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Karen Anderson

Publications and source records attributed to Karen Anderson.

10 recordsLinked to original sources

Functional evidence that vascular endothelial growth factor may act as an autocrine factor on human podocytes.

Vascular endothelial growth factor (VEGF) is expressed by renal glomerular epithelial cells (podocytes) and is thought to be protective against nephrotoxic agents. VEGF has been shown to be an autocrine survival factor in neuropilin-1-positive, VEGF receptor-negative breast carcinoma cells. Normal human podocytes are also known to express neuropilin-1, VEGF, and are VEGF-R2 negative. Here, we investigated whether a similar VEGF autocrine loop may exist in podocytes. Podocyte cytosolic calcium concentration ([Ca(2+)](i)) was analyzed in primary cultured and conditionally immortalized podocytes using ratiometric fluorescence measurement. Cytotoxicity was determined by lactate dehydrogenase assay, proliferation by [(3)H]-thymidine incorporation, and cell counts by hemocytometric assay. VEGF decreased [Ca(2+)](i) in primary podocytes (from 179 +/- 36 to 121 +/- 25 nM, P < 0.05) and conditionally immortalized podocytes (from 95 +/- 10 to 66 +/- 8 nM, P < 0.02) in the absence of extracellular calcium. The type III receptor tyrosine-kinase inhibitor PTK787/ZK222584 abolished this reduction. VEGF increased podocyte [(3)H]-thymidine incorporation (3,349 +/- 283 cpm, control 2,364 +/- 301 cpm, P < 0.05) and cell number (4.5 +/- 0.7 x 10(4)/ml, control 2.6 +/- 0.5 x 10(4)/ml, P < 0.05) and decreased cytotoxicity (5.9 +/- 0.7%, control 12 +/- 3%, P < 0.05), whereas a monoclonal antibody to VEGF increased cytotoxicity. Electron microscopy of normal human glomeruli demonstrated that the glomerular VEGF is mostly podocyte cell membrane associated. These results indicate that one of the functions of VEGF secreted from podocytes may be to act as an autocrine factor on calcium homeostasis and cell survival.

Adult↗

Stopping the active intervention: CARET.

The Carotene and Retinol Efficacy Trial (CARET) was a large, multicenter randomized chemoprevention trial designed to test a combined lung cancer prevention agent in heavy smokers and workers exposed to asbestos. In January 1996, the CARET Steering Committee decided to stop the intervention due to an adverse effect. This paper describes the decision process used to apply the stopping rules and the activities engaged in by CARET participants and staff to implement the decision. The most important activity was to draft and mail a letter to the participants informing them of the disappointing CARET results and asking them to stop taking the study vitamins and to return any unused study vitamins. The steering committee, with the support of the National Cancer Institute, planned to follow participants for disease endpoints and smoking behavior for 5 years. These activities led to smooth closure of active intervention and maintained high retention rates during the transition.

Asbestos↗

Immunity to malaria after administration of ultra-low doses of red cells infected with Plasmodium falciparum.

BACKGROUND: The ability of T cells, acting independently of antibodies, to control malaria parasite growth in people has not been defined. If such was shown to be effective, an additional vaccine strategy could be pursued. Our aim was to ascertain whether or not development of cell-mediated immunity to Plasmodium falciparum blood-stage infection could be induced in human beings by exposure to malaria parasites in very low density. METHODS: We enrolled five volunteers from the staff at our research institute who had never had malaria. We used a cryopreserved inoculum of red cells infected with P falciparum strain 3D7 to give them repeated subclinical infections of malaria that we then cured early with drugs, to induce cell-mediated immune responses. We tested for development of immunity by measurement of parasite concentrations in the blood of volunteers by PCR of the multicopy gene STEVOR and by following up the volunteers clinically, and by measuring antibody and cellular immune responses to the parasite. FINDINGS: After challenge and a extended period without drug cure, volunteers were protected against malaria as indicated by absence of parasites or parasite DNA in the blood, and absence of clinical symptoms. Immunity was characterised by absence of detectable antibodies that bind the parasite or infected red cells, but by the presence of a proliferative T-cell response, involving CD4+ and CD8+ T cells, a cytokine response, consisting of interferon gamma but not interleukin 4 or interleukin 10, induction of high concentrations of nitric oxide synthase activity in peripheral blood mononuclear cells, and a drop in the number of peripheral natural killer T cells. INTERPRETATION: People can be protected against the erythrocytic stage of malaria by a strong cell-mediated immune response, in the absence of detectable parasite-specific antibodies, suggesting an additional strategy for development of a malaria vaccine

Animals↗

A multi-center evaluation of the McGill Pain Questionnaire: results from more than 1700 chronic pain patients.

We argue that the conflicting results reported in previous studies examining the factor structure of the McGill Pain Questionnaire Pain Rating Index (PRI) can be explained by differences in the patient samples and statistical analyses used across studies. In an effort to clarify the factor structure of the PRI, 3 different factor models were compared using confirmatory factor analysis in 2 samples of low-back pain patients (N = 1372) and in a third sample of patients suffering from other chronic pain problems (N = 423). A 4-factor model, similar to those obtained in previous studies where multiple criteria were used to determine the number of factors extracted, best explained covariation among PRI subclasses. However, relatively high interfactor correlations (approximately two-thirds of the variance explained by the best fitting factor structure was common variance) cast doubt on the discriminant validity of PRI subscales; examination of relationships between the PRI and MMPI subscales also failed to provide evidence of the discriminant validity or clinical utility of PRI subscales. Reducing the information from the 10 PRI sensory subclasses to a single subscale score may seriously limit the usefulness of the PRI. Alternate methods of using PRI data are suggested.

Adolescent↗

Elevation of the soft palate in speech and swallowing in normal female participants and females with motor neuron disease: an innovative procedure for measuring palatal elevation.

The aim was to measure the angle of elevation of the soft palate during the separate conditions of swallowing of pudding, swallowing of liquid and during production of 'may/pay', using videofluroscopy and innovative computer software. We then determined whether soft palate elevation (as reflected in measures of an angle) differed in those separate conditions. Twelve female participants were studied, aged 40-70 years. The trends observed were that the highest soft palate elevation was displayed in the liquid-swallowing condition and the lowest soft palate elevation was displayed in the speech conditions. The results did not reach statistical significance, but the findings support the suggestions of Rubesin et al. (1987) and Fritzell (1969) that soft palate elevation is higher during swallowing than during speech. This same method was then used to measure soft palate elevation under the same three conditions in nine females, all aged > 40 years, who had motor neuron disease. Again, the highest soft palate elevation was displayed when swallowing liquid, but this time the lowest elevation occurred when swallowing pudding. Owing to small numbers, results did not reach statistical significance, but the trends may be important to replicate in a larger study. This pilot study developed a comprehensive and accurate method of measuring the soft palate elevation using digitization and computer software.

Adult↗

AIDS turns 21.

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Acquired Immunodeficiency Syndrome↗