tbuckley/cabot-search huggingface dataset:
LSC 2011 Abstract: Cigarette smoke-induced inflammation promotes melanoma cell metastasis in lung parenchyma
Authors: Sandrine Bekaert, Natacha Rocks, Maud Gueders, Geneviève Paulissen, Agnès Noël, Didier Cataldo
Journal: European Respiratory Journal (2011)

It is only during the last decade that clear evidence has been obtained that inflammation plays a critical role in different stages of tumor development, including initiation, promotion, malignant conversion, invasion and metastasis. There is increasing evidence that an inflammatory microenvironment is an essential component of all tumors (Psaila and Lyden, Nat Rev Cancer, 2009 Apr;9(4):285-93).  In the present study, we assessed  in vivo  the impact of cigarette smoke (CS) on the tumor cell extravasation in lungs after tail vein injection of B16F10 melanoma cells. We first characterized airway inflammation obtained after smoke exposure (reference cigarettes 3R4F) for varied time periods (1, 2, 4, 8 and 12 weeks). Smoke exposure was performed 5 days a week. Neutrophils, alveolar macrophages, interstitial macrophages, dendritic cells, T cells and natural killer T (NKT) cells, were characterized in lung tissues of mice exposed to CS and AIR using flow cytometry.  In Vitro , the direct effect of cigarette smoke extract (CSE) on proliferation of B16F10 melanoma cells was determined for 1 to 5 days.  In vivo,  mice exposed for 2 weeks to cigarette smoke or air were injected with B16F10 melanoma cells in the tail vein. After 3 weeks, hematoxylin-eosin staining allowed quantification of lung metastasis (tumor area/total lung area). An increase of metastasis and implantation site in lungs was observed in CS exposed group. Conceivably, CS constituents significantly promote extravasation of melanoma cells in lung tissues. The mechanism or signaling pathway responsible for this dissemination needs to be further investigated.
Are switches from oral to subcutaneous methotrexate or addition of ciclosporin to methotrexate useful steps in a tight control treatment strategy for rheumatoid arthritis? A post hoc analysis of the CAMERA study
Authors: M. F. Bakker, J. W. G. Jacobs, P. M. J. Welsing, J. H. van der Werf, S. P. Linn-Rasker, M. J. van der Veen, F. P. J. G. Lafeber, J. W. J. Bijlsma
Journal: Annals of the Rheumatic Diseases (2010)

<h3>Objective</h3> To investigate the effects of a switch from oral methotrexate (MTX) to subcutaneous MTX (scMTX) or adding ciclosporin to oral MTX with a simultaneous reduction of the MTX dose, in case of adverse events (AE) or insufficient effect (IE) in rheumatoid arthritis (RA). <h3>Methods</h3> The tight control treatment arm of the Computer Assisted Management in Early RA (CAMERA) trial was evaluated. The change in 28-joint Disease Activity Score (DAS28) after taking scMTX (over 1 month) or adding ciclosporin (over 3 months) was compared to the average monthly change in the preceding 3 months. Analyses were performed separately for strategy steps because of AE or IE. <h3>Results</h3> Of 151 patients, 57 needed the scMTX strategy step (21 because of AE, 36 because of IE) and 40 the following ciclosporin strategy step (20 and 20, respectively). The decrease in DAS28 after taking the scMTX strategy step was 0.30 points (p&lt;0.05); no significant change in DAS28 was seen after the ciclosporin strategy step. In both strategy steps for AE or IE, quite similar observations were made. Of the patients who took the scMTX strategy step, 63% showed improvement. <h3>Conclusion</h3> scMTX seems a useful treatment step after oral MTX in a tight control strategy, whereas the ciclosporin step seems ineffective.
DACH1 inhibits cyclin D1 expression, cellular proliferation and tumor growth of renal cancer cells
Authors: Qian Chu, Na Han, Xun Yuan, Xin Nie, Hua Wu, Yu Chen, Mingzhou Guo, Shiying Yu, Kongming Wu
Journal: Journal of Hematology & Oncology (2014)

Renal cell carcinoma (RCC) is a complex with diverse biological characteristics and distinct molecular signature. New target therapies to molecules that drive RCC initiation and progression have achieved promising responses in some patients, but the total effective rate is still far from satisfaction. Dachshund (DACH1) network is a key signaling pathway for kidney development and has recently been identified as a tumor suppressor in several cancer types. However, its role in renal cell carcinoma has not been fully investigated.Immunohistochemical staining for DACH1, PCNA and cyclin D1 was performed on human renal tissue microarrays and correlation with clinic-pathological characteristics was analyzed. In vitro proliferation, apoptosis and in vivo tumor growth were evaluated on human renal cancer cell lines with decitabine treatment or ectopic expression of DACH1. Downstream targets and potential molecular mechanism were investigated through western blot, immunoprecipitation and reporter gene assays.Expression of DACH1 was significantly decreased in human renal carcinoma tissue. DACH1 protein abundance was inversely correlated with the expression of PCNA and cyclin D1, tumor grade, and TNM stage. Restoration of DACH1 function in renal clear cell cancer cells inhibited in vitro cellular proliferation, S phase progression, clone formation, and in vivo tumor growth. In mechanism, DACH1 repressed cyclin D1 transcription through association with AP-1 protein.Our results indicated that DACH1 was a novel molecular marker of RCC and it attributed to the malignant behavior of renal cancer cells. Re-activation of DACH1 may represent a potential therapeutic strategy.
Serum Macrophage Inhibitory Cytokine 1 as a Marker of Pancreatic and Other Periampullary Cancers
Authors: Jens Koopmann, Phillip Buckhaults, David A. Brown, Marianna L. Zahurak, Norihiro Sato, Noriyoshi Fukushima, Lori J. Sokoll, Daniel W. Chan, Charles J. Yeo, Ralph H. Hruban, Samuel N. Breit, Kenneth W. Kinzler, Bert Vogelstein, Michael Goggins
Journal: Clinical Cancer Research (2004)

Abstract Purpose: Patients with pancreatic ductal adenocarcinoma usually present with advanced-stage disease and a dismal prognosis. One effective strategy likely to improve the morbidity and mortality from pancreatic cancer would be the identification of accurate, noninvasive diagnostic markers that would enable earlier diagnosis of symptomatic patients and earlier detection of cancer in asymptomatic individuals at high risk for developing pancreatic cancer. In this study, we evaluated serum macrophage inhibitory cytokine-1 (MIC-1) as a marker of pancreatic cancer. Experimental Design: MIC-1 expression in primary pancreatic cancers, intraductal papillary mucinous neoplasms, and pancreatic cancer cell lines was determined using the National Center for Biotechnology Information serial analysis of gene expression database, oligonucleotide microarrays analysis, in situ hybridization, and immunohistochemistry. Serum MIC-1 levels were determined by ELISA in 80 patients with pancreatic adenocarcinomas, in 30 patients with ampullary and cholangiocellular carcinomas, in 42 patients with benign pancreatic tumors, in 76 patients with chronic pancreatitis, and in 97 healthy control subjects. The diagnostic performance of serum MIC-1 as a marker of pancreatic cancer was compared with that of serum CA19–9. Results: Oligonucleotide microarray and serial analysis of gene expression data demonstrated that MIC-1 RNA levels were higher in primary pancreatic cancers, intraductal papillary mucinous neoplasms, and pancreatic cancer cell lines than in nonneoplastic pancreatic ductal epithelium. MIC-1 expression was localized to the malignant epithelium in pancreatic adenocarcinomas by in situ hybridization. MIC-1 protein was expressed in 14 of 16 primary pancreatic adenocarcinomas (88%) by immunohistochemistry and was also expressed in some pancreata affected by pancreatitis but not in normal pancreas. Serum MIC-1 levels were significantly higher in patients with pancreatic ductal adenocarcinoma (mean ± SD, 2428 ± 2324 pg/ml) and in patients with ampullary and cholangiocellular carcinomas (2123 ± 2387 pg/ml) than in those with benign pancreatic neoplasms (940 ± 469 pg/ml), chronic pancreatitis (1364 ± 1236 pg/ml), or in healthy controls (546 ± 262 pg/ml). An elevated serum MIC-1 (defined as 2 SD above the mean for healthy controls) performed as well as CA19–9 (area under the receiver operating characteristic curve, 0.81 and 0.77, respectively), and the combination of MIC-1 and CA19–9 significantly improved diagnostic accuracy (P &amp;lt; 0.05; area under the receiver operating characteristic curve, 0.87; sensitivity, 70%; specificity, 85%). Conclusion: Serum MIC-1 measurement can aid in the diagnosis of pancreatic adenocarcinoma.
Omeprazole before Endoscopy in Patients with Gastrointestinal Bleeding
Authors: James Y. Lau, Wai K. Leung, Justin C.Y. Wu, Francis K.L. Chan, Vincent W.S. Wong, Philip W.Y. Chiu, Vivian W.Y. Lee, Kenneth K.C. Lee, Frances K.Y. Cheung, Priscilla Siu, Enders K.W. Ng, Joseph J.Y. Sung
Journal: New England Journal of Medicine (2007)

A neutral gastric pH is critical for the stability of clots over bleeding arteries. We investigated the effect of preemptive infusion of omeprazole before endoscopy on the need for endoscopic therapy.
Correspondence between clinical prediction and outcome in patients with acute hypercapnic respiratory failure (AHRF) due to restrictive lung disease
Authors: Vikas Punamiya, Shiva Bikmalla, Harjeevan Gill, Sushil Agarwal, Ben Beauchamp, Emma Gallagher, Rahul Mukherjee
Journal: European Respiratory Journal (2012)

Introduction : Non-invasive ventilation (NIV) is widely used for the treatment of patients in decompensated ventilatory failure due to Restrictive Lung disease (RLD: thoracic cage and neuromuscular diseases) with AHRF in acute hospitals in the United Kingdom. The information on the accuracy of clinical prediction of survival of patients presenting with AHRF secondary to RLD is scarce.

Aims : We set out to establish how well the clinical prediction of poor prognosis during admission leading to use of NIV as ceiling of care with AHRF from RLD correlates with the actual outcome.

Method : A scientific survey was undertaken of 331 admissions due to AHRF secondary to RLD over a 6-year period ending 31 October 2010, to our 11-bedded ward based NIV unit (catchment population = 450000 approx.). In-hospital mortality was established in patients who were clinically assigned ward-based NIV as ceiling of care and compared with that in those considered clinically suitable for further escalation to intubation and invasive ventilation on Critical Care Unit if needed.

Results : In the 331 episodes, the odds ratio of death in the ceiling of care group versus the escalation group was 4.41 and was highly significant (p<0.000001).

Conclusion : Our data suggest good correspondence between clinical prediction and outcome in patients with AHRF due to RLD - further prospective studies are needed to establish this in detail. As NIV is increasingly used acutely on critically ill patients beyond the originally supposed indication of AHRF in selected patients (and even in palliative care), the use of NIV as the ceiling of care needs consistent monitoring.
Clinically Meaningful Improvement in Symptoms and Quality of Life for Patients With Non-Small-Cell Lung Cancer Receiving Gefitinib in a Randomized Controlled Trial
Authors: David Cella, Roy S. Herbst, Thomas J. Lynch, Diane Prager, Chandra P. Belani, Joan H. Schiller, Anne Heyes, Judith S. Ochs, Michael K. Wolf, Andrea C. Kay, Mark G. Kris, Ronald B. Natale
Journal: Journal of Clinical Oncology (2005)

Purpose Evaluation of disease-related symptom improvement rate by the Lung Cancer Subscale (LCS) of the Functional Assessment of Cancer Therapy-Lung (FACT-L) questionnaire was a coprimary end point of the pivotal phase II trial of gefitinib (Iressa; AstraZeneca, Wilmington, DE) conducted in the United States. This report includes the results of analyses exploring the relationship between weekly LCS scores and radiographic response and survival, as well as detailed protocol-specified analysis of symptom and quality-of-life data. Patients and Methods In this trial, 216 symptomatic patients with advanced non-small-cell lung cancer (NSCLC) who had at least two prior chemotherapy regimens received gefitinib 250 or 500 mg/d. Disease-related symptoms were assessed weekly and quality of life was assessed monthly by LCS and FACT-L, respectively. Results Symptom improvement was rapid and correlated with tumor response and survival. At the recommended gefitinib dose of 250 mg/d, median overall survival times were 13.6 and 4.6 months for patients with and without symptom improvement, respectively, and 9.7 months for patients with symptom improvement without tumor response. Among patients with stable disease or disease progression, those with symptom improvement had significantly better overall survival than those without improvement. At 250 mg/d, 30% of patients showed a quality-of-life improvement that was correlated with tumor response. Conclusion This triadic analysis of response, survival, and symptom data supports the hypothesis that tumor response and symptom response are related and that each predicts survival. Among these NSCLC patients treated with gefitinib, symptom improvement was complementary to and, for most patients, preceded evidence of radiographic regression.
Interruption of the aortic arch
Authors: R. H. Kinsley, H. L. Utian, D. N. Fuller, P. E. Marchand
Journal: Thorax (1972)

Interruption of the aortic arch is an uncommon malformation in which there is no direct continuity between the aortic arch and the descending aorta, the latter arising through a patent ductus arteriosus. Three types are described, depending upon the site of interruption in relation to the arch vessels. A large ventricular septal defect is present in 94% of cases. It is to be distinguished from aortic arch atresia, which should be regarded as a severe form of preductal coarctation in which the luminal continuity of the arch and descending aorta is absent. Three cases are described: the first demonstrates the natural outcome of the uncorrected anomaly with progression to Eisenmenger9s syndrome; the second illustrates the feasibility of surgical treatment in the neonate; the third is an example of total correction of aortic arch interruption with the common associated anomalies. Diagnosis in infancy is difficult in view of the paucity of definite clinical criteria. Surgery in the infant should consist of reconstruction of the aortic arch together with pulmonary artery banding. In older children total correction can usually be performed electively in a two-stage procedure.
Clinical Features, Management, and Prognosis of Spontaneous Coronary Artery Dissection
Authors: Marysia S. Tweet, Sharonne N. Hayes, Sridevi R. Pitta, Robert D. Simari, Amir Lerman, Ryan J. Lennon, Bernard J. Gersh, Sherezade Khambatta, Patricia J.M. Best, Charanjit S. Rihal, Rajiv Gulati
Journal: Circulation (2012)

Spontaneous coronary artery dissection (SCAD) is an acute coronary event of uncertain origin. Clinical features and prognosis remain insufficiently characterized.A retrospective single-center cohort study identified 87 patients with angiographically confirmed SCAD. Incidence, clinical characteristics, treatment modalities, in-hospital outcomes, and long-term risk of SCAD recurrence or major adverse cardiac events were evaluated. Mean age was 42.6 years; 82% were female. Extreme exertion at SCAD onset was more frequent in men (7 of 16 versus 2 of 71; P<0.001), and postpartum status was observed in 13 of 71 women (18%). Presentation was ST-elevation myocardial infarction in 49%. Multivessel SCAD was found in 23%. Initial conservative management (31 of 87) and coronary artery bypass grafting (7 of 87) were associated with an uncomplicated in-hospital course, whereas percutaneous coronary intervention was complicated by technical failure in 15 of 43 patients (35%) and 1 death. During a median follow-up of 47 months (interquartile range, 18-106 months), SCAD recurred in 15 patients, all female. Estimated 10-year rate of major adverse cardiac events (death, heart failure, myocardial infarction, and SCAD recurrence) was 47%. Fibromuscular dysplasia of the iliac artery was identified incidentally in 8 of 16 femoral angiograms (50%) undertaken before closure device placement and in the carotid arteries of 2 others with carotid dissection.SCAD affects a young, predominantly female population, frequently presenting as ST-elevation myocardial infarction. Although in-hospital mortality is low regardless of initial treatment, percutaneous coronary intervention is associated with high rates of complication. Risks of SCAD recurrence and major adverse cardiac events in the long term emphasize the need for close follow-up. Fibromuscular dysplasia is a novel association and potentially causative factor.
Effect of coronary blood flow on glycolytic flux and intracellular pH in isolated rat hearts.
Authors: J R Neely, J T Whitmer, M J Rovetto
Journal: Circulation Research (1975)

The rate of coronary blood flow was varied in isolated working rat heart preparations to determine its influence on the rate of glocose utilization, tissue high-energy phosphates, and intracellular pH. A 60% reduction in coronary blood flow resulted in a 30% reduction in oxygen consumption, an accelerated rate of glusoe utilization, lower tissue levels of high-energy phosphate, and higher tissue levels of lactate and H+. Ventricular performance deteriorated as reflected by a decrease in heart rate and peak systolic pressure. Further reductions in coronary blood flow resulted in inhibition of glycolysis, a greater decrease in tissue levels of high-energy phosphates, and higher tissue levels of both lactate and H+. These changes in glycolytic flux, tissue metabolites, and ventricular performance were proportional to the degree of restriction in coronary blood flow. The importance of coronary blood flow and washout of the interstitial space in the maintenance of accelerated glycolytic flux in oxygen-deficient hearts is emphasized. It is concluded that acceleration of ATP production from glycolysis can occur only in the marginally ischemic tissue in the peripheral area of tissue supplied by an occluded artery. The central area of tissue which receives a low rate of coronary blood flow will have a reduced rate of ATP production due to both a lack of oxygen and an inhibition of glycolysis.
THE TRANSMISSION OF AGGLUTININS OF BACILLUS ABORTUS FROM COW TO CALF IN THE COLOSTRUM
Authors: Ralph B. Little, Marion L. Orcutt
Journal: The Journal of Experimental Medicine (1922)

The agglutinins towards Bacillus abortus found in the blood serum of new-born calves are obtained from the mother through the colostrum. Calves at birth, unfed, are without agglutinins. The problem of the production of agglutinins by the fetus in whose tissues Bacillus abortus has multiplied and which is subsequently expelled prematurely is not touched by these observations.
Targeting α-synuclein for treatment of Parkinson's disease: mechanistic and therapeutic considerations
Authors: Benjamin Dehay, Mathieu Bourdenx, Philippe Gorry, Serge Przedborski, Miquel Vila, Stéphane Hunot, Andrew Singleton, C Warren Olanow, Kalpana M Merchant, Erwan Bezard, Gregory A Petsko, Wassilios G Meissner
Journal: The Lancet Neurology (2015)
Cardiovascular Responses to Static Exercise (Isometrics, Anyone?)
Authors: ALEXANDER R. LIND
Journal: Circulation (1970)

Cardiovascular Responses to Static Exercise (Isometrics, Anyone?) ANYONE with a stethoscope, a sphygmomanometer, and an open mind can readily satisfy himself that static effort or "isometrics" may raise the blood pressure to high levels.Yet, isometrics, as a form of 1970 NO.
Adherent Ia+ murine tumor lines with characteristics of dendritic cells. I. Morphology, surface phenotype, and induction of syngeneic mixed lymphocyte reactions.
Authors: D A Cohen, A M Kaplan
Journal: The Journal of Experimental Medicine (1981)

Several adherent cell lines that express surface Ia antigens have been cloned from the P388 leukemia. These cell lines express many morphological and functional similarities to dendritic cells of the spleen. Adherent clones express H-2 gene products from the I and D regions, but do not possess Fc or C3b receptors or surface Ig. The cytoplasm of the adherent P388 clones has an abundance of mitochondria but few phagolysosomes. The adherent clones all strongly stimulate the proliferation of syngeneic or allogeneic T lymphocytes in the absence of antigen; however, cytotoxic T cells directed against the stimulators are induced only during allogeneic stimulation. Nonadherent clones of P388, which also express Ia antigens, do not stimulate either allogeneic or syngeneic T cell proliferation. The isolation of Ia-bearing adherent cell lines makes it possible to study Ia-mediated events in both antigen-dependent and independent immune systems using homogeneous accessory cell populations.
Recognition and Incidence of Intrapulmonary Lymph Nodes
Authors: D. H. Trapnell
Journal: Thorax (1964)

Lymph nodes are normally found in man in the mediastinum and around the main bronchi at the hilum of the lung. A few such nodes, which have confusingly been called intrapulmonary (Pidry and Jacques, 1906; Johnston, Davies, and Davies, 1958), may also be present alongside lobar bronchi as far into the lung as the third or fourth branching of the bronchi. Aggregations of lymphocytes are common at the bifurcations of bronchi and beneath the pleura, as Miller (1911) clearly showed. However, definite nodes with a capsule and lymphoid follicles may be found in some individuals far out in the lung and even close to the pleura. These are truly intrapulmonary and must be distinguished from those near the hilum of the lung or in the mediastinum, which may conveniently be grouped together as tracheo-bronchial lymph nodes. According to Heller (1895), the first to describe subpleural lymph nodes was Meinel (1869), whose work was soon followed by that of Sanderson (1869) and Is (1876). Arnold (1880) showed the truly lymphoid character of these nodules and that they occurred in normal lungs. Later, Luders (1892), Heller (1895), and Bossuet (1905) confirmed the work of the earlier authors. They showed that subpleural nodes were visible macroscopically, varying in size up to that of a lentil, being abundant in some cases and rare or absent in others. Miller (1911, 1947) investigated the lungs of dogs and other animals as well as those of man, and failed to show definite lymph nodes in normal lungs but found in each instance small masses of lymphoid tissue. Elsewhere in his 1911 paper he said he had found definite intrapulmonary and subpleural lymph nodes: he suggested that these occurred only in abnormal lungs and that the nodes must have developed from normal masses of lymphoid tissue. However, no evidence was given to support this. Later, in 1924 and 1947, he suggested that there was a definite increase in the