tbuckley/cabot-search huggingface dataset:
The expression of CD39 mRNA is altered in peripheral blood of patients with allergic asthma
Authors: Linlin Wang, Guochao Shi, Huanying Wan
Journal: European Respiratory Journal (2013)

The ecto-enzyme CD39 can hydrolyze extracellular ATP which has pro-inflammatory effects. But the role of CD39 in patients with allergic asthma remains unknown. Eighteen patients with persistent asthma allergic to house dust mites and nineteen healthy volunteers were enrolled.The expression of CD39, GATA3, ROR-γt and Foxp3 mRNA in PBMC were determined by SYRB Green Real-time PCR.The cytokines IL-4, IL-17A, TGF-β and DP.sIgE were detected by ELISA. Our data showed that the expression of CD39 mRNA in PBMC from asthmatics was significantly lower than that in normal controls (1.49±0.59×10 -3  vs 2.17±0.77×10 -3 ,  P  P  P  P  P  P  P =0.122). These data suggest that CD39 mRNA expression was down-regulated in peripheral blood of asthmatics, which was positively relevant to serum IL-4, IL-17A and GATA3 and negatively relevant to serum TGF-β and Foxp3, and was not relevant to ROR-γt. We speculated that CD39 may participate in the occurrence and progress of allergic asthma.
Effects of Daunomycin and Anthramycin on Electrocardiogram and Mitochondrial Metabolism of the Rat Heart2
Authors: Colin Cargill, Elisabeth Bachmann, Gerhard Zbinden
Journal: JNCI Journal of the National Cancer Institute (1974)

Journal Article Effects of Daunomycin and Anthramycin on Electrocardiogram and Mitochondrial Metabolism of the Rat Heart Get access Colin Cargill, B.V.Sc., Ph.D., Colin Cargill, B.V.Sc., Ph.D. Search for other works by this author on: Oxford Academic PubMed Google Scholar Elisabeth Bachmann, Dr.Sc.nat., Elisabeth Bachmann, Dr.Sc.nat. Search for other works by this author on: Oxford Academic PubMed Google Scholar Gerhard Zbinden, M.D Gerhard Zbinden, M.D 5 5Address reprint requests to Dr. Zbinden. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 53, Issue 2, August 1974, Pages 481–486, https://doi.org/10.1093/jnci/53.2.481 Published: 01 August 1974 Article history Received: 01 February 1974 Accepted: 16 April 1974 Published: 01 August 1974
Plasmodium vivax Liver Stage Development and Hypnozoite Persistence in Human Liver-Chimeric Mice
Authors: Sebastian A. Mikolajczak, Ashley M. Vaughan, Niwat Kangwanrangsan, Wanlapa Roobsoong, Matthew Fishbaugher, Narathatai Yimamnuaychok, Nastaran Rezakhani, Viswanathan Lakshmanan, Naresh Singh, Alexis Kaushansky, Nelly Camargo, Michael Baldwin, Scott E. Lindner, John H. Adams, Jetsumon Sattabongkot, Stefan H.I. Kappe
Journal: Cell Host & Microbe (2015)
Randomized Trial of Breast Irradiation Schedules After Lumpectomy for Women With Lymph Node-Negative Breast Cancer
Authors: T. Whelan
Journal: JNCI Journal of the National Cancer Institute (2002)

Background: Breast irradiation after lumpectomy is an integral component of breast-conserving therapy that reduces the local recurrence of breast cancer. Because an optimal fractionation schedule (radiation dose given in a specified number of fractions or treatment sessions over a defined time) for breast irradiation has not been uniformly accepted, we examined whether a 22-day fractionation schedule was as effective as the more traditional 35-day schedule in reducing recurrence. Methods: Women with invasive breast cancer who were treated by lumpectomy and had pathologically clear resection margins and negative axillary lymph nodes were randomly assigned to receive whole breast irradiation of 42.5 Gy in 16 fractions over 22 days (short arm) or whole breast irradiation of 50 Gy in 25 fractions over 35 days (long arm). The primary outcome was local recurrence of invasive breast cancer in the treated breast. Secondary outcomes included cosmetic outcome, assessed with the European Organisation for Research and Treatment of Cancer (EORTC) Cosmetic Rating System. All statistical tests were two-sided. Results: From April 1993 through September 1996, 1234 women were randomly assigned to treatment, 622 to the short arm and 612 to the long arm. Median follow-up was 69 months. Five-year local recurrence-free survival was 97.2% in the short arm and 96.8% in the long arm (absolute difference = 0.4%, 95% confidence interval [CI] = –1.5% to 2.4%). No difference in disease-free or overall survival rates was detected between study arms. The percentage of patients with an excellent or good global cosmetic outcome at 3 years was 76.8% in the short arm and 77.0% in the long arm; the corresponding data at 5 years were 76.8% and 77.4%, respectively (absolute difference = –0.6%, 95% CI = –6.5% to 5.5%). Conclusion: The more convenient 22-day fractionation schedule appears to be an acceptable alternative to the 35-day schedule.
<i>Lnc</i> ing Epigenetic Control of Transcription to Cardiovascular Development and Disease
Authors: Gizem Rizki, Laurie A. Boyer
Journal: Circulation Research (2015)

Transcriptional and epigenetic regulation is critical for proper heart development, cardiac homeostasis, and pathogenesis. Long noncoding RNAs have emerged as key components of the transcriptional regulatory pathways that govern cardiac development as well as stress response, signaling, and remodeling in cardiac pathologies. Within the past few years, studies have identified many long noncoding RNAs in the context of cardiovascular biology and have begun to reveal the key functions of these transcripts. In this review, we discuss the growing roles of long noncoding RNAs in different aspects of cardiovascular development as well as pathological responses during injury or disease. In addition, we discuss diverse mechanisms by which long noncoding RNAs orchestrate cardiac transcriptional programs. Finally, we explore the exciting potential of this novel class of transcripts as biomarkers and novel therapeutic targets for cardiovascular diseases.
Thymic development beyond β-selection requires phosphatidylinositol 3-kinase activation by CXCR4
Authors: Michelle L. Janas, Gabriele Varano, Kristjan Gudmundsson, Mamiko Noda, Takashi Nagasawa, Martin Turner
Journal: The Journal of Experimental Medicine (2009)

T cell development requires phosphatidylinositol 3-kinase (PI3K) signaling with contributions from both the class IA, p110δ, and class IB, p110γ catalytic subunits. However, the receptors on immature T cells by which each of these PI3Ks are activated have not been identified, nor has the mechanism behind their functional redundancy in the thymus. Here, we show that PI3K signaling from the preTCR requires p110δ, but not p110γ. Mice deficient for the class IB regulatory subunit p101 demonstrated the requirement for p101 in T cell development, implicating G protein–coupled receptor signaling in β-selection. We found evidence of a role for CXCR4 using small molecule antagonists in an in vitro model of β-selection and demonstrated a requirement for CXCR4 during thymic development in CXCR4-deficient embryos. Finally, we demonstrate that CXCL12, the ligand for CXCR4, allows for Notch-dependent differentiation of DN3 thymocytes in the absence of supporting stromal cells. These findings establish a role for CXCR4-mediated PI3K signaling that, together with signals from Notch and the preTCR, contributes to continued T cell development beyond β-selection.
Metformin and Breast Cancer Risk
Authors: Sara Gandini, Aliana Guerrieri-Gonzaga, Matteo Puntoni, Andrea DeCensi
Journal: Journal of Clinical Oncology (2013)

However, it remains important to demonstrate predictive value for a biomarker in an initial historic data set.These predictive analyses require a control group and single-arm studies are insufficient.An ideal trial to demonstrate this predictive utility of LDH for the benefit of mTOR inhibition would have a control arm that mirrors current clinical practice, such as treatment with sunitinib or pazopanib.Future comparative trials of mTOR versus VEGF inhibitors will need to validate LDH as a predictive biomarker across a range of RCC treatment settings before our results can be generalized.Though progression-free survival rates were shorter in patients with high LDH who were treated with interferon than those with normal LDH (2.5 v 3.4 months), this difference was quite marginal and is not likely to explain the survival benefit of temsirolimus in the high versus low LDH subset or in the entire study.It is also noteworthy that patients with poor risk RCC who obtained a decline in LDH with interferon did have a more prolonged survival, suggesting that LDH could be useful as a biomarker of response to interferon in this population as well.The opposite result with temsirolimus was noted: a rise in LDH with treatment had a favorable prognostic association, indicating that the serial measurements of LDH may also have some clinical utility.We did not evaluate hypertension development in this trial because hypertension development with mTOR inhibitors is not common, unlike the class effect observed with most VEGF inhibitors.In conclusion, we agree that future phase III trial data sets should be analyzed in RCC and other tumor types to examine the predictive role of LDH for PI3K/AKT/ mTOR pathway inhibition.Ideally, this would be conducted in trials against contemporary control groups (ie, with anti-VEGF agents) that were positive for overall survival, similar to the current temsirolimus data set because LDH was not predictive of progression-free survival in our study.
Obinutuzumab (GA101) Monotherapy in Relapsed/Refractory Diffuse Large B-Cell Lymphoma or Mantle-Cell Lymphoma: Results From the Phase II GAUGUIN Study
Authors: Franck Andre Morschhauser, Guillaume Cartron, Catherine Thieblemont, Philippe Solal-Céligny, Corinne Haioun, Reda Bouabdallah, Pierre Feugier, Krimo Bouabdallah, Elina Asikanius, Guiyuan Lei, Michael Wenger, Elisabeth Wassner-Fritsch, Gilles Andre Salles
Journal: Journal of Clinical Oncology (2013)

Obinutuzumab (GA101), a type II, glycoengineered, humanized anti-CD20 monoclonal antibody, was superior to rituximab in human diffuse large B-cell lymphoma (DLBCL) and mantle-cell lymphoma (MCL) xenograft models. In phase I of our study, obinutuzumab (GA101) exhibited encouraging activity but no clear dose-response relationship, and few patients had aggressive histologies. The efficacy and safety of two doses of obinutuzumab (GA101) were explored in our randomized phase II trial in patients with heavily pretreated DBLCL and MCL.Patients were randomly assigned to receive eight cycles of obinutuzumab (GA101) either as a flat dose of 400 mg for all infusions (days 1 and 8 of cycle 1; day 1 of cycles 2 to 8) or 1,600 mg on days 1 and 8 of cycle 1 and 800 mg on day 1 of cycles 2 to 8.Forty patients were enrolled: 21 patients in the 400/400-mg treatment arm (DLBCL, n = 10; MCL, n = 11) and 19 patients in the 1,600/800-mg arm (DLBCL, n = 15; MCL, n = 4). End-of-treatment response was 28% (32% and 24% in the 1,600/800-mg and 400/400-mg study arms, respectively). Best overall response rates were 37% in the 1,600/800-mg arm and 24% in the 400/400-mg study arm (DLBCL, eight [32%] of 25 patients; MCL, four [27%] of 15 patients). Five (20%) of 25 rituximab-refractory patients exhibited treatment response, including four of 12 in the 1,600/800-mg group. The most common adverse events were infusion-related reactions (IRRs), which were manageable. Three patients had grade 3/4 IRRs. Grade 3/4 neutropenia was seen in only one patient.Obinutuzumab (GA101) 1,600/800 mg achieves early steady-state concentration and clinical activity with an acceptable safety profile in relapsed/refractory DLBCL and MCL, supporting further exploration.
Alteration of the immune response to nontypeable haemophilus influenzae (NTHI) during COPD exacerbation in mice
Authors: Riti Sharan, Gaëlle Rémy, Gwenola Kervoaze, Eva Vilain, Philippe Gosset, Muriel Pichavant
Journal: European Respiratory Journal (2013)

Background: Acute episodes of bacterial exacerbations mark the progression of chronic obstructive pulmonary disorder (COPD). These exacerbations result in an increased lung inflammation. NTHI is commonly isolated bacteria during these episodes. Mechanisms responsible for the increased susceptibility to this pathogen are unknown.  Objectives: Our aim is to define the alteration of the immune response to NTHI infection by using a mouse model of COPD.  Methods: C57BL/6 wild type mice were chronically exposed to cigarette smoke for 12 weeks. The mice were intranasally challenged with a sub-lethal dose of NTHI (5x107cfu) and sacrificed at day 2 post-infection. Inflammation and immune responses, bacterial burden and pathological changes were evaluated.  Results: An increased bacterial load was observed in infected COPD mice as compared to air control mice. There was an increase in the levels of IL-1β, IL-6, TNFα and IFNγ in the lung and BAL of infected COPD mice. IL-22 levels were decreased in the infected COPD mice. There was an increased mobilization and activation of innate cells and T lymphocytes in COPD mice. This was associated with an increased production of IFN-γ and IL-17 in the NTHI-restimulated lung cells. There was a strong inflammation in the lung with mucus secretion and remodelling in infected COPD mice.  Conclusions: An increased susceptibility to H. influenzae infection was observed in COPD mice. The decrease in IL-22 production might be involved in the increased susceptibility to infection by NTHI. In contrast, the inflammatory cytokine storm and the neutrophil recruitment might trigger exacerbation-induced progression of COPD.
Prognosis of chronic duodenal ulcer: a prospective study of the effects of demographic and environmental factors and ulcer healing.
Authors: R W Nasiry, J H McIntosh, K Byth, D W Piper
Journal: Gut (1987)

The aim of this prospective study of 370 community based duodenal ulcer patients was to define the effect on duodenal ulcer course (from the aspect of symptom occurrence) of demographic and environmental factors, and of proven healing of index ulcer within four months. Follow up was three monthly, for up to three years. By survival analysis, it was found that marriage breakup adversely affected duodenal ulcer course, that age 50 years and under, female sex, and aspirin use tended to do so, and that smoking, alcohol ingestion, and paracetamol use did not. Proven healing of index ulcer within four months was associated with a small and non-significant reduction in symptom occurrence over time.
Overcoming acquired resistance to cetuximab by dual targeting HER family receptors with antibody-based therapy
Authors: Mari Iida, Toni M Brand, Megan M Starr, Evan J Huppert, Neha Luthar, Harsh Bahrar, John P Coan, Hannah E Pearson, Ravi Salgia, Deric L Wheeler
Journal: Molecular Cancer (2014)

Cetuximab, an anti-EGFR monoclonal antibody, is used to treat several cancers. However, many patients who initially respond to cetuximab acquire resistance. To examine mechanisms of acquired resistance, we developed a series of cetuximab-resistant (CtxR) clones derived from the cetuximab sensitive (CtxS) non-small cell lung cancer (NSCLC) cell line H226. Previous studies characterizing this model revealed that: 1) EGFR was robustly overexpressed in CtxR clones due to decreased EGFR ubiquitination and degradation and 2) CtxR clones expressed increased HER2 and HER3 activation resulting in constitutive activation of the PI3K/AKT signaling axis. These findings suggest that dual targeting HER family receptors would be highly beneficial in the CtxR setting. Since HER3 has been implicated in resistance to EGFR inhibitors, the efficacy of dually targeting both EGFR and HER3 in CtxR models was evaluated. First, EGFR and HER3 expression were knocked down with siRNAs. Compared to the CtxS parental cell line (HP), all CtxR clones exhibited robust decreases in cell proliferation upon dual knockdown. Analysis of CtxR clones indicated that neuregulin-1 was highly overexpressed compared to HP cells. Incubation of HP cells with neuregulin-1 rendered them resistant to cetuximab. Next, dual treatment of CtxR clones with cetuximab and the HER3 neutralizing monoclonal antibody (mAb) U3-1287 led to potent anti-proliferative effects. Blockade of EGFR with cetuximab resulted in inactivation of MAPK, while blockade of HER3 with U3-1287 resulted in the inactivation of AKT. Treatment with both mAbs resulted in knockdown of both signaling pathways simultaneously. HER2 was also strongly inactivated upon dual mAb therapy, suggesting that this treatment regimen can diminish signaling from three HER family receptors. De novo CtxR H226 mouse xenografts were established to determine if dual therapy could overcome acquired resistance to cetuximab in vivo. Tumors that had acquired resistance to cetuximab were significantly growth delayed upon dual treatment of U3-1287 and cetuximab compared to those continued on cetuximab only. Combinatorial-treated xenograft tumors expressed decreased Ki67 and increased cleaved caspase-3 levels compared to tumors treated with either monotherapy. These studies demonstrate that dually targeting HER family receptors with antibody-based therapies can overcome acquired resistance to cetuximab.
Accumulation of Immature Langerhans Cells in Human Lymph Nodes Draining Chronically Inflamed Skin
Authors: F. Geissmann, M.C. Dieu-Nosjean, C. Dezutter, J. Valladeau, S. Kayal, M. Leborgne, N. Brousse, S. Saeland, J. Davoust
Journal: The Journal of Experimental Medicine (2002)

The coordinated migration and maturation of dendritic cells (DCs) such as intraepithelial Langerhans cells (LCs) is considered critical for T cell priming in response to inflammation in the periphery. However, little is known about the role of inflammatory mediators for LC maturation and recruitment to lymph nodes in vivo. Here we show in human dermatopathic lymphadenitis (DL), which features an expanded population of LCs in one draining lymph node associated with inflammatory lesions in its tributary skin area, that the Langerin/CD207+ LCs constitute a predominant population of immature DCs, which express CD1a, and CD68, but not CD83, CD86, and DC–lysosomal-associated membrane protein (LAMP)/CD208. Using LC-type cells generated in vitro in the presence of transforming growth factor (TGF)-β1, we further found that tumor necrosis factor (TNF)-α, as a prototype proinflammatory factor, and a variety of inflammatory stimuli and bacterial products, increase Langerin expression and Langerin dependent Birbeck granules formation in cell which nevertheless lack costimulatory molecules, DC–LAMP/CD208 and potent T cell stimulatory activity but express CCR7 and respond to the lymph node homing chemokines CCL19 and CCL21. This indicates that LC migration and maturation can be independently regulated events. We suggest that during DL, inflammatory stimuli in the skin increase the migration of LCs to the lymph node but without associated maturation. Immature LCs might regulate immune responses during chronic inflammation.
Contribution of Polyol Pathway to Diabetes-Induced Oxidative Stress
Authors: Stephen S.M. Chung, Eric C.M. Ho, Karen S.L. Lam, Sookja K. Chung
Journal: Journal of the American Society of Nephrology (2003)

ABSTRACT. Diabetes causes increased oxidative stress, which is thought to play an important role in the pathogenesis of various diabetic complications. However, the source of the hyperglycemia-induced oxidative stress is not clear. It was found that the polyol pathway is the major contributor to oxidative stress in the lenses and nerves of diabetic mice. The first enzyme in the pathway, aldose reductase (AR), reduces glucose to sorbitol, which is then converted to fructose by sorbitol dehydrogenase (SDH). Transgenic mice that overexpress AR specifically in their lenses showed a significant increase in oxidative stress when they became hyperglycemic, as indicated by a decrease in GSH and an increase in malondialdehyde in their lenses. Introducing an SDH-deficient mutation into these transgenic mice significantly normalized the GSH and malondialdehyde levels. These results indicate that both enzymes of the polyol pathway contributed to hyperglycemia-induced oxidative stress in the lens. In the wild-type mice, diabetes caused a significant decrease in GSH in their sciatic nerves, indicative of oxidative stress. In the AR null mutant mice, diabetes did not lead to any decrease in the nerve GSH level. These results indicate that similar to the situation in the lens, AR is also the major contributor to hyperglycemia-induced oxidative stress in the nerve. Although increased flux of glucose through the polyol pathway leads to diabetic lesions in both the lenses and nerve, the mechanisms may be different. AR-induced osmotic stress seems to be the cause of diabetic cataract, whereas AR-induced oxidative stress is probably the cause of neuronal dysfunction. E-mail: [email protected]
Early versus late pulmonary rehabilitation on anxiety and depression in chronic obstructive pulmonary disease patients with acute exacerbations
Authors: Ze guang Zheng, Shao ying Liang, Hui Hong Cen, Qin Chen
Journal: European Respiratory Journal (2012)

Objective:  Compare the effects of early and late pulmonary rehabilitation on anxiety and depression in COPD inpatients with exacerbations.  Methods:  We randomized 113 COPD patients with exacerbation to early(76) or late(37) pulmonary rehabilitation.After discharging from exacerbation,the early pulmonary rehabilitation started a rehabilitation program with 8-weeks.While the late accepted assessment again in the eight week after discharging. Taked the change of pre-post discharging as those patients who did not attend rehabilitation program.After finishing the second assessment, the late group also accepted a rehabilitation program as the early. Primary outcomes were anxiety and depression assessed by BDI and STAI. Secondary outcomes included lung function, dyspnea and 6-minutes wallk distance(6MWD).  Results:  (1) Only 26 patients of the early and 20 patients of the late finished the program(≥70%). (2) Overall, patients9 lung function were not improved. Anxiety, depression,dyspnea and 6MWD all were improved significantly over 8 weeks among three groups. Moreover, the improvement in the early pulmonary rehabilitation were better than the late and the not rehabilitation group. (3) Prevalence of anxiety and depression were not changed significantly pre-post or between groups, except the pre-post rehabilitation in the early.  Conclusion:  Early and late pulmonary rehabilitation, as well as the usual discharge with the exacerbation, are effective treatment in terms of improving anxiety, drperssion, dyspnea and exercise capacity in COPD patients with exacerbation. And the early pulmonary rehabilitation provides the most benefits.