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Biomedical subjects

R Currie

Publications and source records attributed to R Currie.

15 recordsLinked to original sources

Chronic heart failure in Australian general practice. The Cardiac Awareness Survey and Evaluation (CASE) Study.

OBJECTIVES: To investigate the frequency and general practitioner awareness of patients with chronic heart failure (CHF), and to evaluate a cardiac algorithm and document cardiac investigations performed in establishing this diagnosis. DESIGN AND SETTING: Between March and August 1998, consecutive patients aged 60 years and older presenting to their GP were assessed. In patients previously diagnosed with CHF, aetiology and diagnostic assessments were documented. In patients with suspected CHF (by a standardised algorithm, based on World Health Organization guidelines), further investigations and GP diagnosis were recorded. PATIENTS: 80 consecutive patients were assessed by each of 341 GPs throughout Australia, reflecting the Australian metropolitan/rural population mix of 1996. This provided a total of 22060 evaluable patients. MAIN OUTCOME MEASURES: Estimated numbers of patients with CHF in general practice (previously and newly diagnosed); major aetiological factors; use of ancillary diagnostic tests; drugs prescribed. RESULTS: CHF was diagnosed in 2905 of 22060 patients (13.2%) (2485 previously diagnosed and 420 newly diagnosed). Major aetiological factors were ischaemic heart disease and hypertension. Echocardiography had been performed in 64% of previously diagnosed patients, but was performed in only 22% of possible CHF patients. Angiotensin-converting enzyme (ACE) inhibitors were prescribed in 58.1% of patients with CHF. Patients with evidence of left ventricular dysfunction were more likely to have received ACE inhibitors. CONCLUSIONS: CHF appears to be very common in the elderly, based on GP diagnosis of the condition. Of 100 patients aged 60 years and over presenting to their GP, two new cases of CHF will be detected using a simple clinical algorithm in conjunction with appropriate diagnostic tests. ACE inhibitors appear to be underutilised.

Aged↗

Evidence that 3-phosphoinositide-dependent protein kinase-1 mediates phosphorylation of p70 S6 kinase in vivo at Thr-412 as well as Thr-252.

Protein kinase B and p70 S6 kinase are members of the cyclic AMP-dependent/cyclic GMP-dependent/protein kinase C subfamily of protein kinases and are activated by a phosphatidylinositol 3-kinase-dependent pathway when cells are stimulated with insulin or growth factors. Both of these kinases are activated in cells by phosphorylation of a conserved residue in the kinase domain (Thr-308 of protein kinase B (PKB) and Thr-252 of p70 S6 kinase) and another conserved residue located C-terminal to the kinase domain (Ser-473 of PKB and Thr-412 of p70 S6 kinase). Thr-308 of PKBalpha and Thr-252 of p70 S6 kinase are phosphorylated by 3-phosphoinositide-dependent protein kinase-1 (PDK1) in vitro. Recent work has shown that PDK1 interacts with a region of protein kinase C-related kinase-2, termed the PDK1 interacting fragment (PIF). Interaction with PIF converts PDK1 from a form that phosphorylates PKB at Thr-308 alone to a species capable of phosphorylating Ser-473 as well as Thr-308. This suggests that PDK1 may be the enzyme that phosphorylates both residues in vivo. Here we demonstrate that PDK1 is capable of phosphorylating p70 S6 kinase at Thr-412 in vitro. We study the effect of PIF on the ability of PDK1 to phosphorylate p70 S6 kinase. Surprisingly, we find that PDK1 bound to PIF is no longer able to interact with or phosphorylate p70 S6 kinase in vitro at either Thr-252 or Thr-412. The expression of PIF in cells prevents insulin-like growth factor 1 from inducing the activation of the p70 S6 kinase and its phosphorylation at Thr-412. Overexpression of PDK1 in cells induces the phosphorylation of p70 S6 kinase at Thr-412 in unstimulated cells, and a catalytically inactive mutant of PDK1 prevents the phosphorylation of p70 S6K at Thr-412 in insulin-like growth factor 1-stimulated cells. These observations indicate that PDK1 regulates the activation of p70 S6 kinase and provides evidence that PDK1 mediates the phosphorylation of p70 S6 kinase at Thr-412.

3-Phosphoinositide-Dependent Protein Kinases↗

Spatial and temporal trends of contaminants in Canadian Arctic freshwater and terrestrial ecosystems: a review.

The state of knowledge of contaminants in Canadian Arctic biota of the freshwater and terrestrial ecosystems has advanced enormously since the publication of the first major reviews by Lockhart et al. and Thomas et al. in The Science of the Total Environment in 1992. The most significant gains are new knowledge of spatial trends of organochlorines and heavy metal contaminants in terrestrial animals, such as caribou and mink, and in waterfowl, where no information was previously available. Spatial trends in freshwater fish have been broadened, especially in the Yukon, where contaminant measurements of, for example, organochlorines were previously non-existent. A review of contaminants data for fish from the Northwest Territories, Yukon and northern Quebec showed mercury as the one contaminant which consistently exceeds guideline limits for subsistence consumption or commercial sale. Lake trout and northern pike in the Canadian Shield lakes of the Northwest Territories and northern Quebec generally had the most elevated levels. Levels of other heavy metals were generally not elevated in fish. Toxaphene was the major organochlorine contaminant in all fish analyzed. The concentrations of organochlorine contaminants in fish appear to be a function not only of trophic level but of other aspects of the lake ecosystem. Among Arctic terrestrial mammals, PCBs and cadmium were the most prominent contaminants in the species analyzed. Relatively high levels (10-60 micrograms g-1) of cadmium were observed in kidney and liver of caribou from the Yukon, the Northwest Territories and northern Quebec, with concentrations in western herds being higher than in those from the east. For the organochlorine contaminants, a west to east increase in zigma PCBs, HCB and zigma HCH was found in caribou, probably as a result of the predominant west to east/north-east atmospheric circulation pattern which delivers these contaminants from industrialized regions of central and eastern North America to the Arctic via long-range atmospheric transport. Radiocesium contamination of lichens and caribou has continued to decrease. Significant contamination by PCBs and lead of soils and vascular plants was observed in the immediate vicinity and within a 20-km radius of DEW line sites in the Canadian Arctic. There was also evidence for transfer of PCBs from plants to lemmings. There was no evidence, however, that large mammals such as caribou living in the general area of the DEW line sites had elevated levels of PCBs. There is very limited temporal trend information for most contaminants in biota of Arctic terrestrial and freshwater environments.

Animals↗

PDK1 acquires PDK2 activity in the presence of a synthetic peptide derived from the carboxyl terminus of PRK2.

BACKGROUND: Protein kinase B (PKB) is activated by phosphorylation of Thr308 and of Ser473. Thr308 is phosphorylated by the 3-phosphoinositide-dependent protein kinase-1 (PDK1) but the identity of the kinase that phosphorylates Ser473 (provisionally termed PDK2) is unknown. RESULTS: The kinase domain of PDK1 interacts with a region of protein kinase C-related kinase-2 (PRK2), termed the PDK1-interacting fragment (PIF). PIF is situated carboxy-terminal to the kinase domain of PRK2, and contains a consensus motif for phosphorylation by PDK2 similar to that found in PKBalpha, except that the residue equivalent to Ser473 is aspartic acid. Mutation of any of the conserved residues in the PDK2 motif of PIF prevented interaction of PIF with PDK1. Remarkably, interaction of PDK1 with PIF, or with a synthetic peptide encompassing the PDK2 consensus sequence of PIF, converted PDK1 from an enzyme that could phosphorylate only Thr308 of PKBalpha to one that phosphorylates both Thr308 and Ser473 of PKBalpha in a manner dependent on phosphatidylinositol (3,4,5) trisphosphate (PtdIns(3,4,5)P3). Furthermore, the interaction of PIF with PDK1 converted the PDK1 from a form that is not directly activated by PtdIns(3,4,5)P3 to a form that is activated threefold by PtdIns(3,4,5)P3. We have partially purified a kinase from brain extract that phosphorylates Ser473 of PKBalpha in a PtdIns(3,4,5)P3-dependent manner and that is immunoprecipitated with PDK1 antibodies. CONCLUSIONS: PDK1 and PDK2 might be the same enzyme, the substrate specificity and activity of PDK1 being regulated through its interaction with another protein(s). PRK2 is a probable substrate for PDK1.

3-Phosphoinositide-Dependent Protein Kinases↗

Residential status and risk of hip fracture.

OBJECTIVE: to examine the association between residential status and risk of hip fracture in older people. DESIGN: population-based case-control study. SETTING: Auckland, New Zealand. SUBJECTS: a random sample of all individuals > or = 60 years, hospitalized with a fracture of the proximal femur between July 1991 and February 1994. Controls were age and gender frequency-matched to the cases, randomly selected from a random sample of general practitioners. MAIN OUTCOME MEASURES: radiographically-confirmed fracture of the proximal femur. Fractures sustained as a result of major trauma, such as in a motor vehicle crash, and those associated with pre-existing pathological conditions were excluded. RESULTS: individuals living in institutions were almost four times more likely to sustain a hip fracture [age- and gender-adjusted odds ratio (OR)=3.8; 95% confidence interval (CI): 3.0-4.8] than those living in private homes. After adjustment for potential confounding factors, the risk of hip fracture associated with living in an institution remained significantly increased (P< 0.0001), although the magnitude of the risk was somewhat diminished (OR=2.2; 95% (CI: 1.5-3.5). CONCLUSIONS: living in an institution is associated with an increased risk of hip fracture in older people. Specific factors that place these individuals at increased risk need to be identified, in order to develop intervention strategies.

Aged↗

A prospective cohort study of blood donors: methodological issues in the investigation of injuries and chronic diseases.

Blood donors have made important contributions to research, most notably in cross-sectional seroprevalence studies. The proposed New Zealand Blood Donors Health Study is a prospective cohort study of 30,000 New Zealand donors designed to investigate the determinants of common injuries, cardiovascular disease and cancer. While robust from an analytic perspective, the execution of prospective cohort studies in many settings is impeded by methodological, economic and organisational barriers. We examined the operational considerations of implementing a large-scale cohort study at a transfusion centre and evaluated measures taken to optimise data collection procedures. A pilot study of 1,000 participants revealed donor motivation to participate in this research was high (91% response rate). Comprehensive exposure data on lifestyle, behavioural and psychosocial factors were obtained from 95% of participants. Substantial heterogeneity in levels of potential risk factors was noted among respondents. Detailed dietary habit information and a study blood sample were obtained from 67% and 100% of participants, respectively. Study recruitment and baseline data collection was feasible during routine donor visits with minimal interruption to donor centre staff and procedures. We conclude the study design and characteristics of the regional donor program enhance the efficiency and significance of the proposed research.

Adolescent↗

Hip fracture incidence among older people in Auckland: a population-based study.

AIM: To determine the incidence of hip fractures among those aged 60 years or older in the Auckland region. METHODS: Demographic data were obtained on all older people hospitalised with a fracture of the femoral neck in Auckland, between 8 July 1991 and 7 February 1994. Incidence rates were calculated using the 1991 census data. RESULTS: An average incidence of 733 hip fractures or 710 individuals sustaining hip fractures each year was observed. Age-adjusted incidence rates were 571.5 per 100,000 for women and 318.2 per 100,000 for men. 97.0% of the hip fractures were sustained by those identified in the records as European, with the rates for Maori and Pacific Island populations 25-50% lower than for Europeans. Among Maori and Pacific Island populations, incidence rates were similar for men and women. Overall, 41.8% of the hip fractures were sustained by those > or = 85 years, with 67.0% sustained by those > or = 80 years. Incidence rates increased with age, with the rates continuing to increase in those > or = 85 years. CONCLUSION: Among Europeans, hip fracture incidence rates in Auckland are similar to those found for other caucasian populations. However, the rates among Maori and Pacific Island populations are among the lowest internationally and are similar for men and women. The increase in incidence rates with age continues in those > or = 85 years.

Aged↗

Dissociative experiences in the general population: a factor analysis.

The 28-item Dissociative Experiences Scale was administered to a stratified cluster sample of 1,055 respondents in the general population of Winnipeg. Dissociative experiences were common in the sample and were not related to socioeconomic status, sex, education, religion, or place of birth, although they declined with age in both sexes. A principal components analysis identified three factors accounting for 47.1 percent of the combined variance of the scores. The first factor, absorption-imaginative involvement, is composed of common, benign experiences, such as missing part of a conversation and being able to ignore pain. The other two factors, activities of dissociated states and depersonalization-derealization, composed of less common experiences such as not recognizing friends or family members and not recognizing one's reflection in a mirror, may be powerful predictors of DSM-III-R dissociative disorders.

Adult↗

Dissociative experiences in the general population.

The Dissociative Experiences Scale was administered to a random sample of 1,055 adults in the city of Winnipeg. Results showed that scale scores did not differ between men and women and were not influenced by income, employment status, education, place of birth, religious affiliation, or number of persons in the respondent's household. Dissociative experiences are common in the general population and decline with age. The findings suggest that dissociative disorders may also be common in the general population.

Adult↗

Enzymes and cancer. Preparation and some properties of guanase from rabbit liver.

1. Guanase has been purified 200-fold in 20% yield from the supernatant fraction of rabbit-liver homogenates, by using ammonium sulphate fractionation, calcium phosphate-gel adsorption and chromatography on DEAE-cellulose and Sephadex G-200. 2. K(m) with guanine as substrate at the optimum pH of 7.7 was found to be 1.05x10(-5)m. Q(10) was 1.4 between 23 degrees and 48 degrees . 3. Substrate activity and pH optima of compounds related to guanine have been studied. 8-Azaguanine, 1-methylguanine, thioguanine and 1-methylthioguanine are all substrates.

Aminohydrolases↗