tbuckley/cabot-search huggingface dataset:
Rapid Identification of UCA1 as a Very Sensitive and Specific Unique Marker for Human Bladder Carcinoma
Authors: Xiao-Song Wang, Zheng Zhang, Hong-Cheng Wang, Jian-Liang Cai, Qing-Wen Xu, Meng-Qiang Li, Yi-Cheng Chen, Xiao-Ping Qian, Tian-Jing Lu, Li-Zhang Yu, Yu Zhang, Dian-Qi Xin, Yan-Qun Na, Wei-Feng Chen
Journal: Clinical Cancer Research (2006)

Abstract Purpose: The most common genitourinary malignancy in China is bladder transitional cell carcinoma (TCC). Early diagnosis of new and recurrent bladder cancers, followed by timely treatment, will help decrease mortality. There are currently no satisfactory markers for bladder cancer available in clinics. Better diagnostic methods are highly demanded. Experimental Design: In this research, we have used comprehensive expressed sequence tag analysis, serial analysis of gene expression, and microarray analysis and quickly discovered a candidate marker, urothelial carcinoma associated 1 (UCA1). The UCA1 gene was characterized and its performance as a urine marker was analyzed by reverse transcription-PCR with urine sediments. A total of 212 individuals were included in this study, 94 having bladder cancers, 33 ureter/pelvic cancers, and 85 normal and other urinary tract disease controls. Results: UCA1 was identified as a novel noncoding RNA gene dramatically up-regulated in TCC and it is the most TCC-specific gene yet identified. The full-length cDNA was 1,439 bp, and sequence analysis showed that it belonged to the human endogenous retrovirus H family. Clinical tests showed that UCA1 assay was highly specific (91.8%, 78 of 85) and very sensitive (80.9%, 76 of 94) in the diagnosis of bladder cancer and was especially valuable for superficial G2-G3 patients (sensitivity 91.1%, 41 of 45). It showed excellent differential diagnostic performance in various urinary tract diseases without TCC. Conclusions: UCA1 is a very sensitive and specific unique marker for bladder cancer. It could have important implications in postoperative noninvasive follow-up. This research also highlights a shortcut to new cancer diagnostic assays through integration of in silico isolation methods with translational clinical tests based on RNA detection protocols.
Case report of four patients with erythrodermic cutaneous T-cell lymphoma and severe photosensitivity mimicking chronic actinic dermatitis
Authors: N. Agar, S. Morris, R. Russell-Jones, J. Hawk, S. Whittaker
Journal: British Journal of Dermatology (2008)

The marked photosensitivity associated with chronic actinic dermatitis (CAD) is presumed to be due to a T cell-mediated response to ultraviolet (UV)-induced epidermal neoantigens. Photosensitivity is, however, a rare occurrence in cutaneous T-cell lymphoma (CTCL). We discuss a series of four patients with erythrodermic CTCL who exhibited marked photosensitivity mimicking CAD. Significantly, the tumour cells had a CD8 phenotype in half of these patients. All patients had T-cell clones in skin and also demonstrated identical peripheral T-cell clones in blood or lymph node involvement. Sézary cell counts ranged from 6% to 20%, CD4/CD8 ratios from 0.22 to 23.5. Clinical presentation was striking for a marked photosensitive distribution. Monochromator irradiation testing revealed reduced minimal erythema doses throughout UVB and UVA ranges, findings consistent with those seen in CAD. All patients subsequently died from systemic disease. These findings suggest that, rarely, malignant clonal T-cell populations may recognize a unique UV-induced neoantigen, resulting in the clinical features of severe photosensitivity mimicking those seen in CAD.
Cholinergic effects on human gastric motility
Authors: H P Parkman, D M Trate, L C Knight, K L Brown, A H Maurer, R S Fisher
Journal: Gut (1999)

Cholinergic regulation of chronotropic (frequency) and inotropic (force) aspects of antral contractility and how these impact on gastric emptying are not well delineated.To determine the effects of cholinergic stimulation and inhibition on myoelectric, contractile, and emptying parameters of gastric motility.Ten normal subjects underwent three studies each, using simultaneous electrogastrography (EGG), antroduodenal manometry, and gastric emptying with dynamic antral scintigraphy (DAS). After 30 minutes of baseline fasting manometry and EGG, subjects received saline intravenously, atropine (0.6 mg then 0.25 mg/hour intravenously), or bethanechol (5 mg subcutaneously). This was followed by another 30 minutes' recording and by three hours of postprandial recording after ingestion of a technetium-99m labelled solid meal.During fasting, atropine decreased, whereas bethanechol increased, the antral manometric motility index and EGG power. Postprandially, atropine decreased the amplitude of antral contractions by DAS, decreased the postprandial antral manometric motility index, and slowed gastric emptying. Atropine caused a slight increase in postprandial frequency of antral contractions by DAS and gastric myoelectrical activity by EGG. Bethanechol slightly increased the amplitude, but slightly decreased the frequency of antral contractions by DAS and decreased the frequency of gastric myoelectrical activity by EGG, with no significant increase in the motility index or gastric emptying.Cholinergic antagonism with atropine reduces antral contractility and slows gastric emptying. Cholinergic stimulation with bethanechol increases antral contractility, but decreases the frequency of antral contractions, without altering the antral motility index or gastric emptying.
Influence of calcium on neointimal growth following drug-eluting and bare metal stents implantation: A 3-D intravascular ultrasound substudy of the SCORE trial
Authors: Toru Kataoka, Yoshihiro Morino, Brian K. Courtney, Rachna Basisht, Seung-Ho Hur, Paul G. Yock, Eberhard Grube, Peter J. Fitzgerald, Yasuhiro Honda
Journal: Journal of the American College of Cardiology (2003)
T-Cell Levels Are Prognostic in Mantle Cell Lymphoma
Authors: Lina Nygren, Agata M. Wasik, Stefanie Baumgartner-Wennerholm, Åsa Jeppsson-Ahlberg, Monika Klimkowska, Patrik Andersson, Daren Buhrkuhl, Birger Christensson, Eva Kimby, Björn E. Wahlin, Birgitta Sander
Journal: Clinical Cancer Research (2014)

The purpose of this study was to investigate the impact of T-cell subsets on pathologic and clinical features including disease outcome in mantle cell lymphoma (MCL).Cell populations were investigated using flow cytometry in diagnostic MCL (n = 153) and reactive (n = 26) lymph node biopsies. Levels of tumor cells, T cells, T-cell subsets, and the CD4:CD8 ratio were assessed and related to pathologic and clinical parameters.MCL cases with diffuse and nodular histologic subtypes showed lower levels of T cells, especially CD4(+) T cells, than those with mantle zone growth pattern. Both CD3 and CD4 levels were lower in the nodular subtype than in mantle zone (P = 0.007; P = 0.003) and in the diffuse compared with the nodular subtype (P = 0.022; P = 0.015). The CD4:CD8 ratios were inversely correlated to tumor cell proliferation (P = 0.003). Higher levels of CD3(+) and CD4(+) T cells and higher CD4:CD8 ratios were associated with indolent disease (P = 0.043, 0.021, and 0.003 respectively). In univariate analysis, a high CD4:CD8 ratio, but not the histologic subtype, was correlated to longer overall survival (OS). In multivariate analysis, the CD4:CD8 ratio correlated with OS independently of Mantle Cell Lymphoma International Prognostic Index (MIPI) and high p53 expression (P = 0.023).CD3(+), CD8(+), and particularly CD4(+) T-cell levels are higher in indolent MCL and decrease with more aggressive histology as reflected by a diffuse growth pattern. High CD4:CD8 ratio correlated independently of other high-risk prognostic factors with longer OS, suggesting a prognostic role for T cells in MCL.
Pertuzumab, Trastuzumab, and Docetaxel in HER2-Positive Metastatic Breast Cancer
Authors: Sandra M. Swain, José Baselga, Sung-Bae Kim, Jungsil Ro, Vladimir Semiglazov, Mario Campone, Eva Ciruelos, Jean-Marc Ferrero, Andreas Schneeweiss, Sarah Heeson, Emma Clark, Graham Ross, Mark C. Benyunes, Javier Cortés
Journal: New England Journal of Medicine (2015)

In patients with metastatic breast cancer that is positive for human epidermal growth factor receptor 2 (HER2), progression-free survival was significantly improved after first-line therapy with pertuzumab, trastuzumab, and docetaxel, as compared with placebo, trastuzumab, and docetaxel. Overall survival was significantly improved with pertuzumab in an interim analysis without the median being reached. We report final prespecified overall survival results with a median follow-up of 50 months.We randomly assigned patients with metastatic breast cancer who had not received previous chemotherapy or anti-HER2 therapy for their metastatic disease to receive the pertuzumab combination or the placebo combination. The secondary end points of overall survival, investigator-assessed progression-free survival, independently assessed duration of response, and safety are reported. Sensitivity analyses were adjusted for patients who crossed over from placebo to pertuzumab after the interim analysis.The median overall survival was 56.5 months (95% confidence interval [CI], 49.3 to not reached) in the group receiving the pertuzumab combination, as compared with 40.8 months (95% CI, 35.8 to 48.3) in the group receiving the placebo combination (hazard ratio favoring the pertuzumab group, 0.68; 95% CI, 0.56 to 0.84; P<0.001), a difference of 15.7 months. This analysis was not adjusted for crossover to the pertuzumab group and is therefore conservative. Results of sensitivity analyses after adjustment for crossover were consistent. Median progression-free survival as assessed by investigators improved by 6.3 months in the pertuzumab group (hazard ratio, 0.68; 95% CI, 0.58 to 0.80). Pertuzumab extended the median duration of response by 7.7 months, as independently assessed. Most adverse events occurred during the administration of docetaxel in the two groups, with long-term cardiac safety maintained.In patients with HER2-positive metastatic breast cancer, the addition of pertuzumab to trastuzumab and docetaxel, as compared with the addition of placebo, significantly improved the median overall survival to 56.5 months and extended the results of previous analyses showing the efficacy of this drug combination. (Funded by F. Hoffmann-La Roche and Genentech; CLEOPATRA ClinicalTrials.gov number, NCT00567190.).
Synergism Between Platelets and Neutrophils in Provoking Cardiac Dysfunction After Ischemia and Reperfusion
Authors: Allan M. Lefer, Barry Campbell, Rosario Scalia, David J. Lefer
Journal: Circulation (1998)

Background —Neutrophils (PMNs) are known to contribute to both cardiac dysfunction and myocardial necrosis after reperfusion of an ischemic heart. Moreover, platelets are also important blood cells that can aggravate myocardial ischemic injury. This study was designed to test the effects of PMNs and platelets separately and together in provoking cardiac dysfunction in isolated perfused rat hearts after ischemia and reperfusion. Methods and Results —Control rat hearts not subjected to ischemia were perfused without blood cells for 80 minutes. Additional control rat hearts were perfused with 75×10 6 PMNs, with 100×10 6 platelets, or with 75×10 6 PMNs+100×10 6 platelets over a 5-minute perfusion followed by a 75-minute observation period. No significant reduction in coronary flow, left ventricular developed pressure (LVDP), or the first derivative of LVDP (dP/dt max ) was observed at the end of the observation period in any nonischemic group. Similarly, global ischemia (I) for 20 minutes followed by 45 minutes of reperfusion (R) produced no sustained effects on the final recovery of any of these parameters in any group of hearts perfused in the absence of blood cells. However, I/R hearts perfused with either PMNs or platelets alone exhibited decreases in these variables of 10% to 12% ( P &lt;0.05 from control). Furthermore, I/R hearts perfused with both PMNs and platelets exhibited decreases of 50% to 60% in all measurements of cardiac function ( P &lt;0.001). These dual-cell–perfused I/R hearts also exhibited marked increases in cardiac myeloperoxidase (MPO) activity, indicating a significant PMN infiltration, and enhanced P-selectin expression on the coronary microvascular endothelium. All cardiodynamic effects as well as MPO accumulation and PMN infiltration were markedly attenuated by a sialyl Lewis X -oligosaccharide or a recombinant soluble P-selectin ligand, which inhibits selectin-mediated cell adhesion. Conclusions —These results provide evidence that platelets and neutrophils act synergistically in provoking postreperfusion cardiac dysfunction and that this may be largely due to cell-to-cell interactions mediated by P-selectin. These findings may help explain the reperfusion injury phenomenon.
Effect of Membrane Permeability on Survival of Hemodialysis Patients
Authors: Francesco Locatelli, Alejandro Martin-Malo, Thierry Hannedouche, Alfredo Loureiro, Menelaos Papadimitriou, Volker Wizemann, Stefan H. Jacobson, Stanislaw Czekalski, Claudio Ronco, Raymond Vanholder
Journal: Journal of the American Society of Nephrology (2008)

The effect of high-flux hemodialysis membranes on patient survival has not been unequivocally determined. In this prospective, randomized clinical trial, we enrolled 738 incident hemodialysis patients, stratified them by serum albumin ≤4 and &gt;4 g/dl, and assigned them to either low-flux or high-flux membranes. We followed patients for 3 to 7.5 yr. Kaplan-Meier survival analysis showed no significant difference between high-flux and low-flux membranes, and a Cox proportional hazards model concurred. Patients with serum albumin ≤4 g/dl had significantly higher survival rates in the high-flux group compared with the low-flux group (<i>P</i> = 0.032). In addition, a secondary analysis revealed that high-flux membranes may significantly improve survival of patients with diabetes. Among those with serum albumin ≤4 g/dl, slightly different effects among patients with and without diabetes suggested a potential interaction between diabetes status and low serum albumin in the reduction of risk conferred by high-flux membranes. In summary, we did not detect a significant survival benefit with either high-flux or low-flux membranes in the population overall, but the use of high-flux membranes conferred a significant survival benefit among patients with serum albumin ≤4 g/dl. The apparent survival benefit among patients who have diabetes and are treated with high-flux membranes requires confirmation given the <i>post hoc</i> nature of our analysis.
Enhanced TNF-α–induced apoptosis in Fanconi anemia type C–deficient cells is dependent on apoptosis signal-regulating kinase 1
Authors: Khadijeh Bijangi-Vishehsaraei, M. Reza Saadatzadeh, Adam Werne, Kristina A. Wilson McKenzie, Reuben Kapur, Hidenori Ichijo, Laura S. Haneline
Journal: Blood (2005)
Expression and localization of COX-2 in human airways and cultured airway epithelial cells
Authors: D.N. Watkins, D.J. Peroni, C. Lenzo, D.A. Knight, M.J. Garlepp, P.J. Thompson
Journal: European Respiratory Journal (1999)

Cyclo-oxygenase is the rate-limiting enzyme in the prostanoid pathway. Although expression of the inducible isoform of cyclo-oxygenase (COX-2) is associated with cytokine-mediated inflammation, recent evidence suggests a homeostatic role for epithelial COX-2 in the gastrointestinal tract. The aim of this study was to examine the expression and localization of COX-2 in human airway epithelium both in vivo and in vitro. Human airway specimens from patients undergoing lung resection surgery for primary lung tumours (n=10) or nasal mucosal resection for non-inflammatory nasal obstruction (n=5) were examined for COX-2 expression by in situ hybridization and immunohistochemistry. COX-2 expression was also studied in two human airway epithelial cell lines (BEAS-2B and A549) using reverse transcription polymerase chain reaction and Northern and Western blot analysis. COX-2 messenger ribonucleic acid (mRNA) and protein were localized to individual columnar epithelial cells and to airway resident inflammatory cells in 9/10 lower and 5/5 upper airway specimens. Expression of COX-2 did not correlate with evidence of airway inflammation. Focal expression of COX-2 mRNA and protein was observed in bronchus-associated lymphoid tissue. Both COX-2 mRNA and protein were detected in BEAS-2B and A549 cells cultured under standard conditions. In conclusion, expression of COX-2 in human airway epithelium occurs in the upper and lower airways, is widespread in airway epithelial and airway resident inflammatory cells in the absence of overt airway inflammation, and is detectable in cultured human airway epithelial cells in the absence of inflammatory cytokine stimulation. These data suggest a potentially important homeostatic role for COX-2 in the regulation of human airway contractility, inflammation and immune responses.
Natural history of compensated viral cirrhosis: a prospective study on the incidence and hierarchy of major complications
Authors: L Benvegnu
Journal: Gut (2004)

The natural history of initially compensated cirrhosis due to hepatitis B (HBV) or hepatitis C (HCV) virus is only partially defined. We have investigated morbidity and mortality rates and the hierarchy of complications in compensated viral cirrhosis over a long follow up period.A cohort of Italian patients with initially compensated cirrhosis of viral aetiology were followed up at six monthly intervals with laboratory tests to identify major complications (ascites, gastrointestinal bleeding, portal-systemic encephalopathy, hepatocellular carcinoma) and to assess the progression of Child's stage and mortality rate due to liver related causes.Between 1986 and 1996, 312 patients (43 HBV positive, 254 HCV positive, and 15 HBV and HCV coinfected) were included. During a median follow up of 93 (range 14-194) months, 102 (32.6%) patients developed at least one complication (HCV positive 31.1%; HBV positive 34.8%; HBV and HCV coinfected 53.3%). Overall, the most frequent complication was hepatocellular carcinoma which occurred in 65 (20.8%) cases, followed by ascites (61 cases, 19.5%), gastrointestinal bleeding (14 cases, 4.5%), and portal-systemic encephalopathy (six cases, 1.9%). Progression of Child's stage was observed in 62 patients (19.8%). Death from liver disease occurred in 58 (18.6%) cases and in 70.7% this was due to hepatocellular carcinoma. Hepatocellular carcinoma was the first complication to develop in 59 cases and represented the most frequent first complication in both HCV and HBV/ HCV related cirrhosis.These results indicate significant morbidity and mortality during the first decade after diagnosis of compensated cirrhosis due to HBV and/or HCV, and identify hepatocellular carcinoma as the most frequent and life threatening complication, particularly in HCV positive cases.
Cilazapril and early atherosclerotic changes after balloon injury of porcine carotid arteries.
Authors: J Y Lam, L Lacoste, M G Bourassa
Journal: Circulation (1992)

BACKGROUND Cilazapril, a converting enzyme inhibitor, has been shown to significantly decrease the extent of intimal smooth muscle cell proliferation after arterial injury in a normotensive rat model. METHODS AND RESULTS To assess the influence of cilazapril on myofibrotic changes after balloon injury, control (n = 7) or cilazapril-treated (n = 9) (20 mg/kg b.i.d.) normal 3-month-old pigs underwent dilatation angioplasty of the right, and deendothelialization of the left common carotid artery. Carotid arteries isolated at 4 weeks were examined morphometrically with a computerized digitizer after in situ glutaraldehyde fixation. Both in the deendothelialized and dilated arteries, the surface area in square millimeters of the neointima and media were similar in the treated and control animals; therefore, the ratio of neointima to media was again not different. The neointimal changes included a combination of proliferative changes as well as organization of mural thrombus and were equally well distributed in the two groups of animals. At the time that the animals were killed, blood pressure (38.2 +/- 2.1 versus 56.8 +/- 4.8 mm Hg, p = 0.003) and plasma angiotensin converting enzyme activity (5.6 +/- 4.1 versus 182.3 +/- 70.4, p = 0.02) were lower in treated than in control pigs, but aortic media thrombogenicity (as assessed in an ex vivo perfusion flow chamber) and serum lipids were not different between groups. CONCLUSIONS In pigs, cilazapril did not alter the development of myofibrotic changes after mild or severe balloon injury despite plasma angiotensin converting enzyme activity inhibition.
S81 Primary type II alveolar epithelial cells respond differentially to bacterial virulence factors
Authors: O L Moncayo Nieto, M Brittan, T S Wilkinson, A Conway Morris, K Dhaliwal, W S Walker, A J Simpson
Journal: Thorax (2010)

<h3>Introduction and objectives</h3> The pathogens most commonly implicated in ventilator-associated pneumonia (VAP) are <i>Pseudomonas aeruginosa</i> and <i>Staphylococcus aureus</i>. Although a florid inflammatory response characteristically occurs in the alveolar space in VAP, the underlying mechanisms remain unclear, partly owing to a lack of adequate models of alveolar injury. We therefore sought to characterise the response of primary human type II alveolar epithelial (ATII) cells to virulence factors from these pathogens. <h3>Methods</h3> Primary ATII cells were derived from seven patients undergoing surgical resection for lung cancer. Lung tissue was refrigerated overnight; flushed with saline; incubated with trypsin; diced; incubated with DNAse I; and strained/filtered. Macrophages and fibroblasts were removed by adherence. The resulting cell population was centrifuged, washed, resuspended and plated onto tissue culture plates pre-coated with type I bovine collagen at 2×10<sup>6</sup> cells/ml. When cells achieved confluence medium was replenished and the following were added for 24 h: 100 ng/ml <i>P aeruginosa</i> lipopolysaccharide (LPS); 10 ug/ml <i>S aureus</i> lipoteichoic acid (LTA); 10 ug/ml <i>S aureus</i> peptidoglycan (PGN); 10 ng/ml human recombinant tumour necrosis factor alpha (TNFα); or control medium. Supernatant was aspirated at 24 h and cytokines were measured by cytometric bead array. <h3>Results</h3> Interleukin (IL)-1β, IL-6, IL-8 IL-10, IL-12p70 and TNFα were all detectable in control medium at 24 h. None of the measured cytokines were significantly altered by application of LPS or LTA. In contrast, PGN induced a significant rise in concentrations of IL-1β, IL-6, IL-8 IL-10 and TNFα. Addition of TNFa induced a significant increase in IL-6, IL-8 and IL-10. The only cytokine to be uniformly uninfluenced by stimulation was IL-12p70. <h3>Conclusions</h3> In our hands primary ATII cells appeared to be unresponsive to <i>P aeruginosa</i> LPS or to <i>S aureus</i> LTA. By contrast, <i>S aureus</i> PGN provoked a brisk and significant inflammatory response simultaneously affecting a range of cytokines. These data suggest that ATII cells have strikingly different responses to individual bacterial virulence factors. They further suggest that PGN (but not LTA) contributes, at least in part, to the florid inflammatory response seen in Staphylococcal pneumonia.