tbuckley/cabot-search huggingface dataset:
Protective effect of curcumin on pulmonary and cardiovascular effects induced by repeated exposure to diesel exhaust particles
Authors: Abderrahim Nemmar, Shaheen Zia, Deepa Subramaniyan, Badreldin Ali
Journal: European Respiratory Journal (2012)

Particulate air pollution has been linked to increased risk of cardiopulmonary diseases. However, the underlying mechanisms are not fully understood. We have previously demonstrated that single dose exposure to diesel exhaust particle (DEP) causes lung inflammation and peripheral thrombotic events. Here, we evaluated several cardiopulmonary endpoints two days after repeated doses of DEP (15 µg/mouse) every other day for 6 days, and the potential protective effect of curcumin (the yellow pigment isolated from turmeric) thereon. DEP exposure increased macrophage and neutrophil numbers, tumor necrosis factor α (TNF α) [but not interleukin-6 (IL-6)] in the bronchoalveolar lavage (BAL) fluid, and enhanced airway resistance to methacoline measured invasively using Flexivent. DEP also significantly increased Plasma C-reactive protein and TNFα concentrations, systolic blood pressure (SBP), as well as the pial arteriolar thrombosis. It also significantly enhanced the plasma D-dimer and plasminogen activator inhibitor-1. Pretreatment with curcumin 1h before exposure to DEP significantly prevented the influx of inflammatory cells and the increase of TNF α in BAL, and the increased airway resistance caused by DEP. Likewise, curcumin prevented the increase of SBP, CRP, TNF α, D-dimer and PAI. The thrombosis was partially but significantly mitigated. Our findings suggest that repeated exposure to DEP induces increases in airway and systemic inflammation, TNF α production in both in BAL and plasma, airway resistance, SBP, and coagulation. In conclusion, pretreatment with curcumin prevented the cardiopulmonary effect and inhibited the release of TNF α induced by DEP.
Characteristics of Behavior Controlled by Scheduled Injections of Drugs
Authors: R.T. Kelleher
Journal: Pharmacological Reviews (1975)

It has been well established that the injections of various classes of drugs can reinforce behavior in experimental animals; however, there is a need to characterize the properties of drugs as reinforcers. The maintenance of behavior by self-administration of drugs is determined by various conditions in addition to the direct effects of the drug itself. The present paper has emphasized the importance of the schedule of drug injections in determining how drugs function as reinforcers. In this context, it was shown that certain secondorder schedules provide a technique for establishing powerful control over behavior with drugs as diverse as cocaine, methohexital, and morphine.
P-110 Hepatocellular carcinoma in elderly patients: Final results of the Italian cohort of GIDEON study
Authors: T. Zolfino, V. Lorusso, S. D'Angelo, D. Sansonno, L. Giannitrapani, A. Benedetti, V. Montesarchio, A. Attili, A. Buonadonna, S. Barni, A. Gasbarrini, M. Pirisi, U. Cillo, A. Picciotto, E. Villa, P. Giovanis, G. Pinotti, G. Raimondo, C. Erminero, M. De Giorgio, B. Daniele
Journal: Annals of Oncology (2015)
Dynamic colonisation by different Pneumocystis jirovecii genotypes in cystic fibrosis patients
Authors: M.A. Montes-Cano, C. de la Horra, F.J. Dapena, I. Mateos, V. Friaza, N. Respaldiza, F. Muñoz-Lobato, F.J. Medrano, E.J. Calderon, J.M. Varela
Journal: Clinical Microbiology and Infection (2007)
TAS-108: A Novel Steroidal Antiestrogen
Authors: Aman U. Buzdar
Journal: Clinical Cancer Research (2005)

TAS-108 is a novel steroidal antiestrogen compound that has a strong binding affinity to the estrogen receptor and, in preclinical studies, has antitumor activity against tamoxifen-resistant breast cancer cell lines. Its molecular mechanisms of actions are different from those of tamoxifen and fulvestrant. TAS-108 showed tissue-selective agonist activity in the bone and cardiovascular systems and, in preclinical and phase I studies, did not show any effect on the endometrium. In a phase I study, TAS-108 was well tolerated at doses ranging from 40 to 160 mg/d with no maximum tolerated dose. Toxicities included hot flashes, headache, and nausea and vomiting. The drug has linear pharmacokinetics. In the phase I study, there was evidence of biological antitumor activity, with stable disease noted in several patients. A phase II study is ongoing, and phase III studies are being planned with the drug.
Thymic B Cells Are Licensed to Present Self Antigens for Central T Cell Tolerance Induction
Authors: Tomoyoshi Yamano, Jelena Nedjic, Maria Hinterberger, Madlen Steinert, Sandra Koser, Sheena Pinto, Norbert Gerdes, Esther Lutgens, Naozumi Ishimaru, Meinrad Busslinger, Benedikt Brors, Bruno Kyewski, Ludger Klein
Journal: Immunity (2015)
The transcription factor Bcl11b is specifically expressed in group 2 innate lymphoid cells and is essential for their development
Authors: Yong Yu, Cui Wang, Simon Clare, Juexuan Wang, Song-Choon Lee, Cordelia Brandt, Shannon Burke, Liming Lu, Daqian He, Nancy A. Jenkins, Neal G. Copeland, Gordon Dougan, Pentao Liu
Journal: The Journal of Experimental Medicine (2015)

Group 2 innate lymphoid cells (ILCs), or ILC2s, are a subset of recently identified ILCs, which play important roles in innate immunity by producing type 2 effector cytokines. Several transcription factors have been found to have critical functions in the development of both ILC2s and T cells. We report here that Bcl11b, a transcription factor essential in T cell lineage commitment and maintenance, is specifically expressed in progenitors committed to the ILC2 lineage and is required for ILC2 development. The Bcl11b gene is expressed in ∼28% of ILC progenitors (ILCPs; common helper innate lymphoid progenitors or ILCPs expressing either ID2 or promyelocytic leukemia zinc finger, respectively). Both in vitro and in vivo, these Bcl11b-expressing early ILCPs generate only ILC2s. Inactivation of Bcl11b causes a complete loss of ILC2 development from hematopoietic progenitors, which is confirmed upon immune challenge with either papain administration or influenza virus infection.
Discrimination of expanded dendritic cell populations in lung tissues from COPD patients
Authors: Michiko Mori, Cecilia Andersson, Anders Bergqvist, Chris Van Hove, Claes-Göran Löfdahl, Jonas Erjefält
Journal: European Respiratory Journal (2011)

Rationale:  Dendritic cells (DCs) are highly plastic and their characterization in human tissues has been hampered by lack of standardized immunohistochemical identification strategies. This study validates an immunohistochemical method for masking confounding non-DC cells and characterizes multiple DC populations in COPD-affected lungs.   Methods:  Lung specimens were obtained from 27 COPD patients and divided into three levels of severity; GOLD I (n=6), GOLD II-III (n=11) and GOLD IV (n=10). Never-smokers (n=8) and non-COPD smokers (n=6) served as controls. Paraffin sections were double stained for combinations of macrophage and DC markers.   Results:  Using the non-soluble DAB as the first detection chromogen it was possible to mask confounding non-DC cells e.g. CD68 +  macrophages at a bright microscopic level. Using this approach two populations of CD68 - CD11c +  and CD68 - CD123 +  cells were identified, indicative of myeloid and plasmacytoid DCs, respectively. The myeloid DCs, which were foremost BDCA3 - , were significantly increased in diseased areas of COPD lungs, in particular in patchy areas of fibrosis and granuloma formation. Both CD68 - CD11c +  and CD68 - CD123 +  cells displayed a dendritic morphology and were observed in epithelial and subepithelial compartments of small airways and alveolar walls as well as in lymphoid aggregates amidst CD21 +  follicular DCs. Further combination of markers could discriminate intraepithelial myeloid and plasmacytoid DCs from CD207 +  and CD1a +  epithelial DCs.   Conclusions:  This study demonstrates that masking of confounding non-DC populations improves the identification of lung DC populations and reveals novel aspects of their dynamics and heterogeneity in COPD lungs.
DNA Replication Patterns in Chromosomes of Several Transplantable Ascites Hepatomas of the Rat<xref ref-type="fn" rid="FN2">2</xref>
Authors: Motomichi Sasaki
Journal: JNCI Journal of the National Cancer Institute (1971)

Patterns of terminal DNA synthesis of chromosomes were studied in 7 aneuploid strains of transplantable ascites hepatomas of rats by means of the short-term in vitro incubation method with tritiated thymidine autoradiography. Of the 7 tumors used, AH-130, AH-66, and AH-13 were of female origin, while AH-41c, AH-7974, AH-414, and AH-272 were of male origin. Usually 4 hours' incubation in the presence of the isotope was sufficient for study of the chromosomal replication pattern in the late S phase, except for AH-13 that rarely showed labeled metaphases, possibly due to G2 blockade in vitro. The stemline karyotypes of the remaining 6 tumors each exhibited a characteristic replicatory pattern considerably different from the normal one, though the morphological assessment of the rearranged chromosomes in cancer cells was difficult in comparison to the karyotype and labeling pattern of normal cells. Tumors AH-130, AH-41c, and AH-7974 exhibited late-replicating elements resembling the late-X or the Y chromosome of the normal complement in both morphology and labeling pattern. Similar features were also noted for some other members morphologically similar to the largest pairs of telocentrics and subtelocentrics of the normal karyotype. No consistent morphological and replicatory patterns were detected among these aneuploid tumors, within the limits of these autoradiographic analyses.
Prognostic Significance of Serum Alphafoetoprotein Early Decline in Ovarian Yolk Sac Tumor
Authors: T. De La Motte Rouge, P. Pautier, P. Duvillard, A. Rey, P. Morice, C. Haie Meder, P. Kerbrat, S. Culine, K. Fizazi, C. Lhomme
Journal: Annals of Oncology (2014)
Developmental Stage of the Rat Mammary Gland as Determinant of Its Susceptibility to 7, 12-Dimethylbenz[&lt;italic&gt;a&lt;/italic&gt;]anthracene&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: Irma H. Russo, Jose Russo
Journal: JNCI Journal of the National Cancer Institute (1978)

Postnatal development of the mammary gland was studied in 80 noninbred Sprague-Dawley virgin rats ranging in age from 2 to 112 days, and the changes induced by 7,12-dimethylbenz[a]anthracene (DMBA) were studied in 60 noninbred Sprague-Dawley virgin rats that, at the age of 55 days, were inoculated intragastrically with 10 mg DMBA/100 g body weight. To correlate the sequential structural changes in the two groups, animals of both groups were killed weekly and their mammary glands removed and processed for wholemount. Terminal endbuds (TEB), terminal ducts (TD), alveolar buds (AB), and lobules per square millimeter were counted in wholemount preparations under a stereomicroscope. During postnatal development, the mammary gland tree grew by sprouting numerous ducts ending in club-shaped TEB. The density of TEB reached a peak when the rats were 21 days old (25 +/- 2 TEB/mm2), decreased sharply until the animals were 63 days old, and then decreased slowly until they were 84 days of age. The number of TEB decreased because of their differentiation mainly into AB or their evolution to TD. AB later differentiated into lobules. AB increased in number steadily to a plateau when the animals were 70--84 days old. After DMBA was administered to the rats at 55 days of age, the number of TEB remained higher than that in the control animals and the TEB became larger and had higher mitotic activities. Such TEB were called intraductal proliferations (IDP); they evolved to adenocarcinomas. DMBA increased the number of TD and decreased the number of AB and lobules in relation to the control animals. These findings led to the conclusion that DMBA administration to 55-day-old rats alters the differentiation of TEB leads to AB leads to lobules, inducing instead the sequence TEB leads to IDP leads to adenocarcinoma.
Net antitumoral immunity and the predictive power of conventional prognosticators in diffuse large B-cell lymphoma.
Authors: Colm Keane, Frank Vari, Mark S. Hertzberg, Michael R Green, Erica Han, John Francis Seymour, Rodney J Hicks, Devinder Singh Gill, Pauline Crooks, Clare Gould, Kimberley Jones, Kristen Radford, Lyn Griffiths, Dipti Talaulikar, Sanjiv Jain, Josh Tobin, Maher K. Gandhi
Journal: Journal of Clinical Oncology (2014)

8542 Background: Immunity represents a balance between immune-effectors and immune-checkpoints. In DLBCL, circulating lymphocyte:monocyte ratios are prognostic, implicating them as surrogate immune-effectors and immune-checkpoints within the tumor microenvironment (TME). Detailed assessment of blood would enable identification of the optimal TME immune-effector and monocyte/macrophage-checkpoints to assist sub-stratification of conventional prognosticators. Methods: Blood from 140 R-CHOP treated DLBCL patients in the NHL21 Australasian Leukaemia and Lymphoma Group trial were analysed. A circulating immune-effector:monocyte-checkpoint signature segregating interim-PET/CT positivity was identified. Intratumoral applicability was tested in two independent R-CHOP treated DLBCL cohorts, with cell-of-origin (COO) and international prognostic index (IPI) as co-variates. Results: Patient monocytes suppressed T-cell proliferation and NK-cell rituximab-ADCC. Both CD14+HLA-DRlo monocytoid-myeloid derived suppressor cells (moMDSC) and arginase activity were elevated (P<0.0001 and P=0.0005 respectively) and correlated with CD163 (r=0.4, P<0.0001 and r=0.45, P=0.002 respectively). CD8+:CD163+moMDSC ratios were highest in interim-PET/CT-ve patients (P≤0.0001). Digital bar-coding in 191 DLBCL tissues demonstrated co-clustering of CD8 with immune-checkpoints (CD163/PD1/PDL1/PDL2/TIM3/LAG3, all P<0.0001), indicating an adaptive immune-checkpoint response to immune-effector activation. In 128 R-CHOP treated patients (median FU 3.9yrs), CD8:CD163 ratios (net anti-tumoral immunity) were prognostic, independent of IPI and COO. Combining CD8:CD163 ratio with the germinal centre B cell marker LMO2 (LMO2/CD8:CD163) strengthened the predictive ability. Results were externally validated in 233 R-CHOP patients, separating good-risk (0-2) IPI into two categories of 85% and 48% (P=0.0003), and poor-risk (3-5) IPI into 66% and 36% 4 year survival (P=0.0007). Conclusions: Net anti-tumoral immunity within the TME is a powerful new prognosticator, independent of IPI and COO in DLBCL. LMO2/CD8:CD163 adds to the predictive ability of IPI.
American Heart Association Response to the 2015 Institute of Medicine Report on Strategies to Improve Cardiac Arrest Survival
Authors: Robert W. Neumar, Brian Eigel, Clifton W. Callaway, N.A. Mark Estes, James G. Jollis, Monica E. Kleinman, Laurie J. Morrison, Mary Ann Peberdy, Alejandro Rabinstein, Thomas D. Rea, Sue Sendelbach
Journal: Circulation (2015)

The American Heart Association (AHA) commends the recently released Institute of Medicine (IOM) report, Strategies to Improve Cardiac Arrest Survival: A Time to Act (2015). The AHA recognizes the unique opportunity created by the report to meaningfully advance the objectives of improving outcomes for sudden cardiac arrest. For decades, the AHA has focused on the goal of reducing morbidity and mortality from cardiovascular disease though robust support of basic, translational, clinical, and population research. The AHA also has developed a rigorous process using the best available evidence to develop scientific, advisory, and guideline documents. These core activities of development and dissemination of scientific evidence have served as the foundation for a broad range of advocacy initiatives and programs that serve as a foundation for advancing the AHA and IOM goal of improving cardiac arrest outcomes. In response to the call to action in the IOM report, the AHA is announcing 4 new commitments to increase cardiac arrest survival: (1) The AHA will provide up to $5 million in funding over 5 years to incentivize resuscitation data interoperability; (2) the AHA will actively pursue philanthropic support for local and regional implementation opportunities to increase cardiac arrest survival by improving out-of-hospital and in-hospital systems of care; (3) the AHA will actively pursue philanthropic support to launch an AHA resuscitation research network; and (4) the AHA will cosponsor a National Cardiac Arrest Summit to facilitate the creation of a national cardiac arrest collaborative that will unify the field and identify common goals to improve survival. In addition to the AHA's historic and ongoing commitment to improving cardiac arrest care and outcomes, these new initiatives are responsive to each of the IOM recommendations and demonstrate the AHA's leadership in the field. However, successful implementation of the IOM recommendations will require a timely response by all stakeholders identified in the report and a coordinated approach to achieve our common goal of improved cardiac arrest outcomes.
Idiopathic portal hypertension: Natural history and long-term outcome
Authors: Sith Siramolpiwat, Susana Seijo, Rosa Miquel, Annalisa Berzigotti, Angeles Garcia-Criado, Anna Darnell, Fanny Turon, Virginia Hernandez-Gea, Jaume Bosch, Juan Carlos Garcia-Pagán
Journal: Hepatology (2013)

Idiopathic portal hypertension (IPH) is a rare cause of intrahepatic portal hypertension. Data on natural history and prognosis of IPH are limited. We sought to describe the complications and long-tem outcome of IPH by retrospectively studying 69 biopsy-proven cases of IPH. Mean duration of follow-up was 6.7 ± 4.6 years. All patients had evidence of portal hypertension (PH) at diagnosis, and 42% were symptomatic. Variceal bleeding (VB) was the most common manifestation. In those without bleeding at diagnosis, 74% had varices at first endoscopy. In those with large varices, the 1-year probability of first bleeding despite primary prophylaxis was 9%. The 1-year probability of rebleeding was 22%. Ascites and hepatic encephalopathy was documented in 26% and 7% of patients, respectively, at least once during the clinical course. The 1-year probability of developing portal vein thrombosis (PVT) was 9%, and 53% of patients receiving anticoagulation achieved recanalization. Human immunodeficiency virus (HIV) infection and VB at diagnosis were the independent predictors of PVT. Seven patients died (6 as a result of an IPH-related cause) and 2 were transplanted. Probability of liver transplantation-free survival was 82% at 10 years. Presence of a severe associated disorder and ascites as a presenting symptom were associated with poor survival. Variceal bleeding is a major complication of IPH. Using, in IPH patients, the same management approach for PH as in cirrhosis is safe and maintains a low incidence of first bleeding and rebleeding in IPH patients. PVT is a frequent complication, particularly in those with HIV infection. Despite several complications, overall survival of patients with IPH is considerably good.
A Meta-Analysis on the Interaction between HER-2 Expression and Response to Endocrine Treatment in Advanced Breast Cancer
Authors: Michele De Laurentiis, Grazia Arpino, Erminia Massarelli, Angela Ruggiero, Chiara Carlomagno, Fortunato Ciardiello, Giampaolo Tortora, Diego D'Agostino, Francesca Caputo, Giuseppe Cancello, Emilia Montagna, Luca Malorni, Luigia Zinno, Rossella Lauria, Angelo Raffaele Bianco, Sabino De Placido
Journal: Clinical Cancer Research (2005)

Abstract Purpose: Experimental data suggest a complex cross-talk between HER-2 and estrogen receptor, and it has been hypothesized that HER-2-positive tumors may be less responsive to certain endocrine treatments. Clinical data, however, have been conflicting. We have conducted a meta-analysis on the interaction between the response to endocrine treatment and the overexpression of HER-2 in metastatic breast cancer. Experimental Design: Studies have been identified by searching the Medline, Embase, and American Society of Clinical Oncology abstract databases. Selection criteria were (a) metastatic breast cancer, (b) endocrine therapy (any line of treatment), and (c) evaluation of HER-2 expression (any method). For each study, the relative risk for treatment failure for HER-2-positive over HER-2-negative patients with 95% confidence interval was calculated as an estimate of the predictive effect of HER-2. Pooled estimates of the relative risk were computed by the Mantel-Haenszel method. Results: Twelve studies (n = 2,379 patients) were included in the meta-analysis. The overall relative risk was 1.42 (95% confidence interval, 1.32-1.52; P &amp;lt; 0.00001; test for heterogeneity = 0.380). For studies involving tamoxifen, the pooled relative risk was 1.33 (95% confidence interval, 1.20-1.48; P &amp;lt; 0.00001; test for heterogeneity = 0.97); for studies involving other hormonal drugs, a pooled relative risk of 1.49 (95% confidence interval, 1.36-1.64; P &amp;lt; 0.00001; test for heterogeneity = 0.08) was estimated. A second meta-analysis limited to tumors that were either estrogen receptor positive, estrogen receptor unknown, or estrogen receptor negative/progesterone receptor positive yielded comparable results. Conclusions: HER-2-positive metastatic breast cancer is less responsive to any type of endocrine treatment. This effect holds in the subgroup of patients with positive or unknown steroid receptors.
Late-breaking abstract: Pneumococcal serotypes causing community-acquired pneumonia (CAP) among hospitalized adults in Spain using a new urinary antigen detection (UAD) test. The CAPA study
Authors: Rosario Menéndez, Antoni Torres, Pedro Pablo España, Emilio Pérez-Trallero, José Luis López Hontangas, Francesc Marco, Ana Patricia Martínez de la Fuente, José María Marimón, Alexandra Gimeno, Catia Cilloniz, Ane Uranga, María Ercibengoa, César Balseiro, Cristina Méndez
Journal: European Respiratory Journal (2014)

Background and objective: Widespread use of PCV7/PCV13 in children has resulted in a significant reduction of pneumococcal diseases in adults. Pneumococcal pneumonias due to PCV13 vaccine serotypes particularly in CAP without bacteremia are not known. In Spain, where PCV13 is mainly available in private market for healthy children (estimated uptake ≈70%), we assessed the burden of disease caused by PCV13 serotypes in immunocompetent subjects >18 years hospitalized with CAP in 3 Spanish hospitals (November 2011-May 2013).

Methods: In subjects hospitalized with CAP, microbiological confirmation was sought by the novel UAD (Pfizer's PCV13 serotype specific urinary antigen detection test), BinaxNow & conventional cultures. Serotyping of pneumococcal isolates was accomplished in a central laboratory using Quellung reaction.

Results: S. pneumoniae infection was microbiologically confirmed in 232 cases (30.7%) of 756 enrolled patients by any diagnostic test. Positivity rates for the different tests were: UAD: 63%; BinaxNow: 57.3%; blood cultures: 16.8%; pleural fluid culture: 2.5%; sputum: 9.4% and others: 0.8%. Table shows PCV13 vaccine type distribution in invasive1 and non-invasive2 pneumococcal CAP.

![Figure][1] 



Conclusion: Almost 20% of hospitalized CAP in immunocompetent adults in Spain were caused by one of the serotypes included in PCV13.

 [1]: pending:yes
Tumor Hybrid Cells: An Immunotherapeutic Agent2
Authors: Robertson Parkman
Journal: JNCI Journal of the National Cancer Institute (1974)

Hybrid tumor cells were formed by the spontaneous and virus-induced fusion of EL-4 lymphoma cells with C3H fibroblasts. Some resultant hybrid cell lines specifically immunized C57BL/6 and (C57BL/6 × C3H)F1 mice against subsequent lethal EL-4 challenge. The immune response to the hybrid tumor cells was superior to the response to irradiated EL-4 cells. The possibility of hybrid tumor cells as a specific immunotherapeutic agent was discussed.