tbuckley/cabot-search huggingface dataset:
Perspectives for Induced Pluripotent Stem Cell Technology
Authors: Naoki Nagata, Shinya Yamanaka
Journal: Circulation Research (2014)

Induced pluripotent stem cell technology makes in vitro reprogramming of somatic cells from individuals with various genetic backgrounds possible. By applying this technology, it is possible to produce pluripotent stem cells from biopsy samples of arbitrarily selected individuals with various genetic backgrounds and to subsequently maintain, expand, and stock these cells. From these induced pluripotent stem cells, target cells and tissues can be generated after certain differentiation processes. These target cells/tissues are expected to be useful in regenerative medicine, disease modeling, drug screening, toxicology testing, and proof-of-concept studies in drug development. Therefore, the number of publications concerning induced pluripotent stem cells has recently been increasing rapidly, demonstrating that this technology has begun to infiltrate many aspects of stem cell biology and medical applications. In this review, we discuss the perspectives of induced pluripotent stem cell technology for modeling human diseases. In particular, we focus on the cloning event occurring through the reprogramming process and its ability to let us analyze the development of complex disease-harboring somatic mosaicism.
Flow cytometric evaluation of cytotoxic peripheral blood lymphocytes in acute renal graft rejection.
Authors: N R Sridhar, M Blanton, L Whitacre, K Balakrishnan, M R First
Journal: Journal of the American Society of Nephrology (1992)

The presence of the S6F1+ epitope on the surface of CD8+ lymphocytes is believed to be uniquely representative of cytotoxic subpopulations. A preliminary study was conducted to evaluate the CD8+ S6F1+ peripheral lymphocytes by flow cytometry in patients undergoing renal allograft biopsy for allograft dysfunction. Lymphocytes, obtained at the time of biopsy, were analyzed by flow cytometry with CD8-FITC/S6F1-RD1 as the test monoclonal antibody and MsIgG-RD1/MsIgG-FITC as internal control. A 100% increase in S6F1+ cells over internal control was considered to be positive result. The results were correlated with the histopathologic findings in 14 instances of allograft dysfunction occurring 26.5 +/- 11.6 days posttransplantation. The histopathologic diagnosis was acute cellular rejection in eight cases, acute tubular necrosis in four, and cyclosporine nephrotoxicity in two. Flow cytometric detection of an increase in S6F1+ cells yielded a sensitivity of 87.5% and a specificity of 83.3% for the diagnosis of acute rejection. It would appear that the use of a monoclonal antibody to detect increases in the number of CD8+ S6F1+ peripheral lymphocytes is a valuable test for the detection of acute allograft rejection in the initial period after transplantation.
Cytomegalovirus infection and disease after autologous CD34-selected peripheral blood stem cell transplantation for multiple myeloma: no evidence of increased incidence based on polymerase-chain-reaction monitoring
Authors: Karl S. Peggs, Stuart J. Ings, Panagiotis D. Kottaridis, Kwee Yong, Catherine D. Williams, Anthony H. Goldstone, Stephen Mackinnon
Journal: Blood (2000)
Granulocyte colony stimulating factor exacerbates antineutrophil cytoplasmic antibody vasculitis
Authors: Simon J Freeley, Alice M Coughlan, Reena J Popat, Deborah K Dunn-Walters, Michael G Robson
Journal: Annals of the Rheumatic Diseases (2012)

Objectives Granulocyte colony stimulating factor (GCSF) is important in mobilising neutrophils from the bone marrow but also has a range of proinflammatory effects. We therefore decided to investigate the role of GCSF in antineutrophil cytoplasmic antibody (ANCA) vasculitis. Methods We measured GCSF levels in the serum of 38 patients with active ANCA vasculitis compared with 31 age-matched controls, and assessed the effect of GCSF priming on the response of human neutrophils to ANCA. We also examined the effect of exogenous GCSF administration in a murine model of antimyeloperoxidase (anti-MPO) vasculitis, and the effect of GCSF on murine neutrophil activation. Results The serum levels of GCSF in patients with active ANCA vasculitis were significantly higher than those of age matched healthy controls (mean 38.04 vs 18.35 pg/ml, p&lt;0.001). Furthermore, we demonstrated that GCSF primed human neutrophils in vitro for a respiratory burst in response to anti-MPO ANCA. In an anti-MPO antibody transfer model, mice given GCSF had more crescents (mean 29.1% vs 5.8% per glomerular cross section, p&lt;0.05), more macrophages (mean 3.2 vs 1.2 per glomerular cross-section, p&lt;0.01), higher serum creatines (mean 13.6 vs 8.3 μmol/l, p&lt;0.05) and more haematuria (p&lt;0.05) compared with controls. In vivo administration of GCSF with lipopolysaccharide (LPS), but not LPS alone, led to upregulation of CD11c on murine neutrophils. Conclusions These data suggest that GCSF, which is raised in patient serum, may play an important role in exacerbating disease in ANCA vasculitis. In addition, GCSF therapy for neutropenia should be used with caution in these patients.
Nutritional status of pulmonary rehabilitation patients
Authors: Heinz Juergen Stark, Dragan Stojanovic, Konrad Schultz
Journal: European Respiratory Journal (2012)

Introduction   Only about one-third of all adult German men and about 50% of women are normal weight. By contrast, the percent of overweight/obesity has reached epidemic proportions. Underweight is relatively rare. The nutritional status of the pneumologically ill varies considerably from this disease pattern. The prevalence of underweight in COPD III and IV (FEV1    Aims and objectives   The aim of the present study is to ascertain the nutritional status of a pneumological patient population and the respective frequency and meaning of underweight and overweight/obesity, using a large database.   Methods   From 2005 to end of 2011, the nutritional status of all pneumological patients was ascertained at a German inpatient rehabilitation clinic (n=13804). Additional from July 2010 until January 2012 the nutritional status of COPD patients with severity levels of III and IV based on GOLD was also ascertained for a sub-population.   Results   Of all patients (n=13804), the percent of underweight was 8.4%, normal weight 27.5% and overweight/obese 64.1%. Of all COPD patients (n=5470), 10.8% were underweight, 28.3% normal weight and 60.9% overweight /obese. Of the COPD III patients 20.6% were underweight and of the COPD IV group even 25.1%. The asthmatic (n=3811) had a lower percent of underweight (4.1%) but 72.5% overweight/obese.   Conclusions  The prevalence of underweight and obesity in a pneumological patient population is strikingly manifest when compared to a normal population. The percentage of underweight is significantly higher for COPD. Within the COPD, results show considerable differences, depending on degree of severity.
Bronchoalveolar lavage fluid findings in children with hypersensitivity pneumonitis
Authors: F. Ratjen, U. Costabel, M. Griese, K. Paul
Journal: European Respiratory Journal (2003)

Bronchoalveolar lavage (BAL) has been shown to be useful in the diagnosis of hypersensitivity pneumonitis (HP) in adults, the typical constellation being lymphocytosis with a decrease in the CD4/CD8 ratio. Only limited data exist for the diagnostic value of BAL cytology in paediatric patients with this disorder. Children aged 6–15 yrs (n=9) with acute HP were studied. BAL was performed before initiation of anti­inflammatory treatment via a flexible bronchoscope in the middle lobe with 3 mL·kg body weight −1 normal saline warmed to body temperature; BAL cytology and lymphocyte surface markers were compared with age­matched controls. The percentage of lymphocytes was significantly increased in all patients with HP. No significant differences were observed in the CD4/CD8 ratio between children without lung disease and those with HP. Increased expression of human leukocyte antigen­DR was found in seven of eight children with HP, whereas natural killer cells were elevated in five of eight children. Every patient had at least one of these two alterations in BAL fluid in addition to lymphocytosis. It was concluded that while lymphocytosis is generally present in children with hypersensitivity pneumonitis, the CD4/CD8 ratio is not increased in these patients. Assessing natural killer cells and human leukocyte antigen­DR expression appears to be a helpful adjunct in the diagnosis of paediatric patients with this disorder.
Long-Term Prognosis of Diabetic Foot Patients and Their Limbs
Authors: Stephan Morbach, Heike Furchert, Ute Gröblinghoff, Heribert Hoffmeier, Kerstin Kersten, Gerd-Thomas Klauke, Ulrike Klemp, Thomas Roden, Andrea Icks, Burkhard Haastert, Gerhard Rümenapf, Zulfiqarali G. Abbas, Manish Bharara, David G. Armstrong
Journal: Diabetes Care (2012)

There is a dearth of long-term data regarding patient and limb survival in patients with diabetic foot ulcers (DFUs). The purpose of our study was therefore to prospectively investigate the limb and person survival of DFU patients during a follow-up period of more than 10 years.Two hundred forty-seven patients with DFUs and without previous major amputation consecutively presenting to a single diabetes center between June 1998 and December 1999 were included in this study and followed up until May 2011. Mean patient age was 68.8 ± 10.9 years, 58.7% were male, and 55.5% had peripheral arterial disease (PAD). Times to first major amputation and to death were analyzed with Kaplan-Meier curves and Cox multiple regression.A first major amputation occurred in 38 patients (15.4%) during follow-up. All but one of these patients had evidence of PAD at inclusion in the study, and 51.4% had severe PAD [ankle-brachial pressure index ≤0.4]). Age (hazard ratio [HR] per year, 1.05 [95% CI, 1.01-1.10]), being on dialysis (3.51 [1.02-12.07]), and PAD (35.34 [4.81-259.79]) were significant predictors for first major amputation. Cumulative mortalities at years 1, 3, 5, and 10 were 15.4, 33.1, 45.8, and 70.4%, respectively. Significant predictors for death were age (HR per year, 1.08 [95% CI, 1.06-1.10]), male sex ([1.18-2.32]), chronic renal insufficiency (1.83 [1.25-2.66]), dialysis (6.43 [3.14-13.16]), and PAD (1.44 [1.05-1.98]).Although long-term limb salvage in this modern series of diabetic foot patients is favorable, long-term survival remains poor, especially among patients with PAD or renal insufficiency.
Poorer outcome of elderly patients treated with extended-field radiotherapy compared with involved-field radiotherapy after chemotherapy for Hodgkin's lymphoma: an analysis from the German Hodgkin Study Group
Authors: B. Klimm, H.T. Eich, H. Haverkamp, A. Lohri, P. Koch, F. Boissevain, G. Trenn, P. Worst, E. Dühmke, R.P. Müller, K. Müller-Hermelink, B. Pfistner, V. Diehl, A. Engert
Journal: Annals of Oncology (2006)
The Social Mission of Medical Education: Ranking the Schools
Authors: Fitzhugh Mullan
Journal: Annals of Internal Medicine (2010)

This article has been corrected. The original version (PDF) is appended to this article as a supplement. Background: The basic purpose of medical schools is to educate physicians to care for the national population. Fulfilling this goal requires an adequate number of primary care physicians, adequate distribution of physicians to underserved areas, and a sufficient number of minority physicians in the workforce. Objective: To develop a metric called the social mission score to evaluate medical school output in these 3 dimensions. Design: Secondary analysis of data from the American Medical Association (AMA) Physician Masterfile and of data on race and ethnicity in medical schools from the Association of American Medical Colleges and the American Association of Colleges of Osteopathic Medicine. Setting: U.S. medical schools. Participants: 60 043 physicians in active practice who graduated from medical school between 1999 and 2001. Measurements: The percentage of graduates who practice primary care, work in health professional shortage areas, and are underrepresented minorities, combined into a composite social mission score. Results: The contribution of medical schools to the social mission of medical education varied substantially. Three historically black colleges had the highest social mission rankings. Public and community-based medical schools had higher social mission scores than private and non–community-based schools. National Institutes of Health funding was inversely associated with social mission scores. Medical schools in the northeastern United States and in more urban areas were less likely to produce primary care physicians and physicians who practice in underserved areas. Limitations: The AMA Physician Masterfile has limitations, including specialty self-designation by physicians, inconsistencies in reporting work addresses, and delays in information updates. The public good provided by medical schools may include contributions not reflected in the social mission score. The study was not designed to evaluate quality of care provided by medical school graduates. Conclusion: Medical schools vary substantially in their contribution to the social mission of medical education. School rankings based on the social mission score differ from those that use research funding and subjective assessments of school reputation. These findings suggest that initiatives at the medical school level could increase the proportion of physicians who practice primary care, work in underserved areas, and are underrepresented minorities. Primary Funding Source: Josiah Macy, Jr. Foundation.
Bromodomain inhibitor JQ1 attenuates TGF-β-suppressed SOD2 expression and reduces proliferation in human primary pulmonary fibroblasts
Authors: Gisela Lindahl, Patricia Leoni, Carmel Stock, Charalambos Michaeloudes, Harpreet Lota, Andrew Nicholson, Toby Maher, Athol Wells, Ian Adcock, Elisabetta Renzoni
Journal: European Respiratory Journal (2013)

Background: SOD2 converts intracellular superoxide to hydrogen peroxide and acts as an antioxidant enzyme. Low expression levels of SOD2 have been associated with smooth muscle cell activation and proliferation. We have identified low SOD2 expression in pulmonary fibroblasts from SSc and IPF fibrotic lung, in which fibro-proliferation is an early desease hallmark. A BRD4 inhibitor, JQ1 is being investigated for its inhibitory effects on cell proliferation in cancer. Here we investigate the effect of TGF-β on SOD2 expression, and the potential beneficial effects of JQ1 on SOD2 expression and proliferation in adult lung fibroblasts.

Methods: Human primary adult lung fibroblasts where quiesced for 24 hrs in serum free DMEM and pre-treated with DMSO (0.1%), 300nM JQ1+, or its enantiomer JQ1-, for 2 hrs before stimulation with TGF-β1 at 2ng/ml for a further 24 hrs. SOD2 mRNA expression was determined in cell extracts by qRT-PCR. Proliferation assays were performed in 3% serum, with or without JQ1 for 24 hrs and 48 hrs, by assessing BrdU incorporation (Roche) during a 5 hr period before the time point. Cell toxicity was assessed by LDH assay.

Results: Expression of SOD2 was reduced by approximately 70% (p<0.01) by TGF-β1 in the presence of the JQ1 enantiomer, which had no effect on expression. TGF-β suppressed SOD2 expression was enhanced 2 fold (p<0.01) by JQ1+ at 300 nM. This concentration of JQ1+ (but not of its enantiomer JQ1-) inhibited BrdU incorporation by 77% (p<0.01) and 43% (p<0.01), respectively.

Conclusion: The data suggests bromodomain inhibitor JQ1 enhances SOD2 expression and inhibits proliferation in activated human pulmonary fibroblasts.
Protective effects of spironolactone against anthracycline‐induced cardiomyopathy
Authors: Mahmut Akpek, Ibrahim Ozdogru, Omer Sahin, Mevlude Inanc, Ali Dogan, Cevat Yazici, Veli Berk, Halit Karaca, Nihat Kalay, Abdurrahman Oguzhan, Ali Ergin
Journal: European Journal of Heart Failure (2014)
Suppression of normal human erythropoiesis by gamma interferon in vitro. Role of monocytes and T lymphocytes.
Authors: S W Mamus, S Beck-Schroeder, E D Zanjani
Journal: Journal of Clinical Investigation (1985)

Interferons (IFN) have been shown to suppress the proliferation of human erythroid progenitors (erythroid burst-forming units [BFU-E] and colony-forming units [CFU-E]) in vitro. To examine the mechanism(s) underlying this inhibitory activity, the effect of different doses (50-10,000 U) of a highly purified preparation of recombinant DNA produced human gamma-IFN on erythroid colony formation by normal human bone marrow BFU-E and CFU-E in the presence and absence of monocytes and/or T lymphocytes was studied. The addition of gamma-IFN to whole marrow caused suppression of BFU-E (6-65%) and CFU-E (31-79%) in a dose-dependent fashion. This inhibition occurred both with the direct addition of gamma-IFN to the culture plates as well as by the preincubation of marrow cells with gamma-IFN followed by the washing of the cells; at the highest concentration of gamma-IFN (10,000 U), near-maximal inhibition of colony formation occurred with as little as 15 min of preexposure (BFU-E, 50%; CFU-E, 81%). Removal of monocytes and/or T lymphocytes before the addition of gamma-IFN significantly reduced the inhibitory effects of this lymphokine (BFU-E, -1 to 38%; CFU-E, -8 to 67%). Co-culture of purified autologous monocytes or T cells preexposed to gamma-IFN with monocyte and T cell-depleted marrow cells resulted in highly significant inhibition of erythroid colony formation even when these treated cells comprised less than 1% of the total nucleated cell populations in culture. The inhibitory action of gamma-IFN was not prevented or reversed by erythropoietin. These results demonstrate that the inhibitory effects of gamma-IFN on erythropoiesis are mediated to a significant degree through accessory cell populations, and suggest that gamma-IFN may represent a useful tool in the study of the role of immunocompetent cells in the regulation of erythropoiesis in vitro.
Impact of different bone marrow cell preparations on left ventricular remodelling after experimental myocardial infarction
Authors: Stefan Frantz, Duttu Vallabhapurapu, Jochen Tillmanns, Nikos Brousos, Helga Wagner, Kristina Henig, Georg Ertl, Albrecht M. Müller, Johann Bauersachs
Journal: European Journal of Heart Failure (2008)
Endoscopic Biliary Drainage by Nasobiliary Drain or by Stent Placement in Patients with Acute Cholangitis
Authors: B. Sharma, R. Kumar, N. Agarwal, S. Sarin
Journal: Endoscopy (2005)

Endoscopic biliary drainage is an established mode of treatment for acute cholangitis. We compared the safety and efficacy of nasobiliary drain (NBD) placement and stent placement for biliary drainage in patients with acute cholangitis.We recruited a total of 150 patients with severe cholangitis who required endoscopic biliary drainage. Patients were randomized to have either a 7-Fr NBD or a 7-Fr straight flap stent placed during endoscopy. Outcome measures included complications related to endoscopic retrograde cholangiopancreatography (ERCP) and the clinical outcome.Of the 150 patients, 75 were randomized to the NBD group and 75 to the stent group. The most common causes of biliary obstruction were common bile duct stones (n = 102) and biliopancreatic malignancies (n = 37). The site of the biliary obstruction was predominantly found to be the lower part of common bile duct in both the NBD group (n = 58) and the stent group (n = 59). Indications for biliary drainage were: a fever of > 100.4 degrees F (n = 140), hypotension (n = 23), peritonism (n = 40), impaired consciousness (n = 29), and failure to improve with conservative management (n = 45). Biliary drainage was achieved in 147 patients. Abdominal pain, fever, jaundice, hypotension, peritonism and altered sensorium improved after a median period of 2 days in both groups. Leukocyte counts became normal after a median time of 7 days in the NBD group and 6 days in the stent group. There were no ERCP-related complications. There were no instances of displacement or kinking of an NBD, occlusion of an NBD or stent, or of stent migration. Four patients died (two in the NBD group and two in the stent group) as a result of uncontrolled cholangitis after 1, 2, 4, and 6 days of biliary drainage. The success rates of biliary drainage in cholangitis were not affected by the type of endoprosthesis used (72/74 for NBD patients vs. 71/73 for stent patients), the etiology of the biliary obstruction (110/112 for benign obstruction vs. 33/35 for malignant obstruction), or the site of the biliary obstruction (28/30 for upper common bile duct obstruction vs. 115/117 for obstruction at the lower end of common bile duct).Biliary drainage by nasobiliary drain and drainage by stent are equally safe and effective treatments for patients with severe cholangitis.
Clinical Utility as a Criterion for Revising Psychiatric Diagnoses
Authors: Michael B. First, Harold Alan Pincus, John B. Levine, Janet B.W. Williams, Bedirhan Ustun, Roger Peele
Journal: American Journal of Psychiatry (2004)

OBJECTIVE: Changes in DSM-IV were guided by empirical data that mostly focused on improving diagnostic validity and reliability. Although many changes were made explicitly to improve clinical utility, no formal effort was made to empirically determine actual improvements in clinical utility. The authors propose that future revisions of DSM empirically demonstrate improvement in clinical utility to clarify whether the advantages of changing the diagnostic criteria outweigh potential negative consequences. METHOD: The authors provide a formal definition of clinical utility and then suggest that the merits of a proposed change to DSM be evaluated by considering 1) its impact on the use of the diagnostic system, 2) whether it enhances clinical decision making, and 3) whether it improves clinical outcome. RESULTS: Evaluating a change based on its impact on use considers both user acceptability and accuracy in application of the diagnostic criteria. User acceptability can be measured by surveying users’ reactions, assessing user acceptability in a field trial setting, and measuring the effects on ease of use. Assessment of the correct application of diagnostic criteria entails comparing the clinician’s diagnostic assessment to expert diagnostic assessment. Assessments of the impact on clinical decision making use methods developed for evaluating adherence to practice guidelines. Improvement in outcome entails measuring reduction in symptom severity or improvement in functioning or in documenting the prevention of a future negative outcome. CONCLUSIONS: Empirical methods should be applied to the assessment of changes that purport to improve clinical utility in future revisions of DSM.
Global environmental change and health: impacts, inequalities, and the health sector
Authors: A J McMichael, S Friel, A Nyong, C Corvalan
Journal: BMJ (2008)

Human pressures on the environment are damaging the world’s biophysical and ecological systems. <b>A J McMichael and colleagues</b> discuss the resulting unequal effects on health and set out strategies to help prevent and lessen the harm