tbuckley/cabot-search huggingface dataset:
The Combination of Ionizing Radiation and Peripheral Vaccination Produces Long-term Survival of Mice Bearing Established Invasive GL261 Gliomas
Authors: Elizabeth W. Newcomb, Sandra Demaria, Yevgeniy Lukyanov, Yongzhao Shao, Tona Schnee, Noriko Kawashima, Li Lan, J. Keith Dewyngaert, David Zagzag, William H. McBride, Silvia C. Formenti
Journal: Clinical Cancer Research (2006)

Abstract Purpose: High-grade glioma treatment includes ionizing radiation therapy. The high invasiveness of glioma cells precludes their eradication and is responsible for the dismal prognosis. Recently, we reported the down-regulation of MHC class I (MHC-I) products in invading tumor cells in human and mouse GL261 gliomas. Here, we tested the hypothesis that whole-brain radiotherapy (WBRT) up-regulates MHC-I expression on GL261 tumors and enhances the effectiveness of immunotherapy. Experimental Design: MHC-I molecule expression on GL261 cells was analyzed in vitro and in vivo by flow cytometry and immunohistochemistry, respectively. To test the response of established GL261 gliomas to treatment, mice with measurable (at CT imaging) brain tumors were randomly assigned to four groups receiving (a) no treatment, (b) WBRT in two fractions of 4 Gy, (c) vaccination with irradiated GL261 cells secreting granulocyte-macrophage colony-stimulating factor, or (d) WBRT and vaccination. Endpoints were tumor response and survival. Results: An ionizing radiation dose of 4 Gy maximally up-regulated MHC-I molecules on GL261 cells in vitro. In vivo, WBRT induced the expression of the β2-microglobulin light chain subunit of the MHC class I complex on glioma cells invading normal brain and increased CD4+ and CD8+ T cell infiltration. However, the survival advantage obtained with WBRT or vaccination alone was minimal. In contrast, WBRT in combination with vaccination increased long-term survival to 40% to 80%, compared with 0% to 10% in the other groups (P &amp;lt; 0.002). Surviving animals showed antitumor immunity by rejecting challenge tumors. Conclusion: Ionizing radiation can be successfully combined with peripheral vaccination for the treatment of established high-grade gliomas.
Oxygen modulates growth of human cells at physiologic partial pressures.
Authors: A K Balin, A J Fisher, D M Carter
Journal: The Journal of Experimental Medicine (1984)

We have examined the growth of human diploid fibroblasts (WI-38 and IMR90) as a function of initial seeding density and oxygen tension. Cells at young and mid-passage levels were subcultivated in Dulbecco's modified Eagle's medium with 10% fetal bovine serum at 0.005, 0.01, 0.03, 0.1, 0.3, 1, and 2 X 10(4) cells/cm2. Flasks were equilibrated before and after seeding with 1 of 10 gas mixtures containing the desired oxygen tension (9-591 mm Hg) and placed in incubators that measure and maintain a preset oxygen tension. The partial pressure of oxygen (PO2) in media of all flasks was determined at harvest. Cells were shielded from light of wavelength less than 500 nm. Cell growth varied inversely with oxygen tension and seeding density. At 50 cells/cm2, growth was maximal at PO2 9 and 16 mm Hg. Growth was progressively inhibited as the oxygen tension was increased. The population doubling increase at 14 d was 8.6 for PO2 9 and 16 mm Hg, 5.8 for PO2 42 mm Hg, 3.8 for PO2 78 mm Hg, 3.8 for PO2 104 mm Hg, and 3 for PO2 138 mm Hg. As the seeding density was increased, the differences in growth at PO2 less than 140 mm Hg were progressively minimized, such that at seeding densities of 10(4) cells/cm2 there was little difference in the rate of exponential growth or the final saturation density of cells cultivated between PO2 9 and 96 mm Hg. At all seeding densities tested, growth was progressively inhibited when the PO2 was increased greater than 140 mm Hg. The seeding density dependence of oxygen's influence on cellular growth is not explained by oxygen consumption of higher density cultures. Oxygen acts directly on the cells and not by destroying some essential medium component. We have found that oxygen regulates the growth of human cells under pressures of oxygen physiologic to humans, and that oxygen toxicity contributes to the seeding density dependence of cellular growth commonly seen in cell culture.
Association of Cerebrovascular Events With Antidepressant Use: A Case-Crossover Study
Authors: Chi-Shin Wu, Sheng-Chang Wang, Yu-Cheng Cheng, Susan Shur-Fen Gau
Journal: American Journal of Psychiatry (2011)

The authors sought to assess the risk of cerebrovascular events associated with use of antidepressant medications.The authors conducted a case-crossover study of 24,214 patients with stroke enrolled in the National Health Insurance Research Database in Taiwan from 1998 to 2007. The authors compared the rates of antidepressant use during case and control time windows of 7, 14, and 28 days. Adjustments were made for time-dependent variables, such as health system utilization and proposed confounding medications. Stratified analyses were performed for valuing the interaction between the stroke risk of antidepressant use and age, sex, presence of mood disorder, stroke type, severity of chronic illness, and duration of antidepressant treatment. A conditional logistic regression model was used to determine the odds of antidepressant use during case time windows.The adjusted odds ratio of stroke risk with antidepressant exposure was 1.48 (95% confidence interval=1.37-1.59) using 14-day time windows. Stroke risk was negatively associated with the number of antidepressant prescriptions reported. Use of antidepressants with high inhibition of the serotonin transporter was associated with a greater risk of stroke than use of other types of antidepressants.These findings suggest that antidepressant use may be associated with an increased risk of stroke. However, the underlying mechanisms remain unclear.
Center Effects in Anemia Management of Dialysis Patients
Authors: Jeffrey C. Fink, Van Doren Hsu, Min Zhan, Lori D. Walker, C. Daniel Mullins, Charlotte Jones-Burton, Patricia Langenberg, Stephen L. Seliger
Journal: Journal of the American Society of Nephrology (2007)

This study set out to determine whether there is a center effect on anemia management in hemodialysis patients. The US Renal Data System and Medicare standard analysis files were analyzed. Between-center variation and within-facility correlations in hematocrit values were examined in two separate data sets (years 2000 and 2001) and compared with simulated samples that were composed of random values that assumed no center effect. Mixed-effect models were used to adjust for multiple factors and quantify the within-facility correlation in hematocrit values. Expected hematocrit values were compared in patients who underwent dialysis at poor and superior performing facilities with fixed characteristics including epoetin alpha dosing. There was a wider center variation in hematocrit for the actual versus simulated data and a coefficient of variation of 4.1% for the former versus 1.7% for the latter, in both years. The within-facility correlation for hematocrit was 0.053 (95% confidence interval 0.050 to 0.056; P < 0.001) in 2000 with similar values in 2001 but no within-facility correlation in the simulated data. The impact of these findings was demonstrated with a difference in expected hematocrit for a patient who was treated with fixed-dosage epoetin alpha in the poorest versus best performing units (mean difference in expected hematocrit 3.06; 95% confidence interval 3.03 to 3.09; P < 0.001). Key attributes of a center effect on anemia management in hemodialysis have been identified. The presence of a center effect suggests that there are facility-specific processes that influence performance in dialysis anemia management and are independent of commonly titrated inputs, such as dosing of erythropoietic agents.
Genome-Wide High-Density SNP Linkage Search for Glioma Susceptibility Loci: Results from the Gliogene Consortium
Authors: Sanjay Shete, Ching C. Lau, Richard S. Houlston, Elizabeth B. Claus, Jill Barnholtz-Sloan, Rose Lai, Dora Il'yasova, Joellen Schildkraut, Siegal Sadetzki, Christoffer Johansen, Jonine L. Bernstein, Sara H. Olson, Robert B. Jenkins, Ping Yang, Nicholas A. Vick, Margaret Wrensch, Faith G. Davis, Bridget J. McCarthy, Eastwood Hon-chiu Leung, Caleb Davis, Rita Cheng, Fay J. Hosking, Georgina N. Armstrong, Yanhong Liu, Robert K. Yu, Roger Henriksson, Beatrice S. Melin, Melissa L. Bondy
Journal: Cancer Research (2011)

Abstract Gliomas, which generally have a poor prognosis, are the most common primary malignant brain tumors in adults. Recent genome-wide association studies have shown that inherited susceptibility plays a role in the development of glioma. Although first-degree relatives of patients exhibit a two-fold increased risk of glioma, the search for susceptibility loci in familial forms of the disease has been challenging because the disease is relatively rare, fatal, and heterogeneous, making it difficult to collect sufficient biosamples from families for statistical power. To address this challenge, the Genetic Epidemiology of Glioma International Consortium (Gliogene) was formed to collect DNA samples from families with two or more cases of histologically confirmed glioma. In this study, we present results obtained from 46 U.S. families in which multipoint linkage analyses were undertaken using nonparametric (model-free) methods. After removal of high linkage disequilibrium single-nucleotide polymorphism, we obtained a maximum nonparametric linkage score (NPL) of 3.39 (P = 0.0005) at 17q12-21.32 and the Z-score of 4.20 (P = 0.000007). To replicate our findings, we genotyped 29 independent U.S. families and obtained a maximum NPL score of 1.26 (P = 0.008) and the Z-score of 1.47 (P = 0.035). Accounting for the genetic heterogeneity using the ordered subset analysis approach, the combined analyses of 75 families resulted in a maximum NPL score of 3.81 (P = 0.00001). The genomic regions we have implicated in this study may offer novel insights into glioma susceptibility, focusing future work to identify genes that cause familial glioma. Cancer Res; 71(24); 7568–75. ©2011 AACR.
B cell helper factors. I. Requirement for both interleukin 2 and another 40,000 mol wt factor.
Authors: H J Leibson, P Marrack, J W Kappler
Journal: The Journal of Experimental Medicine (1981)

A helper factor(s) distinct from interleukin 2 (IL-2) was shown to be present in the concanavalin A-stimulated supernatant of normal mouse spleen cells (normal Con A Sn). Spleen cells thoroughly depleted of T cells required both IL-2 and this factor to produce antibody-secreting cells in response to sheep erythrocytes, although in the presence of IL-2 and a few T cells the requirement for the factor was less apparent. The factor had an apparent approximately 40,000 mol wt. The factor was found in normal Con A Sn that had been depleted of IL-2 by absorption with IL-2-dependent T cells and was absent from Con A-stimulated supernatants of the IL-2-producing T cell hybridoma, FS6-14.13. These results indicate that multiple helper factors control the B cell response to antigen and that IL-2, in addition to its T cell growth promoting activity, plays a direct role in B cell responses.
Identification of protein antigens of group B streptococci, with special reference to the Ibc antigens.
Authors: G J Russell-Jones, E C Gotschlich
Journal: The Journal of Experimental Medicine (1984)

The protein antigens of prototypes of five types of group B streptococcal strains were extracted with HCl or Triton X-100, separated by sodium dodecyl sulfate polyacrylamide electrophoresis, transferred to nitrocellulose, and examined by immunochemical staining. The Ibc proteins are shown to consist of at least two distinct protein antigens and their breakdown products. One antigen, the "beta" antigen, exists primarily as a 130,000 mol wt protein that is also able to bind human IgA. The "alpha" antigen, which has no known function, appears as a number of proteins of various molecular weights from 20,000 to 120,000. Another set of antigens, the R protein antigens of type III strains, has been identified as a group of acid-labile proteins varying in molecular weight from 100,000 to 130,000. In addition, two previously undescribed antigens have been found that are common to all five group B types.
Prophylactic Anticoagulation in Nephrotic Syndrome
Authors: Richard J. Glassock
Journal: Journal of the American Society of Nephrology (2007)

It has long been recognized that nephrotic syndrome is associated with an increased risk for thromboembolic complications, including deep venous thrombosis, renal vein thrombosis, and pulmonary embolism. This risk varies with the nature of the underlying disease and seems to be greatest for membranous nephropathy. Other factors, including the level of serum albumin, previous thromboembolic episodes, and a genetically determined predisposition to thrombosis, may also be involved. Prevention of thromboembolic events with oral anticoagulants in nephrotic syndrome requires a careful case-by-case analysis of the risks for thromboembolic events balanced by the risks for anticoagulant induced bleeding. Markov-based decision analysis using literature-based assumptions regarding these risks has suggested that prophylactic anticoagulants may be indicated in certain circumstances. Such decisions need to take into account the nature of the underlying disease, the severity of the nephrotic syndrome (as assessed by serum albumin concentration), preexisting thrombophilic states, and the overall likelihood of serious bleeding events consequent to oral anticoagulation (as assessed by the international normalized ratio for prothrombin time). The optimal duration of prophylactic anticoagulation is unknown but very likely extends to the duration of the nephrotic state per se.
Syphilis in China: results of a national surveillance programme
Authors: Zhi-Qiang Chen, Guo-Cheng Zhang, Xiang-Dong Gong, Charles Lin, Xing Gao, Guo-Jun Liang, Xiao-Li Yue, Xiang-Sheng Chen, Myron S Cohen
Journal: The Lancet (2007)

After a massive syphilis epidemic in the first half of the 20th century, China was able to eliminate this infection for 20 years (1960-80). However, substantial changes in Chinese society have been followed by a resurgent epidemic of sexually transmitted diseases. Sporadic reports have provided clues to the magnitude of the spread of syphilis, but a national surveillance effort is needed to provide data for planning and intervention.We collected and assessed case report data from China's national sexually transmitted disease surveillance system and sentinel site network.In 1993, the reported total rate of cases of syphilis in China was 0.2 cases per 100,000, whereas primary and secondary syphilis alone represented 5.7 cases per 100,000 persons in 2005. The rate of congenital syphilis increased greatly with an average yearly rise of 71.9%, from 0.01 cases per 100,000 livebirths in 1991 to 19.68 cases per 100 000 livebirths in 2005.The results suggest that a range of unique biological and social forces are driving the spread of syphilis in China. A national campaign for detection and treatment of syphilis, and a credible prevention strategy, are urgently needed.
Suppression of calcific fibrous-fatty plaque formation in rabbits by agents not affecting elevated serum cholesterol levels. The effect of thiophene compounds.
Authors: C T Chan, H Wells, D M Kramsch
Journal: Circulation Research (1978)

We tested the suppressive effect of antihypercalcemic-hyperphosphatemic agents on atherogenesis. We studied five groups of rabbits for 8 weeks, one control group and four groups on a fibrogenic atherogenic diet. One group received the atherogenic diet alone, and the remaining three atherogenic groups were treated simultaneously with 2-thiophenecarboxylic acid (ThCA), 5-methyl-2-thiophenecarboxylic acid (5-CH3-ThCA), and 5-bromo-2-thiophenecarboxaldehyde (5-Br-ThCA). Rabbits receiving the atherogenic diet alone developed: (1) elevations of serum cholesterol, calcium, and phosphorus; (2) massive fibrous-fatty aortic plaques with excessive accumulation of aortic collagen, elastin, and lipids; (3) marked deposition of calcium and phosphorus in both aortic tissue and elastin; and (4) severe lipid infiltration of the liver. Treatment with all three drugs normalized the elevated serum calcium but not the cholesterol levels, and effectively inhibited all aspects of the atherosclerotic process as determined morphologically and biochemically. The order of effectiveness was: 5-CH3-ThCa greater than 5-Br-ThCA greater than ThCA. No bone resorption occurred in the treated groups. The normalizing effects of the thiophene compounds on serum phosphorus levels were not significant at the dosages used.
Intestinal intraepithelial lymphocytes: the plot thickens.
Authors: P Poussier, M Julius
Journal: The Journal of Experimental Medicine (1994)

Over the last few years, the characterization of T lyraphocytes within the intestinal epithelium (ilEL) has revealed phenotypic and functional heterogeneity that rivals only that observed within the thymus. Of note in this context is that thymic and intestinal epithdia share the same embryologic origin in that they are both derived from endoderm. Several lines of evidence have led to the conclusion that T lymphopoiesis occurs within the intestinal epithelium. This observation raises several fundamental questions some of which have been recently addressed in this and other journals. Specifically, are all iIEL of gut origin, and do the phenotypic and functional peculiarities of the various ilEL subsets reveal novel pathways of T cell development? Origin of ilEL. The phenotypic and functional heterogeneity of iIEL has been recently reviewed (1, 2). Briefly, as in the thymus, all ilEL are T cells expressing either TCKy/g or TCR-odfl, although the proportions of these two lineages vary among species. In the mouse, a high proportion of iIEL express TCR-~//8, the majority of which coexpress
Innate immunity and HCV
Authors: Markus H. Heim
Journal: Journal of Hepatology (2012)

Hepatitis C virus (HCV) infections become chronic in the majority of infected individuals, and chronic hepatitis C (CHC) can lead to cirrhosis and hepatocellular carcinoma. The innate immune system is central to host-virus interactions during the entire natural course of the disease. The HCV NS3/4A protease efficiently cleaves and inactivates two important signaling molecules in the sensory pathways that react to HCV pathogen-associated molecular patterns (PAMPs) to induce interferons (IFNs), i.e., mitochondrial antiviral signaling protein (MAVS) and Toll-IL-1 receptor domain-containing adaptor inducing IFN-β (TRIF). Despite this viral escape mechanism, the innate immune system strongly reacts to HCV within the first days after infection. The sensory pathways, the type(s) of IFNs involved and the cellular source of IFNs are largely unknown. After 4-8weeks, HCV specific T cells are recruited to the liver. IFN-γ-stimulated genes get strongly expressed in the liver. In about 30% of patients, the virus is eliminated during the acute phase of the infection by T cell-mediated antiviral mechanisms. In the remaining 70% of patients, HCV persists for decades. During this phase, T cell-derived IFN-γ cannot be detected any more in liver biopsies. Instead, in about half of the patients, hundreds of type I or III IFN-stimulated genes become again strongly expressed. However, this innate immune reaction is ineffective against HCV. Moreover, patients with constitutive IFN-stimulated gene (ISG) expression have a poor response to treatment with pegylated IFN-α (PegIFN-α) and ribavirin. The viral escape mechanisms that protect HCV from IFN-mediated innate immune reactions are not entirely understood, but might involve blockade of ISG protein translation at the ribosome, localization of viral replication to cells with refractory IFN signal transduction pathways or to cell compartments that are not accessible to antiviral IFN-stimulated effector systems. Recently, genetic variations near the IL28B (IFN-λ3) were found to be strongly associated with spontaneous clearance of HCV and response to treatment with PegIFN-α and ribavirin. The finding supports a central role of the innate immune response in host-viral interactions. The signaling pathways that link genetic variants of IL28B with immune answers to HCV remain to be elucidated. The present review article attempts to summarize current knowledge of some central aspects of the interactions of HCV with the innate immune system.
Characteristics and outcome of 27 elbow periprosthetic joint infections: results from a 14-year cohort study of 358 elbow prostheses
Authors: Y. Achermann, M. Vogt, C. Spormann, C. Kolling, C. Remschmidt, J. Wüst, B. Simmen, A. Trampuz
Journal: Clinical Microbiology and Infection (2010)
Chemoprevention Strategies Utilizing Combinations of Inhibitors of Carcinogenesis
Authors: W. F. Malone, G. J. Kelloff
Journal: JNCI Journal of the National Cancer Institute (1989)

s of 316 journal articles were among the selections in the ONCOLOGY OVERVIEW concerning the Diagnosis and Treatment of the Acquired Immunodeficiency Syndrome. Two leading researchers in the field selected the most significant abstracts from more than 3,000 sources, and contributed an editorial commentary on the status and future of AIDS. Every year about 15 important cancer topics receive similar attention in separate OVERVIEWS. The 150 to 500 abstracts in each issue are conveniently divided by category and indexed by author and keyword. Turn to ONCOLOGY OVERVIEWS for the best available resource on cancer research findings involving a single topic ONCOLOGY OVERVIEWS are one of NCI's well-rounded family of computerized cancer databases, scientific journals and publications. They're all part of the mission to reduce cancer deaths by one half by the year 2000.
A review of the British Thoracic Society scientific meeting 1-3 December 2010
Authors: C. Church, H. K. Bayes, A. J. Fisher
Journal: Thorax (2011)

This review presents the inaugural report of the British Thoracic Society Winter Scientific Meeting held from 1(st)-3(rd) December 2010. Although a wide spectrum of respiratory research was presented at the meeting the content of the review focuses specifically on three key themes of inflammation and lung injury, airways disease and respiratory infection. Advances in both clinical and translational respiratory research presented within the major symposia and spoken sessions related to these themes are summarised.
Determination of Cardiac Output by the Fick Method, Thermodilution, and Acetylene Rebreathing in Pulmonary Hypertension
Authors: MARIUS M. HOEPER, ROMAN MAIER, JOERN TONGERS, JOST NIEDERMEYER, JENS M. HOHLFELD, MICHAEL HAMM, HELMUT FABEL
Journal: American Journal of Respiratory and Critical Care Medicine (1999)

Assessment of cardiac output is an important part of the management of patients with pulmonary hypertension. The accuracy of the thermodilution technique in patients with low cardiac output or severe tricuspid regurgitation has been questioned. To address this issue, we simultaneously compared 105 cardiac output measurements by the Fick method and thermodilution in 35 patients with pulmonary hypertension. Moreover, we evaluated the acetylene rebreathing technique, a noninvasive method of determining cardiac output. The mean difference +/- 95% limit of agreement between thermodilution and the Fick method was +0.01 +/- 1.1 L/min. The mean difference +/- 95% limit of agreement between acetylene rebreathing and the Fick method was -0.23 +/- 1.14 L/min. Neither the mean agreement nor the 95% limits of agreement of both thermodilution and acetylene rebreathing with the Fick method were affected by the presence of low cardiac output or severe tricuspid regurgitation. We conclude that thermodilution and acetylene rebreathing are useful tools for assessing cardiac output in patients with pulmonary hypertension, even in the presence of low cardiac output or severe tricuspid regurgitation.