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R McKay

Publications and source records attributed to R McKay.

At least 37 records · Page 2Linked to original sources
PubMed2000

Antisense methods for discrimination of phenotypic properties of closely related gene products: Jun kinase family.

Methods for the selection and characterization of antisense oligonucleotides for specifically eliminating closely related gene family members are available. High-throughput semiautomated methods using 96-well plate formats and array technology and improved assays are under active development that will streamline many steps and will likely merge. Second-generation 20-mer antisense phosphorothioate oligonucleotides containing 2'-methoxyethyl groups at the first and last 6 nucleotides with improved nuclease resistance and RNA affinity are becoming available.

Animals↗
PubMed2000

Management of diabetic retinopathy by Australian ophthalmologists. Working Group on Evaluation of the NHMRC Retinopathy Guideline Distribution. National Health and Medical Research Council.

OBJECTIVE: To describe current management practices of diabetic retinopathy used by Australian ophthalmologists. SETTING: Two-page self-administered questionnaire mailed to 622 ophthalmologists listed with the Royal Australian College of Ophthalmologists. METHODS: The survey included questions about practice details such as size and location; specialty; current practice with regard to management of patients with diabetes; confidence in screening for diabetic retinopathy; and a number of patient scenarios related to screening, follow-up and treatment of diabetic retinopathy. RESULTS: Of the 577 eligible ophthalmologists, 475 (82%) completed the questionnaire. They had been practicing ophthalmology between 1 and 50 years (median 16 years) and 89 (19%) indicated that they had a subspecialty interest either in vitreo-retinal surgery or in medical retina. For 145 (30.5%) of the ophthalmologists, at least one of their practices was located in a country area. The estimated percentage of patients with diabetes ranged from 0.1 to 60% (mean = 9.9%). Retinal specialists perform between 0 and 750 macular focal photocoagulation procedures per year (mean = 94) compared with a range of 0-350 for nonretinal specialists (mean = 10.3) (t = 6.1, P < 0.001). The ophthalmologists were presented with a hypothetical patient with cataract requiring surgery and clinically significant macular oedema that would be difficult to treat (but not impossible) because of the cataract. Seventy-seven ophthalmologists (16%) said they would delay the macular laser therapy until after the cataract surgery had been performed. In multivariate logistic regression models, nonretinal specialists were 4.44 times as likely to perform the cataract surgery first (95%CL = 1.57, 12.6) and ophthalmologists who had been in practice more than 15 years were 2.50 times as likely to perform cataract surgery first (95%CL = 1.47, 4.26). There were other examples of practice that differed from the National Health and Medical Research Council (NHMRC) guidelines in patient scenarios. The majority of ophthalmologists (60%) expressed a moderate or strong need to learn more about the management of diabetic retinopathy. DISCUSSION: The variability in the management of diabetic retinopathy by Australian ophthalmologists and the desire of ophthalmologists to learn more about diabetic retinopathy provide evidence to support the need for the NHMRC Guidelines for Diabetic Retinopathy. These data will be used to evaluate changes in practice as a result of the implementation of the guidelines.

Diabetic Retinopathy↗
PubMed2000

Diabetes in Victoria, Australia: the Visual Impairment Project.

OBJECTIVES: To establish the prevalence and characteristics of self-reported diabetes in a representative sample of Victorian residents aged 40 years and older, and to compare the vision between people with and without self-reported diabetes. DESIGN: Cross-sectional survey. SETTING: Nine randomly selected suburban Melbourne clusters and four randomly selected rural Victorian clusters. PARTICIPANTS: 4,744 subjects (86% participation rate) aged > or = 40 years. MAIN OUTCOME MEASURES: Subjects answered a detailed questionnaire which provided demographic details, body mass index, and the duration and treatment of any diagnosis of diabetes. Refraction was performed and best-corrected visual acuity was measured. RESULTS: The prevalence of self-reported diabetes was 5.1%. In a multivariate analysis, self-reported diabetes was positively associated with age (p < 0.01), male sex (p = 0.01), higher body mass index (p = 0.01), Mediterranean ethnicity (p = 0.01), unemployment (p = 0.05) and lack of private health insurance (p < 0.05). People with self-reported diabetes were more likely to have mild or moderate levels of visual impairment than people who reported no previous diagnosis of diabetes (p < 0.01). CONCLUSIONS: Diabetes in Victoria is more prevalent among men and among people of Mediterranean origin. When planning educational programs and health service delivery, it is also important to consider that, compared with the general population, people with diabetes are less likely to be employed or to have private health insurance, and are more likely to have impaired vision.

Adult↗
PubMed2000

Diabetic retinopathy in Victoria, Australia: the Visual Impairment Project.

AIM: To establish the prevalence, severity, and risk factors for diabetic retinopathy in a representative sample of Victorian residents aged 40 years and older. METHODS: A population based, cluster sampling method was used to recruit 4744 participants (86% participation rate). Nine randomly selected, suburban Melbourne clusters and four randomly selected, rural Victorian clusters were used. Participants provided a detailed medical and personal history and underwent an ocular examination including funduscopy and fundus photography. Rural participants provided a blood sample, from which the glycosylated haemoglobin percentage was measured. The diagnosis of diabetic retinopathy was based on fundus photographs from participants with self reported diabetes. RESULTS: The prevalence of diabetic retinopathy among people with self reported diabetes was 29. 1%. The prevalence of untreated, vision threatening retinopathy was 2.8%. Retinopathy was positively associated with a longer reported duration of diabetes diagnosis (p<0.01) and with higher fractions of glycosylated haemoglobin (p<0.01). Retinopathy was not significantly associated with age, ethnicity, body mass index, glaucoma, myopia or intake of alcohol, tobacco, or aspirin (all p > 0.05). CONCLUSIONS: Most people in Victoria with proliferative diabetic retinopathy or clinically significant macular oedema have received laser treatment. There remains however, a small but important group who have not received treatment and whose vision is threatened. People with diabetes should be encouraged to maintain strict glycaemic control and to undergo regular screening to delay or prevent the development of retinopathy.

Adult↗
PubMed1999

Management of diabetic retinopathy by Australian optometrists. Working Group on Evaluation of NHMRC Retinopathy Guideline Distribution. National Health and Medical Research Council.

PURPOSE: To describe current practices related to the management of diabetic retinopathy by Australian optometrists. SETTING AND METHODS: A two-page self-administered questionnaire was mailed to a random sample of 504 Australian optometrists. The survey included questions about the practice (such as size and location); current practice with regard to management of patients with diabetic retinopathy; barriers to use of dilating drops; and a number of patient scenarios related to screening, follow-up and treatment of diabetic retinopathy. RESULTS: Completed questionnaires were returned by 407 of the 473 eligible optometrists (86%). They had been practising optometry between 1 and 50 years (median 14). Of the 243 optometrists who provided details about the location of their practices, 145 (37%) had at least one of their practices in a rural area. The estimated percentage of patients with diagnosed diabetes ranged from 0.5 to 40% (median = 5.0%). Three-hundred and twenty-two optometrists (79%) reported that they would often or almost always ask new patients over the age of 40 whether they have diabetes. The majority of optometrists (n = 387, 95%) would often or almost always ask their new patients with diabetes about their control of blood glucose levels and the majority of optometrists (n = 330, 81%) would often or almost always tell their patients with diabetes about the importance of strict glucose control in delaying retinopathy. The most common barrier to dilated ophthalmoscopy was patients not wanting to be dilated, with 38.1% of optometrists reporting this to be a moderate or major barrier. The next most common barrier was fear of precipitating angle closure glaucoma; 17.1% of optometrists reported this to be a moderate or major barrier CONCLUSION: The National Health and Medical Research Council (NHMRC) guidelines for the management of diabetic retinopathy are timely in relation to the expressed desire of Australian optometrists to learn more about management of diabetic retinopathy These data will be used prospectively to assess changes in management of patients with diabetic retinopathy as a result of the release of the NHMRC guidelines.

Australia↗
PubMed1999

The Jun kinase 2 isoform is preferentially required for epidermal growth factor-induced transformation of human A549 lung carcinoma cells.

We have previously found that epidermal growth factor (EGF) mediates growth through the Jun N-terminal kinase/stress-activated kinase (JNK/SAPK) pathway in A549 human lung carcinoma cells. As observed here, EGF treatment also greatly enhances the tumorigenicity of A549 cells, suggesting an important role for JNK in cancer cell growth (F. Bost, R. McKay, N. Dean, and D. Mercola, J. Biol. Chem. 272:33422-33429, 1997). Several isoforms families of JNK, JNK1, JNK2, and JNK3, have been isolated; they arise from alternative splicing of three different genes and have distinct substrate binding properties. Here we have used specific phosphorothioate oligonucleotides targeted against the two major isoforms, JNK1 and JNK2, to discriminate their roles in EGF-induced transformation. Multiple antisense sequences have been screened, and two high-affinity and specific candidates have been identified. Antisense JNK1 eliminated steady-state mRNA and JNK1 protein expression with a 50% effective concentration (EC50) of <0.1 microM but did not alter JNK2 mRNA or protein levels. Conversely, antisense JNK2 specifically eliminated JNK2 steady-state mRNA and protein expression with an EC50 of 0.1 microM. Antisense JNK1 and antisense JNK2 inhibited by 40 and 70%, respectively, EGF-induced total JNK activity, whereas sense and scrambled-sequence control oligonucleotides had no effect. The elimination of mRNA, protein, and JNK activities lasted 48 and 72 h following a single Lipofectin treatment with antisense JNK1 and JNK2, respectively, indicating sufficient duration for examining the impact of specific elimination on the phenotype. Direct proliferation assays demonstrated that antisense JNK2 inhibited EGF-induced doubling of growth as well as the combination of active antisense oligonucleotides did. EGF treatment also induced colony formation in soft agar. This effect was completely inhibited by antisense JNK2 and combined-antisense treatment but not altered by antisense JNK1 alone. These results show that EGF doubles the proliferation (growth in soft agar as well as tumorigenicity in athymic mice) of A549 lung carcinoma cells and that the JNK2 isoform but not JNK1 is utilized for mediating the effects of EGF. This study represents the first demonstration of a cellular phenotype regulated by a JNK isoform family, JNK2.

Agar↗
PubMed1998

Resolution of the heterogeneous fluorescence in multi-tryptophan proteins: ascorbate oxidase.

Ascorbate oxidase is a copper-containing enzyme which catalyzes a redox reaction between vitamin C and molecular oxygen. The protein, which shows a complex tertiary structure, is an homodimer of monomers, each containing three domains and 14 tryptophan residues. Recently, we have demonstrated by spectroscopic and ultracentrifugation techniques the existence of a stable dimeric intermediate along the unfolding pathway of this enzyme [Mei, G., Di Venere, A., Buganza, M., Vecchini, P., Rosato, N. & Finazzi Agrò, A. (1997) Biochemistry 36, 10917-10922]. In this study, the steady-state and dynamic fluorescence features of ascorbate oxidase have been exploited in order to find a way of monitoring the individual subsystems of the protein. The fluorescence intensity and anisotropy upon excitation at 295 nm are extremely sensitive functions of the emission wavelength, indicating a great heterogeneity of the system. The emission decay collected through a cut-off filter can be analyzed in terms of two continuous distributions of lifetimes. Using a monochromator in emission or an optical multichannel analyzer, the two distributions may be attributed to distinct components of the fluorescence spectrum. Differential quenching by cesium chloride also confirmed that the several tryptophan residues present in the protein structure may be grouped into two main classes, each with a different environment. Once the complex fluorescence decay of ascorbate oxidase was analyzed and resolved, a comparison with the crystallographic data allowed a first, approximate attribution of the protein spectroscopic properties to some of the tryptophan residues. This might provide a powerful tool of investigation about the role of definite segments of the protein in its three-dimensional structure and catalytic activity. Furthermore, the methodology set up for ascorbate oxidase can be usefully extended to other multitryptophan proteins.

Ascorbate Oxidase↗
PubMed1998

Open-heart correction of tetralogy of Fallot in an acyanotic dog.

Tetralogy of Fallot was diagnosed in an acyanotic 11-month-old dog. Predicted pressure gradient across the pulmonic valve, as assessed by use of continuous wave Doppler echocardiography, was 94.5 mm Hg. Bidirectional shunting was identified by means of selective angiography. Open-heart correction was performed, using a transatrial approach with limited ventriculotomy and cardiopulmonary bypass. The hypertrophied infundibulum was resected, the ventricular septal defect was closed primarily, and a transannular pericardial patch graft was applied. Pressure gradients across the pulmonic valve were 52.9 and 22.8 mm Hg 2 weeks and 4 months after surgery, respectively. Advances in cardiopulmonary bypass, anesthetic management, and use of the transatrial approach may improve the success of open-heart correction of tetralogy of Fallot in dogs.

Animals↗
PubMed1998

Report of two sibs with Knobloch syndrome (encephalocoele and viteroretinal degeneration) and other anomalies.

We report on two sibs with high myopia, vitreoretinal degeneration (VRD), and occipital encephalocoele or scalp lesion. We review the literature on Knobloch syndrome, discuss possible causes, and suggest a possible involvement of mesoderm in the morphogenesis. One case presents with very early onset of severe eye disease, whereas the other is notable for the very mild scalp defect. In addition, both appear to have an unusual pulmonary lymphatic condition.

Abnormalities, Multiple↗
PubMed1998

Fibromuscular Dysplasia of the Aorta Presenting as Multiple Recurrent Thoracic Aneurysms

A 17-year-old boy, who had undergone resection of aortic coarctation with a large saccular aneurysm 10 years previously, developed recurrent aneurysms above and below the site of a Gore-Tex interposition graft. These were resected using femoral-femoral bypass, and the upper thoracic aorta was replaced with a Hemashield Dacron tube. Histology of the aorta showed fibromuscular dysplasia. In addition to aortic dissection and aortic rupture, such patients may be at risk of forming further aneurysms.

Journal Article↗
PubMed1998

Plasticity and stem cells in the vertebrate nervous system.

How and when do vertebrate neural precursor cells choose their fates? While some studies suggest a series of commitments on the road to fate choice, many recent experiments indicate that precursor fate choices can often be changed. Additionally, the identification of common gene control mechanisms in precursors suggest that these cells share fundamental properties throughout development.

Animals↗
PubMed1998

Stem cells and neurogenesis in the adult brain.

A new interest in replacing neurons lost to trauma or disease has been generated by findings that challenge the traditional view of the static (irreparable) adult brain. The discovery of stem cells and neurogenesis in the adult central nervous system is responsible for much of this interest.

Adult↗