tbuckley/cabot-search huggingface dataset:
SLE immune complexes upregulate the expression of slamf7 (cd319) on plasmacytoid dendritic cells
Authors: Niklas Hagberg, Jakob Theorell, Gunnar V Alm, Maija-Leena Eloranta, Yenan Bryceson, Lars Rönnblom
Journal: Annals of the Rheumatic Diseases (2012)

<h3>Background and objectives</h3> Patients with SLE have an activated type I interferon (IFN)-system due to an ongoing IFNα production by plasmacytoid dendritic cells (pDCs) stimulated by nucleic acid-containing immune complexes (ICs). The IFNα production is promoted by NK cells via MIP-1β, and LFA-1-mediated cell-cell contact. Because genome-wide linkage studies in SLE have shown a strong association with the 1q23-region, which harbors the genes for the signaling lymphocyte activation molecules (SLAMs), the authors investigated whether any of the SLAM family members were involved in the pDC-NK cell cross-talk. <h3>Materials and methods</h3> PBMCs and purified pDCs or NK cells from healthy donors were stimulated with medium or IC consisting of purified SLE-IgG and U1snRNP particles (SLE-IC). The mRNA-expression of the SLAM genes was determined in cell cultures of pDCs or NK cells. Surface expression of SLAMF1-7 on pDCs and NK cells in PBMC cultures were assessed by flow cytometry. Intracellular staining of IFNα was correlated to SLAM expression. The expression of SLAMF7 on pDCs and NK cells was compared between healthy donors and patients with SLE (n=9). <h3>Results</h3> The most prominent change in SLAM mRNA-expression following SLE-IC-stimulation was seen for <i>SLAMF7</i> on NK cells (2.1-fold increase). In PBMCs stimulated with SLE-IC, the median fluorescence intensity (MFI) for SLAMF7 increased on pDCs and CD56<sup>dim</sup> NK cells (2.7- and 2.0-fold, respectively). In purified SLE-IC-stimulated pDC- or NK cell-cultures, SLAMF7-expression was only increased on CD56<sup>dim</sup> NK cells. Co-cultivation of pDCs and NK cells restored the up-regulation of SLAMF7 on pDCs. SLAMF7-expression was significantly higher on IFNα producing pDCs compared to IFNα negative pDCs (p=0.048; 5255±1302 vs 3046±1519 (MFI±SD)). The frequency of SLAMF7<sup>+</sup> CD56<sup>bright</sup> NK cells were higher in patients with SLE compared to controls (p=0.0497; 18.3%±9.8% vs 10.0%±6.4% (mean±SD)). No difference in SLAMF7-expression between patients and controls was detected on pDCs or CD56<sup>dim</sup> NK cells. <h3>Conclusions</h3> The authors have shown that the co-stimulatory molecule SLAMF7 is induced on pDCs and CD56<sup>dim</sup> NK cells by SLE-IC and that the upregulation on pDCs is dependent on NK cells. The IFNα producing pDCs were characterised by a higher expression of SLAMF7 and an increased frequency of SLAMF7<sup>+</sup> CD56<sup>bright</sup> NK cells were seen in patients with SLE. The functional consequence of the increased SLAMF7 expression for pDC-NK cell cross-talk is currently being investigated. Because SLAMF7 increases NK cell cytotoxicity and B cell proliferation, the observed SLE-IC-mediated upregulation of SLAMF7 may be of importance in the autoimmune disease process.
Health care in poor countries must be defended against privatisation, Oxfam says
Authors: P. Moszynski
Journal: BMJ (2009)

Extracellular heat shock proteins (HSP) can activate dendritic cells (DC) and monocytes/macrophages, and HSP derived from tumor cells have been regarded as potent adjuvant facilitating presentation of tumor Ags and induction of antitumor immunity. However, the roles and the underlying mechanisms of releasable HSP in the induction of antitumor immunity have not been fully elucidated. In this study, we report that heat stress can induce the release of various HSP from tumor cells, which, in turn, activate tumor cells to produce chemokines for chemoattraction of DC and T cells via TLR4 signaling pathway. In vivo, we find that the infiltration and function of DC and T cells within tumor after local hyperthermia are increased significantly. We also provide evidence that HSP70 proteins released by tumor cells and TLR4 expressed by tumor cells/DC are essential for the chemoattraction of DC/T cells and for the subsequent induction of tumor-specific antitumor immunity. Therefore, our study suggests that heat stress-induced releasable HSP70 proteins from tumor cells play important roles in the initiation of antitumor immunity by inducing tumor cell production of chemokines and by activating the chemoattracted DC via TLR4 pathway.
Substance P antagonist improves both obesity and asthma in a mouse model
Authors: R. Ramalho, J. Almeida, M. Beltrão, A. Pirraco, R. Costa, O. Sokhatska, L. Guardão, C. Palmares, J. T. Guimarães, L. Delgado, A. Moreira, R. Soares
Journal: Allergy (2012)

Abstract Background Evidence suggests a causal relationship between obesity and asthma; however, the underlying mechanisms remain unknown. Substance P ( SP ), involved in neurogenic inflammation by acting through its receptor NK 1‐R, seems to participate in obese–asthma phenotype in mice. Objectives To evaluate the effect of a selective substance P receptor antagonist on a mouse model of diet‐induced obesity and asthma. Methods Diet‐induced obese B alb/c mice were sensitized and challenged with ovalbumin ( OVA ) and treated with a selective NK 1‐ R antagonist or placebo. Serum glucose, insulin, IL ‐6, resistin, and OVA ‐specific IgE levels were quantified. A score for peribronchial inflammation in lung histology was used. Cells were counted in bronchoalveolar lavage fluid. Adipocyte sizes were measured. Results Ovalbumin‐obese mice treated with NK 1‐ R antagonist had lower weight ( P = 0.0002), reduced daily food intake ( P = 0.0021), reduced daily energy intake ( P = 0.0021), reduced surface adipocyte areas ( P &lt; 0.0001), lower serum glucose ( P = 0.04), lower serum insulin ( P = 0.03), lower serum IL ‐( P = 0.0022), lower serum resistin ( P = 0.0043), lower serum OVA ‐specific IgE ( P = 0.035), and lower peribronchial inflammation score ( P &lt; 0.0001) than nontreated OVA ‐obese mice. We observed an interaction between obesity, allergen sensitization, and treatment with NK 1‐ R antagonist for metabolic and systemic biomarkers, and for allergen sensitization and bronchial inflammation, showing a synergy between these variables. Conclusion &amp; Clinical Relevance In an experimental model of obesity and asthma in mice, NK 1‐R blockade improved metabolic and systemic biomarkers, as well as allergen sensitization and bronchial inflammation. These positive effects support a common pathway in the obese–asthma phenotype and highlight SP as a target with potential clinical interest in the obese–asthma epidemics.
Licensure, Competence, and Manpower Distribution
Authors: Arlene Goldblatt, Louis Wolf Goodman, Stephen S. Mick, Rosemary Stevens
Journal: New England Journal of Medicine (1975)

Medical statistics report United States medical graduates licensed at higher rates than foreign medical graduates. This difference is often interpreted to show greater medical competence of United States graduates. This study questions this interpretation by analyzing 1971 licensure rates for both groups who had been interns and residents in 1963. We found that factors unrelated to competence--namely, visa-citizenship status and state of examination--are associated with holding a license. Moreover, quality of medical education is not an accurate predictor of licensure. It follows that the use of licensure rates as measures of medical competence distorts understanding of the quality of medical care in the United States. More probably, the difficulties in obtaining medical licensure experienced by foreign graduates result from the use of such graduates to relieve specific medical-manpower shortages.
OCCUPATIONAL DERMATITIS FOLLOWING EXPOSURE TO INORGANIC SELENIUM COMPOUNDS
Authors: P. PRINGLE
Journal: British Journal of Dermatology (1942)

Journal Article OCCUPATIONAL DERMATITIS FOLLOWING EXPOSURE TO INORGANIC SELENIUM COMPOUNDS Get access P. PRINGLE, LL.B., M.R.C.S., L.R.C.P. P. PRINGLE, LL.B., M.R.C.S., L.R.C.P. Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology and Syphilis, Volume 54, Issue 2, 1 February 1942, Pages 54–58, https://doi.org/10.1111/j.1365-2133.1942.tb10611.x Published: 01 February 1942
A Simple Noninvasive Index Can Predict Both Significant Fibrosis and Cirrhosis in Patients With Chronic Hepatitis C
Authors: Chun-Tao Wai, Joel K. Greenson, Robert J. Fontana, John D. Kalbfleisch, Jorge A. Marrero, Hari S. Conjeevaram, Anna S.-F. Lok
Journal: Hepatology (2003)

Information on the stage of liver fibrosis is essential in managing chronic hepatitis C (CHC) patients. However, most models for predicting liver fibrosis are complicated and separate formulas are needed to predict significant fibrosis and cirrhosis. The aim of our study was to construct one simple model consisting of routine laboratory data to predict both significant fibrosis and cirrhosis among patients with CHC. Consecutive treatment–naive CHC patients who underwent liver biopsy over a 25–month period were divided into 2 sequential cohorts: training set (n = 192) and validation set (n = 78). The best model for predicting both significant fibrosis (Ishak score ≥ 3) and cirrhosis in the training set included platelets, aspartate aminotransferase (AST), and alkaline phosphatase with an area under ROC curves (AUC) of 0.82 and 0.92, respectively. A novel index, AST to platelet ratio index (APRI), was developed to amplify the opposing effects of liver fibrosis on AST and platelet count. The AUC of APRI for predicting significant fibrosis and cirrhosis were 0.80 and 0.89, respectively, in the training set. Using optimized cut–off values, significant fibrosis could be predicted accurately in 51% and cirrhosis in 81% of patients. The AUC of APRI for predicting significant fibrosis and cirrhosis in the validation set were 0.88 and 0.94, respectively. In conclusion, our study showed that a simple index using readily available laboratory results can identify CHC patients with significant fibrosis and cirrhosis with a high degree of accuracy. Application of this index may decrease the need for staging liver biopsy specimens among CHC patients.
The Evolving Role of Adjuvant Chemotherapy.
Authors: E. Winer
Journal: Cancer Research (2009)

Abstract Decision-making for the medical oncologist was once far simpler than it is today. Following the 2000 NIH Consensus Conference on the treatment of early stage breast, almost all women with tumors &amp;gt; 1cm or positive lymph nodes were offered a course of adjuvant chemotherapy. There were some choices to be made in terms of the specific adjuvant regimen, but the oncologist could rely upon the results of large, randomized trials and choose a regimen that had been shown to be beneficial. Indeed, some might argue that a medical oncologist in 2009 could take the same approach. But the breast cancer world has evolved substantially over the past 5-7 years, and such an approach would not take full advantage of our understanding of breast cancer in 2009. We now understand that there is a great degree of intrinsic heterogeneity across breast tumors, and that the benefits associated with adjuvant chemotherapy vary substantially by subtype of disease. At minimum, we should consider three groups of patients separately: 1) individuals with HER2 positive disease; 2) individuals with triple negative disease; and 3) individuals with ER+ and HER2 non-amplified, non-overexpressed disease, who represent the vast majority of the patients with breast cancer in the United States. For patients with HER2+ disease, trastuzumab-based therapy has become the standard of care for all but women who have very small (T1a) tumors in the setting of negative lymph. Even in those women, there are physicians who would recommend a course of adjuvant trastuzumab-based chemotherapy. The major question is what chemotherapy to use in combination with trastuzumab, and this is a matter of considerable debate. In addition, uncertainty exists surrounding the optimal treatment for individuals who have indeterminate HER2 test results. For women with triple negative breast cancer, chemotherapy is also given to almost all patients apart from those with the very smallest tumors in the context of negative lymph nodes. For most patients, one of the standard anthracycline-taxane regimens remains the usual course of therapy. For patients with a low disease burden, first or second generation regimens such as AC, TC, or CMF are reasonable considerations. The most difficult questions arise concerning the use of chemotherapy in women with ER+ and HER2 normal disease. In this setting, the average benefit associated with chemotherapy is far less than in women with HER2+ or triple negative disease. Recent retrospective studies suggest that there are large groups of women who likely derive almost no or almost no benefit from chemotherapy. Increasingly, assays such as the Oncotype Dx Recurrence Score are used to aid clinical decisions, but even these complex genetic assays do not always provide a clear roadmap. Controversies and practical considerations surrounding the use of chemotherapy in women with ER+ and HER2 normal disease will be discussed in detail. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr CS1-2.
Retrobulbar, Intracranial, and Cutaneous Secondary Plasmacytomas in a Patient with Atypical Multiple Myeloma
Authors: Martin R. Weihrauch, Volker Diehl
Journal: New England Journal of Medicine (2001)

To the Editor: Drazner et al. (Aug.23 issue) 1 report the prognostic value of elevated jugular venous pressure and a third heart sound in patients with heart failure.Their review of data from the Studies of Left Ventricular Dysfunction trial 2 indicates that the presence of one or both of these findings predicts an increased risk of death or hospitalization over a 32-month period, with relative risks ranging from 1.17 to 1.47.These numbers may be helpful when one is considering an entire population of patients with heart failure, but when I as a clinician am examining an individual patient, I need diagnostic tests that will help me discern who has a better or poorer prognosis.When sensitivity and specificity are calculated and combined into likelihood ratios for the prediction of death from all causes or hospitalization for congestive heart failure, elevated jugular venous pressure has a positive likelihood ratio of only 1.67 and a negative likelihood ratio of 0.93.Similarly, for the prediction of death from all causes, a third heart sound has a positive likelihood ratio of only 1.27 and a negative likelihood ratio of 0.92, and the positive and negative likelihood ratios for the prediction of hospitalization for congestive heart failure are only 1.5 and 0.86.Thus, when I examine an individual patient, the presence or absence of elevated jugular venous pressure or a third heart sound actually does very little to help me predict the likelihood of death or rehospitalization during the next three years.These findings may indicate the severity of heart failure at a given time, but the numbers reported by Drazner et al. indicate that they are not helpful for predicting long-term outcome.
Characteristics of nonsmoking women exposed to spouses who smoke: epidemiologic study on environment and health in women from four Italian areas.
Authors: F Forastiere, S Mallone, E Lo Presti, S Baldacci, F Pistelli, M Simoni, A Scalera, M Pedreschi, R Pistelli, G Corbo, E Rapiti, N Agabiti, S Farchi, S Basso, L Chiaffi, G Matteelli, F Di Pede, L Carrozzi, G Viegi
Journal: Environmental Health Perspectives (2000)

The aim of this study was to evaluate whether risk factors associated with cardiovascular or respiratory diseases and lung cancer occur differently among nonsmoking women in Italy with and without exposure to environmental tobacco smoke (ETS) from husbands that smoke. We performed a cross-sectional study of 1,938 nonsmoking women in four areas of Italy. Data on respiratory and cardiovascular risk factors and on diet were collected using self-administered questionnaires. Medical examinations and blood tests were administered; urine cotinine levels were measured. Nonsmoking women ever exposed to husbands' smoking were compared with unexposed women for several factors: education, husband's education, household crowding, number of children, current or past occupation, exposure to toxic substances at work, parental diseases, self-perceived health status, physician-diagnosed hypertension, hypercholesterol, diabetes, osteoporosis, chronic respiratory diseases, blood pressure medications, lifestyle and preventive behaviors, dietary variables, systolic and diastolic blood pressure, body mass index, waist-hip ratio, triceps skin folds, plasma antioxidant (pro-) vitamins (- and ss-carotene, retinol, l-ascorbic acid, -tocopherol, lycopene), serum total and HDL cholesterol, and triglycerides. Women married to smokers were more likely to be less educated, to be married to a less educated husband, and to live in more crowded dwellings than women married to nonsmokers. Women married to smokers were significantly less likely to eat cooked [odds ratio (OR) = 0.72; 95% confidence interval (CI), 0.55-0.93] or fresh vegetables (OR = 0.63; CI, 0.49-0.82) more than once a day than women not exposed to ETS. Exposed women had significantly higher urinary cotinine than unexposed subjects (difference: 2.94 ng/mg creatinine). All the other variables were not more prevalent among exposed compared to unexposed subjects. The results regarding demographic factors are easily explained by the social class distribution of smoking in Italy. A lower intake of vegetables among exposed women in our study is consistent with the available literature. Overall, our results do not support previous claims of more frequent risk factors for cardiovascular and pulmonary diseases among ETS-exposed subjects. In Italy, as elsewhere in Europe and North America, women who have never smoked but are married to smokers are likely to be of lower social class than those married to never-smokers. However, once socioeconomic differences are considered, the possibility of confounding in studies on the health effects of ETS is minimal.
Families With High Serum Enzyme Levels
Authors: Nils Tryding
Journal: JAMA (1974)

<h3>To the Editor.—</h3> Elevated heart enzyme levels in apparent absence of myocardial infarction was recently discussed by P. F. Chestnut and J. S. LaDue (227:808, 1974). We want to draw attention to the possibility of an inherited enzyme increase. Determination of serum diamine oxidase (DAO) (EC 1.4.3.6) activity is used as an index of fetoplacental integrity and trophoblastic tumor activity.<sup>1</sup>The serum DAO in a normal population is 4±2 (mean±SD) milliunits/liter for adult men and nonpregnant women.<sup>2</sup>During pregnancy, it is increased about 500 times. Serum DAO is reported to be increased in medullary carcinoma of the thyroid and after heparin administration. The serum enzyme activity in seemingly healthy, nonpregnant individuals might also deviate sharply from the normal. <h3>Report of a Case.—</h3> A 30-year-old, formerly healthy woman was delivered of a hydatidiform male in the fourth month of pregnancy. Repeated determination of serum DAO showed abnormally high values
US strengthens rights of insured patients
Authors: F. Charatan
Journal: BMJ (2000)

The Clinton administration has issued new rules giving Americans in private, employer based health plans the right to obtain faster decisions on their healthcare claims and appeals.

The new rules will take effect in January 2002. They follow the failure of Congress to pass a bill of rights that would have given patients the right to sue companies operating managed care plans.

Under the new rules, if a patient needs an insurer's approval …
Abstract 2218: Radiation-induced hypomethylation triggers urokinase plasminogen activator (uPA) transcription in meningioma cells
Authors: Kiran Kumar Velpula, Venkateswara Rao Gogineni, Arun Kumar Nalla, Dzung H. Dinh, Jasti S. Rao
Journal: Cancer Research (2012)

Abstract Our previous studies have shown the role of radiation-induced urokinase plasminogen activator (uPA) expression in meningioma tumor progression. In the present study, we investigated whether modulation of DNA methylation profiles could regulate uPA expression. Radiation treatment induced hypomethylation in meningioma cells with a decrease in DNMT1 and MBD expression. However, oxidative damage by H2O2 or pretreatment of irradiated cells with NAC did not show any influence on these proteins, thereby indicating a radiation-specific change in the methylation patterns among meningioma cells. Further, we identified that hypomethylation is coupled to an increase in uPA expression in these cells. Azacytidine treatment induced a dose-dependent surge of uPA expression while pretreatment with Sodium butyrate inhibited the radiation-induced uPA expression; these results complement our prior findings. Methylation-specific PCR on bisulfite treated genomic DNA revealed a diminished methylation of uPA promoter in irradiated cells, which supports the role of epigenetics in uPA gene regulation. Transfection with shRNA expressing plasmids targeting CpG islands of the uPA promoter showed a marked decline in uPA expression with subsequent decreases in invasion and proliferation of meningioma cells. Further, radiation treatment is coupled to the recruitment of SP1 transcription into the nuclear extracts, which was abrogated by shRNA treatment. Our experiments to study the signaling events demonstrated the activation of MEK-ERK in radiation treated cells while U0126 (MEK/ERK inhibitor) blocked hypomethylation, recruitment of SP1, and uPA expression. In agreement with our in vitro data, low DNMT1 levels and high uPA were found in intracranial tumors given radiation treatment as compared to untreated tumors. In conclusion, our data suggest radiation-mediated hypomethylation triggers uPA expression in meningioma cells. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2218. doi:1538-7445.AM2012-2218