tbuckley/cabot-search huggingface dataset:
Work-exacerbated rhinitis among bakers – Is it a problem?
Authors: Jolanta Walusiak-Skorupa, Marta Wiszniewska, Agnieszka Lipinska-Ojrzanowska, Ewa Nowakowska-Swirta, Patrycja Krawczyk-Szulc, Cezary Palczynski
Journal: European Respiratory Journal (2011)

Work-exacerbated rhinitis (WER) is pre-existing or concurrent rhinitis that is worsened by workplace exposures, while the disease has not been caused by the work environment. WER is currently less well characterized than the corresponding entity of work-exacerbated asthma and exact data on its prevalence and associated factors are usually not known. The aim of the study was to evaluate the frequency of WER in bakers with suspected respiratory occupational allergy.   Material and methods:  The study group included 393 bakers reporting respiratory symptoms at the workplace. In all subjects questionnaire, spirometry, skin prick tests (SPT), evaluation of serum total and specific IgE level were performed. Recognition of occupational rhinitis (OR) was based on inhalative specific challenge test with evaluation of nasal response (nasal lavage analysis).   Results:  OR was found in 138 (35,1%) bakers while WER was recognized in 116 (29,5%) subjects. 66,7% subjects with OR and 43,1% with WER had positive SPT to common allergens, while occupational SPT were positive in 76,8% and 33,6% subjects respectively. In patients with OR the latency period, i.e. duration of exposure before the occurrence of symptoms was 10,8 whereas in bakers with WER 13,8 years. Generally, bakers who suffered from occupational rhinitis were younger than the patients with WER. Additionally, OR coexisted with asthma more frequently than WER.   Conclusions:  WER is frequent health problem and concerns about 30% of bakers reporting allergic respiratory symptoms. Its differentiation with OR should include specific challenge test, as anamnesis, skin prick tests to occupational allergens and evaluation of serum allergen specific IgE do not display sufficient specificity.
Intermittent Claudication of the Hip and the Syndrome of Chronic Aorto-Iliac Thrombosis
Authors: VICTOR G. DEWOLFE, FAY A. LEFEVRE, ALFRED W. HUMPHRIES, MALIN B. SHAW, GEORGE S. PHALEN
Journal: Circulation (1954)

It is the purpose of this paper to report the not too widely known clinical symptom of hip claudication and its relationship to aortic and iliac artery occlusions. The importance of aortography in the diagnosis of this syndrome is stressed and a technic is described. The results and findings differ from previous reports in the literature and these variations are discussed.
Overexpression of Brain Natriuretic Peptide Facilitates Neutrophil Infiltration and Cardiac Matrix Metalloproteinase-9 Expression After Acute Myocardial Infarction
Authors: Rika Kawakami, Yoshihiko Saito, Ichiro Kishimoto, Masaki Harada, Koichiro Kuwahara, Nobuki Takahashi, Yasuaki Nakagawa, Michio Nakanishi, Keiji Tanimoto, Satoru Usami, Shinji Yasuno, Hideyuki Kinoshita, Hideki Chusho, Naohisa Tamura, Yoshihiro Ogawa, Kazuwa Nakao
Journal: Circulation (2004)

Recent clinical trials have shown that systemic infusion of nesiritide, a recombinant human brain natriuretic peptide (BNP), improves hemodynamic parameters in acutely decompensated hearts. This suggests that BNP exerts a direct cardioprotective effect and might thus be a useful therapeutic agent with which to treat acute myocardial infarction (MI). In the present study, we used BNP-transgenic (BNP-Tg) mice with elevated plasma BNP to determine whether and how BNP contributes to left ventricular remodeling and healing after MI.We examined the accumulation of neutrophils and the expression and activation of matrix metalloproteinase (MMP)-9 in the ventricles of male BNP-Tg mice and their nontransgenic (non-Tg) littermates during the early phase after acute MI. The numbers of neutrophils infiltrating the infarcted area were significantly increased in BNP-Tg mice 3 days after MI. In addition, both the gene expression and zymographic activity of MMP-9, but not MMP-2, were significantly higher in BNP-Tg than non-Tg mice. Double immunostaining revealed that neutrophils are the main source of the MMP-9, although doxycycline, an MMP inhibitor, had no effect on neutrophil infiltration of the infarcted area in BNP-Tg mice.These results demonstrate that elevated plasma BNP facilitates neutrophil infiltration of the infarcted area after MI and increases the activity of the MMP-9 they produce. This suggests that BNP plays a key role in the processes of extracellular matrix remodeling and wound-healing during the early phase after acute MI.
Therapy-Related Myeloid Leukemias Are Observed in Patients With Chronic Lymphocytic Leukemia After Treatment With Fludarabine and Chlorambucil: Results of an Intergroup Study, Cancer and Leukemia Group B 9011
Authors: Vicki A. Morrison, Kanti R. Rai, Bercedis L. Peterson, Jonathan E. Kolitz, Laurence Elias, Frederick R. Appelbaum, John D. Hines, Lois Shepherd, Richard A. Larson, Charles A. Schiffer
Journal: Journal of Clinical Oncology (2002)

Patients with chronic lymphocytic leukemia (CLL) may have disease transformation to non-Hodgkin's lymphoma or prolymphocytic leukemia; however, development of therapy-related acute myeloid leukemia (t-AML) is unusual. A series of patients enrolled onto an intergroup CLL trial were examined for this complication.A total of 544 previously untreated B-cell CLL patients were enrolled onto a randomized intergroup study comparing treatment with chlorambucil, fludarabine, or fludarabine plus chlorambucil. Case report forms from 521 patients were reviewed for t-AML.With a median follow-up of 4.2 years, six patients (1.2%) to date have developed therapy-related myelodysplastic syndrome (t-MDS; n = 3), t-AML (n = 2), or t-MDS evolving to t-AML (n = 1), from 27 to 53 months (median, 34 months) after study entry. This included five (3.5%) of 142 patients treated with fludarabine plus chlorambucil and one (0.5%) of 188 receiving fludarabine; no chlorambucil-treated patients developed t-MDS or t-AML (P =.007). At study entry, the median age among these six patients was 56 years (range, 44 to 72 years); three were male; the CLL Rai stage was I/II (n = 4) or III/IV (n = 2). Response to CLL therapy was complete (n = 4) or partial remission (n = 1) and stable disease (n = 1). Marrow cytogenetics, obtained in three of six cases at diagnosis of t-MDS or t-AML, were complex, with abnormalities in either or both chromosomes 5 and 7. Other abnormalities involved chromosomes X, 1, 8, 12, 17, and 19. Median survival after diagnosis of t-MDS/AML was 3.5 months (range, 0.5 to 10.1 months).Our findings raise the possibility that alkylator-purine analog combination therapy may increase the risk of therapy-related myeloid malignancies, which is of particular relevance with regard to ongoing trials using these combination therapies.
Active management of the third stage of labour with and without controlled cord traction: a randomised, controlled, non-inferiority trial
Authors: A Metin Gülmezoglu, Pisake Lumbiganon, Sihem Landoulsi, Mariana Widmer, Hany Abdel-Aleem, Mario Festin, Guillermo Carroli, Zahida Qureshi, João Paulo Souza, Eduardo Bergel, Gilda Piaggio, Shivaprasad S Goudar, John Yeh, Deborah Armbruster, Mandisa Singata, Cristina Pelaez-Crisologo, Fernando Althabe, Peter Sekweyama, Justus Hofmeyr, Mary-Ellen Stanton, Richard Derman, Diana Elbourne
Journal: The Lancet (2012)
Sex-Specific Immunization for Sexually Transmitted Infections Such as Human Papillomavirus: Insights from Mathematical Models
Authors: Johannes A. Bogaards, Mirjam Kretzschmar, Maria Xiridou, Chris J. L. M. Meijer, Johannes Berkhof, Jacco Wallinga
Journal: PLoS Medicine (2011)

Johannes Bogaards and colleagues use mathematical models to investigate whether vaccinating females only, males only, or both sexes is the best way to achieve the most effective reduction in the population prevalence of sexually-transmitted infections
Tumor Growth Inhibition by Simultaneously Blocking Epidermal Growth Factor Receptor and Cyclooxygenase-2 in a Xenograft Model
Authors: Xin Zhang, Zhuo (Georgia) Chen, Mi Sun Choe, Yan Lin, Shi-Yong Sun, H. Samuel Wieand, Hyung Ju C. Shin, Amy Chen, Fadlo R. Khuri, Dong M. Shin
Journal: Clinical Cancer Research (2005)

Abstract Purpose: Our previous study revealed that simultaneously targeting epidermal growth factor receptor (EGFR) tyrosine kinase and cyclooxygenase-2 (COX-2) additively or synergistically inhibited growth of squamous cell carcinoma of the head and neck (SCCHN) in vitro. However, an in vivo efficacy of this combined treatment in SCCHN has not been studied. Experimental Design: Nude mice were pretreated with control (1% Tween 80), ZD1839 (50 mg/kg) alone, celecoxib (50 mg/kg) alone, or a combination of ZD1839 and celecoxib at the same dosages for 7 days before injection of a human SCCHN cell line Tu212. The animals were continuously treated with the agents 5 days a week for about 11 weeks. Results: Tumor growth in the combined treatment was significantly inhibited compared with the control (P &amp;lt; 0.001), ZD1839 (P = 0.005), or celecoxib (P &amp;lt; 0.001). At the same time, a dramatic delay of tumor progression was observed in the combined treatment compared with all other three groups. Molecular analysis showed that the combined treatment significantly decreased prostaglandin E metabolite production. The cooperative effect of these two agents in combination was also associated with down-regulation of phosphorylated EGFR, phosphorylated extracellular signal-regulated kinase, and phosphorylated signal transducers and activators of transcription 3 levels and reduction of vascular endothelial growth factor and Ki-67 expression. Specifically, gene silencing of both EGFR and COX-2 by small interfering RNA further confirmed the cooperative antitumor effect. Conclusion: The current results strongly suggest that a cooperative effect of the combined treatment on tumor progression is mediated through blocking both EGFR- and COX-2-related pathways. This combination regimen may provide a promising strategy for cancer therapy and chemoprevention in SCCHN.
Biological effects of cobalt-chromium nanoparticles and ions on dural fibroblasts and dural epithelial cells
Authors: Bharat Behl, Iraklis Papageorgiou, Christopher Brown, Richard Hall, Joanne L. Tipper, John Fisher, Eileen Ingham
Journal: Biomaterials (2013)

The introduction of metal-on-metal total disc replacements motivated studies to evaluate the effects of cobalt-chromium (CoCr) nanoparticles on cells of the dura mater. Porcine fibroblasts and epithelial cells isolated from the dura mater were cultured with clinically-relevant CoCr nanoparticles and the ions, generated by the particles over 24 h, at doses up to 121 μm(3)per cell. Cell viability and production of proinflammatory cytokines was assessed over 4 days. The capacity of the particles to induce oxidative stress in the cells was evaluated at 24 h. The CoCr particles and their ions significantly reduced the viability of the dural epithelial cells in a dose-dependent manner but not the fibroblasts. Both cell types secreted IL-8 in response to particle exposure at doses of 60.5 μm(3) (epithelial cells) and 121 μm(3) (fibroblasts, epithelial cells) per cell. No significant release of IL-6 was observed in both cell types at any dose. Reactive oxygen species were induced in both cell types at 50 μm(3) per cell after 24 h exposure. The data suggested novel differences in the resistance of the dural epithelial cells and fibroblasts to CoCr nanoparticle/ion toxicity and demonstrated the inflammatory potential of the particles. The data contributes to a greater understanding of the potential biological consequences of the use of metal-on-metal total disc prostheses.
Prediction of common bile duct stones in the earliest stages of acute biliary pancreatitis
Authors: H. van Santvoort, O. Bakker, M. Besselink, T. Bollen, K. Fischer, V. Nieuwenhuijs, H. Gooszen, K. Erpecum
Journal: Endoscopy (2010)

Background and study aims: Accurate prediction of common bile duct (CBD) stones in acute biliary pancreatitis is warranted to select patients for early therapeutic endoscopic retrograde cholangiopancreatography (ERCP). We evaluated commonly used biochemical and radiological predictors of CBD stones in a large prospective cohort of patients with acute biliary pancreatitis who were undergoing early ERCP.
WNT16B Is a New Marker of Cellular Senescence That Regulates p53 Activity and the Phosphoinositide 3-Kinase/AKT Pathway
Authors: Romuald Binet, Damien Ythier, Ana I. Robles, Manuel Collado, Delphine Larrieu, Claire Fonti, Elisabeth Brambilla, Christian Brambilla, Manuel Serrano, Curtis C. Harris, Rémy Pedeux
Journal: Cancer Research (2009)

Senescence is a tumor suppression mechanism that is induced by several stimuli, including oncogenic signaling and telomere shortening, and controlled by the p53/p21(WAF1) signaling pathway. Recently, a critical role for secreted factors has emerged, suggesting that extracellular signals are necessary for the onset and maintenance of senescence. Conversely, factors secreted by senescent cells may promote tumor growth. By using expression profiling techniques, we searched for secreted factors that were overexpressed in fibroblasts undergoing replicative senescence. We identified WNT16B, a member of the WNT family of secreted proteins. We found that WNT16B is overexpressed in cells undergoing stress-induced premature senescence and oncogene-induced senescence in both MRC5 cell line and the in vivo murine model of K-Ras(V12)-induced senescence. By small interfering RNA experiments, we observed that both p53 and WNT16B are necessary for the onset of replicative senescence. WNT16B expression is required for the full transcriptional activation of p21(WAF1). Moreover, WNT16B regulates activation of the phosphoinositide 3-kinase (PI3K)/AKT pathway. Overall, we identified WNT16B as a new marker of senescence that regulates p53 activity and the PI3K/AKT pathway and is necessary for the onset of replicative senescence.
Fatty Acid Synthase Gene Is Up-regulated by Hypoxia via Activation of Akt and Sterol Regulatory Element Binding Protein-1
Authors: Eiji Furuta, Sudha K. Pai, Rui Zhan, Sucharita Bandyopadhyay, Misako Watabe, Yin-Yuan Mo, Shigeru Hirota, Sadahiro Hosobe, Taisei Tsukada, Kunio Miura, Shuichi Kamada, Ken Saito, Megumi Iiizumi, Wen Liu, Johan Ericsson, Kounosuke Watabe
Journal: Cancer Research (2008)

Abstract The fatty acid synthase (FAS) gene is significantly up-regulated in various types of cancers, and blocking the FAS expression results in apoptosis of tumor cells. Therefore, FAS is considered to be an attractive target for anticancer therapy. However, the molecular mechanism by which the FAS gene is up-regulated in tumor cells is poorly understood. We found that FAS was significantly up-regulated by hypoxia, which was also accompanied by reactive oxygen species (ROS) generation in human breast cancer cell lines. The FAS expression was also activated by H2O2, whereas N-acetyl-l-cystein, a ROS inhibitor, suppressed the expression. We also found that the hypoxia significantly up-regulated sterol regulatory–element binding protein (SREBP)-1, the major transcriptional regulator of the FAS gene, via phosphorylation of Akt followed by activation of hypoxia-inducible factor 1 (HIF1). Moreover, our results of reporter assay and chromatin immunoprecipitation analysis indicate that SREBP-1 strongly bound to the SREBP binding site/E-box sequence on the FAS promoter under hypoxia. In our xenograft mouse model, FAS was strongly expressed in the hypoxic regions of the tumor. In addition, our results of immunohistochemical analysis for human breast tumor specimens indicate that the expressions of both FAS and SREBP-1 were colocalized with hypoxic regions in the tumors. Furthermore, we found that hypoxia-induced chemoresistance to cyclophosphamide was partially blocked by a combination of FAS inhibitor and cyclophosphamide. Taken together, our results indicate that FAS gene is up-regulated by hypoxia via activation of the Akt and HIF1 followed by the induction of the SREBP-1 gene, and that hypoxia-induced chemoresistance is partly due to the up-regulation of FAS. [Cancer Res 2008;68(4):1003–11]
Effects of different treatment regimens of methylprednisolone on rat diaphragm contractility, immunohistochemistry and biochemistry
Authors: RH van Balkom, HF van der Heijden, HT van Moerkerk, JH Veerkamp, JA Fransen, LA Ginsel, HT Folgering, CL van Herwaarden, PN Dekhuijzen
Journal: European Respiratory Journal (1996)

Systemic corticosteroid therapy may affect diaphragm structure and function. We postulated that functional, immunohistochemical and biochemical characteristics of rat diaphragm were less affected by alternate-day methylprednisolone (MP) administration, and more by repeated bursts of MP, in comparison to daily s.c MP. Sixty adult rats were randomized into four groups: saline s.c.; MP continuously (MP-C), 1 mg.kg-1 daily, MP alternate-day therapy (MP-A), 2 mg.kg-1 every other day; or MP in bursts (MP-B), MP 2 mg.kg-1 daily for 2 weeks, saline for 4 weeks, MP 2 mg.kg-1 daily for 2 weeks. The total treatment period was 8 weeks. Contractile properties of isolated diaphragm strips were measured. Antibodies reactive with type I, IIa, IIx and IIb myosin heavy chains were used for immunohistochemical analysis. Biochemical evaluation included markers of fast energy supply, glycogenolytic activity, beta-oxidation capacity and oxidative capacity. The force-frequency curve was depressed in all MP groups. Fibre type I, IIx and IIb cross-sectional area (CSA) decreased in all MP groups. Burst therapy decreased the contribution of type IIb fibres to total diaphragm muscle area. MP-A affected glycogenolytic activity less than MP-C. Burst MP therapy reduced creatine kinase (CK) activity and beta-oxidation capacity compared to MP-C. Oxidative capacity was increased in all MP groups. In conclusion, although the methylprednisolone treatment regimens affected diaphragm muscle morphology and bioenergetic enzyme activities in different ways, force generation decreased in all methylprednisolone treated groups to the same extent.
PGC-1α-responsive genes involved in oxidative phosphorylation are coordinately downregulated in human diabetes
Authors: Vamsi K Mootha, Cecilia M Lindgren, Karl-Fredrik Eriksson, Aravind Subramanian, Smita Sihag, Joseph Lehar, Pere Puigserver, Emma Carlsson, Martin Ridderstråle, Esa Laurila, Nicholas Houstis, Mark J Daly, Nick Patterson, Jill P Mesirov, Todd R Golub, Pablo Tamayo, Bruce Spiegelman, Eric S Lander, Joel N Hirschhorn, David Altshuler, Leif C Groop
Journal: Nature Genetics (2003)
Impact of inhibitors on hemophilia a mortality in the United States
Authors: Christopher E. Walsh, J. Michael Soucie, Connie H. Miller
Journal: American Journal of Hematology (2015)

The previously published mortality studies are limited in hemophilia populations but suggest that there is no increased risk of mortality in factor VIII inhibitor patients. This retrospective study analyzed surveillance data collected on 7,386 males with severe hemophilia A over a 13-year period to assess the association between a current inhibitor and death. During the study period, 432 participants died, among whom 48 were patients with an inhibitor. Clinical characteristics most strongly associated with death were increased number of reported bleeds, signs of liver disease, infection with either HIV or HCV, and the presence of inhibitor. Patients who underwent successful tolerization were not considered inhibitor patients in our analysis. In a multivariable analysis, the odds of death were 70% higher among patients with a current inhibitor compared to those without an inhibitor (P < 0.01). Deaths among patients with inhibitors were much more likely to be attributed to bleeding complications than those among patients without an inhibitor (42 vs. 12%, P < 0.0001). We conclude that males with severe hemophilia A and a current inhibitor are at increased risk of death.
Sources of Tuberculous Infection in an Area Containing Bovine Tuberculosis
Authors: D. F. van Zwanenberg, C. J. Stewart, K. M. Harding, S. T. G. Gray
Journal: BMJ (1956)

The data obtained show consistent changes to take place, the albumin concentration falling and the a2 globulin concentration rising progressively with increasing activity and extent of disease.Conversely, these fractions were restored towards normal as the disease became quiescent and arrested.Treatment with antituberculosis drugs led to a similar effect.As an index of activity in tuberculosis, the albumin/a2 ratio was much more sensitive than the E.S.R.The albumin/ a2 ratio provides a useful objective index for assessing activity of disease in patients with tuber- culosis.
Mitochondrial oxidative stress and CD95 ligand: A dual mechanism for hepatocyte apoptosis in chronic alcoholism
Authors: Juan B. Miñana, Luis Gómez-Cambronero, Ana Lloret, Federico V. Pallardó, Juan Del Olmo, Amparo Escudero, José M. Rodrigo, Antonio Pellíin, Juan R. Viña, José Viña, Juan Sastre
Journal: Hepatology (2002)

Apoptosis plays an important role in the progression of alcohol-induced liver disease to cirrhosis. Oxidative stress is an early event in the development of apoptosis. The major aim of this study was to study the conditions in which oxidative stress occurs in chronic alcoholism and its relationship with apoptosis of hepatocytes. We have found that oxidative stress is associated with chronic ethanol consumption in humans and in rats, in the former independently of the existence of alcohol-induced liver disease. Ethanol or acetaldehyde induces apoptosis in hepatocytes isolated from alcoholic rats, but not in those from control rats. Inhibition of aldehyde dehydrogenase, but not of cytochrome P450 2E1, prevents ethanol-induced cell death. Ethanol-induced apoptosis is caused by increased reactive oxygen species (ROS) driven by increased availability of the reduced form of nicotinamide-adenine dinucleotide (NADH) owing to mitochondrial acetaldehyde metabolism and it is prevented by blocking the opening of mitochondrial permeability transition (MPT) pores with cyclosporine A. Inhibition of nitric oxide (NO) synthase or addition of antioxidant vitamins C and E completely prevented ethanol-induced apoptosis. Mitochondrial oxidative stress, which occurs during chronic alcoholism, renders hepatocytes susceptible to apoptosis. On the other hand, the CD95 ligand expression was up-regulated by acetaldehyde. In conclusion, ethanol induces apoptosis via 2 different pathways: MPT and up-regulation of the expression of CD95-Fas ligand. The overproduction of ROS by mitochondria, driven by acetaldehyde metabolism, is a common trigger of both mechanisms.