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C Cooper

Publications and source records attributed to C Cooper.

At least 379 records · Page 21Linked to original sources

Angiotensin II stimulates the release of phospholipid-derived second messengers through multiple receptor subtypes in heart cells.

The octapeptide angiotensin II (Ang-II) induces both acute functional changes and longer lasting molecular changes in cultured mammalian heart myocytes, yet the underlying molecular mechanisms are poorly understood. In this study, Ang-II was found to stimulate a sustained release (> 30 min) of arachidonic acid (ARA) from cultured neonatal rat cardiac myocytes, with a half-maximal response observed at 0.1 nM. Mass spectroscopy analysis showed that Ang-II stimulated a specific release equivalent to 104 fmol of ARA/micrograms of protein in 10 min. Only Ang-II type 1 (AT1) receptor-specific antagonists were potent inhibitors of hormone-evoked [3H]inositol phosphate accumulation (DuP 753 IC50 approximately 7 nM compared to CGP 42112A IC50 > 1 microM). In contrast, only AT2 receptor-specific antagonists were potent inhibitors of [3H]ARA release (CGP 42112A IC50 approximately 7 nM, EXP 3880 IC50 approximately 2 nM, and PD 123177 IC50 approximately 10 nM). Further studies with phospholipase inhibitors (p-amylcinnamoylanthranilic acid and U73122) revealed that the production of [3H]-inositol phosphates and [3H]ARA occurs through parallel and independent pathways involving phospholipase C and phospholipase A2, respectively. Ang-II also increased the level of lysophosphatidylcholine by 49%, direct evidence that this peptide activated phospholipase A2. Thus, Ang-II stimulates distinct phospholipases in parallel through AT1 and AT2 receptors. These results reveal coordinate signaling roles for multiple Ang-II receptor subtypes in heart.

Angiotensin II↗

Risk of hip fracture in women with vertebral fracture.

In a population-based retrospective cohort study, Rochester women aged 35-69 years who were first diagnosed with one or more vertebral fractures in 1950-1979 were followed for the development of a subsequent hip fracture. The 336 women with no history of hip fracture at the time of their vertebral fracture experienced 52 proximal femur fractures in 4788 person-years of follow-up. The standardized morbidity ratio (SMR) of observed to expected hip fractures was 1.8 (95% CI, 1.3-2.4) and was higher for intertrochanteric than cervical femoral fractures (SMR, 2.3 versus 1.3; P = 0.07). Hip fracture risk among women with symptomatic vertebral fractures was slightly less than in those with asymptomatic vertebral fractures (SMR, 1.8 versus 2.3; not significant), and younger women had no higher risk of a subsequent hip fracture than women who were > or = 60 years of age at the time of their vertebral fracture (SMR, 1.4 versus 1.8; not significant). Alternative explanations are possible, but these data are consistent with heterogeneity in the pathogenesis of different osteoporotic fractures.

Adult↗

Variation in vertebral height ratios in population studies. European Vertebral Osteoporosis Study Group.

Vertebral height ratios are used to define vertebral deformity in clinical and epidemiologic studies of vertebral osteoporosis. However, few data have been obtained on the variation in these ratios in different populations using standard methods. We examined vertebral morphometric measurements obtained in a population survey from three centers: Malmö (Sweden), Montceau-les-Mines (France), and Graz (Austria), to study the influence of sex and the population center on vertebral height ratios. Radiographs were obtained according to a standardized protocol, and morphometric measurements, anterior height Ha, central height Hc, and posterior height Hp, made in Berlin. The height ratios anterior, Ha/Hp, central, Hc/Hp, posterior I, Hp/Hp', and posterior II, Hp/Hp" (Hp' = posterior height of vertebrae above, Hp" = posterior height of vertebrae below) were calculated for each vertebra from T4 to L4. The mean and standard deviation of these ratios for each sex and each center were derived using a statistical trimming procedure to normalize the distribution. Threshold values for defining grade 1 and grade 2 deformities, wedge, biconcavity, and compression, were calculated using these parameters. Anterior and central vertebral height ratios were smaller in males than females (p < 0.01). There were significant differences between the three centers (p < 0.01) both in the trimmed mean values for anterior and central vertebral height ratios and in the thresholds derived using standard criteria for defining wedge and biconcavity deformity. The data confirm the impression from single-center studies that vertebral height ratios vary between populations and suggest that reference values for vertebral height ratios should be derived separately for males and females within individual populations whenever possible.

Aged↗

Hemolytic uremic syndrome: just another case of gastroenteritis?

Hemolytic uremic syndrome (HUS), the most common cause of acute renal failure in childhood, has the potential to progress to a life-threatening illness. Its incidence in North America is increasing. Several studies have shown that Escherichia coli O157:H7 is associated with HUS. Although this pathogen was first recognized more than 10 years ago and is relatively common, many physicians are not aware of this diagnosis let alone the spectrum of illness associated with the bacteria. This case exemplifies what appears initially as gastroenteritis but, ultimately, becomes the final diagnosis of HUS. A case is presented to provide additional education to ensure the E coli O157:H7 infection is considered in the differential diagnosis of persons who present with bloody diarrhea.

Bacterial Infections↗

Reproducibility of a questionnaire on risk factors for osteoporosis in a multicentre prevalence survey: the European Vertebral Osteoporosis Study.

BACKGROUND: The European Vertebral Osteoporosis Study Group (EVOS) developed a questionnaire, back translated into 14 different European languages, for use in a multinational epidemiological study of vertebral osteoporosis. We investigated the reproducibility of this questionnaire in four of the participating study centres. METHODS: In all 151 men and women, aged 50-85 years, from Lubeck (Germany), Malmo (Sweden), Warsaw (Poland) and Oviedo (Northern Spain), were retested with the questionnaire on two occasions using a different observer within a 28-day period. RESULTS: Questions relating to personal or medical history were more reproducible than questions concerning subjective symptoms or aspects of lifestyle. The level of agreement for the non-ordinal categorical variables, as estimated by kappa, varied from 0.38 to 1.00 across the four centres. Agreement for the multicategory ordinal, mainly lifestyle, questions was in general poorer though improved when a weighted analysis was performed. For continuous data the 95% limits of agreement were narrow, and there was no evidence of bias between interviewers. There were no important differences in reproducibility across the four centres for either categorical or continuous data. CONCLUSION: The study indicates that the questionnaire may produce useful and comparable information concerning risk factors for osteoporosis across different countries and in different languages. It also highlights that questionnaire instruments designed for use in multinational population-based studies may provide data of comparable quality across a range of settings.

Aged↗

The functional and psychological outcomes of juvenile chronic arthritis in young adulthood.

The functional and psychological outcome of 43 patients with polyarticular juvenile arthritis was assessed in order to evaluate the impact of disease on their quality of life. Mean disease duration was 19.7 yr (range 10-39 yr), mean age 26.7 yr (range 18-54 yr) with sex ratio 1:3 (male:female). Severe disability was present in 8% of systemic onset, 34% of RF negative (Rh-P), 38% of RF positive (Rh+P) and 86% of extended pauci-articular (ExP) juvenile arthritics-this last high percentage was due to ocular impairment. The Rh+P had more hip (100% of the group) and knee prostheses (31%) compared with Rh-P (77 and 11% respectively). The Rh+P and ExP groups were the most disabled with the highest proportions of patients with currently active disease (85 and 71% respectively). Psychological testing showed that 21% of the patients were clinically depressed and the rate increased (P = 0.06) with the degree of disability. The proportion of patients demonstrating an anxious preoccupation with their disease increased (P = 0.002) with the degree of disability. Despite this, 66% of patients were employed and 38% felt that their arthritis had no effect on their ability to form relationships.

Adult↗

The basic helix-loop-helix-zipper domain of TFE3 mediates enhancer-promoter interaction.

Binding sites for three families of sequence-specific DNA-binding proteins, microE3, C/EBP, and OCT, are found in both the promoters and the intronic enhancer of the immunoglobulin heavy-chain gene. We have used a cotransfection system to investigate how proteins binding these sites may participate in enhancer-promoter interactions. Basic helix-loop-helix-zipper (BHLHZIP) proteins TFE3 and TFEB activate from a distance in this assay, but the basic zipper (BZIP) protein NF-IL6 and endogenous OCT-binding proteins do not. Our results suggest that remotely bound TFE3 is recruited to the initiation site by association with proximally bound TFE3; this interaction is mediated by the BHLHZIP domain and not by activation domains of TFE3. The BZIP domain of Ig/EBP lacks this activity, revealing an important functional difference between these structurally related dimerization domains. We also show that TFE3 can exist as a tetramer in solution and that tetramerization is determined by the HLHZIP domain. These data support a model in which protein-protein interactions between proximally and remotely bound TFE3 recruit TFE3 to the initiation site for activation. The IgH gene is the first example of a cellular gene in which proximal and distal binding sites are found for a protein capable of mediating enhancer-promoter interaction.

3T3 Cells↗

Occupational activity and osteoarthritis of the knee.

OBJECTIVES: To test the hypothesis that specific occupational physical activities are risk factors for knee osteoarthritis (OA). METHODS: A population-based case-control study of knee osteoarthritis was carried out in which 109 men and women with painful, radiographically confirmed knee OA were compared with 218 age and sex matched controls who had not suffered knee pain and had normal radiographs. Information collected included a lifetime occupational history and details of specific workplace physical activities. RESULTS: After adjustment for obesity and Heberden's nodes, the risk of knee OA was significantly elevated in subjects whose main job entailed more than 30 minutes per day squatting (OR 6.9, 95% CI 1.8-26.4) or kneeling (OR 3.4, 95% CI 1.3-9.1), or climbing more than ten flights of stairs per day (OR 2.7, 95% CI 1.2-6.1). The increase in risk associated with kneeling or squatting appeared to be more marked in subjects whose jobs entailed heavy lifting, but the size of the study did not permit precise delineation of any such interaction. CONCLUSIONS: These data suggest that prolonged or repeated knee bending is a risk factor for knee OA, and that risk may be higher in jobs which entail both knee bending and mechanical loading.

Activities of Daily Living↗

Defining osteoarthritis of the hand for epidemiological studies: the Chingford Study.

OBJECTIVES: To explore the relative merits of clinical and radiological examination in defining hand osteoarthritis (OA) for epidemiological purposes. METHODS: A total of 976 women aged 45-64 years were selected from the general population and underwent a structured interview, clinical examination of the hand joints and radiography of the hands and knees. The inter-relationship of the clinical and radiological findings was examined, and also the association of each with hand symptoms and the presence of knee OA. RESULTS: Clinical and radiographic signs of hand OA generally correlated with each other, and each was associated with hand symptoms to a similar degree. When analysed in combination, they were only marginally better at predicting symptoms than when tested individually. However, when they were examined in relation to radiographic features of knee OA, there was a significantly stronger association with radiographic features of hand OA than with clinical features. CONCLUSIONS: Hand radiology provides a better overall assessment of osteoarthritis than physical examination of the interphalangeal joints or carpo-metacarpal joint; in situations where radiology is not available clinical examination is a viable substitute.

England↗

Three-dimensional models of the abdominal vasculature based on helical CT: usefulness in patients with pancreatic neoplasms.

Three-dimensional (3D) rendering of helical (spiral) CT data is used increasingly to show abnormalities of the vascular system [1]. Abdominal applications have focused mainly on the arterial system, but the portal venous system also can be depicted effectively with this technique. In patients with pancreaticobiliary neoplasms, axial display of helical CT images generally allows accurate staging of the lesion [2, 3]. Many surgeons, however, continue to request arteriography to specifically look for evidence of vascular encasement that would preclude surgery or vascular anomalies that would alter the surgical approach [4, 5]. The purpose of this essay is to illustrate the value of 3D rendering of CT data in providing useful information for surgical planning and showing the extent of vascular involvement by tumor.

Abdomen↗

Fracture risk in patients with ankylosing spondylitis: a population based study.

OBJECTIVE: To assess the risk of fractures among patients with ankylosing spondylitis (AS). METHODS: A population based cohort study compared fracture incidence in an inception cohort of 158 Rochester, Minnesota residents newly diagnosed with AS between 1935 and 1989 with expected rates from the same community. RESULTS: In 2,398 person-years of observation, there was no increase in the risk of limb fractures, but there was a pronounced increase in the risk of thoracolumbar compression fractures (standardized morbidity ratio = 7.6; 95% CI, 4.3-12.6) among those with AS. CONCLUSION: These data point to the importance of measures aimed at maintaining axial skeletal status in patients with AS.

Adolescent↗

Emergency care: an overview.

Emergency care is a most important component in general practice. Practitioners are often judged by their ability to deliver appropriate life saving care sometimes in difficult circumstances. An ever present challenge is the maintenance of knowledge and skills necessary to deal effectively with emergencies. Table 3 lists the many emergencies that general practitioners have to consider to be prepared for and that includes regular updating in the basic skills of resuscitation.

Australia↗

Mechanical and constitutional risk factors for symptomatic knee osteoarthritis: differences between medial tibiofemoral and patellofemoral disease.

OBJECTIVE: The generation of effective preventive strategies against knee osteoarthritis (OA) requires precise understanding of the individual risk factors for the condition. To identify these risk factors, we performed a population based case-control study of the disorder. METHODS: We compared 109 men and women with symptomatic, radiographically verified OA in the tibiofemoral (TFJ) and/or patellofemoral (PFJ) compartments of the knee joint with 218 community controls matched for age and sex. Information on risk factors was obtained by a structured interview and examination. RESULTS: Independent risk factors for knee OA included obesity (odds ratio [OR] 3.3; 95% confidence intervals [95% CI] 1.6-6.9), previous knee injury (OR 3.4; 95% CI 1.7-6.7), meniscectomy (OR 4.0; 95% CI 1.0-16.4), family history (OR 2.7; 95% CI 1.3-5.5) and Heberden's nodes (OR 2.0; 95% CI 1.1-3.6). Obesity and meniscectomy were stronger risk factors for medial TFJ disease, while Heberden's nodes and family history were more closely associated with PFJ involvement. CONCLUSION: Although based on small numbers, our results suggest that the relative contribution of mechanical and constitutional factors in the pathogenesis of OA in different compartments of the knee joint might vary. They also confirm the importance of significant knee injury and meniscectomy as risk factors for medial TFJ disease in the general population.

Aged↗