tbuckley/cabot-search huggingface dataset:
The Causal Role of IL-4 and IL-13 in<i>Schistosoma mansoni</i>Pulmonary Hypertension
Authors: Rahul Kumar, Claudia Mickael, Jacob Chabon, Liya Gebreab, Alleluiah Rutebemberwa, Alexandra Rodriguez Garcia, Daniel E. Koyanagi, Linda Sanders, Aneta Gandjeva, Mark T. Kearns, Lea Barthel, William J. Janssen, Thais Mauad, Angela Bandeira, Eric Schmidt, Rubin M. Tuder, Brian B. Graham
Journal: American Journal of Respiratory and Critical Care Medicine (2015)

The etiology of schistosomiasis-associated pulmonary arterial hypertension (PAH), a major cause of PAH worldwide, is poorly understood. Schistosoma mansoni exposure results in prototypical type-2 inflammation. Furthermore, transforming growth factor (TGF)-β signaling is required for experimental pulmonary hypertension (PH) caused by Schistosoma exposure. We hypothesized type-2 inflammation driven by IL-4 and IL-13 is necessary for Schistosoma-induced TGF-β-dependent vascular remodeling. Wild-type, IL-4(-/-), IL-13(-/-), and IL-4(-/-)IL-13(-/-) mice (C57BL6/J background) were intraperitoneally sensitized and intravenously challenged with S. mansoni eggs to induce experimental PH. Right ventricular catheterization was then performed, followed by quantitative analysis of the lung tissue. Lung tissue from patients with schistosomiasis-associated and connective tissue disease-associated PAH was also systematically analyzed. Mice with experimental Schistosoma-induced PH had evidence of increased IL-4 and IL-13 signaling. IL-4(-/-)IL-13(-/-) mice, but not single knockout IL-4(-/-) or IL-13(-/-) mice, were protected from Schistosoma-induced PH, with decreased right ventricular pressures, pulmonary vascular remodeling, and right ventricular hypertrophy. IL-4(-/-)IL-13(-/-) mice had less pulmonary vascular phospho-signal transducer and activator of transcription 6 (STAT6) and phospho-Smad2/3 activity, potentially caused by decreased TGF-β activation by macrophages. In vivo treatment with a STAT6 inhibitor and IL-4(-/-)IL-13(-/-) bone marrow transplantation also protected against Schistosoma-PH. Lung tissue from patients with schistosomiasis-associated and connective tissue disease-associated PAH had evidence of type-2 inflammation. Combined IL-4 and IL-13 deficiency is required for protection against TGF-β-induced pulmonary vascular disease after Schistosoma exposure, and targeted inhibition of this pathway is a potential novel therapeutic approach for patients with schistosomiasis-associated PAH.
Tumor-induced myeloid deviation: when myeloid-derived suppressor cells meet tumor-associated macrophages
Authors: Stefano Ugel, Francesco De Sanctis, Susanna Mandruzzato, Vincenzo Bronte
Journal: Journal of Clinical Investigation (2015)

The generation of an inflammatory environment is favorable and often decisive for the growth of both primary tumors and metastases. Tumor cells either express membrane molecules or release tumor-derived soluble factors able to alter myelopoiesis. Tumor-reprogrammed myeloid cells not only create a tolerogenic environment by blocking T cell functions and proliferation, but also directly drive tumor growth by promoting cancer stemness, angiogenesis, stroma deposition, epithelial-to-mesenchymal transition, and metastasis formation. In this Review, we discuss the interplay between immunosuppressive and protumoral myeloid cells and detail their immune-regulatory mechanisms, the molecular pathways involved in their differentiation, as well as their potential role as prognostic and diagnostic biomarkers and prospective targets for innovative approaches to treat tumor-bearing hosts.
Inflammatory IL-15 is required for optimal memory T cell responses
Authors: Martin J. Richer, Lecia L. Pewe, Lisa S. Hancox, Stacey M. Hartwig, Steven M. Varga, John T. Harty
Journal: Journal of Clinical Investigation (2015)

Due to their ability to rapidly proliferate and produce effector cytokines, memory CD8+ T cells increase protection following reexposure to a pathogen. However, low inflammatory immunizations do not provide memory CD8+ T cells with a proliferation advantage over naive CD8+ T cells, suggesting that cell-extrinsic factors enhance memory CD8+ T cell proliferation in vivo. Herein, we demonstrate that inflammatory signals are critical for the rapid proliferation of memory CD8+ T cells following infection. Using murine models of viral infection and antigen exposure, we found that type I IFN–driven expression of IL-15 in response to viral infection prepares memory CD8+ T cells for rapid division independently of antigen reexposure by transiently inducing cell-cycle progression via a pathway dependent on mTOR complex-1 (mTORC1). Moreover, exposure to IL-15 allowed more rapid division of memory CD8+ T cells following antigen encounter and enhanced their protective capacity against viral infection. Together, these data reveal that inflammatory IL-15 promotes optimal responses by memory CD8+ T cells.
Abstract 2359: Clinical Relevance Of Clopidogrel-hyporesponse To Subacute Stent Thrombosis
Authors: Thomas Wetzel, Martin Schulz, Norbert Schulze-Waltrup, Ralf Dedner, Joachim Weber-Albers, Dietmar Schmitz, Maritta Marks, Hubertus Heuer
Journal: Circulation (2007)

Background: It could be shown in various investigations that a reduced response to clopidogrel (Clo) after PCI and stent placement is associated with a significantly worse cardiovascular outcome. At the moment no generally accepted normal values for clopidogrel-response exist. Methods: The clopidogrel-response was investigated in 2847 patients (mean age 63,5 +/− 10 years, 67% male, 33% female) undergoing PCI with stent placement in a prospective clinical study over 34 months (elective PCI by chronic stable angina: n=1907 (67%) and acute PCI by acute coronary syndrome (STEMI, NSTEMI): n=940 (33%). The platelet aggregation was analysed conventionelly using an aggregometer 6 –24 hours after application of 600 mg clopidogrel (loading dose) by adding 20 μmol/L adenosine diphosphate (ADP) to citrate plasma (Aggregometer PAP 4 MOELAB, Hilden, Germany). Results: In a follow-up period of 30 days after the intervention a subacute stent thrombosis occured in n=51 pts (1,8%). In n=46 (90%) of these patients the ADP-induced platelet final aggregation after Clo (post-treated) was &gt;30% compared with the baseline of each patient without Clo (pre-treated). This corresponds to a platelet inhibition &lt;70%. Taking this value as “cutoff value” results in a responder rate of 68,7% (n=1958) and a hyporesponder rate of 31,2% (n=889) of the entirety of patients. 5,2% (n=46) of the hyporesponders developed a subacute stent thrombosis. Conclusions: Clopidogrel (Clo) hyporesponders have a significantly increased risk of developing a subacute stent thrombosis after coronary stent placement. 90% of these endangered patients are identified with a cutoff value of platelet inhibition &lt;70% respectively final aggregation &gt; 30% showing the importance of periinterventional evaluation of the Clo-response status of each patient. If these patients would profit from an intensified antiplatelet strategy (for example increased doses of Clo) should be investigated in further studies.
Human Cancer Mortality in Relation to Poultry Population, by County, in 10 Southeastern States
Authors: William A. Priester, Thomas J. Mason
Journal: JNCI Journal of the National Cancer Institute (1974)

The possible relationship between human cancer deaths and exposure to poultry was studied in 1019 U.S. counties for 1950–69. Deaths from uterine cervical and ovarian cancers and from multiple myeloma were excessive in high poultry population areas; the significance for the latter 2 cancers disappeared when data from the high poultry population areas were compared with data from the total United States. The excess of uterine cervical cancer was probably due to previously defined social determinants rather than to exposure to poultry. The study did not detect any excess risk of lymphomas, Hodgkin's disease, and leukemia in people occupationally exposed to poultry.
Book: Work Stress: The Making of a Modern Epidemic
Authors: M. Fitzpatrick
Journal: BMJ (2002)

David Wainwright, Michael Calnan Open University Press, £17.99, pp 240 ISBN 0 335 20707 3 Rating: ![Graphic][1]</img>![Graphic][2]</img>![Graphic][3]</img>![Graphic][4]</img> A general practitioner interviewed by the authors of this book confesses: “I think they [GPs] are a very over-complaining lot. And I made a decision some weeks ago to not read Pulse , GP or Medeconomics . Every week [they] go on about all the hours that GPs put in, how stressed they are. They complain all the time, so I think, why read them? They make you feel unhappy, so the only magazine that … [1]: /embed/inline-graphic-1.gif [2]: /embed/inline-graphic-2.gif [3]: /embed/inline-graphic-3.gif [4]: /embed/inline-graphic-4.gif
Prospective study of liver dysfunction in pregnancy in Southwest Wales
Authors: C L Ch'ng
Journal: Gut (2002)

<b>Background:</b> Liver dysfunction in pregnancy has serious consequences. Its frequency and characteristics have not been systematically documented in Britain. We have prospectively determined incidence, causes, and outcome of liver dysfunction in pregnancy in an obstetric unit in Southwest Wales, UK. <b>Methods:</b> A central laboratory identified all abnormal liver tests (bilirubin &gt;25 μmol/l, aspartate transaminase &gt;40 U/l, or γ glutamyl transpeptidase &gt;35 U/l) from patients in antenatal clinics and wards of an obstetric unit serving a population of 250 000. Patients with abnormal liver tests were assessed and followed through after pregnancy. Medical advice was provided to obstetric teams. <b>Findings:</b> There were 4377 deliveries during the 15 month study. A total of 142 patients had abnormal liver tests. There were 206 contributing diagnoses, the great majority being pregnancy specific. Among the most important were pre-eclampsia (68), HELLP (haemolysis, elevated liver enzymes, low platelets) syndrome (30), obstetric cholestasis (23), hyperemesis gravidarum (11), acute fatty liver of pregnancy (five), and hepatic infarct (one). Sepsis, postoperative factors, and placental pathology (51) were not uncommonly responsible but incidental or pre-existing hepatobiliary disease was infrequent (17). Sixty five patients were delivered early by induction or caesarean section because of liver dysfunction. Despite substantial liver related morbidity, there were no maternal deaths and only two intrauterine deaths. <b>Conclusions:</b> Liver dysfunction was seen in 3% of deliveries during a 15 month prospective study and was usually directly related to pregnancy with spontaneous recovery in the puerperium. Incidence of the most serious conditions, acute fatty liver of pregnancy and HELLP syndrome, was much greater than previously reported. Profound effects on maternal and infant health were observed but close medical and obstetric collaboration ensured low mortality.
Second hand smoke (SHS) exposure in asthmatic children is associated with social disadvantage and atopy
Authors: Giuliana Ferrante, Velia Malizia, Maria Tornatore, Roberta Antona, Laura Montalbano, Giuseppe Liotta, Giovanni Corsello, Stefania La Grutta
Journal: European Respiratory Journal (2013)

The evidence of a relationship between second hand smoke (SHS) exposure and atopy is inadequate. Smoke habit prevalence is higher in lower parental educational levels. The aim of this study was to investigate the relationship between SHS and atopy in asthmatic children focusing on socioeconomic status (SES). We studied 62 consecutive outpatient asthmatic children with different levels of asthma (GINA guidelines). Medical history was taken in standardized way to determine prevalence of SHS exposure and maternal smoking during pregnancy. Information about the highest level of parental education was collected as a proxy of SES level. All patients underwent skin prick test (SPT) and spirometry according to international guidelines. Statistical analyses through SPSS 19.0 were performed. 26 (41,9%) SHS exposed (SHSe) and 36 (58,1%) SHS non exposed (SHSne) asthmatic children were analyzed, aged 10.46±2.6 and 10.63±2.2 years, respectively. Exposure to maternal smoke in pregnancy was found only in SHSe (p 0.006). With regard to SHSne, SHSe showed lower percentage of exclusive breastfeeding (4 months) (34.6% vs 63.9%, p 0.02) and frequency of regular sport (46.2% vs 63.9%, p 0.17), as well as higher Body Mass Index (BMI) (21.9±5.70 vs 18.85±3.76, p 0.01), percentage of the lowest level of parental education (34.6% vs 13.9%, p 0.17) and percentage of at least one positive SPT, mainly indoor allergens (92.9% vs 73.7%, p 0.05). No differences were found in pulmonary function tests (PFTs) and level of asthma severity. In conclusion, exposure to SHS in asthmatic children is associated with disadvantaged SES level and atopy.
Characteristics of Gross Virus-Induced Leukemia Cell Clones. II. Oncornavirus Production 2
Authors: M. Marra, D. T. Imagawa
Journal: JNCI Journal of the National Cancer Institute (1976)

Oncornavirus production differed quantitatively among four Gross virus-induced murine leukemia clones. To determine the proportion of cells in each clone that were producing virus particles, the cells were stained by indirect immunofluorescence with antiserum to Gross antigen. All four clones had the same percentage of cells positive for the presence of Gross antigens irrespective of their ability to produce virus particles. A direct correlation was observed between the amount of RNA tumor virus attached to the plasma membrane and agglutination by concanavalin A. The leukemia strain that produced the most virus also had the greatest degree of agglutination. Oncornavirus production was indirectly related to oncogenicity of the cells in vivo: The clones that produced the most virus were the least malignant. The interaction of the host and virus-producing cells was monitored during animal passage, and virus production decreased during animal passage whereas transplantability increased.
Impact of medical education program on HCPs and patient understanding of COPD (joint working with GSK)
Authors: Mukesh Singh, Duncan Short, Joan Manzie, Alison Trundle, Pauline Scott
Journal: European Respiratory Journal (2014)

Background/Aims : Medical education is key to managing COPD. We sought to evaluate the impact of educational intervention on attitudes and understanding of disease and disease management in healthcare professionals (HCPs) and patients in primary care.   Methods : To improve quality of COPD clinical review, we implemented a range of educational interventions (lectures, direct mentoring and on-line learning) for HCPs within 25 primary care practices. Quality of disease understanding and COPD review was measured via validated patient and HCP experience questionnaires using a 10-point rating scale.   Results : Improvements in disease awareness and clinical review were reported by HCPs (n=20) and patients (n=111). For HCPs, education improved knowledge across 6 key areas with a 2.52 increase on a 10-point scale (4.23 vs. 6.75). 100% of HCPs reported improved confidence, knowledge and enthusiasm for COPD management. Patient disease knowledge increased following education with increased scores of ≥8 (74% vs 55%). 94% patients reported satisfaction with the quality of their clinical review.  Fig1:Change in patient understanding of different aspects of COPD (shown in % increase/decrease).   Conclusions : Focused medical education can improve HCP knowledge and attitudes to COPD management. This positively impacts upon HCP and patient disease understanding and satisfaction in COPD management in the primary care setting.
Unusual Presentations of Germ Cell Tumors
Authors: Sandeep T. Laroia, Debra A. Schell, Robert Koch, Anil Potti
Journal: Journal of Clinical Oncology (2001)

Article Tools DIAGNOSIS IN ONCOLOGY Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.2001.19.3.915 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 11157046 Unusual Presentations of Germ Cell Tumors Case 3. Nonseminomatous Extragonadal Germ Cell TumorPresenting with Pulmonary Emboli Sandeep T. LaroiaxSandeep T. LaroiaSearch for articles by this author , Debra A. SchellxDebra A. SchellSearch for articles by this author , Robert KochxRobert KochSearch for articles by this author , Anil PottixAnil PottiSearch for articles by this author Show More University of North Dakota School of Medicine and Health Sciences, Roger Maris Cancer Center, Meritcare Medical Center, and Veterans Affairs Medical Center, Fargo, ND https://doi.org/10.1200/JCO.2001.19.3.915 First Page Full Text PDF Figures and Tables © 2001 by American Society of Clinical Oncology
Brief Communication: Tumor Detection and Nuclear Magnetic Resonance
Authors: W. Bovée, P. Huisman, J. Smidt
Journal: JNCI Journal of the National Cancer Institute (1974)

Nuclear magnetic proton spin-lattice relaxation times (T1) were measured as a function of the water content of several normal and malignant rat tissues. The differences in T1 could be explained by differences in the water content of the tissues.
Long-term follow-up of patients with low-grade malignant lymphomas treated with doxorubicin-based chemotherapy or chemoimmunotherapy.
Authors: B W Dana, S Dahlberg, B N Nathwani, E Chase, C Coltman, T P Miller, R I Fisher
Journal: Journal of Clinical Oncology (1993)

PURPOSE We reviewed survival data of patients with low-grade lymphoma entered on Southwest Oncology Group (SWOG) lymphoma trials in 1972 to 1983 to determine the utility of doxorubicin-containing therapy (cyclophosphamide, doxorubicin, vincristine, and prednisone [CHOP]) in such patients. PATIENTS AND METHODS We identified all patients with low-grade lymphoma, no prior therapy, and stage III or IV disease who were treated with full-dose CHOP induction therapy on any arm of SWOG studies 7204, 7426, or 7713. Survival data for this group of patients were correlated with pretreatment prognostic factors, including histology, patient age, sex, symptom status, performance status, bone marrow or extranodal involvement, and the number of disease sites. The effect of maintenance treatment was also assessed. RESULTS Four hundred fifteen patients met criteria for inclusion in the study group. With median follow-up periods of 12.8 years (maximum, 19.8 years), the median survival duration was 6.9 years. Survival was significantly shorter in patients with follicular mixed or small lymphocytic histology, age greater than 40 years, male sex, B-symptom status, and SWOG performance status greater than 1. Multivariate regression analysis showed histology, age, and sex to be independent predictors of survival. There was no definite survival plateau of cured patients in any subgroup, although the survival curve for follicular mixed histology patients showed long-term survival of approximately 25%. Maintenance therapy did not prolong survival. CONCLUSION Doxorubicin-containing treatment did not prolong the overall median survival of low-grade lymphoma patients compared with results with less-aggressive programs.
Developing hospital admission criteria for electronic pneumonia decision support
Authors: Barbara Jones, Jason Jones, Al Jephson, Naresh Kumar, Ben Briggs, Caroline Vines, Todd Allen, Nathan Dean
Journal: European Respiratory Journal (2012)

RATIONALE:  Severity assessment tools that use objective data available in the electronic medical record to predict mortality include CURB-65, eCURB (an electronic version of CURB-65 using continuous variables), and A-DROP. We developed an electronic decision support tool for the emergency department that recommends admission for patients with 1) eCURB 30-day mortality estimate ≥ 5% 2) ≥3 severe community acquired pneumonia criteria (2007 IDSA/ATS), or 3) PaO2:FiO2 ratio ≥280. Our aim was to compare the tool9s admission rule to the mortality predictors.  METHODS:  We identified pneumonia patients by ICD-9 code plus radiograph in 7 emergency departments Dec 1, 2009-Dec 1, 2010. We extracted initial clinical features, triage information and mortality from the electronic medical record; physician review identified multilobar infiltrates from radiograph reports. Simple agreement with hospital triage (outpatient versus inpatient) and mortality were compared.  RESULTS:  57% of all patients were admitted (54% CAP and 76% HCAP) with a 30-day mortality of 5.5% (3.5% CAP, 17% HCAP). Table shows simple agreement with triage and mortality. While the actual admission rate was 57% with 13 outpatient deaths, the admission rule would have resulted in a 48% admission rate with 9 outpatient deaths.  CONCLUSION:  The tool9s admission rule agreed acceptably with observed triage and might lower admission rate with improved patient safety.
Pharmacokinetics of intraperitoneal docetaxel and S-1 in patients with gastric cancer with peritoneal carcinomatosis
Authors: H. Kamikozuru, K. Hayashi, H. Kuramochi, G. Nakajima, M. Yamamoto
Journal: Journal of Clinical Oncology (2009)

e15626 Background: One of the most causes of death from gastric cancer is peritoneal cartinomatosis. Intraperitoneal docetaxel infusion is expected to be a new strategy for a treatment of peritoneal carcinomatosis. The purpose of this study is to evaluate the plasma and peritoneal pharmacokinetic of intraperitoneal docetaxel infusion in combination with oral administration of S-1. Methods: Eight patients with peritoneal carcinomatosis of advanced gastric cancer were enrolled. Docetaxel was dissolved in an isotonic saline to a final 1 liter solution and administered in 2 hour via an implanted intraperitoneal catheter at dosage of 40mg/m 2 . Five of eight patients were administered S-1 orally at dosage of 80mg/m 2 . Blood and peritoneal fluid were collected before administration, on completion of the docetaxel infusion(hour 0) and at hours 1,2,4,6,12,24,48,and 72 after completion of the infusion of the docetaxel. Plasma and peritoneal fluid concentrations of docetaxel and 5FU were evaluated. Results: The mean peak peritoneal and plasma concentrations of docetaxel were 18.6×10 3 ng/ml (at hour 0) and 45 ng/ml (at hour 0 to 2), respectively. The peritoneal concentrations of docetaxel were remained even after 24 and 72 hours (24 hours: 1150ng/ml, 72 hours: 74ng/ml). In seven out of eight patients, plasma concentrations of docetaxel were disappeared after 24 hours, but in only one patient with severe ascites, concentration of plasma docetaxel at hour 24 could be obtained (20 ng/ml). The mean peritoneal and plasma areas under the curves (AUC) of docetaxel were 141×10 3 ng/ml×hr and 480 ng/ml×hr, respectively. The mean peritoneal concentrations of 5FU kept over 60% of plasma concentrations (plasma: 164.3ng/ml, peritoneal: 105ng/ml). Conclusions: Intaperitoneal docetaxel kept relatively high concentrations even after 72hours. 5FU concentrations were well transfered in peritoneal fluid from plasma via oral S-1 administration. Intraperitoneal docetaxel in combination with S-1 orally may be a useful regimen to the patients with carcinomatosis of advanced gastric cancer. No significant financial relationships to disclose.