tbuckley/cabot-search huggingface dataset:
Quantification of apolipoprotein B in grossly normal human aorta.
Authors: H F Hoff, C L Heideman, J W Gaubatz, A M Gotto, E E Erickson, R L Jackson
Journal: Circulation Research (1977)

A quantitiative electroimmunodiffusion (EID) assay was developed for apolipoprotein B (apoB), the major apoprotein of human plasma low density lipoproteins (LDL) and very low density lipoproteins (VLDL). Specificity, sensitivity (30-200 ng) and reproducibility (11%) were established. We used this system to determine the amount of buffer-soluble apoB in supernatant fractions from homogenates of the intima from grossly normal human aortas. Assays of whole tissue minces yielded only one-third of the apoB in supernatant fractions. Intimal homogenates contained 0.34-18.45 mug of apoB/mg of tissue, dry weight (mean 5.42 +/- 3.95 SD). We also found that no apoB was detected in the homogenates of adjacent tunica media. Furthermore, most of the intimal apoB was found in the LDL density (d) fraction (d 1.006-1.063) after differential ultracentrifugation, while the VLDL (d less than 1.006) fraction contained only negligible amounts of apoB. By electron microscopy, it was determined that the LDL density fraction contained particles 200-250 A in diameter which were similar in size to plasma LDL. These results suggest that grossly normal aortas contain significant quantities of intact LDL.
Caspase-8 deficiency in epidermal keratinocytes triggers an inflammatory skin disease
Authors: Andrew Kovalenko, Jin-Chul Kim, Tae-Bong Kang, Akhil Rajput, Konstantin Bogdanov, Oliver Dittrich-Breiholz, Michael Kracht, Ori Brenner, David Wallach
Journal: The Journal of Experimental Medicine (2009)

Expression of enzymatically inactive caspase-8, or deletion of caspase-8 from basal epidermal keratinocytes, triggers chronic skin inflammation in mice. Unlike similar inflammation resulting from arrest of nuclear factor κB activation in the epidermal cells, the effect induced by caspase-8 deficiency did not depend on TNF, IL-1, dermal macrophage function, or expression of the toll-like receptor adapter proteins MyD88 or TRIF. Both interferon regulatory factor (IRF) 3 and TANK-binding kinase were constitutively phosphorylated in the caspase-8–deficient epidermis, and knockdown of IRF3 in the epidermis-derived cells from these mice abolished the expression of up-regulated genes. Temporal and spatial analyses of the alterations in gene expression that result from caspase-8 deficiency reveal that the changes are initiated before birth, around the time that cornification develops, and occur mainly in the suprabasal layer. Finally, we found that caspase-8–deficient keratinocytes display an enhanced response to gene activation by transfected DNA. Our findings suggest that an enhanced response to endogenous activators of IRF3 in the epidermis, presumably generated in association with keratinocyte differentiation, contributes to the skin inflammatory process triggered by caspase-8 deficiency.
IL-22 suppresses IFN-γ–mediated lung inflammation in asthmatic patients
Authors: Davide Pennino, Pankaj K. Bhavsar, Renate Effner, Simona Avitabile, Pascal Venn, Maria Quaranta, Viviana Marzaioli, Liliana Cifuentes, Stephen R. Durham, Andrea Cavani, Kilian Eyerich, Kian Fan Chung, Carsten B. Schmidt-Weber, Stefanie Eyerich
Journal: Journal of Allergy and Clinical Immunology (2012)
Government wins vote to keep risk assessment of NHS reforms private
Authors: A. O'Dowd
Journal: BMJ (2012)

The government has narrowly defeated a vote in parliament that, if passed, would have raised pressure on it to publish a risk assessment of the impact of the NHS reforms.

After a fiery six hour debate in the House of Commons on 22 February, 246 MPs voted for and 299 against a motion put forward by the Labour Party that called on the government to publish the risk register associated with the Health and Social Care Bill.

The document is a “transition risk register” that relates specifically to the health bill reorganisation and was first drawn up in 2010, but has been reviewed and updated.

To date, the government has resisted a freedom of information ruling in November of last year by the information commissioner that it should publish the document.

The ruling said there …
Effect of adjuvant chemotherapy on survival in FNCLCC grade 3 soft tissue sarcomas: a multivariate analysis of the French Sarcoma Group Database
Authors: A. Italiano, F. Delva, S. Mathoulin-Pelissier, A. Le Cesne, S. Bonvalot, P. Terrier, M. Trassard, J.-J. Michels, J.-Y. Blay, J.-M. Coindre, B. Bui
Journal: Annals of Oncology (2010)
CD28-B7 blockade after alloantigenic challenge in vivo inhibits Th1 cytokines but spares Th2.
Authors: M H Sayegh, E Akalin, W W Hancock, M E Russell, C B Carpenter, P S Linsley, L A Turka
Journal: The Journal of Experimental Medicine (1995)

Blocking the CD28-B7 T cell costimulatory pathway with the fusion protein CTLA4Ig inhibits alloimmune responses in vitro and in vivo and induces tolerance to cardiac allografts in mice and rats, but the mechanisms mediating the tolerant state in vivo are unknown. Here, we report the effects and potential mechanisms of CTLA4Ig in the rat renal allograft model. LEW rats were nephrectomized and received renal allografts from major histocompatibility complex-incompatible WF rats. While all untreated and control immunoglobulin (Ig)-treated animals acutely rejected their allografts and died, 86% of rats that received a single injection of CTLA4Ig on day 2 after transplantation had prolonged survival (&amp;gt; 60-100 days) with preserved renal function. By contrast, only 29% of animals that received CTLA4Ig on the day of engraftment had prolonged survival. Long-term survivors (&amp;gt; 100 days) exhibited donor-specific tolerance, accepting donor-matched WF but acutely rejecting third-party BN cardiac allografts. Immunohistological analysis of grafts sampled at 1 week after transplantation showed that both control and CTLA4Ig-treated animals had mononuclear cell infiltrates, with a higher percentage of CD4+ cells in the CTLA4Ig-treated group. However, while this was associated with vasculitis and tubulitis in control grafts, there was no evidence of tissue injury in CTLA4Ig-treated animals. The immune response leading to graft rejection in control animals was characterized by expression of the T helper (Th) type 1 cytokines interleukin (IL)-2 and interferon-gamma. In contrast, the persistent CD4+ infiltrate without graft rejection in CTLA4Ig-treated animals was associated with increased staining for the Th2-related cytokines IL-4 and IL-10. Furthermore, grafts from CTLA4Ig-treated animals had marked upregulation of intragraft staining for IgG1, but not IgG2a or IgG2b. Administration of rIL-2 to CTLA4Ig-treated animals restored allograft rejection in 50% of animals tested. These results confirm that blockade of the CD28-B7 pathway after alloantigenic challenge induces donor-specific acceptance of vascularized organ allografts, and indicates in this model that CTLA4Ig inhibits Th1 but spares Th2 cytokines in vivo.
Cardioprotection by CaMKII-δB Is Mediated by Phosphorylation of Heat Shock Factor 1 and Subsequent Expression of Inducible Heat Shock Protein 70
Authors: Wei Peng, Yan Zhang, Ming Zheng, Heping Cheng, Weizhong Zhu, Chun-Mei Cao, Rui-Ping Xiao
Journal: Circulation Research (2009)

Ca2+/calmodulin-dependent protein kinase (CaMK)II is a multifunctional kinase involved in vital cellular processes such as Ca(2+) handling and cell fate regulation. In mammalian heart, 2 primary CaMKII isoforms, deltaB and deltaC, localize in nuclear and cytosolic compartments, respectively. Although previous studies have established an essential role of CaMKII-deltaC in cardiomyocyte apoptosis, the functional role of the more abundant isoform, CaMKII-deltaB, remains elusive.Here, we determined the potential role of CaMKII-deltaB in regulating cardiomyocyte viability and explored the underlying mechanism.In cultured neonatal rat cardiomyocytes, the expression of CaMKII-deltaB and CaMKII-deltaC was inversely regulated in response to H2O2-induced oxidative stress with a profound reduction of the former and an increase of the later. Similarly, in vivo ischemia/reperfusion (IR) led to an opposite regulation of these CaMKII isoforms in a rat myocardial IR model. Notably, overexpression of CaMKII-deltaB protected cardiomyocytes against oxidative stress-, hypoxia-, and angiotensin II-induced apoptosis, whereas overexpression of its cytosolic counterpart promoted apoptosis. Using cDNA microarray, real-time PCR and Western blotting, we demonstrated that overexpression of CaMKII-deltaB but not CaMKII-deltaC elevated expression of heat shock protein (HSP)70 family members, including inducible (i)HSP70 and its homolog (Hst70). Moreover, overexpression of CaMKII-deltaB led to phosphorylation and activation of heat shock factor (HSF)1, the primary transcription factor responsible for HSP70 gene regulation. Importantly, gene silencing of iHSP70, but not Hst70, abolished CaMKII-deltaB-mediated protective effect, indicating that only iHSP70 was required for CaMKII-deltaB elicited antiapoptotic signaling.We conclude that cardiac CaMKII-deltaB and CaMKII-deltaC were inversely regulated in response to oxidative stress and IR injury, and that in contrast to CaMKII-deltaC, CaMKII-deltaB serves as a potent suppressor of cardiomyocyte apoptosis triggered by multiple death-inducing stimuli via phosphorylation of HSF1 and subsequent induction of iHSP70, marking both CaMKII-delta isoforms as promising therapeutic targets for the treatment of ischemic heart disease.
Aspirin Enhances the Benefits of Late Reperfusion on Infarct Shape
Authors: Imad A. Alhaddad, Lidia Tkaczevski, Faizi Siddiqui, Rabia Mir, Edward J. Brown
Journal: Circulation (1995)

The time window of the benefits of late reperfusion on infarct shape is limited. In rats, these benefits diminish in a wave front over time, with minimal benefits when reperfusion follows 16 hours of coronary occlusion. The mechanism of the benefits of aspirin on survival after acute myocardial infarction is unknown. The purpose of this study was to test the ability of aspirin to enhance the benefits of late coronary artery reperfusion on infarct shape and to examine the mechanism of the benefits of aspirin on infarct shape.Rats were entered into two different protocols, the morphometric and the histological protocols. In the morphometric protocol, rats were randomized into two groups: the aspirin group, in which rats underwent left coronary artery occlusion followed by treatment with aspirin (12 mg/kg i.v.), and the control group, in which rats underwent left coronary artery occlusion followed by treatment with placebo. Rats in both groups were reperfused 8 hours after coronary occlusion. Rats in the aspirin group received aspirin in the drinking water (12 +/- 2 mg/kg daily). Morphometric analysis was performed 2 weeks after acute myocardial infarction. In the histological protocol, rats underwent the same randomization, coronary occlusion, and reperfusion protocols. Hearts were removed 24 hours after coronary occlusion, and microvessels were assessed for patency. Infarct size expressed as a percent of circumference was similar in the aspirin and placebo treatment groups (28 +/- 2% versus 33 +/- 3%, P = NS). Septal thickness was also similar in both groups (1.8 +/- 0.1 versus 2.1 +/- 0.1 mm, P = NS for aspirin versus placebo). The aspirin-treated group had thicker infarcts compared with the placebo-treated group (0.8 +/- 0.1 versus 0.5 +/- 0.1 mm, P < .05) and less expanded infarcts (expansion index, 1.2 +/- 0.1 versus 2.0 +/- 0.2, P < .05). Aspirin was associated with increased patency of the microvessels in the infarcted area compared with the placebo group (96% versus 64% of microvessels patent, P < .001).Aspirin enhances the benefit of late coronary artery reperfusion on infarct shape after 8 hours of coronary occlusion. The benefits of aspirin on infarct shape after late reperfusion are related to increased patency of the microvessels in the infarcted area.
Everolimus for women with trastuzumab-resistant, HER2-positive, advanced breast cancer (BOLERO-3): a randomised, double-blind, placebo-controlled phase 3 trial
Authors: Fabrice André, Ruth O'Regan, Mustafa Ozguroglu, Masakazu Toi, Binghe Xu, Guy Jerusalem, Norikazu Masuda, Sharon Wilks, Francis Arena, Claudine Isaacs, Yoon-Sim Yap, Zsuzsanna Papai, Istvan Lang, Anne Armstrong, Guillermo Lerzo, Michelle White, Kunwei Shen, Jennifer Litton, David Chen, Yufen Zhang, Shyanne Ali, Tetiana Taran, Luca Gianni
Journal: The Lancet Oncology (2014)
A crucial role of caspase-3 in osteogenic differentiation of bone marrow stromal stem cells
Authors: Masako Miura, Xiao-Dong Chen, Matthew R. Allen, Yanming Bi, Stan Gronthos, Byoung-Moo Seo, Saquib Lakhani, Richard A. Flavell, Xin-Hua Feng, Pamela Gehron Robey, Marian Young, Songtao Shi
Journal: Journal of Clinical Investigation (2004)

Caspase-3 is a critical enzyme for apoptosis and cell survival. Here we report delayed ossification and decreased bone mineral density in caspase-3–deficient (Casp3–/– and Casp3+/–) mice due to an attenuated osteogenic differentiation of bone marrow stromal stem cells (BMSSCs). The mechanism involved in the impaired differentiation of BMSSCs is due, at least partially, to the overactivated TGF-β/Smad2 signaling pathway and the upregulated expressions of p53 and p21 along with the downregulated expressions of Cdk2 and Cdc2, and ultimately increased replicative senescence. In addition, the overactivated TGF-β/Smad2 signaling may result in the compromised Runx2/Cbfa1 expression in preosteoblasts. Furthermore, we demonstrate that caspase-3 inhibitor, a potential agent for clinical treatment of human diseases, caused accelerated bone loss in ovariectomized mice, which is also associated with the overactivated TGF-β/Smad2 signaling in BMSSCs. This study demonstrates that caspase-3 is crucial for the differentiation of BMSSCs by influencing TGF-β/Smad2 pathway and cell cycle progression.
Response to salbutamol in patients with mild asthma treated with nadolol
Authors: N.A. Hanania, B. Mannava, A.E. Franklin, B.J. Lipworth, P.A. Williamson, W.J. Garner, B.F. Dickey, R.A. Bond
Journal: European Respiratory Journal (2010)

Response to salbutamol in patients with mild asthma treated with nadolol
Characterization and Magnetic Resonance Imaging of a Rat Model of Human B-Cell Central Nervous System Lymphoma
Authors: Carole Soussain, Leslie L. Muldoon, Csanad Varallyay, Kristoph Jahnke, Luciana DePaula, Edward A. Neuwelt
Journal: Clinical Cancer Research (2007)

Abstract Purpose: The incidence of primary central nervous system lymphoma (PCNSL) is increasing. Therapeutic approaches remain controversial. An animal model that mimics the clinical situation would be useful for evaluating PCNSL biology and treatment. Experimental Design: Nude rats received intracerebral (caudate nucleus, n = 49) or intraventricular (n = 4) inoculation of human B-lymphoma cell line MC116. Two to five weeks after tumor inoculation, magnetic resonance imaging (MRI) was done (n = 24), and rat brains were assessed for pathology. Five rats each received whole-brain radiotherapy (WBRT, 20 Gy) or high-dose i.v. methotrexate (3 g/m2). Results: Intracerebral tumors developed in 84% of evaluable animals with no pretreatment, 79% of rats pretreated with 4 Gy total body irradiation, and 92% of rats pretreated with cyclophosphamide (300 mg/m2). MRI showed abnormal T2 signal and gadolinium enhancement on T1-weighted images, consistent with tumor growth 19 to 24 days after inoculation. Tumor cells staining positively for B-lymphoma markers infiltrated within the inoculated hemisphere, along fiber tracks to the contralateral hemisphere, and along the subarachnoid space and ventricles. Tumors showed reactive gliosis. Intraventricular tumor cell injection resulted in periventricular parenchymal infiltration in both hemispheres. Radiation and methotrexate were effective in vitro, but only WBRT was clearly effective after 1 week in the intracerebral model. Conclusion: This model closely mimics human PCNSL in terms of imaging, histology, and treatment sensitivity and will be useful for the development of future therapeutic strategies for PCNSL.
Inhibition of HIV-1 infection by lentiviral vectors expressing pol III-promoted anti-HIV RNAs
Authors: Ming-Jie Li, Gerhard Bauer, Alessandro Michienzi, Jiing-Kuan Yee, Nan-Sook Lee, James Kim, Shirley Li, Daniela Castanotto, John Zaia, John J Rossi
Journal: Molecular Therapy (2003)

A primary advantage of lentiviral vectors is their ability to pass through the nuclear envelope into the cell nucleus thereby allowing transduction of nondividing cells. Using HIV-based lentiviral vectors, we delivered an anti-CCR5 ribozyme (CCR5RZ), a nucleolar localizing TAR RNA decoy, or Pol III-expressed siRNA genes into cultured and primary cells. The CCR5RZ is driven by the adenoviral VA1 Pol III promoter, while the human U6 snRNA Pol III-transcribed TAR decoy is embedded in a U16 snoRNA (designated U16TAR), and the siRNAs were expressed from the human U6 Pol III promoter. The transduction efficiencies of these vectors ranged from 96–98% in 293 cells to 15–20% in primary PBMCs. A combination of the CCR5RZ and U16TAR decoy in a single vector backbone gave enhanced protection against HIV-1 challenge in a selective survival assay in both primary T cells and CD34+-derived monocytes. The lentiviral vector backbone-expressed siRNAs also showed potent inhibition of p24 expression in PBMCs challenged with HIV-1. Overall our results demonstrate that the lentiviral-based vectors can efficiently deliver single constructs as well as combinations of Pol III therapeutic expression units into primary hematopoietic cells for anti-HIV gene therapy and hold promise for stem or T-cell-based gene therapy for HIV-1 infection.
Estimation of the Neutrality Index
Authors: N. Stoletzki, A. Eyre-Walker
Journal: Molecular Biology and Evolution (2010)

The McDonald-Kreitman (MK) test is a simple and widely used test of selection in which the numbers of nonsilent and silent substitutions (D(n) and D(s)) are compared with the numbers of nonsilent and silent polymorphisms (P(n) and P(s)). The neutrality index (NI = D(s)P(n)/D(n)P(s)), the odds ratio (OR) of the MK table, measures the direction and degree of departure from neutral evolution. The mean of NI values across genes is often taken to summarize patterns of selection in a species. Here, we show that this leads to statistical bias in both simulated and real data to the extent that species, which show a pattern of adaptive evolution, can apparently be subject to weak purifying selection and vice versa. We show that this bias can be removed by using a variant of the Cochran-Mantel-Haenszel procedure for estimating a weighted average OR. We also show that several point estimators of NI are statistically biased even when cutoff values are employed. We therefore suggest that a new statistic be used to study patterns of selection when data are sparse, the direction of selection: DoS = D(n)/(D(n) + D(s)) - P(n)/(P(n) + P(s)).
Clinical effectiveness of palifermin in prevention and treatment of oral mucositis in children with acute lymphoblastic leukaemia: a case–control study
Authors: Dorina Lauritano, Massimo Petruzzi, Dario Di Stasio, Alberta Lucchese
Journal: International Journal of Oral Science (2013)

The incidence of post-operative pain was compared following single-visit canal treatment in single- and multi-rooted teeth, with and without periapical radiolucency. The article also reviews the issues of postoperative pain and healing, following single-visit and multi-visit endodontic therapy. Single-visit endodontic therapy (SVE) was performed in 50 single-rooted teeth and 60 multiple-rooted teeth.Single-visit endodontic therapy (SVE) was performed in 50 single-rooted teeth and 60 multiple-rooted teeth. The subjects were divided as follows: Group I -Single-rooted teeth with periapical radiolucency (n=25); Group II-Single-rooted teeth without periapical radiolucency (n=25); Group III-Multiple-rooted teeth with periapical radiolucency (n=30); and Group IV-Multiple-rooted teeth without periapical radiolucency (n=30). Assessment of postoperative pain was done at 24hrs, 3 days and 1 week using a self report questionnaire. The data was analyzed using non-parametric Kruskal -Wallis test.No statistically significant difference was observed in postoperative pain following SVE between the single-rooted and multiple-rooted teeth groups at 24hrs, 3 days and 1 week. The presence or absence of periapical radiolucency had no significant influence on the incidence of reported postoperative pain following SVE.There was no difference in incidence of pain in single rooted teeth and multi-rooted teeth with and without periapical radiolucencies following SVE. Thus, incidence of post-operative pain does not seem to be a valid comparison criterion between single- and multiple-visit endodontic therapies. Also, the literature suggests similar success rates with single-visit and multiple-visit root canal treatment. How to cite the article: Raju TB, Seshadri A, Vamsipavani B, Abhilash K, Subhash AV, Kumari KV. Evaluation of Pain in Single and Multi Rooted Teeth Treated in Single Visit Endodontic Therapy. J Int Oral Health 2014;6(1):27-32.
The Natural History of Chronic Airflow Obstruction Revisited
Authors: Robab Kohansal, Pablo Martinez-Camblor, Alvar Agustí, A. Sonia Buist, David M. Mannino, Joan B. Soriano
Journal: American Journal of Respiratory and Critical Care Medicine (2009)

Rationale: Understanding normal lung development and aging in health and disease, both in men and in women, is essential to interpreting any therapeutic intervention.Objectives: We aimed to describe lung function changes in healthy never-smoking males and females, from adolescence to old age, and to determine the effects of smoking and those derived from quitting.Methods: Prospective cohort study within all participants of the Framingham Offspring cohort who had two or more valid spirometry measurements during follow-up (n = 4,391; age range at baseline 13 to 71 yr), with a median follow-up time of 23 years.Measurements and Main Results: To best fit the curves describing FEV1 changes with age to raw data, we used a generalized additive model with smooth terms and incorporating the subject-specific (longitudinal) random effects. We found that: (1) healthy never-smoker females achieve full lung growth earlier than males, and their rate of decline with age was slightly, but not significantly, lower; (2) smoking increases the rate of lung function decline, both in males and in females; (3) there is a range of susceptibility to the effects of smoking. The presence of respiratory symptoms at baseline and/or a respiratory diagnosis during follow-up appears to identify a group of susceptible smokers; and (4) quitting smoking has a beneficial effect at any age, but it is more pronounced in earlier quitters.Conclusions: Lung function changes from adolescence to old age differ in males and females, smoking has similar deleterious effects in both sexes, and quitting earlier is better.
Chronic Infection by Mucoid <i>Pseudomonas aeruginosa</i> Associated with Dysregulation in T-Cell Immunity to Outer Membrane Porin F
Authors: Kathryn J. Quigley, Catherine J. Reynolds, Amelie Goudet, Eleanor J. Raynsford, Ruhena Sergeant, Andrew Quigley, Stefan Worgall, Diana Bilton, Robert Wilson, Michael R. Loebinger, Bernard Maillere, Daniel M. Altmann, Rosemary J. Boyton
Journal: American Journal of Respiratory and Critical Care Medicine (2015)

Pseudomonas aeruginosa (PA) is an environmental pathogen that commonly infects individuals with cystic fibrosis (CF) and non-CF bronchiectasis, impacting morbidity and mortality. To understand the pathobiology of interactions between the bacterium and host adaptive immunity and to inform rational vaccine design, it is important to understand the adaptive immune correlates of disease.