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Biomedical subjects

P Mitchell

Publications and source records attributed to P Mitchell.

At least 235 records · Page 13Linked to original sources
PubMed1998

Cloning of the gene for interstitial collagenase-3 (matrix metalloproteinase-13) from rabbit synovial fibroblasts: differential expression with collagenase-1 (matrix metalloproteinase-1).

Cartilage, bone and the interstitial stroma, composed largely of the interstitial collagens, types I, II and III, are remodelled by three members of the metalloproteinase (MMP) family, collagenase-1 (MMP-1), collagenase-2 (MMP-8) and collagenase-3 (MMP-13). MMP-1 and MMP-13 may contribute directly to disease progression, since they are induced in patients with rheumatoid arthritis and osteoarthritis. The study of MMP-1 and MMP-13 gene regulation in models of arthritic disease has been problematic because mice and rats, which are typically used, only possess a homologue of MMP-13. Here we show that in contrast with mice and rats, rabbits possess distinct genes homologous to human MMP-1 and MMP-13. Furthermore, rabbit MMP-13 is expressed simultaneously with MMP-1 in chondrocytes and synovial fibroblasts in response to the cytokines interleukin-1 and tumour necrosis factor-alpha, or the phorbol ester PMA. The time course of MMP-13 induction is more rapid and transient than that of MMP-1, suggesting that distinct mechanisms regulate the expression of these two collagenases. We have cloned the rabbit MMP-13 gene from synovial fibroblasts and demonstrated that the rabbit gene shares greater homology with human MMP-13 than does the mouse interstitial collagenase. Together with the fact that mice and rats do not possess a homologue to human MMP-1, our data suggest that the rabbit provides an appropriate model for studying the roles of interstitial collagenases in connective-tissue diseases, such as rheumatoid arthritis and osteoarthritis.

Amino Acid Sequence↗
PubMed1998

Retinopathy in older persons without diabetes and its relationship to hypertension.

OBJECTIVE: To assess the prevalence and relationship of retinopathy lesions in older subjects without diabetes to systemic hypertension. METHODS: Three thousand six hundred fifty-four people aged 49 years or older attending the Blue Mountains Eye Study underwent a detailed eye examination, including medical history, blood pressure measurement, and fasting blood collection. Retinopathy lesions (hemorrhages and microaneurysms) were assessed from masked grading of stereoretinal photographs. Subjects with a history of diabetes or an elevated blood glucose level were excluded. Hypertension was defined as the current use of antihypertensive medications or an elevated blood pressure measurement on examination. RESULTS: Retinopathy was present in 325 subjects without diabetes, a prevalence of 9.8% (95% confidence interval [CI], 8.9%-10.9%), which increased with age. An increased age-adjusted relative risk (RR) for retinopathy was found for women (RR, 1.67; 95% CI, 1.26-2.21) and men (RR, 1.47; 95% CI, 1.07-2.00) with hypertension. In people using antihypertensive medications, retinopathy prevalence was higher for uncontrolled compared with controlled blood pressure but was not related to hypertension duration. Significant (P=.02 to P=.001) trends were found between increasing blood pressure quartiles and age-adjusted retinopathy prevalence, a relationship that was maintained after adjusting for fasting plasma glucose level at 3 diagnostic cut points for diabetes. CONCLUSIONS: This study supports the Beaver Dam Eye Study findings that retinal hemorrhages and microaneurysms are relatively frequent lesions in older people without diabetes and are significantly related to the presence and severity of hypertension.

Aged↗
PubMed1998

Plasma fibrinogen levels, other cardiovascular risk factors, and age-related maculopathy: the Blue Mountains Eye Study.

OBJECTIVE: To assess the relationship between stages of age-related maculopathy (ARM) and cardiovascular disease and cardiovascular disease risk factors, including serum lipid and plasma fibrinogen levels, smoking, cardiovascular events, systemic hypertension, diabetes mellitus, and obesity. DESIGN: A cross-sectional study of 3654 subjects from a defined geographic area identified subjects with late age-related macular degeneration (ARMD) and early ARM from the masked grading of retinal photographs. The history, physical examination findings, and fasting blood samples provided data on possible risk factors. Logistic regression, adjusting for age, sex, and possible confounders, and 2-way analysis of variance were used to assess associations. RESULTS: The only factors significantly associated with ARM included the 2 established risk factors, smoking and family history of ARMD (odds ratios, 4.1 and 4.2, for late ARMD, respectively), and the 2 variables, body mass index (odds ratio, 1.78 for obese compared with normal body mass index for early ARM) and plasma fibrinogen level (odds ratio, 6.7 for a fibrinogen level of >4.5 g/L [highest quartile] compared with a fibrinogen level of <3.4 g/L [lowest quartile] for late ARMD). CONCLUSIONS: These findings support the concepts that associations exist between plasma fibrinogen levels and late ARMD, a body mass index outside the normal range, and early ARM, and between the family history and smoking and any ARM. We found no other significant associations with any history of cardiovascular disease or other risk factors for cardiovascular disease.

Blood Pressure↗
PubMed1998

Choroidal nevi in a white population: the Blue Mountains Eye Study.

OBJECTIVE: To determine the prevalence, morphologic characteristics, associations, and frequency of features reported to predict growth of choroidal nevi in a large population-based sample. METHODS: A total of 3654 subjects aged 49 to 97 years participating in the Blue Mountains Eye Study had a detailed eye examination, including photography of 6 standard retinal fields. Nevi were graded from photographs. RESULTS: Nevi were present in 6.5% of the population (n = 232), and were distributed equally between eyes. There was a slight decrease in nevus prevalence with increasing age. Nevus prevalence was higher in women than men, but this difference was not statistically significant. The mean nevus diameter was 1.25 mm (SD, 0.72 mm; range, 0.5 to >4.5 mm). Eighty-seven percent of nevi were blue gray and 6% had a hypomelanotic or amelanotic appearance. There were no significant associations between nevi and iris or skin color or sun-induced skin damage, but nevi were significantly less frequent in persons with blond hair. No nevus associations were found with visual impairment, cataract, or glaucoma. Clearly visible drusen were seen on 42% of nevi and were larger and more centrally distributed as nevus size increased. Features previously identified as predicting nevus growth, such as serous elevation and orange or other pigment, were seen rarely. CONCLUSION: Choroidal nevi in the general population are frequent, small, have few features that are commonly reported to indicate potential for growth, and rarely affect visual acuity.

Age Distribution↗
PubMed1998

Does mitochondrial genome mutation in subjects with maternally inherited diabetes and deafness decrease severity of diabetic retinopathy?

Two types of retinopathy, diabetic and pigmentary, may be seen in subjects with maternal inheritance diabetes and deafness. The potential for interactions between the two retinopathies has not been explored. The mitochondrial mutation may affect development of diabetic retinopathy in subjects with MIDD by altering normal pathways of glucose metabolism. We identified five unrelated MIDD kindreds with 61 living maternal line family members. Twenty-three of the family members, 12 with diabetes mellitus and 11 without volunteered to be studied. Subjects were graded for severity of diabetic retinopathy and presence or absence of pigmentary retinopathy after slit lamp biomicroscopy, retinal photography of seven standard fields and fluorescein angiography. Blood was taken, in the fasted state, from MIDD subjects (duration of diabetes 17.0+/-6.9 yr) and non-diabetic subjects with the mutation, for assay of sorbitol and glucose and values compared with diabetic and non-diabetic control subjects without the mutation. Diabetic retinopathy was absent in 9/12 subjects (75%), with 3 having mild non-proliferative retinopathy. No one had cataract. Red blood cell sorbitol levels, adjusted for ambient blood glucose, were significantly lower in MIDD subjects compared with diabetic subjects (1.16+/-0.5 cf. 2.03+/-1.1, x 10(-3) g mmol(-1), p=0.04). Pigmentary retinopathy was present in 15 of 23 subjects, of whom 13 had some abnormality of glucose tolerance. Abnormal glucose tolerance was strongly associated with the development of pigmentary retinopathy (odds ratio 19.5, p=0.008). In conclusion, there appears to be a decreased prevalence of diabetic retinopathy and cataract in MIDD, which we propose is due to reduced glucose metabolism by the polyol pathway. Abnormal glucose tolerance increases the clinical expression of pigmentary retinopathy in subjects with a mitochondrial genome mutation. A greater understanding of the metabolic effects of mitochondrial DNA mutations has the potential to give insight into the mechanisms of diabetic retinopathy and other complications of diabetes mellitus.

Adult↗
PubMed1998

Young children's difficulty acknowledging false belief: realism and deception.

This study was designed to help clarify some of the circumstances under which young children find it easier to acknowledge a false belief held by another person. In Experiment 1, preschoolers (mean age, 3 years; 11 months) watched a movie in which Ness had previously opened a familiar box in Jon's absence to reveal the stereotypical content, which she proceeded to replace with an atypical item. In a second movie, the box was seen to house an atypical content all along. Half the children watched Ness play the script in a neutral manner, while the rest watched her play it in a deceptive manner. There was a highly significant improvement in acknowledging Jon's false belief when children saw the stereotypical content of the box preliminary to its exchange for something atypical. In contrast, children gained no benefit from the way Ness played the script. The effect was replicated in a second experiment in which children were involved directly in the task. We conclude that presenting a physical instantiation of a false belief helps children to a small but reliable extent to correctly report that belief.

Child Behavior↗
PubMed1998

Cataract associations with pinguecula and pterygium: the Blue Mountains Eye Study.

PURPOSE: To determine associations between cataract types and pinguecula and pterygium. METHODS: The Blue Mountains Eye Study examined 3,654 persons aged 49 to 97 years near Sydney, Australia. A questionnaire was used to collect information on cataract risk factors. Slit-lamp examination recorded pinguecula and pterygium. Masked lens photograph grading assessed cataract. RESULTS: Pinguecula, found in 2,418 right eyes and 2,437 left eyes, was statistically significantly associated with cortical cataract (odds ratio [OR] = 1.40) after multivariate adjustment. Pterygium, found in 199 right eyes and 188 left eyes, was associated with posterior subcapsular cataract (OR = 1.90). CONCLUSIONS: Associations were found between cataract and the presence of either pinguecula or pterygium. These findings provide indirect support for Watermen Study findings, which link ultraviolet radiation to cataract.

Aged↗
PubMed1998

Prevalence and causes of amblyopia in an adult population.

OBJECTIVE: The study aimed to determine the prevalence, causes, and associations with amblyopia in a defined older population. DESIGN: In a population-based study, 3654 persons 49 years of age or older from an area west of Sydney, Australia, underwent a detailed eye examination and history, including objective and subjective refraction, cover testing, and retinal and lens photography. Amblyopia was diagnosed in eyes with reduced best-corrected visual acuity in the absence of any other cause. RESULTS: Amblyopia was diagnosed in 118 participants, or 3.2% of the population using a visual acuity criterion of 20/30 or less and 2.9% using a visual acuity criterion of 20/40 or less. Using a two-line visual acuity difference between the eyes, the amblyopia prevalence was 2.6% and 2.5%, respectively, for the above criteria. The underlying amblyogenic causes assessed were anisometropia (50%), strabismus (19%), mixed strabismus and anisometropia (27%), and visual deprivation (4%). The visual acuity of the amblyopic eye was 20/200 or worse (19%), 20/80 to 20/160 (19%), 20/40 to 20/63 (52%), and 20/30 (11%). No statistically significant associations were found between amblyopia and gender or eye affected. The most frequent pattern of strabismus was esotropia, whereas hypermetropia was the most frequent refractive error in amblyopic eyes. The mean age at diagnosis was earlier for strabismic and mixed amblyopia (7.4 years) than for anisometropic amblyopia (12.7 years). CONCLUSION: This study has provided prevalence and cases of amblyopia in an older population. Amblyopia is a frequent cause of lifelong unilateral visual impairment.

Aged↗
PubMed1998

Optic disc hemorrhages in a population with and without signs of glaucoma.

OBJECTIVE: This study aimed to determine the prevalence and associations of optic disc hemorrhage in a well-defined older Australian population. DESIGN: The study design was a population-based, cross-sectional study. PARTICIPANTS: A total of 3654 persons 49 years of age or older, representing 88% of permanent residents from an area west of Sydney, participated in the study. MAIN OUTCOME MEASURES: Participants underwent a detailed eye examination. The diagnosis of optic disc hemorrhage was made from masked photographic grading; disc hemorrhages were subclassified as flame or blot in shape. Open-angle glaucoma was diagnosed from matching visual field loss and optic disc rim thinning. RESULTS: The overall prevalence of disc hemorrhage in either or both eyes was 1.4%. Disc hemorrhage prevalence was higher in women (odds radios [OR], 1.9; confidence interval [CI], 1.0-3.5) and increased with age (OR, 2.2 per decade; CI, 1.7-2.8 per decade). The overall prevalence in subjects with open-angle glaucoma was 13.8% (8% in high-pressure glaucoma and 25% in low-pressure glaucoma) and 1.5% in subjects with ocular hypertension. Disc hemorrhages were associated with increasing intraocular pressure (OR, 1.7 per 5 mmHg; CI, 1.3-2.3 per 5 mmHg), pseudoexfoliation (OR, 3.5; CI, 1.1-11.8), diabetes (OR, 2.9; CI, 1.4-6.3), and increasing systolic blood pressure (OR, 1.1 per 10 mmHg; CI, 1.0-1.3) after adjusting for age and gender. Among subjects without open-angle glaucoma, disc hemorrhages were more frequent in eyes with larger vertical cup-disc ratios and in subjects with a history of typical migraine headache (OR, 2.2; CI, 1.1-4.6). No associations were found among subjects with a history of vascular events, smoking, regular aspirin use, or myopia. CONCLUSIONS: Disc hemorrhage prevalence in this population is higher than that in the two previous population-based reports. Although the strong association of disc hemorrhage with open-angle glaucoma was confirmed (particularly low-pressure glaucoma), most disc hemorrhages (70%) were found in participants without definite signs of glaucoma.

Age Distribution↗