tbuckley/cabot-search huggingface dataset:
TLR4 Engagement during TLR3-Induced Proinflammatory Signaling in Dendritic Cells Promotes IL-10–Mediated Suppression of Antitumor Immunity
Authors: Dusan Bogunovic, Olivier Manches, Emmanuelle Godefroy, Alice Yewdall, Anne Gallois, Andres M. Salazar, Isabelle Marie, David E. Levy, Nina Bhardwaj
Journal: Cancer Research (2011)

Abstract Toll-like receptor (TLR) agonists are promising adjuvants for immune therapy of cancer, but their potential efficacy as single or combinatorial agents has yet to be fully evaluated. Here, we report that among all TLR agonists tested, dendritic cells (DC) stimulated with the TLR3 agonist polyI:C displayed the strongest activity in stimulating proinflammatory responses and the production of melanoma antigen-specific CD8+ T cells. Simultaneous treatment with TLR7/8 agonists further improved these responses, but the inclusion of bacterial lipopolysaccharide (LPS), a TLR4 agonist, suppressed proinflammatory cytokine production. This inhibition was contingent upon rapid induction of the suppressive cytokine interleukin (IL)-10 by LPS, leading to dysregulated immune responses and it could be reversed by signal transducers and activators of transcription 3 knockdown, p38 blockade or antibodies to IL-10 and its receptor. Our findings show how certain TLR agonist combinations can enhance or limit DC responses associated with antitumor immunity, through their relative ability to induce IL-10 pathways that are immune suppressive. Cancer Res; 71(16); 5467–76. ©2011 AACR.
Transthoracic Incremental Monophasic Versus Biphasic Defibrillation by Emergency Responders (TIMBER)
Authors: Peter J. Kudenchuk, Leonard A. Cobb, Michael K. Copass, Michele Olsufka, Charles Maynard, Graham Nichol
Journal: Circulation (2006)

Although biphasic, as compared with monophasic, waveform defibrillation for cardiac arrest is increasing in use and popularity, whether it is truly a more lifesaving waveform is unproven.Consecutive adults with nontraumatic out-of-hospital ventricular fibrillation cardiac arrest were randomly allocated to defibrillation according to the waveform from automated external defibrillators administered by prehospital medical providers. The primary event of interest was admission alive to the hospital. Secondary events included return of rhythm and circulation, survival, and neurological outcome. Providers were blinded to automated defibrillator waveform. Of 168 randomized patients, 80 (48%) and 68 (40%) consistently received only monophasic or biphasic waveform shocks, respectively, throughout resuscitation. The prevalence of ventricular fibrillation, asystole, or organized rhythms at 5, 10, or 20 seconds after each shock did not differ significantly between treatment groups. The proportion of patients admitted alive to the hospital was relatively high: 73% in monophasic and 76% in biphasic treatment groups (P=0.58). Several favorable trends were consistently associated with receipt of biphasic waveform shock, none of which reached statistical significance. Notably, 27 of 80 monophasic shock recipients (34%), compared with 28 of 68 biphasic shock recipients (41%), survived (P=0.35). Neurological outcome was similar in both treatment groups (P=0.4). Earlier administration of shock did not significantly alter the performance of one waveform relative to the other, nor did shock waveform predict any clinical outcome after multivariate adjustment.No statistically significant differences in outcome could be ascribed to use of one waveform over another when out-of-hospital ventricular fibrillation was treated.
Acadesine reduces myocardial infarct size by an adenosine mediated mechanism
Authors: Z.-Q. Zhao, M. W Williams, H. Sato, D. A Hudspeth, D S. McGee, J. Vinten-Johansen, D. G. Van Wylen
Journal: Cardiovascular Research (1995)

The aim was to test the hypotheses that acadesine (1) augments endogenous interstitial fluid (ISF) adenosine during ischaemia, and (2) reduces infarct size by adenosine receptor mediated mechanisms.To test these hypotheses, the left coronary artery of anaesthetised rabbits (n = 33) was occluded for 30 min and reperfused for 120 min. Acadesine (1 mg.kg-1.min-1 for 5 min, then 0.2 mg.kg-1.min-1) was infused intravenously beginning 30 min before coronary occlusion and ending 30 min after reperfusion. The area at risk was comparable in all groups, averaging 34.7 (SEM 2.2%) of the left ventricle. In separate studies (n = 22), estimates of ISF adenosine and adenosine metabolites were obtained by cardiac microdialysis. Although dialysate adenosine levels increased significantly in the area at risk during ischaemia in the untreated group [from 0.044(0.008) to 0.339(0.146) microM], acadesine did not significantly augment dialysate adenosine levels before or during ischaemia [preischaemia = 0.094(0.032) microM; ischaemia = 0.542(0.262) microM]. In addition, there was no significant difference in dialysate adenosine concentrations during the first 10 min of reperfusion, after which adenosine levels returned to baseline levels. A 2.5-fold large dose failed to increase interstitial fluid adenosine. However, the adenosine receptor blocker 8-p-sulphophenyltheophylline (SPT) in the presence of acadesine increased ISF adenosine fourfold. Acadesine significantly (P < 0.05) reduced infarct size [n = 8, 19.7(2.9)% of risk area] compared with the untreated group [n = 8, 29.4(1.3)%]. This infarct size reduction with acadesine was antagonised by SPT given during ischaemia-reperfusion [n = 8, 46.2(3.0)%] or only during reperfusion [n = 9, 42.7(2.6)%.Acadesine reduces infarct size by an adenosine mediated mechanism, but this cardioprotective action is not associated with significantly augmented interstitial fluid adenosine levels.
The Insulin-like Growth Factor I Receptor/Insulin Receptor Tyrosine Kinase Inhibitor PQIP Exhibits Enhanced Antitumor Effects in Combination with Chemotherapy Against Colorectal Cancer Models
Authors: Sara A. Flanigan, Todd M. Pitts, S. Gail Eckhardt, John J. Tentler, Aik Choon Tan, Andrew Thorburn, Stephen Leong
Journal: Clinical Cancer Research (2010)

Abstract Purpose: There is growing evidence implicating the importance of the insulin-like growth factor (IGF) pathway in colorectal cancer based upon the results of population studies and preclinical experiments. However, the combination of an IGF-I receptor (IGF-IR) inhibitor with standard colorectal cancer chemotherapies has not yet been evaluated. In this study, we investigated the interaction between PQIP, the dual IGF-IR/insulin receptor tyrosine kinase inhibitor, and standard chemotherapies in colorectal cancer cell line models. Experimental Design: The antiproliferative effects of PQIP, as a single agent and in combination with 5-fluorouracil, oxaliplatin, or SN38, were analyzed against four colorectal cancer cell lines. Downstream effector proteins, apoptosis, and cell cycle were also assessed in the combination of PQIP and SN-38. Lastly, the efficacy of OSI-906 (a derivative of PQIP) combined with irinotecan was further tested using a human colorectal cancer xenograft model. Results: Treatment with the combination of PQIP and each of three chemotherapies resulted in an enhanced decrease in proliferation of all four colorectal cancer cell lines compared with single-agent treatment. This inhibition was not associated with a significant induction of apoptosis, but was accompanied by cell cycle arrest and changes in phosphorylation of Akt. Interestingly, antitumor activity between PQIP and SN-38 in vitro was also reflected in the human colorectal cancer xenograft model. Conclusions: Combination treatment with PQIP, the dual IGF-IR/insulin receptor tyrosine kinase inhibitor, and standard colorectal cancer chemotherapy resulted in enhanced antiproliferative effects against colorectal cancer cell line models, providing a scientific rationale for the testing of OSI-906 and standard colorectal cancer treatment regimens. Clin Cancer Res; 16(22); 5436–46. ©2010 AACR.
Depression, Immunity, and Survival in Patients With Hepatobiliary Carcinoma
Authors: Jennifer L. Steel, David A. Geller, T. Clark Gamblin, Marion C. Olek, Brian I. Carr
Journal: Journal of Clinical Oncology (2007)

The aims of the present study were to assess the prevalence of depressive symptoms at diagnosis, test the association between depressive symptoms and survival, and preliminarily test a mediational model of depression, immunity, and survival in patients with hepatobiliary carcinoma (HBC).One hundred one patients diagnosed with HBC were prospectively studied. Depressive symptoms were measured at diagnosis using the Center for Epidemiological Studies Depression Scale (CES-D). Sociodemographic and disease-specific data were gathered from the patients' charts. In a subsample of patients, stress; alcohol, tobacco, and drug use; sleep quality; physical activity; social support; natural killer (NK) cell number and cytotoxicity; and plasma levels of interleukin (IL) -4, IL-5, tumor necrosis factor alpha, and interferon gamma were measured. Survival was measured from date of diagnosis to death.At diagnosis, 37% of patients reported a CES-D score of > or = 16 (clinical range). Using Cox regression analysis, sociodemographic and disease-specific variables and CES-D score significantly predicted survival (Breslow chi2 = 32.4, P = .006). Only vascular invasion (P = .001) and CES-D score > or = 16 (P = .03) were significant predictors. In a subsample of 23 patients, patients who reported a CES-D score of > or = 16 were found to have significantly lower NK cell numbers than patients who reported a CES-D score of less than 16 (F1,21 = 9.39, P = .003). A robust trend was found in which NK cell number was associated with survival. A mediational model linking depressive symptoms and survival, with NK cell number as a mediator, was preliminarily supported.Secondary to the high prevalence of depressive symptoms and impact on survival, psychological and pharmacologic interventions should be designed and implemented in patients diagnosed with HBC.
A Case of Perforating Wound of the Abdomen: In which the Superior Mesenteric Vein was Wounded: Ligature of Vein: Lavage of Abdomen: Transfusion: Recovery
Authors: A. W. M. Robson
Journal: BMJ (1897)

PERFORATING WOOUND OF ABDOMEN.KA JO.A 77 cured, as she had informed me on several occasions.Naturally desirous of being certain how far the bromidism contributed to the result, I determined to test the question by excluding other conditions.
Upregulated expression of cardiac endothelin-1 participates in myocardial cell growth in Bio14.6 Syrian cardiomyopathic hamsters
Authors: Tsukasa Inada, Hisayoshi Fujiwara, Koji Hasegawa, Makoto Araki, Rikako Yamauchi-Kohno, Hideo Yabana, Takako Fujiwara, Masaru Tanaka, Shigetake Sasayama
Journal: Journal of the American College of Cardiology (1999)
Plasma Adiponectin Levels Are Associated With Coronary Lesion Complexity in Men With Coronary Artery Disease
Authors: Fumiyuki Otsuka, Seigo Sugiyama, Sunao Kojima, Hidetomo Maruyoshi, Tohru Funahashi, Kunihiko Matsui, Tomohiro Sakamoto, Michihiro Yoshimura, Kazuo Kimura, Satoshi Umemura, Hisao Ogawa
Journal: Journal of the American College of Cardiology (2006)
Decreased plasma levels of the endothelial protective sphingosine-1-phosphate are associated with dengue-induced plasma leakage
Authors: Meta Michels, Lukasz Japtok, Bachti Alisjahbana, Rudi Wisaksana, Uun Sumardi, Mita Puspita, Burkhard Kleuser, Quirijn de Mast, Andre J.A.M. van der Ven
Journal: Journal of Infection (2015)
Elevated NF-κB p50 complex formation and Bcl-3 expression in classical Hodgkin, anaplastic large-cell, and other peripheral T-cell lymphomas
Authors: Stephan Mathas, Korinna Jöhrens, Stefan Joos, Andreas Lietz, Franziska Hummel, Martin Janz, Franziska Jundt, Ioannis Anagnostopoulos, Kurt Bommert, Peter Lichter, Harald Stein, Claus Scheidereit, Bernd Dörken
Journal: Blood (2005)
Insulin and Cognitive Function in an Elderly Population: The Rotterdam Study
Authors: Ronald P Stolk, Monique M B Breteler, Alewijn Ott, Huibert A P Pols, Steven W J Lamberts, Dlederick E Grobbee, Albert Hofman
Journal: Diabetes Care (1997)

To examine the association between insulin and cognitive function in the population-based Rotterdam Study.Serum insulin was measured 2 h after an oral glucose load, while global cognitive function was assessed by the Mini Mental State Examination in 5,510 subjects, aged 55 years and over.An increase in postload insulin only in women was associated with a decrease in cognitive function (age-adjusted regression coefficient -0.10 per 50 mU/l insulin; 95% CI -0.16 to -0.04). The association between insulin resistance, assessed by the ratio of postload insulin over glucose, and cognitive function was not statistically significant. Further adjustment for the individual risk factors of serum glucose, BMI, HDL, systolic blood pressure, smoking, or use of estrogen did not change the results. The association was present in women with and without cardiovascular disease and present after excluding subjects with diabetes. Women with dementia, the extreme of cognitive dysfunction, had increased age-adjusted insulin levels (76.3 +/- 4.9 vs. 66.8 +/- 1.0 mU/l [means +/- SE], P = 0.06).The results of this study suggest that increased serum insulin may be associated with decreased cognitive function and dementia in women. These findings are more compatible with a direct effect of insulin on the brain than with an effect through an increase in cardiovascular risk factors.
Intrauterine Environment and Breast Cancer Risk in Women: A Population-Based Study
Authors: A. Ekbom, H.-O. Adami, C.-c. Hsieh, L. Lipworth, D. Trichopoulos
Journal: JNCI Journal of the National Cancer Institute (1997)

Background: The established risk factors for female breast cancer, including nulliparity, age at first birth, age at menarche, and age at menopause, do not adequately explain the occurrence pattern of this cancer. Therefore, additional factors need to be considered to advance our understanding of the causes of breast cancer. Evidence obtained from animals and humans indicates that the perinatal period may be particularly important. Our earlier studies, based on a subsample of the present investigation, suggested that factors thought to be positively associated with estrogen levels during pregnancy are positively associated with breast cancer risk. However, the associated confidence intervals (CIs) were generally wide, indicating considerable variability in the data. Purpose: We studied a large number of incident breast cancer case patients and evaluated several perinatal variables in relation to breast cancer risk. These variables included some not previously studied, such as gestational age and neonatal jaundice. We also investigated twin membership as a predictor variable and death from breast cancer, in addition to occurrence of breast cancer, as an alternative outcome variable. Methods: Birth records for all deliveries at five different hospitals in Sweden during the period from 1874 through 1961 were used to define a large cohort of women. Incident case patients with breast cancer in this cohort were ascertained through the National Cancer Registry or the Uppsala Regional Cancer Registry from 1958 through 1994. In a case-control study nested in the cohort, we abstracted data from birth records on 1068 women with incident breast cancer and on 2727 control subjects individually matched to the case patients on date of birth. We modeled the data through conditional logistic regression. All P values were derived from two-sided statistical tests. Results: We found a markedly reduced risk for breast cancer in women whose mothers had pregnancy toxemia (odds ratio [OR] = 0.41; 95% CI = 0.22–0.79) and an excess risk on women who had neonatal jaundice (OR = 2.16; 95% CI = 1.27–3.67) or who were born before 33 weeks of gestation (OR = 3.96; 95% CI = 1.45–10.81). Compared with the risk for breast cancer in the singleton, the risk for breast cancer in dizygotic twins was increased, although this increase was not statistically significant (OR = 1.72; 95% CI = 0.92–3.20). There was no evidence in these data for a statistically significant or substantial association of breast cancer risk with birth size indicators (i.e., weight and length at birth and placental weight). Conclusion and Implications: Because pregnancy toxemia is associated with low levels of estrogens and neonatal jaundice, severe prematurity, and dizygotic twins with high levels of estrogens, our findings suggest that estrogens and other hormonal factors, known to influence breast cancer risk in the adult, may also play a critical role during the intrauterine period.
Passive smoking and asthma death
Authors: G. Invernizzi, R. Boffi, A. Ruprecht, A. Lazzaro, L. M. Fabbri
Journal: European Respiratory Journal (2008)

To the Editors: 

In 1998 during a flight from Athens (Greece) to San Francisco (CA, USA), A.M. Hanson, an asthmatic doctor aged 52 yrs, died due to an asthmatic reaction to second-hand cigarette smoke. In 2004, the US Supreme Court ruled that Olympic Airways was to pay the widow of A.M. Hanson US$1.4 million. This …
Metabolic characterization of breast tumors with positron emission tomography using F-18 fluorodeoxyglucose.
Authors: N Avril, J Dose, F Jänicke, S Bense, S Ziegler, C Laubenbacher, W Römer, H Pache, M Herz, B Allgayer, W Nathrath, H Graeff, M Schwaiger
Journal: Journal of Clinical Oncology (1996)

To evaluate the diagnostic value of position emission tomographic (PET) imaging with F-18 fluorodeoxyglucose (FDG) in differentiating between benign and malignant breast tumors.Fifty-one patients, with suspicious breast lesions newly discovered either by physical examination or by mammography, underwent PET imaging before exploratory surgery. FDG-PET images of the breast were analyzed visually and quantitatively for objective assessment of regional tracer uptake.Primary breast cancer was identified visually with a sensitivity of 68% to 94% and a specificity of 84% to 97% depending on criteria used for image interpretation. Quantitative analysis of FDG uptake in tumors using standardized uptake values (SUV) showed a significant difference between benign (1.4 +/- 0.5) and malignant (3.3 +/- 1.8) breast tumors (P < .01). Receiver operating characteristic (ROC) curve analysis exhibited a sensitivity of 75% and a specificity of 100% at a threshold SUV value of 2.5. Sensitivity increased to 92% with a corresponding specificity of 97% when partial volume correction of FDG uptake was performed based on independent anatomic information.PET imaging allowed accurate differentiation between benign and malignant breast tumors providing a high specificity. Sensitivity for detection of small breast cancer ( < 1 cm) was limited due to partial volume effects. Quantitative image analysis combined with partial volume correction may be necessary to exploit fully the diagnostic accuracy. PET imaging may be helpful as a complimentary method in a subgroup of patients with indeterminate results of conventional breast imaging.
Atherosclerotic Renal Artery Stenosis
Authors: Stephen C. Textor
Journal: Journal of the American Society of Nephrology (2008)

Despite evidence of only moderate clinical benefit, application of renal endovascular stent procedures has increased at least four-fold in the past decade. Medicare is reviewing national coverage regarding reimbursement, questioning whether outcome data warrant many of these procedures. Several prospective, randomized trials are now in progress to compare outcomes with optimized medical therapy with and without stenting. Current imaging methods establish primarily the presence and severity of vascular occlusive disease. Optimal treatment for individual patients remains in flux and is reviewed here. Most important, nephrologists await development of tools to predict reliably when renal parenchymal injury is beyond recovery and/or when revascularization can produce meaningful salvage of kidney function.
Fresh Red Blood Cell Transfusion and Short-Term Pulmonary, Immunologic, and Coagulation Status
Authors: Daryl J. Kor, Rahul Kashyap, Richard B. Weiskopf, Gregory A. Wilson, Camille M. van Buskirk, Jeffrey L. Winters, Michael Malinchoc, Rolf D. Hubmayr, Ognjen Gajic
Journal: American Journal of Respiratory and Critical Care Medicine (2012)

Transfusion-related pulmonary complications are leading causes of morbidity and mortality attributed to transfusion. Observational studies suggest an important role for red blood cell (RBC) storage duration in these adverse outcomes.To evaluate the impact of RBC storage duration on short-term pulmonary function as well as immunologic and coagulation status in mechanically ventilated patients receiving RBC transfusion.This is a double-blind, randomized, clinical trial comparing fresh (≤5 d of storage) versus standard issue single-unit RBC transfusion in adult intubated and mechanically ventilated patients. The primary outcome is the change in pulmonary gas exchange as assessed by the partial pressure of arterial oxygen to fraction of inspired oxygen concentration ratio (ΔPa(O(2))/Fi(O(2))). Secondary outcomes include changes in immune and coagulation status.Fifty patients were randomized to receive fresh RBCs and an additional 50 patients to standard issue RBCs. Median storage age was 4.0 days (interquartile range, 3.0-5.0) and 26.5 days (interquartile range, 21.0-36.0) in the fresh RBC group and standard issue RBC group, respectively. No differences were noted in the primary outcome of ΔPa(O(2))/Fi(O(2)) (difference between the mean ΔPa(O(2))/Fi(O(2)) in the standard issue RBC group vs. the fresh RBC group, -11.5; 95% confidence interval, -35.3 to 12.3; P = 0.22). Similarly, no significant differences were noted in markers of immunologic or coagulation status.In this randomized clinical trial, no differences were noted in early measures of pulmonary function or in immunologic or coagulation status when comparing fresh versus standard issue single-unit RBC transfusion. Clinical trial registered with ClinicalTrials.gov (NCT00751322).
Very Low Birth Weight and Behavioral Symptoms of Attention Deficit Hyperactivity Disorder in Young Adulthood: The Helsinki Study of Very-Low-Birth-Weight Adults
Authors: Sonja Strang-Karlsson, Katri Räikkönen, Anu-Katriina Pesonen, Eero Kajantie, E. Juulia Paavonen, Jari Lahti, Petteri Hovi, Kati Heinonen, Anna-Liisa Järvenpää, Johan G. Eriksson, Sture Andersson
Journal: American Journal of Psychiatry (2008)

Children with very low birth weight (<1500 g) are at increased risk for attention deficit hyperactivity disorder (ADHD). Whether this increased risk continues into adulthood is unknown. The authors assessed behavioral symptoms of ADHD in a well-characterized cohort of very-low-birth-weight young adults who were either small for gestational age (less than two standard deviations below the Finnish mean) or appropriate for gestational age (within two standard deviations of the mean).A total of 162 very-low-birth-weight subjects (small for gestational age: N=52; appropriate for gestational age: N=110) and 172 term comparison subjects 18 to 27 years of age completed the Adult Problem Questionnaire, which yielded six exploratory factor analysis-derived subscales. Participants were also asked about substance use.Very-low-birth-weight adults in the small for gestational age subgroup scored higher on the executive dysfunctioning and emotional instability subscales of the Adult Problem Questionnaire than did those in the appropriate for gestational age subgroup and the comparison group. The appropriate for gestational age and comparison groups had similar scores on these subscales. On the alcohol use subscale of the Adult Problem Questionnaire, both the appropriate and small for gestational age subgroups scored lower than comparison subjects and also reported fewer risk-taking behaviors (alcohol, smoking, and use of recreational drugs) than did comparison subjects.Rather than very low birth weight per se, intrauterine growth retardation, as reflected by small for gestational age status in the very-low-birth-weight subjects, confers a risk for behavioral and emotional adversity related to ADHD in young adulthood.