemic injury in neonatal rats. Because has concentration-dependent activities other than chelation, we measured levels and calculated pharmacokinetic parameters. produced to right hemisphere 7-day-old rats by...
Iron can contribute to hypoxic-ischemic brain damage by catalyzing the formation of free radicals. The immature has high iron levels and limited antioxidant defenses. objective this study was describe early alterations in nonheme histochemistry following a (HI) insult neonatal rats. We induced HI right cerebral hemisphere groups 7-day-old Rats were anesthetized, then their brains perfused fixed at 0, 1, 4, 8, 24 hr, 2, 3 weeks recovery. Forty-micron-thick frozen sections stained for using...
Recently, separate genome-wide association analyses have identified nonsynonymous SNPs in IL23R and ATG16L1 (rs11209026; c1142G>A, R381Q, rs2241880; c1338A>G, T300A, respectively) as strong candidate susceptibility factors for Crohn's disease (CD) whites. The aim of our study was to test whether these are associated with CD a population-based cohort New Zealand Caucasian inflammatory bowel (IBD) patients.Allele frequencies rs11209026 rs2241880 were determined 496 patients, 466 ulcerative...
Autophagy is an intracellular pathway that can contribute to innate antiviral immunity by delivering viruses lysosomes for degradation or be beneficial providing specialized membranes virus replication. Here, we show the picornavirus foot-and-mouth disease (FMDV) induces formation of autophagosomes. Induction was dependent on Atg5, involved processing LC3 LC3II, and led a redistribution from cytosol punctate vesicles indicative authentic Furthermore, FMDV yields were reduced in cells lacking...
OBJECTIVES: Human β-defensin 2 (hBD-2orDEFB4) is a highly inducible, antimicrobial peptide, which may have an important role in the innate immune response at epithelial surfaces. Genomic copy number ofDEFB4is polymorphic, with most individuals possessing 3–5 copies. IncreasedDEFB4copy susceptibility factor for psoriasis, whereas single study Crohn's disease (CD) cohort reported that decreasedDEFB4copy associated colonic inflammation. Here, we analyze association ofDEFB4copy CD New Zealand...
Objectives To determine whether genetic polymorphisms within the folate pathway are associated with red blood cell (RBC) methotrexate (MTX) polyglutamate concentrations, RBC concentrations and MTX efficacy/toxicity. Methods Disease activity in 200 rheumatoid arthritis patients on was assessed by swollen tender joint counts Activity Score 28. Genetic shown to have an effect gene expression or protein function were examined. Results significantly MTHFR 677C>T (P=0.002), MTRR 66A>G (P<0.0001),...
OBJECTIVES: Perianal Crohn's disease (CD) affects around one-quarter of CD patients and represents a distinct phenotype. The objective this study was to investigate large population-based cohort inflammatory bowel (IBD) identify clinical genetic risk factors for perianal CD. METHODS: Data were collected in the Canterbury IBD database, estimated include 91% all with Canterbury, New Zealand. Genotyping performed selected loci previously demonstrated be associated Patients then compared both...
Cationic liposome (lipoplex) and polymer (polyplex)-based vectors have been developed for nonviral gene delivery. These bind DNA enter cells via endosomes, but intracellular transfer of to the nucleus is inefficient. Here we show that lipoplex polyplex in activate autophagy generate tubulovesicular autophagosomes. Activation was dependent on ATG5, resulting lipidation LC3, did not require PtdIns 3-kinase activity PIK3C3/VPS34. The autophagosomes generated by fused with each other, delivery...
Methotrexate (MTX) exerts at least part of its anti-inflammatory effects through adenosine receptors (ADOR). The aims this study were to determine the expression all four receptor genes (ADORA1, ADORA2A, ADORA2B, ADORA3 and ADORA3variant) in rheumatoid synovial tissue any influence MTX exposure on expression. Furthermore, we investigated whether polymorphisms within associated with response and/or adverse MTX.Adenosine gene was undertaken using PCR 20 arthritis (RA) samples. A separate...
To define the incidence of Mycobacterium avium subspecies paratuberculosis (MAP) in patients with Crohn's disease (CD) and control subjects.Blood samples from 361 CD a previously described population-based inflammatory bowel (IBD) cohort 200 blood donor controls, known NOD2 genotype, were screened by PCR for MAP-specific IS900 DNA. These results correlated genotype.The assay was capable detecting 20 fg purified MAP DNA, equivalent to roughly 100 cells/mL blood. DNA detected 33.8% cases 21.5%...
Abstract Background: Azathioprine and 6‐mercaptopurine (6‐MP) are well established for the treatment of inflammatory bowel disease (IBD). Assessing thiopurine methyltransferase (TPMT) status has been recommended to reduce risk serious toxicity. Measuring red blood cell (RBC) 6‐thioguanine nucleotide (6‐TGN) concentrations dose adjustment. Aim: To describe results measuring TPMT activity genotype, 6‐TGN concentration in New Zealand. Methods: Canterbury Health Laboratories provided these...