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Biomedical subjects

Helen Griffiths

Publications and source records attributed to Helen Griffiths.

14 recordsLinked to original sources
PubMed2006

Reduced secretion of fibulin 5 in age-related macular degeneration and cutis laxa.

Age-related macular degeneration (ARMD) is the leading cause of irreversible visual loss in the Western world, affecting approximately 25 million people worldwide. The pathogenesis is complex and missense mutations in FBLN5 have been reported in association with ARMD. We have investigated the role of fibulin 5 in ARMD by completing the first European study of the gene FBLN5 in ARMD (using 2 European cohorts of 805 ARMD patients and 279 controls) and by determining the functional effects of the missense mutations on fibulin 5 expression. We also correlated the FBLN5 genotype with the ARMD phenotype. We found two novel sequence changes in ARMD patients that were absent in controls and expressed these and the other nine reported FBLN5 mutations associated with ARMD and two associated with the autosomal recessive disease cutis laxa. Fibulin 5 secretion was significantly reduced (P<0.001) for four ARMD (p.G412E, p.G267S, p.I169 T, and p.Q124P) and two cutis laxa (p.S227P, p.C217R) mutations. These results suggest that some missense mutations associated with ARMD lead to decreased fibulin 5 secretion with a possible corresponding reduction in elastinogenesis. This study confirms the previous work identifying an association between FBLN5 mutations and ARMD and for the first time suggests a functional mechanism by which these mutations can lead to ARMD. It further demonstrates that FBLN5 mutations can be associated with different phenotypes of ARMD (not limited to the previously described cuticular drusen type). Such knowledge may ultimately lead to the development of novel therapies for this common disease.

Age Factors↗
PubMed2005

The effect of binocular and monocular distractors on saccades in participants with normal binocular vision.

We tested the effect of visual distractors presented monocularly and binocularly on saccade latency and accuracy to determine whether differences occur in saccadic planning with binocular or monocular visual input. For five participants with normal binocular single vision (BSV), saccade latency and accuracy were compared with distractors presented to the dominant eye, non-dominant eye or to both eyes. Eye movements of the dominant eye were recorded using a Skalar infra-red recorder. In the presence of normal BSV, the effect of distractors is significantly larger for saccade latency and accuracy with binocular distractor presentation than for monocular presentations, with no difference between distrators presented to the dominant or non-dominant eye. The implications of these results are discussed with regard to saccade programming.

Adult↗
PubMed2005

Girls' night out.

Explore the source record for details and available documents.

Adolescent↗
PubMed2004

Plasma antioxidant status, immunoglobulin g oxidation and lipid peroxidation in demented patients: relevance to Alzheimer disease and vascular dementia.

A large body of evidence supports a role of oxidative stress in Alzheimer disease (AD) and in cerebrovascular disease. A vascular component might be critical in the pathophysiology of AD, but there is a substantial lack of data regarding the simultaneous behavior of peripheral antioxidants and biomarkers of oxidative stress in AD and vascular dementia (VaD). Sixty-three AD patients, 23 VaD patients and 55 controls were included in the study. We measured plasma levels of water-soluble (vitamin C and uric acid) and lipophilic (vitamin E, vitamin A, carotenoids including lutein, zeaxanthin, beta-cryptoxanthin, lycopene, alpha- and beta-carotene) antioxidant micronutrients as well as levels of biomarkers of lipid peroxidation [malondialdehyde (MDA)] and of protein oxidation [immunoglobulin G (IgG) levels of protein carbonyls and dityrosine] in patients and controls. With the exception of beta-carotene, all antioxidants were lower in demented patients as compared to controls. Furthermore, AD patients showed a significantly higher IgG dityrosine content as compared to controls. AD and VaD patients showed similar plasma levels of plasma antioxidants and MDA as well as a similar IgG content of protein carbonyls and dityrosine. We conclude that, independent of its nature-vascular or degenerative-dementia is associated with the depletion of a large spectrum of antioxidant micronutrients and with increased protein oxidative modification. This might be relevant to the pathophysiology of dementing disorders, particularly in light of the recently suggested importance of the vascular component in AD development.

Aged↗
PubMed2003

Novel monoclonal antibody recognition of oxidative DNA damage adduct, deoxycytidine-glyoxal.

Glyoxal, a reactive aldehyde, is a decomposition product of lipid hydroperoxides, oxidative deoxyribose breakdown, or autoxidation of sugars, such as glucose. It readily forms DNA adducts, generating potential carcinogens such as glyoxalated deoxycytidine (gdC). A major drawback in assessing gdC formation in cellular DNA has been methodologic sensitivity. We have developed an mAb that specifically recognizes gdC. Balb/c mice were immunized with DNA, oxidatively modified by UVC/hydrogen peroxide in the presence of endogenous metal ions. Although UVC is not normally considered an oxidizing agent, a UVC/hydrogen peroxide combination may lead to glyoxalated bases arising from hydroxyl radical damage to deoxyribose. This damaging system was used to induce numerous oxidative lesions including glyoxal DNA modifications, from which resulted a number of clones. Clone F3/9/H2/G5 showed increased reactivity toward glyoxal-modified DNA greater than that of the immunizing antigen. ELISA unequivocally showed Ab recognition toward gdC, which was confirmed by gas chromatography-mass spectrometry of the derivatized adduct after formic acid hydrolysis to the modified base. Binding of Ab F3/9 with glyoxalated and untreated oligomers containing deoxycytidine, deoxyguanosine, thymidine, and deoxyadenosine assessed by ELISA produced significant recognition (p > 0.0001) of glyoxal-modified deoxycytidine greater than that of untreated oligomer. Additionally, inhibition ELISA studies using the glyoxalated and native deoxycytidine oligomer showed increased recognition for gdC with more than a 5-fold difference in IC(50) values. DNA modified with increasing levels of iron (II)/EDTA produced a dose-dependent increase in Ab F3/9 binding. This was reduced in the presence of catalase or aminoguanidine. We have validated the potential of gdC as a marker of oxidative DNA damage and showed negligible cross-reactivity with 8-oxo-2'-deoxyguanosine or malondialdehyde-modified DNA as well as its utility in immunocytochemistry. Formation of the gdC adduct may involve intermediate structures; however, our results strongly suggest Ab F3/9 has major specificity for the predominant product, 5-hydroxyacetyl-dC.

Animals↗
PubMed2003

Caring for sexual assault survivors. The value of choice.

Over the past 10 years, Helen Griffiths has been interviewing registered nurses throughout British Columbia and writing articles for Nursing BC on how these registered nurses meet RNABC's Standards for Registered Nursing Practice in their practice. For this issue, we asked Helen to write about her own practice as a registered nurse with the B.C. Women's Hospital and Health Centre Sexual Assault Service.

Adult↗
PubMed2002

Iron-deficiency anaemia: developing a nurse-led integrated care pathway.

Current investigation of asymptomatic iron-deficiency anaemia (IDA) is considered incomplete and inappropriate (BSG 2000). Previous investigation has focused on specific sinister features, but IDA can be the sole presenting symptom of serious underlying pathology and systematic investigation of patients with IDA is of prime importance. While participating in a management education scheme by open learning (MESOL) in association with the NHS Executive, Open University and Institute of Healthcare Management, the author undertook a project to evaluate the investigation of IDA within a district general hospital using evolving evidence to reconfigure existing services.

Anemia, Iron-Deficiency↗