tbuckley/cabot-search huggingface dataset:
Use of a preclinical model of pancreas cancer to identify potential candidates for rapalogue therapy
Authors: Kenneth K Takeuchi, Howard C Crawford
Journal: Gut (2014)

The oft-repeated statistics are dismal: pancreatic ductal adenocarcinoma (PDA) has only a 6% 5-year survival rate that has not changed significantly in 30 years and the vast majority of PDA patients perish within 6 months of diagnosis. Several possible reasons contribute to these grim results. PDA is difficult to detect, it is recalcitrant to most targeted treatments and conventional therapies only have a modest effect on survival. Compared with other cancers, PDA was revealed to be remarkably genetically homogenous with 95% or more of PDA harbouring oncogenic mutations in the Kras gene,1 generating hope that finding effective ways of interrupting Kras signalling would increase survival for PDA patients. However, Kras-targeted therapies have proven elusive thus far, leaving its downstream effectors as the most obvious potential targets.

The true genetic heterogeneity of PDA has just begun to be appreciated2 ,3 within a background of the almost universal presence of Kras mutation and the statistically predictable identities of many of the subsequent tumour suppressor mutations that propel its progression and metastasis. Of course, …
Avian influenza A(H10N7) virus involvement in mass mortality of harbour seals (Phoca vitulina) in Sweden, March through October 2014
Authors: S Zohari, A Neimanis, T Härkönen, C Moraeus, J F Valarcher
Journal: Eurosurveillance (2014)

We provide the first scientific report of influenza A virus involvement in a mass mortality event among harbour seals (Phoca vitulina) off the west coast of Sweden. Avian influenza A (H10N7) virus was detected in the lungs of two affected animals. This subtype has not been reported in seals to date, nor has influenza A-associated mortality been reported in seals in Europe. Circulation of avian influenza viruses in mammals may have implications for public health.
Natural-orifice transluminal endoscopic surgery (NOTES) in Europe: summary of the working group reports of the Euro-NOTES meeting 2010
Authors: A. Meining, H. Feussner, P. Swain, G. Yang, K. Lehmann, R. Zorron, S. Meisner, J. Ponsky, H. Martiny, N. Reddy, J. Armengol-Miro, P. Fockens, A. Fingerhut, G. Costamagna
Journal: Endoscopy (2011)

The fourth Euro-NOTES workshop took place in September 2010 and focused on enabling intensive scientific dialogue and interaction between participants to discuss the state of the practice and development of natural-orifice transluminal endoscopic surgery (NOTES) in Europe. Five working groups were formed, consisting of participants with varying scientific and medical backgrounds. Each group was assigned to an important topic: the correct strategy for dealing with bacterial contamination and related complications, the question of the ideal entry point and secure closure, interdisciplinary collaboration and indications, robotics and platforms, and matters related to training and education. This review summarizes consensus statements of the working groups to give an overview of what has been achieved so far and what might be relevant for research related to NOTES in the near future.
Impaired Integrin-Dependent Function in Wiskott-Aldrich Syndrome Protein-Deficient Murine and Human Neutrophils
Authors: Hong Zhang, Ulrich Y. Schaff, Chad E. Green, Hua Chen, Melissa R. Sarantos, Yongmei Hu, Diane Wara, Scott I. Simon, Clifford A. Lowell
Journal: Immunity (2006)
Involvement of Peripheral Benzodiazepine Receptor in the Oxidative Stress, Death-Signaling Pathways, and Renal Injury Induced by Ischemia-Reperfusion
Authors: Oxana R. Kunduzova, Ghislaine Escourrou, France De La Farge, Robert Salvayre, Marie-Hélène Séguélas, Nathalie Leducq, Franc[COMBINING CEDILLA]oise Bono, Jean-Marc Herbert, Angelo Parini
Journal: Journal of the American Society of Nephrology (2004)

The peripheral benzodiazepine receptor (PBR) is a critical component of the mitochondrial permeability transition pore, which is involved in the regulation of cell death. In the present study we investigated the role of PBR in the regulation of signaling pathways leading to apoptotic and necrotic damage and renal dysfunction in a rat model of ischemia-reperfusion. Renal ischemia-reperfusion led to extended tubular apoptosis and necrosis that were associated with peroxidative damage, high levels of proapoptotic Bax expression, and low levels of antiapoptotic Bcl-2 expression, cleavage of death substrate, poly(ADP-ribose) polymerase (PARP), and activation of a key effector of apoptosis, caspase-3. Rat pretreatment with a novel PBR antagonist, SSR180575, significantly decreased postreperfusion oxidative stress and tubular apoptosis and necrosis. This effect was associated with inhibition of caspase-3 activation and PARP cleavage, upregulation of Bcl-2, and downregulation of Bax. Furthermore, inhibition of PBR accelerated the recovery of normal renal function, as assessed by measurement of levels of plasma creatinine and blood urea nitrogen. These findings reveal a role for PBR as a modulator of necrotic and apoptotic cell death induced by ischemia-reperfusion and suggest that regulation of PBR may provide new therapeutic implications for the prevention of acute renal failure.
Conserved rules govern genetic interaction degree across species
Authors: Elizabeth N Koch, Michael Costanzo, Jeremy Bellay, Raamesh Deshpande, Kate Chatfield-Reed, Gordon Chua, Gennaro D'Urso, Brenda J Andrews, Charles Boone, Chad L Myers
Journal: Genome biology (2012)

Synthetic genetic interactions have recently been mapped on a genome scale in the budding yeast Saccharomyces cerevisiae, providing a functional view of the central processes of eukaryotic life. Currently, comprehensive genetic interaction networks have not been determined for other species, and we therefore sought to model conserved aspects of genetic interaction networks in order to enable the transfer of knowledge between species.Using a combination of physiological and evolutionary properties of genes, we built models that successfully predicted the genetic interaction degree of S. cerevisiae genes. Importantly, a model trained on S. cerevisiae gene features and degree also accurately predicted interaction degree in the fission yeast Schizosaccharomyces pombe, suggesting that many of the predictive relationships discovered in S. cerevisiae also hold in this evolutionarily distant yeast. In both species, high single mutant fitness defect, protein disorder, pleiotropy, protein-protein interaction network degree, and low expression variation were significantly predictive of genetic interaction degree. A comparison of the predicted genetic interaction degrees of S. pombe genes to the degrees of S. cerevisiae orthologs revealed functional rewiring of specific biological processes that distinguish these two species. Finally, predicted differences in genetic interaction degree were independently supported by differences in co-expression relationships of the two species.Our findings show that there are common relationships between gene properties and genetic interaction network topology in two evolutionarily distant species. This conservation allows use of the extensively mapped S. cerevisiae genetic interaction network as an orthology-independent reference to guide the study of more complex species.
Serotonin 2C receptors in pro-opiomelanocortin neurons regulate energy and glucose homeostasis
Authors: Eric D. Berglund, Chen Liu, Jong-Woo Sohn, Tiemin Liu, Mi Hwa Kim, Charlotte E. Lee, Claudia R. Vianna, Kevin W. Williams, Yong Xu, Joel K. Elmquist
Journal: Journal of Clinical Investigation (2013)

Energy and glucose homeostasis are regulated by central serotonin 2C receptors. These receptors are attractive pharmacological targets for the treatment of obesity; however, the identity of the serotonin 2C receptor-expressing neurons that mediate the effects of serotonin and serotonin 2C receptor agonists on energy and glucose homeostasis are unknown. Here, we show that mice lacking serotonin 2C receptors (Htr2c) specifically in pro-opiomelanocortin (POMC) neurons had normal body weight but developed glucoregulatory defects including hyperinsulinemia, hyperglucagonemia, hyperglycemia, and insulin resistance. Moreover, these mice did not show anorectic responses to serotonergic agents that suppress appetite and developed hyperphagia and obesity when they were fed a high-fat/high-sugar diet. A requirement of serotonin 2C receptors in POMC neurons for the maintenance of normal energy and glucose homeostasis was further demonstrated when Htr2c loss was induced in POMC neurons in adult mice using a tamoxifen-inducible POMC-cre system. These data demonstrate that serotonin 2C receptor-expressing POMC neurons are required to control energy and glucose homeostasis and implicate POMC neurons as the target for the effect of serotonin 2C receptor agonists on weight-loss induction and improved glycemic control.
Hemodynamic effects of n-acetylprocainamide compared with procainamide in conscious dogs.
Authors: F R Badke, R A Walsh, M H Crawford, T Ludden, R A O'Rourke
Journal: Circulation (1981)

We examined the hemodynamic actions of clinically relevant i.v. doses (20 mg/kg and 10 mg/kg) of n-acetyl procainamide (NAPA) in conscious dogs preinstrumented with a left ventricular (LV) micromanometer, LV and aortic catheters, and ultrasonic crystals for measurement of LV internal diameter shortening (% delta D). Within 30 seconds after the 20-mg/kg dose, there were significant increases in heart rate (27 +/- 7 beats/min, mean +/- SEM; n = 6), maximum dP/dt (655 +/- 206 mm Hg/sec), and % delta D (2.2 +/- 0.9%; all p less than or equal to 0.05). However, by 6 hours after the dose there were reductions compared with control in peak LV pressure (19 +/- 9 mm Hg), dP/dt (610 +/- 210 mm Hg/sec), and % delta D (2.3 +/- 0.6%; all p less than or equal to 0.05). In contrast, equimolar doses of procainamide or drug vehicle alone evoked no response, as did NAPA after pretreatment with reserpine (0.25 mg/kg/day for 2 days) or hexamethonium (10-15 mg/kg). These data suggest NAPA produces a biphasic hemodynamic response with enhancement of LV performance early and a decrease later; this response is different from that of the parent compound, procainamide. These effects are likely mediated by the adrenergic nervous system at either a ganglionic or a central level.
Effect of omeprazole 20 mg twice daily on duodenogastric and gastro-oesophageal bile reflux in Barrett’s oesophagus
Authors: R E K Marshall, A Anggiansah, D K Manifold, W A Owen, W J Owen
Journal: Gut (1998)

Background —Both acid and duodenal contents are thought to be responsible for the mucosal damage in Barrett’s oesophagus, a condition often treated medically. However, little is known about the effect of omeprazole on duodenogastric reflux (DGR) and duodenogastro-oesophageal reflux (DGOR). Aims —To study the effect of omeprazole 20 mg twice daily on DGR and DGOR, using the technique of ambulatory bilirubin monitoring. Methods —Twenty three patients with Barrett’s oesophagus underwent manometry followed by 24 hour oesophageal and gastric pH monitoring. In conjunction with pH monitoring, 11 patients (group 1) underwent oesophageal bilirubin monitoring and 12 patients (group 2) underwent gastric bilirubin monitoring, both before and during treatment with omeprazole 20 mg twice daily. Results —In both groups there was a significant reduction in oesophageal acid (pH&lt;4) reflux (p&lt;0.005) and a significant increase in the time gastric pH was above 4 (p&lt;0.005). In group 1, median total oesophageal bilirubin exposure was significantly reduced from 28.9% to 2.4% (p&lt;0.005). In group 2, median total gastric bilirubin exposure was significantly reduced from 24.9% to 7.2% (p&lt;0.005). Conclusions —Treatment of Barrett’s oesophagus with omeprazole 20 mg twice daily results in a notable reduction in the exposure of the oesophagus to both acid and duodenal contents. In addition, delivery of duodenal contents to the upper gastric body is reduced.
The evaluation of iron status in hemodialysis patients.
Authors: S Fishbane, E A Kowalski, L J Imbriano, J K Maesaka
Journal: Journal of the American Society of Nephrology (1996)

Effective treatment of anemia in hemodialysis patients requires ongoing monitoring of iron status. The purpose of this study was to determine levels of commonly used iron indices predictive of iron deficiency in this population. Forty-seven patients with baseline serum ferritin levels < 600 ng/mL were treated with intravenous iron dextran (INFeD; Schein Pharmaceutical Inc., Florham Park, NJ), 1000 mg over ten hemodialysis treatments. Patients whose hematocrit value increased by 5% or who had a 10% decrease in their erythropoietin dose by 2 months were classified as having iron deficiency (N = 31; 66%). All other subjects were classified as having adequate iron (N = 16; 34%). There was no statistically significant difference in baseline serum ferritin, transferrin saturation, mean cell volume, mean cell hemoglobin content, or red cell distribution width between the two groups. Receiver operator curves demonstrated that none of the iron indices had a high level of utility (both sensitivity and specificity > 80%). Two tests had marginal utility, serum ferritin at a level of < 150 ng/mL, and transferrin saturation < 21%. It was concluded that because of the tests' marginal utility, they should only be interpreted in the context of the patient's underlying erythropoietin, responsiveness. In patients who are responsive to erythropoietin, a transferrin saturation value < 18% or serum ferritin level < 100 ng/mL should be used to indicate inadequate iron. When erythropoietin resistance is present, transferrin saturation of < 27% or serum ferritin < 300 ng/mL should be used to guide iron management.
Anemia in Tumor-Bearing Rats and Some Effects of Bacterial Contamination
Authors: Ralph F. Kampschmidt, Herbert F. Upchurch
Journal: JNCI Journal of the National Cancer Institute (1965)

The anemia of rats bearing the Jensen sarcoma was partially corrected by the contamination of the tumor with Salmonella typhimurium. The animals with bacteria had less iron accumulation in and around the tumor tissue. Transfer of labeled iron from transferrin to erythrocytes and the number of reticulocytes both indicated that the alleviation of the anemia in rats with bacteria was not due to increased synthesis of erythrocytes. Injection of labeled red blood cells indicated less trapping and destruction of these cells in the tumors of animals contaminated with S. typhimurium. The results suggest that the bacteria help keep the small blood vessels in and around the tumor intact and thereby decrease the loss of erythrocytes.
Assays for Thyroid Growth Immunoglobulins and Their Clinical Implications: Methods, Concepts, and Misconceptions
Authors: J. E. DUMONT, P. P. ROGER, M. LUDGATE
Journal: Endocrine Reviews (1987)

GRAVES' disease is characterized by thyroid hyperfunction and hyperplasia which lead to thyrotoxicosis and goiter. Hyperthyroidism has been clearly related to the presence in plasma of immunoglobulins which stimulate the TSH receptor via its adenylate cyclase, the thyroid stimulatory immunoglobulins (TSI) (1–4). With regard to growth, several facts have suggested that additional mechanisms may be involved. There is no simple relationship between level of function in Graves' disease and goiter size; indeed there are cases of hyperthyroidism with little increase in thyroid size and others with slight thyrotoxicosis and large goiters. Moreover, the presence of circulating growth-stimulating factors in euthyroid and hypothyroid patients with goiter has been reported (5–10). On the other hand, depending on the species, several biochemical pathways may be involved in the regulation of thyroid cell proliferation: 1) the TSH-activated adenylate cyclase-cAMP cascade (11–13); 2) the cAMP-independent epidermal growth factor mechanism, probably involving protein tyrosine phosphorylation (11,13); and 3) as in other types of cells, the phosphatidylinositol-Ca2+ cascade (14).
A life table and Cox regression analysis of patients with combined proximal left anterior descending and proximal left circumflex coronary artery disease: non-left main equivalent lesions (CASS).
Authors: B R Chaitman, K Davis, L D Fisher, M G Bourassa, M B Mock, J Lespérance, W J Rogers, D Fray, D H Tyras, M P Judkins
Journal: Circulation (1983)

Combined proximal left anterior descending and proximal left circumflex artery stenoses greater than or equal to 70% have been referred to as "left main equivalent" lesions. We compared the survival rates of medically treated patients who have this type of coronary anatomic characteristics with the survival rates of patients who have left main coronary artery stenoses greater than or equal to 70% by use of a stratified life table approach and a Cox regression model. Comparison of the patients with left main coronary artery stenoses with those who have left main equivalent lesions by use of life table analysis and three different calculations of patient exposure time revealed a poorer prognosis for the patients who had left main coronary artery disease (p less than or equal to .04 for all three methods). The stepwise Cox analysis also determined that patients who had left main artery stenoses had a significantly poorer prognosis than patients who had left main equivalent coronary disease (p = .002), even after consideration of important baseline variables known to affect survival rates. We then compared the patients who had combined proximal left anterior descending and proximal left circumflex artery disease with patients who had combined stenoses greater than or equal to 70% in the nonproximal left anterior descending stenosis influenced survival rates. The 5 year to determine if location of the left anterior descending stenosis influenced survival rates. The 5 year survival rate was not as high for the patients who had proximal left anterior descending artery disease (55% vs 70%, p = .001). In conclusion, combined proximal left anterior descending and proximal left circumflex artery disease identifies a high-risk (as determined by angiography) patient subset.(ABSTRACT TRUNCATED AT 250 WORDS)
Overexpression of the long non-coding RNA PVT1 is correlated with leukemic cell proliferation in acute promyelocytic leukemia
Authors: Chengwu Zeng, Xibao Yu, Jing Lai, Lijiang Yang, Shaohua Chen, Yangqiu Li
Journal: Journal of Hematology & Oncology (2015)

Acute promyelocytic leukemia (APL) is associated with chromosomal translocation t(15;17), which results in the proliferation of morphologically abnormal promyelocytes. Gain of supernumerary copies of the 8q24 chromosomal region, which harbors MYC and PVT1, has been shown to be the most common secondary alteration in human APL. Increased MYC can accelerate the development of myeloid leukemia in APL. However, the role that the expression of the long non-coding RNA (lncRNA) PVT1 plays in the pathogenesis of APL remains largely unknown. In this study, we first analyzed the lncRNA PVT1 expression level in peripheral blood cells from 28 patients with de novo APL, and significantly upregulated PVT1 was found in APL patients compared with healthy donors. We then observed significantly lower MYC and PVT1 expression during all-trans retinoic acid (ATRA)-induced differentiation and cell cycle arrest in the APL cell line. MYC knockdown in NB4 cells led to PVT1 downregulation. Moreover, PVT1 knockdown by RNA interference led to suppression of the MYC protein level, and cell proliferation was inhibited. Our findings reveal that the lncRNA PVT1 may play an important role in the proliferation of APL cells and may be useful for future therapeutic management.
Prevalence and reversibility of lung hyperinflation in adult asthmatics with poorly controlled disease or significant dyspnea
Authors: T. Perez, P. Chanez, D. Dusser, P. Devillier
Journal: Allergy (2015)

In asthma, inflammation affects both the proximal and distal airways and may induce significant hyperinflation (HI). This study sought to evaluate the prevalence of HI in asthmatic patients with poorly controlled disease and/or dyspnea.Poor asthma control was defined by an Asthma Control Test (ACT) score <20 (n = 287), and dyspnea was defined as a modified Medical Research Council score ≥1 (n = 18). HI was defined as either a residual volume/total lung capacity (RV/TLC) above the upper limit of normal (RV-HI) or a functional residual capacity (FRC) >120% predicted (FRC-HI). HI reversibility after administration of salbutamol (400 μg) was defined as a decrease in RV >20% or a reduction in FRC >10%. Changes in dyspnea and chest tightness were evaluated on a visual analogue scale.Both RV-HI and FRC-HI were observed in 48% of the 305 patients (mean ± SD age: 49 ± 17; FEV1 : 75 ± 18% predicted) included in the study. The prevalence of HI was higher in patients with a FEV1 <60% predicted (93% for RV-HI and 71% for FRC-HI, vs 21% and 41% in patients with a FEV1 > 80%). In patients with HI, the ACT score was lower and chest tightness higher. HI reversibility was obtained in 38% of the asthmatics with FRC-HI and 29% of the asthmatics with RV-HI, whereas FEV1 reversibility was obtained in half of these patients.HI is highly prevalent in poorly controlled asthmatics suggesting small airway dysfunction and may represent an additional criteria for evaluating responsiveness to bronchodilators.
Established and experimental medical therapy of pulmonary sarcoidosis
Authors: Robert P. Baughman, Hilario Nunes, Nadera J. Sweiss, Elyse E. Lower
Journal: European Respiratory Journal (2013)

The treatment options for pulmonary sarcoidosis have increased over the past 10 years. As new treatments have been introduced, the best way to assess and compare treatments remains unknown. The goal of this review is to discuss the standard treatments for pulmonary sarcoidosis, including glucocorticoids, and cytotoxic agents, such as methotrexate, azathioprine and leflunomide, and compare them to the newer biological agents, such as infliximab and adalimumab. We also discuss some novel treatments which are currently being evaluated. To compare these different regimens, we look at the measures used to assess response. These include pulmonary function, chest imaging, steroid sparing potential and, more recently, improvements in quality of life measures. While there is, as yet, no standard assessment for response, there is a growing consensus that response to treatment may include improvement of one or more of the following: forced vital capacity, chest imaging and steroid sparing. Several drugs used for pulmonary sarcoidosis have demonstrated improvement in one or more of these measures.