17 research outputs found

    Murine mesothelin: characterization, expression, and inhibition of tumor growth in a murine model of pancreatic cancer

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    Background Mesothelin has attracted much interest as a tumor specific antigen; it has been reported to promote tumor development and to be a good target for cancer treatment. Most studies to date have used human mesothelin in immunocompromised mice. Since these models do not allow for study of the natural immune response to mesothelin expressing tumors, we have undertaken the characterization of mouse mesothelin so the effects of this protein can be assessed in immunocompetent mouse strains. Methods We analyzed mouse mesothelin expression, tissue distribution, shedding and biochemistry. In addition we constructed stable mesothelin overexpressing lines of the pancreatic cancer line Panc02 by two methods and tested them for growth and tumorigencity in vitro and in vivo. Results We show here that mouse mesothelin is similar to human mesothelin in biochemical characteristics, tumor expression and tissue distribution, suggesting the mouse may be a suitable model for study of mesothelin. Stable overexpression of mesothelin in a pancreatic cancer cell line did not increase cell proliferation or anchorage-independent growth in vitro, suggesting that mesothelin is not necessarily a tumor progression factor. Surprisingly overexpression of mesothelin inhibited tumor formation in vivo in immunocompetent mice. Conclusion The mouse may be a good model for studying mesothelin in the context of an intact immune response. Mesothelin is not necessarily a tumor progression factor, and indeed mesothelin overexpression inhibited tumor growth in immunocompetent mice

    Improving the uptake of pulmonary rehabilitation in patients with COPD:: qualitative study of experiences and attitudes

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    BackgroundPulmonary rehabilitation can improve the quality of life and ability to function of patients with chronic obstructive pulmonary disease (COPD). It may also reduce hospital admission and inpatient stay with exacerbations of COPD. Some patients who are eligible for pulmonary rehabilitation may not accept an offer of it, thereby missing an opportunity to improve their health status.AimTo identify a strategy for improving the uptake of pulmonary rehabilitation.Design of studyQualitative interviews with patients.SettingPatients with COPD were recruited from a suburban general practice in north-east Derbyshire, UK.MethodIn-depth interviews were conducted on a purposive sample of 16 patients with COPD to assess their concerns about accepting an offer of pulmonary rehabilitation. Interviews were analysed using grounded theory.ResultsFear of breathlessness and exercise, and the effect of pulmonary rehabilitation on coexisting medical problems were the most common concerns patients had about taking part in the rehabilitation. The possibility of reducing the sensation of breathlessness and regaining the ability to do things, such as play with their grandchildren, were motivators to participating.ConclusionA model is proposed where patients who feel a loss of control as their disease advances may find that pulmonary rehabilitation offers them the opportunity to regain control. Acknowledging patients\u27 fears and framing pulmonary rehabilitation as a way of &lsquo;regaining control&rsquo; may improve patient uptake.<br /

    Murine mesothelin: characterization, expression, and inhibition of tumor growth in a murine model of pancreatic cancer

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    Background: Mesothelin has attracted much interest as a tumor specific antigen; it has been reported to promotetumor development and to be a good target for cancer treatment. Most studies to date have used humanmesothelin in immunocompromised mice. Since these models do not allow for study of the natural immuneresponse to mesothelin expressing tumors, we have undertaken the characterization of mouse mesothelin so theeffects of this protein can be assessed in immunocompetent mouse strains.Methods: We analyzed mouse mesothelin expression, tissue distribution, shedding and biochemistry. In addition we constructed stable mesothelin overexpressing lines of the pancreatic cancer line Panc02 by two methods and tested them for growth and tumorigencity in vitro and in vivo.Results: We show here that mouse mesothelin is similar to human mesothelin in biochemical characteristics, tumor expression and tissue distribution, suggesting the mouse may be a suitable model for study of mesothelin. Stable overexpression of mesothelin in a pancreatic cancer cell line did not increase cell proliferation or anchorageindependent growth in vitro, suggesting that mesothelin is not necessarily a tumor progression factor. Surprisingly overexpression of mesothelin inhibited tumor formation in vivo in immunocompetent mice.Conclusion: The mouse may be a good model for studying mesothelin in the context of an intact immune response. Mesothelin is not necessarily a tumor progression factor, and indeed mesothelin overexpression inhibited tumor growth in immunocompetent mice

    Perforated gastric corpus in a strangulated paraesophageal hernia: a case report

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    Introduction: Patients with paraesophageal hernias often present secondary to chronic symptomatology. Infrequently acute intestinal ischemia and perforation can occur as a consequence of paraesophageal hernias with potentially dire consequences. Case presentation: An 86-year-old obtunded male presented to the emergency department with hypotension and severe back and abdominal pain. An emergency abdominal CT scan was ordered with a presumptive diagnosis of ruptured abdominal aortic aneurysm. CT topograms revealed extensive free intra-abdominal air and herniated abdominal viscera into the right hemithorax. Prior to completion of the CT study the patient sustained a cardiopulmonary arrest. Surgery was consulted but the patient was unable to be revived. Post-mortem examination revealed gross contamination within the abdomen and a giant incarcerated hiatal hernia with organoaxial volvulus and ischemic perforation. Conclusion: Current recommendations call for prompt repair of giant hiatal hernias before they become symptomatic due to the increased risk of strangulation. Torsion of the stomach in large hiatal hernias frequently leads to a fatal complication such as this warranting elective repair as soon as possible. Originally published Journal of Medical Case Reports Vol. 3 No. 6507 May 200

    Shajaó – histories of an invented savage

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    Through multiple stories about Shajaó, an untold history of the Peruvian Amazon unfolds. This article, based on extensive archival research and fieldwork, brings together multivocal accounts about an Ese Eja man who allegedly killed a Catholic priest in 1932 and who, despite the large-scale expeditions sent out to capture him, was not apprehended until 1942. Through ongoing tales of Shajaó, the intersubjective ways in which memory is shaped and employed to influence and make sense of sociopoltical contexts is revealed in the exchanges between a notable “savage” and various economies in different historical settings—the rubber boom, extractivism upheld by debt-peonage, Catholic missionization and today's environmental service economy. This exploration questions the construction, reproduction and transformation of the multiple, though not always shared, experiential and interpretive frameworks that shape the historical consciousness of individual and collective memories over time. It also suggests that “disremembering”, in archival and oral accounts, reflects a critical political awareness of history's valid flexibility. Here, narratives are rewoven so that history continues to be told in ways that ensure that “Shajaó stories” never truly end
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