tbuckley/cabot-search huggingface dataset:
Tumor Immunotherapy Targeting Fibroblast Activation Protein, a Product Expressed in Tumor-Associated Fibroblasts
Authors: Jaewoo Lee, Martin Fassnacht, Smita Nair, David Boczkowski, Eli Gilboa
Journal: Cancer Research (2005)

Murine studies have shown that immunologic targeting of the tumor vasculature, a key element of the tumor stroma, can lead to protective immunity in the absence of significant pathology. In the current study, we expand the scope of stroma-targeted immunotherapy to antigens expressed in tumor-associated fibroblasts, the predominant component of the stroma in most types of cancer. Mice were immunized against fibroblast activation protein (FAP), a product up-regulated in tumor-associated fibroblasts, using dendritic cells transfected with FAP mRNA. Using melanoma, carcinoma, and lymphoma models, we show that tumor growth was inhibited in tumor-bearing mice vaccinated against FAP and that the magnitude of the antitumor response was comparable to that of vaccination against tumor cell-expressed antigens. Both s.c. implanted tumors and lung metastases were susceptible to anti-FAP immunotherapy. The antitumor response could be further enhanced by augmenting the CD4+ T-cell arm of the anti-FAP immune response, achieved by using a lysosomal targeting sequence to redirect the translated FAP product into the class II presentation pathway, or by covaccination against FAP and a tumor cell-expressed antigen, tyrosinase-related protein 2. No morbidity or mortality was associated with anti-FAP vaccination except for a small delay in wound healing. The study suggests that FAP, a product which is preferentially expressed in tumor-associated fibroblasts, could function as a tumor rejection antigen in a broad range of cancers.
Glycol-split nonanticoagulant heparins are inhibitors of hepcidin expression in vitro and in vivo
Authors: Maura Poli, Michela Asperti, Annamaria Naggi, Natascia Campostrini, Domenico Girelli, Michela Corbella, Marina Benzi, Celine Besson-Fournier, Helene Coppin, Federica Maccarinelli, Dario Finazzi, Paolo Arosio
Journal: Blood (2014)
Fluticasone propionate induced alterations to lung function and the immunopathology of asthma over time
Authors: J. L Faul, C. T Leonard, C. M Burke, V. J Tormey, L. W Poulter
Journal: Thorax (1998)

<h3>BACKGROUND</h3> Inhaled corticosteroids are the most widely used treatment for asthma, a disease characterised by both functional and immunopathological abnormalities. This study investigated the relative effects of inhaled corticosteroids on these two features of asthma over time. <h3>METHODS</h3> A randomised, double blind, placebo controlled, parallel group study with inhaled fluticasone propionate, (FP 2 mg daily) was conducted in 27 patients with asthma. Following baseline analysis, the study tested the effects of short term (two weeks) and longer term (eight weeks) treatment. At each time point (0, 2, and 8 weeks) lung function tests were performed and endobronchial biopsy specimens obtained to determine the distribution and number of lymphocyte, macrophage and eosinophil subsets using immunohistological analysis. Twenty three patients completed the study, 11 on FP and 12 placebo. <h3>RESULTS</h3> FEV<sub>1</sub>, ΔFEV<sub>1</sub>, FEF<sub>25–75</sub>, and FEV<sub>1</sub>/FVC all improved after two weeks of FP treatment. This improvement was maintained but not increased after eight weeks. PC<sub>20</sub>FEV<sub>1</sub> showed a trend to increase but was not significantly improved at eight weeks. No significant changes were seen in the placebo group. The numbers of T cells, macrophages, and eosinophils in the bronchial wall were reduced by two weeks of treatment with FP but were unaltered by placebo. The improvement offered by FP continued over the eight week period. Reductions in CD4:CD8 ratio and numbers of activated (EG2+) eosinophils were only significant after eight weeks of treatment. <h3>CONCLUSIONS</h3> These results reveal that FP influences both functional and immunopathological parameters of asthma. Temporal relationships suggest that these are parallel but not necessarily interrelated effects. While short term treatment is effective in "normalising" the functional abnormalities in asthma, the impact of FP on bronchial inflammation appears to be progressive, taking up to eight weeks and more.
Parental Cardiovascular Disease as a Risk Factor for Cardiovascular Disease in Middle-aged Adults
Authors: Donald M. Lloyd-Jones, Byung-Ho Nam, Ralph B. D'Agostino, Sr, Daniel Levy, Joanne M. Murabito, Thomas J. Wang, Peter W. F. Wilson, Christopher J. O'Donnell
Journal: JAMA (2004)

Whether parental cardiovascular disease confers increased risk independent of other risk factors remains controversial. Prior studies relied on offspring report, without complete validation of parental events.To determine whether parental cardiovascular disease predicts offspring events independent of traditional risk factors, using a prospective design for both parents and offspring, and uniform criteria to validate events.Inception cohort study.Framingham Heart Study, a US population-based epidemiologic cohort begun in 1948 with the offspring cohort established in 1971.All Framingham Offspring Study participants (aged > or =30 years) who were free of cardiovascular disease and both parents in the original Framingham cohort.We examined the association of parental cardiovascular disease with 8-year risk of offspring cardiovascular disease, using pooled logistic regression.Among 2302 men and women (mean age, 44 years), 164 men and 79 women had cardiovascular events during follow-up. Compared with participants with no parental cardiovascular disease, those with at least 1 parent with premature cardiovascular disease (onset age <55 years in father, <65 years in mother) had greater risk for events, with age-adjusted odds ratios of 2.6 (95% confidence interval [CI], 1.7-4.1) for men and 2.3 (95% CI, 1.3-4.3) for women. Multivariable adjustment resulted in odds ratios of 2.0 (95% CI, 1.2-3.1) for men and 1.7 (95% CI, 0.9-3.1) for women. Nonpremature parental cardiovascular disease and parental coronary disease were weaker predictors. Addition of parental information aided in discriminating event rates, notably among offspring with intermediate levels of cholesterol and blood pressure, as well as intermediate predicted multivariable risk.Using validated events, we found that parental cardiovascular disease independently predicted future offspring events in middle-aged adults. Addition of parental information may help clinicians and patients with primary prevention of cardiovascular disease, when treatment decisions may be difficult in patients at intermediate risk based on levels of single or multiple risk factors. These data also support further research into genetic determinants of cardiovascular risk.
TREM-1 Expression in Tumor-associated Macrophages and Clinical Outcome in Lung Cancer
Authors: Chao-Chi Ho, Wei-Yu Liao, Cheng-Yi Wang, Yin-Hsiu Lu, Hsin-Yi Huang, Hsuan-Yu Chen, Wing-Kai Chan, Huei-Wen Chen, Pan-Chyr Yang
Journal: American Journal of Respiratory and Critical Care Medicine (2007)

Rationale: Triggering receptor expressed on myeloid cells (TREM)-1 is a molecule crucial for the triggering and amplification of inflammatory response and a new biomarker for sepsis. Tumor-associated macrophages and inflammation in the tumor microenvironment are also involved in cancer progression.Objectives: To determine the role of TREM-1 in tumor-associated macrophage and cancer progression.Methods: Using ELISA and Western blot, we measured soluble TREM-1 levels in 65 pleural effusions of various etiologies. We evaluated TREM-1–positive cells by immunocytochemistry in malignant pleural effusion and in lung tumor versus adjacent normal tissue in surgical specimens from 68 patients with non–small cell lung cancer (NSCLC). TREM-1 expression was correlated with patient survival. TREM-1 expression in primary isolated peripheral blood macrophages cocultured with lung cancer cell lines was determined by quantitative real-time reverse transcriptase–polymerase chain reaction.Measurements and Main Results: Soluble TREM-1 and tumor-associated macrophage TREM-1 expression was increased in malignant pleural effusions in patients with NSCLC. Lung cancer cells could directly up-regulate TREM-1 and proinflammatory cytokine (tumor necrosis factor-α, IL-1β) expression in primary isolated peripheral blood macrophages in coculture experiments. Increased TREM-1–positive tumor-associated macrophages in tumor tissue of patients with NSCLC were associated with reduced disease-free (P = 0.011) and overall survival (P = 0.004). Multivariate Cox regression analysis indicated that TREM-1 was an independent predictor of patient survival (hazard ratio, 2.72; 95% confidence interval, 1.33–5.57; P = 0.006).Conclusions: Cancer cells can directly up-regulate TREM-1 expression in patients' macrophages. TREM-1 expression in tumor-associated macrophages is associated with cancer recurrence and poor survival of patients with NSCLC. TREM-1 and the inflammatory response may play an important role in cancer progression.
Testing for Human Immunodeficiency Virus
Authors: Joseph A. Stankaitis, John P. Bigos
Journal: Annals of Internal Medicine (1986)

Letters and Corrections1 December 1986Testing for Human Immunodeficiency VirusJOSEPH A. STANKAITIS, M.D., M.P.H., JOHN P. BIGOS, M.D., M.P.H.JOSEPH A. STANKAITIS, M.D., M.P.H.Search for more papers by this author, JOHN P. BIGOS, M.D., M.P.H.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-105-6-967_2 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: Dr. Goedert's editorial on the testing for human immunodeficiency virus (HIV) (1) admirably points out the importance of disease prevalence for screening programs. He notes that in low-prevalence groups, the positive predictive value for the enzyme-linked immunosorbent assay (ELISA) may be as low as 2% for specimens from donors with no risk factors for HIV. This 2% means that out of 100 samples that test positive from this group, only 2 will be truly positive. Thus, it makes greater sense to target screening to high-risk or high-prevalence groups, rather than to general populations.One might argue that...References1. GOEDERT J. Testing for human immunodeficiency virus [Editorial]. Ann Intern Med. 1986;105:609-10. LinkGoogle Scholar2. LUNDBERG G. The age of AIDS: a great time for defensive living. JAMA. 1985;253:3440-1. CrossrefMedlineGoogle Scholar3. REDFIELDWRIGHTTRAMONT RDE. The Walter Reed staging classification for HTLV III/LAV infection. N Engl J Med. 1986;314:131-2. CrossrefMedlineGoogle Scholar4. DENTZERCOHNRAINECARROLQUADE SBGGV. Can you pass the job test? Newsweek. 1986; May 5:46-53. Google Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAuthors: JOSEPH A. STANKAITIS, M.D., M.P.H.; JOHN P. BIGOS, M.D., M.P.H. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 December 1986Volume 105, Issue 6Page: 967-967KeywordsEnzyme linked immunosorbent assayHIVHIV-1Medical risk factorsPopulation statisticsPositive predictive value ePublished: 1 December 2008 Issue Published: 1 December 1986 PDF downloadLoading ...
Relation of regional function, perfusion, and metabolism in patients with advanced coronary artery disease undergoing surgical revascularization.
Authors: J vom Dahl, D T Eitzman, Z R al-Aouar, H L Kanter, R J Hicks, G M Deeb, M M Kirsh, M Schwaiger
Journal: Circulation (1994)

BACKGROUND Imaging of myocardial glucose metabolism using [18F]fluorodeoxyglucose (FDG) with positron emission tomography (PET) has been proposed for identification of tissue viability in patients with advanced coronary artery disease. This study was designed to evaluate the predictive value of flow and metabolic imaging for functional recovery after revascularization in myocardial segments of varying degrees of dysfunction. METHODS AND RESULTS Thirty-seven patients (mean age, 59 +/- 11 years) with coronary artery disease and impaired left ventricular function (ejection fraction, 34 +/- 10%) were studied with PET using FDG and [13N]ammonia before surgical coronary revascularization (3 +/- 1 grafts per patient). Tissue was scintigraphically characterized as normal, nonviable (concordant reduction of perfusion and FDG uptake), viable without discordance of perfusion and metabolism (mildly reduced perfusion and metabolism), or ischemically compromised (mismatch of reduced perfusion and maintained FDG uptake). Functional outcome was assessed by serial radionuclide ventriculography before and at 13 +/- 13 weeks (median interval of 8 weeks) after coronary revascularization. Preoperatively impaired regional wall motion improved significantly in ischemically compromised (mismatch) revascularized segments but not in nonviable myocardium or in viable myocardium without discordance of perfusion and metabolism. The negative predictive value of PET for functional recovery was 86%, whereas the positive predictive value in revascularized regions ranged from 48% to 86% depending on severity of baseline wall motion abnormalities. CONCLUSIONS PET identifies metabolically active tissue, which benefits from revascularization. Although the negative predictive value of PET for recovery was high, functional improvement of viable but ischemically compromised tissue was less frequent than previously reported. The predictive value of PET was highest in left ventricular segments with severe dysfunction and a mismatch or reduced perfusion but preserved metabolism. Integration of PET, angiographic, and functional data is necessary for the optimal selection of patients with advanced coronary artery disease and impaired left ventricular function for revascularization.
Intact apoptosis signaling in myeloid leukemia cells determines treatment outcome in childhood AML
Authors: Lüder H. Meyer, Manon Queudeville, Sarah M. Eckhoff, Ursula Creutzig, Dirk Reinhardt, Leonid Karawajew, Wolf-Dieter Ludwig, Karsten Stahnke, Klaus-Michael Debatin
Journal: Blood (2007)
Systematic review of tattoo-associated skin infection with rapidly growing mycobacteria and public health investigation of a cluster in Scotland, 2010
Authors: P D Conaglen, I F Laurenson, A Sergeant, S N Thorn, A Rayner, J Stevenson
Journal: Eurosurveillance (2013)

Sporadic cases and outbreaks of tattoo-associated skin infection with rapidly growing mycobacteria have been reported although they often contain few details of public health investigations and have not previously been systematically collated. We present the details of the public health investigation of a cluster of cases, which occurred in Scotland in 2010. Investigation of the cluster involved case finding, environmental investigation of the tattoo studio and pathological and microbiological investigation of possible cases and tattoo ink. Mycobacterium chelonae was isolated from one case and three probable cases were identified. M. chelonae was grown from an opened bottle of ink sourced from the studio these cases had attended. In addition, in order to identify all published cases, we conducted a systematic review of all reported cases of tattoo-associated skin infection with rapidly growing mycobacteria. A total of 25 reports were identified, describing 71 confirmed and 71 probable cases. Mycobacteria were isolated in 71 cases and M. chelonae was cultured from 48 of these. The most frequently postulated cause of infection was the dilution of black ink with tap water. Reports of tattoo-associated rapidly growing mycobacterial skin infection are increasing in frequency. Interested agencies must work with the tattoo industry to reduce the risk of contamination during tattoo ink manufacture, distribution and application.
A novel technique for partial stent-in-stent placement of three metal biliary stents using a short double-balloon enteroscope
Authors: Koichiro Tsutsumi, Hironari Kato, Hiroyuki Okada, Kazuhide Yamamoto
Journal: Endoscopy (2014)

The endoscopic partial stent-in-stent (PSIS) placement of self-expandable metal stents (SEMSs) is effective for the palliation of malignant hilar biliary strictures [1] [2] [3] [4] [5]. Despite its efficacy, however, PSIS placement is technically challenging, especially when placing second or subsequent stents. We report a novel technique for PSIS placement of three SEMSs using a short double-balloon enteroscope (DBE), which was used in a patient with a malignant hilar biliary stricture and surgically altered anatomy.
Utility of serum tumor markers, imaging, and biliary cytology for detecting cholangiocarcinoma in primary sclerosing cholangitis
Authors: Phunchai Charatcharoenwitthaya, Felicity B. Enders, Kevin C. Halling, Keith D. Lindor
Journal: Hepatology (2008)

There is limited information on test performance for detecting cholangiocarcinoma in primary sclerosing cholangitis (PSC), particularly when used sequentially. This study aimed to characterize diagnostic performance of serum carbohydrate antigen 19-9 (CA 19-9), ultrasonography, computed tomography, magnetic resonance imaging, cholangiography, and biliary cytologic techniques for detecting cholangiocarcinoma in PSC. All consecutive patients with PSC were screened and followed for development of cholangiocarcinoma from 2000 through 2006. Of 230 patients, 23 developed cytopathologically confirmed cholangiocarcinoma with an annual incidence of 1.2%. The optimal cutoff value for serum CA 19-9 was 20 U/mL, which yielded a sensitivity of 78%, specificity of 67%, positive predictive value (PPV) of 23%, and negative predictive value (NPV) of 96%. Serum CA 19-9 combined with either ultrasonography, computed tomography, or magnetic resonance imaging provided a sensitivity of 91%, 100%, and 96%, specificity of 62%, 38%, and 37%, PPV of 23%, 22%, and 24%, and NPV of 98%, 100%, and 98%, respectively, if at least one method was positive. Subsequent cholangiographic examinations in these patients increased specificity to 69% and PPV to 42% while maintaining sensitivity of 91% and NPV of 96%. Following this group, conventional cytology, aneuploidy detection by digital imaging analysis, and aneusomy detection by fluorescence in situ hybridization in brushing samples of biliary strictures had a sensitivity of 50%, 57%, and 86%, specificity of 97%, 94%, and 83%, PPV of 86%, 89%, and 80%, and NPV of 83%, 74%, and 88%, respectively, for detecting cholangiocarcinoma. Conclusion: Tumor serology combined with cross-sectional liver imaging may be useful as a screening strategy and cholangiography with cytologic examination is helpful for the diagnosis of cholangiocarcinoma in patients with PSC. (HEPATOLOGY 2008.)
Increased Incidence of Malformations—Chance or Change?
Authors: Gilbert W. Mellin, Michael Katzenstein
Journal: JAMA (1964)

Fetal Life Study data on 15,333 deliveries, prospectively followed from 1946 to 1962, show a fluctuation in incidence of meningomyelocele well within the range of chance. The use of quality control methods similar to those used in industry is suggested as a possibility for the monitoring of malformations in the future. In a surveillance system, factors of alertness, accuracy, and numbers must be considered. Evaluation of data and interpretation of the rare event require thorough investigation and caution.
VERY LONG-TERM (1 AND 2-YEAR) COMPARISON OF BIORESORBABLE VS. PERMANENT POLYMER LIMUS-ELUTING STENTS IN A PORCINE CORONARY ARTERY MODEL
Authors: Armando Tellez, Athanasios Peppas, Gerard Conditt, Geng-Hua Yi, Jennifer McGregor, Renu Virmani, Juan Granada, Greg Kaluza
Journal: Journal of the American College of Cardiology (2012)
P11 Cardio-respiratory fitness at work; the effects of public health guidance?
Authors: M. Naughton, J. Gaynor, L. Bradshaw, A. Curran, S. Till, D. Fishwick
Journal: Thorax (2010)

Physical activity is important to improve and maintain cardiorespiratory fitness. More recently, additional wider health benefits of physical exercise have been highlighted, including reduction in obesity and promoting mental wellbeing. Increased recognition of these benefits has led NICE to issue recent public health guidance in this area (PH13; promoting physical activity in the workplace). These recommendations aim to help employers and workplace health professionals prevent diseases associated with a lack of physical activity. We have audited the approach taken to physical activity at work taken by two large organisations, using PH13 to develop 23 appropriate gold standards (GS). For example, GS1 states that ‘There is an organisational policy to encourage and support employees to be more physically active’, GS5 that ‘There are organisational goals for physical activity in the workforce’ and GS10 that ‘There are policies to encourage employees to be physically active while travelling to work (eg, walking and cycling)’. 44 employees from a health provider (Health) and 63 employees from a public sector organisation (PSO) underwent a self-completed questionnaire enquiring about a broad range of workplace-based exercise issues, each question mapping to an a priori defined gold standard. Various clear differences emerged between organisations in attaining the GS, although compliance by both with certain of these was good. For example, GS7 stated ‘A multi-component programme is in place to encourage and support employees to exercise’. Overall, employees from Health and PSO were positive about the facilities to encourage exercise, the majority of employees being aware of various facilities in place including safe bike storage (PSO; 73.0%, Health 52.3%) and showers (PSO; 87.3%, Health; 40.9%). Compliance with other GS was poor. For example, GS9 required that there was employee knowledge of an ‘incentive schemes to encourage exercise’. Despite the presence of incentives to exercise at each site, only 14.3% of PSO employees (Health; 13.6%) were aware of financial incentives and 9.5% (Health; 9.1%) aware of non-financial incentives to exercise. Whilst exercise is an important contributor to health, further work is required to ensure that recent PH guidance aimed at improving exercise at work has maximal worker benefit.
Standard-dose versus high-dose conformal radiotherapy with concurrent and consolidation carboplatin plus paclitaxel with or without cetuximab for patients with stage IIIA or IIIB non-small-cell lung cancer (RTOG 0617): a randomised, two-by-two factorial phase 3 study
Authors: Jeffrey D Bradley, Rebecca Paulus, Ritsuko Komaki, Gregory Masters, George Blumenschein, Steven Schild, Jeffrey Bogart, Chen Hu, Kenneth Forster, Anthony Magliocco, Vivek Kavadi, Yolanda I Garces, Samir Narayan, Puneeth Iyengar, Cliff Robinson, Raymond B Wynn, Christopher Koprowski, Joanne Meng, Jonathan Beitler, Rakesh Gaur, Walter Curran, Hak Choy
Journal: The Lancet Oncology (2015)