tbuckley/cabot-search huggingface dataset:
Is there an excess risk for colorectal cancer in patients with ulcerative colitis and concomitant primary sclerosing cholangitis? A population based study
Authors: D Kornfeld, A Ekbom, T Ihre
Journal: Gut (1997)

Background —Patients with ulcerative colitis have an increased risk of colorectal cancer. Duration, age, and extent of the disease at diagnosis are the only established risk factors. Patients with ulcerative colitis and concomitant primary sclerosing cholangitis (PSC) have been reported to have a higher frequency of colonic DNA aneuploidy and/or dysplasia than expected, findings indicating an increased risk of colorectal cancer compared with other patients with ulcerative colitis. Methods —A population based cohort consisting of 125 patients with a verified diagnosis of PSC was followed up by linkage to the Swedish Cancer Registry for the occurrence of colorectal cancer. Results —There were 12 colorectal cancers. Six cancers were diagnosed prior to the diagnosis of PSC. Among the 104 patients with an intact colon at the time of the diagnosis of PSC there was a cumulative risk for colorectal cancer of 16% after 10 years. Among the 58 patients with a diagnosis of ulcerative colitis and colorectal cancer prior to the diagnosis of PSC, there were five colorectal cancers corresponding to a cumulative risk of 25% after 10 years. Conclusions —Patients with ulcerative colitis and concomitant PSC seem to constitute a subgroup with a high risk for colorectal cancer.
JAK2/STAT5 inhibition by nilotinib with ruxolitinib contributes to the elimination of CML CD34+ cells in vitro and in vivo
Authors: Paolo Gallipoli, Amy Cook, Susan Rhodes, Lisa Hopcroft, Helen Wheadon, Anthony D. Whetton, Heather G. Jørgensen, Ravi Bhatia, Tessa L. Holyoake
Journal: Blood (2014)
Fetal alcohol spectrum disorder: an overview
Authors: R. A S Mukherjee
Journal: Journal of the Royal Society of Medicine (2006)

There has been an increase in awareness of fetal alcohol spectrum disorders in both the lay and academic press of late. However, evidence from national, regional and local conferences as well as a pilot survey of awareness (unpublished data) suggests they remain a set of conditions that are poorly understood in the UK both by the general public and health practitioners. This is despite the conditions being relevant to specialties as diverse as obstetrics, paediatrics, general practice, neurology, public health and psychiatry. This article provides an overview to inform medical practitioners of important aspects related to their practice.
Upregulation of the calcium-dependent protease, calpain, during keratinocyte differentiation
Authors: None Garach-Jehoshua, None Ravid, None Liberman, None Reichrath, None Glaser, None Koren
Journal: British Journal of Dermatology (1998)

Calpain is a ubiquitous neutral calcium-activated thiol protease that is implicated in various cellular functions including exocytosis, cell fusion, apoptosis and proliferation. The calpain system is composed of the enzymes mu-calpain and m-calpain and their endogenous inhibitor, calpastatin. We employed the spontaneously immortalized human HaCaT keratinocytes, which retain their ability to differentiate in vitro and in vivo, to study the modulation of the calpain system during keratinocyte differentiation. The cellular levels of keratinocyte differentiation markers and of the components of the calpain system were monitored by immunoblotting. Three established differentiation stimuli: increase in cell density as a function of time in culture, elevation of extracellular calcium concentration and exposure to 1,25-dihydroxyvitamin D3 enhanced the expression of the three keratinocyte differentiation markers keratin 10, involucrin and transglutaminase. The differentiation of HaCaT cells was accompanied by elevation of the components of the calpain system, although the pattern of increase varied according to the specific differentiation stimulus. A higher increase in calpains as compared with the increase in calpastatin suggests an increase in net calpain activity during differentiation. Such an increase may play a part in the differentiation process itself and/or in the regulation of key events in differentiating keratinocyte metabolism.
Neoadjuvant concurrent radiochemotherapy in locally advanced (IIIA–IIIB) non-small-cell lung cancer: long-term results according to downstaging
Authors: L. Trodella, P. Granone, S. Valente, S. Margaritora, G. Macis, A. Cesario, R.M. D’Angelillo, V. Valentini, G.M. Corbo, V. Porziella, S. Ramella, G. Tonini, D. Galetta, M. Ciresa, B. Vincenzi, N. Cellini
Journal: Annals of Oncology (2004)
Respiratory symptoms and inflammatory responses to Difflam throat-spray intervention in half-marathon runners: a randomised controlled trial
Authors: A J Cox, M Gleeson, D B Pyne, P U Saunders, R Callister, P A Fricker
Journal: British Journal of Sports Medicine (2008)

Objective In this study, the effects of Difflam Forte Anti-inflammatory Throat Spray on the incidence of upper respiratory symptoms (URS) and inflammatory responses after a half-marathon race were investigated. Design and setting Double-blind placebo-controlled randomised trial conducted in association with a half-marathon event. Participants 45 well-trained half-marathon runners. Interventions Difflam (n = 25) or placebo (n = 20) throat sprays were self-administered three times daily for 1 week before and 2 weeks after the race. Main outcome measures Self-reported respiratory symptoms; plasma prostaglandin E 2 , myeloperoxidase, interleukin (IL) 6, IL8, IL10 and IL1 receptor antagonist (IL1ra) concentrations; and salivary myeloperoxidase and IL6 concentrations. Results All subjects completed the intervention without reporting any adverse events. The proportion of athletes reporting URS was not substantially different between Difflam (52%) and placebo (56%) groups (p = 0.82). However, symptom severity scores were ∼29% lower during Difflam treatment (4.7 (7.4) vs 6.6 (9.6)) AU). Post-exercise responses in plasma inflammatory markers did not differ substantially between Difflam and placebo groups. Post-race increases in salivary myeloperoxidase (∼63%; trivial to moderate difference; p = 0.13) and salivary IL6 (∼50%; trivial to moderate difference; p = 0.25) were greater in the Difflam group. Conclusions Prophylactic use of the Difflam reduced the severity, but not the frequency, of URS among half-marathon runners. Post-race increases in systemic inflammatory markers were not altered by Difflam use, but markers of local inflammation (salivary myeloperoxidase and IL6) were augmented in the Difflam compared with the placebo group.
Correlating measurements across samples improves accuracy of large-scale expression profile experiments
Authors: Mariano Javier Alvarez, Pavel Sumazin, Presha Rajbhandari, Andrea Califano
Journal: Genome biology (2009)

Abstract Gene expression profiling technologies suffer from poor reproducibility across replicate experiments. However, when analyzing large datasets, probe-level expression profile correlation can help identify flawed probes and lead to the construction of truer probe sets with improved reproducibility. We describe methods to eliminate uninformative and flawed probes, account for dependence between probes, and address variability due to transcript-isoform mixtures. We test and validate our approach on Affymetrix microarrays and outline their future adaptation to other technologies.
Cellular and humoral observations in a patient with allergic bronchopulmonary aspergillosis during a nonasthmatic exacerbation
Authors: H.F. Kauffman, G.H. Koëter, S. van der Heide, J.G.R. de Monchy, E. Kloprogge, K. de Vries
Journal: Journal of Allergy and Clinical Immunology (1989)
Intracoronary Adenovirus Encoding Adenylyl Cyclase VI Increases Left Ventricular Function in Heart Failure
Authors: N. Chin Lai, David M. Roth, Mei Hua Gao, Tong Tang, Nancy Dalton, Yin Yin Lai, Matthew Spellman, Paul Clopton, H. Kirk Hammond
Journal: Circulation (2004)

Background— We tested the hypothesis that intracoronary delivery of an adenovirus encoding adenylyl cyclase type VI (Ad.AC VI ) would be associated with increased left ventricular (LV) function in pigs with congestive heart failure. Methods and Results— Pigs (52±6 kg; n=16) underwent placement of pacemakers, LV pressure transducers, and left atrial and aortic catheters. Physiological and echocardiographic studies were obtained from conscious animals 13 days later, and pacing was initiated (220 bpm). Seven days later, measures of LV function were reduced, documenting severe LV dysfunction and dilation. Pigs then received intracoronary Ad.AC VI (1.4×10 12 vp; n=7) or saline (PBS; n=9) (randomized, blinded), with concomitant infusion of nitroprusside (50 μg/min, 6.4 minutes) to increase gene transfer. Pacing was continued for 14 days, and final studies were obtained. The a priori key end point was change in LV dP/dt during isoproterenol infusion (pre-Ad.AC VI value minus value after 21 days of pacing). Pigs receiving Ad.AC VI showed a smaller decrease in both LV +dP/dt ( P =0.0014) and LV −dP/dt ( P =0.0008). Serial echocardiography showed that Ad.AC VI treatment was associated with increased LV function and reduced LV dilation and that end-systolic wall stress was reduced. AC-stimulated cAMP production was increased 1.7-fold in LV samples from Ad.AC VI -treated pigs ( P =0.006), and B-type natriuretic peptide was reduced (0.035). Gene transfer was confirmed by polymerase chain reaction. Conclusions— AC VI gene transfer increases LV function and attenuates deleterious LV remodeling in congestive heart failure.
Preliminary findings of quorum signal molecules in clinically stable lung allograft recipients
Authors: C Ward, M Cámara, I Forrest, R Rutherford, G Pritchard, M Daykin, A Hardman, A de Soyza, A J Fisher, P Williams, P A Corris
Journal: Thorax (2003)

<b>Background:</b> Infection with bacteria such as <i>Pseudomonas</i> is common in lung allograft recipients, particularly during chronic rejection. Analysis of sputum samples from patients with cystic fibrosis infected with <i>Pseudomonas aeruginosa</i> or <i>Burkholderia cepacia</i> has indicated the presence of bacterial <i>N</i>-acylhomoserine lactones (AHLs) quorum sensing signalling molecules. AHLs not only control the expression of bacterial virulence genes but are also involved in stimulating the maturation of antibiotic resistant biofilms and host chemokine release. It was hypothesised that AHLs may be detected even in clinically stable lung transplant recipients free of clinical infection or rejection. <b>Methods:</b> Three 60 ml samples of bronchoalveolar lavage (BAL) fluid were taken from nine stable lung transplant recipients 3–12 months after transplantation. Detection of AHLs was carried out on dichloromethane extracted supernatants using the bioluminescence based AHL reporter plasmid pSB1075. This responds to the presence of AHLs with long acyl chains (C10–C14), generating light. Synthetic AHLs were included as positive controls. <b>Results:</b> Five of the nine BAL fluid supernatants exhibited AHL activity, suggesting the presence of AHLs with long N-acyl chains. There was no correlation between the levels of AHLs detected or their absence and BAL fluid microbiology or diagnosis before transplantation. <b>Conclusions:</b> This is the first evidence for the presence of AHL quorum sensing signals in human lung allograft recipients, even in subjects with no rejection or apparent infection. Further longitudinal follow up of these preliminary findings is required to elucidate potential links with infection, rejection, and allograft deterioration.
Herpes zoster is associated with herpes simplex and other infections in under 60 year-olds
Authors: Benson Ogunjimi, Frank Buntinx, Stephaan Bartholomeeusen, Ita Terpstra, Inke De haes, Lander Willem, Steven Elli, Joke Bilcke, Pierre Van Damme, Samuel Coenen, Philippe Beutels
Journal: Journal of Infection (2014)
Fine-Scale Analysis of X Chromosome Inactivation in the Male Germ Line of Drosophila melanogaster
Authors: C. Kemkemer, W. Hense, J. Parsch
Journal: Molecular Biology and Evolution (2010)

Inactivation of the X chromosome in the male germ line has been suggested to contribute to the excess of gene movement off the X chromosome and the paucity of X-linked male-biased genes that have been observed in Drosophila species. Recent experimental work has demonstrated the transcriptional inactivation of the X chromosome during spermatogenesis, but it is not known if some regions of the X escape inactivation. To test this, we analyzed the expression of 112 precisely-mapped, testis-specific reporter gene insertions along the X chromosome. All of the reporter gene insertions showed low levels of expression that were significantly less than those of autosomal insertions, suggesting that the X chromosome is globally inactivated in the male germ line. There was no evidence for regions of the X chromosome escaping inactivation, including cytological region 19, which appears to be a hot spot for newly evolved, testis-expressed genes.
THE EFFECT OF PROPRANOLOL ON ACNE VULGARIS AND THE RATE OF SEBUM EXCRETION
Authors: W. J. CUNLIFFE, J. COTTERILL
Journal: British Journal of Dermatology (1970)

Propranolol, given orally for 8–10 weeks, had no effect on acne vulgaris nor on the rate of sebum excretion in 14 patients.
Tumor-Associated Antigen Preferentially Expressed Antigen of Melanoma (PRAME) Induces Caspase-Independent Cell Death <i>In vitro</i> and Reduces Tumorigenicity <i>In vivo</i>
Authors: Nicolas Tajeddine, Jean-Luc Gala, Magali Louis, Monique Van Schoor, Bertrand Tombal, Philippe Gailly
Journal: Cancer Research (2005)

Abstract Preferentially expressed antigen of melanoma (PRAME) is expressed in a wide variety of tumors, but in contrast with most other tumor associated antigens, it is also expressed in leukemias. The physiologic role of PRAME remains elusive. Interestingly, PRAME expression is correlated with a favorable prognosis in childhood acute leukemias. Moreover, a high expression of PRAME seems to be predominantly found in acute leukemias carrying a favorable prognosis. On these clinical observations, we assumed that PRAME could be involved in the regulation of cell death or cell cycle. In this study, we show that transient overexpression of PRAME induces a caspase-independent cell death in cultured cell lines (CHO-K1 and HeLa). Cells stably transfected with PRAME also exhibit a decreased proliferation rate due, at least partially, to an elevated basal rate of cell death. Immunocytochemistry of a FLAG-tagged PRAME, in vivo imaging of an enhanced green fluorescent protein–tagged PRAME, and Western blotting after cell fractionation reveal a nuclear localization of the protein. Using a microarray-based approach, we show that KG-1 leukemic cells stably transfected with PRAME present a significant decrease of expression of the heat-shock protein Hsp27, the cyclin-dependent kinase inhibitor p21, and the calcium-binding protein S100A4. The expression of these three proteins is known to inhibit apoptosis and has been associated with an unfavorable prognosis in a series of cancers. Finally, repression of PRAME expression by a short interfering RNA strategy increases tumorigenicity of K562 leukemic cells in nude mice. We suggest that all these observations might explain the favorable prognosis of the leukemias expressing high levels of PRAME.
Transmission of hepatitis C virus by organ transplantation in the United Kingdom
Authors: Timothy G. Wreghitt, James J. Gray, Jean-Pierre Allain, Joanne Poulain, Jeremy A. Garson, Robert Deaville, Christopher Maple, Jayan Parameshwar, Roy Y. Calne, John Wallwork, Graeme J.M. Alexander
Journal: Journal of Hepatology (1994)
More on the right ventricle in pulmonary hypertension
Authors: Robert Naeije, Stefano Ghio
Journal: European Respiratory Journal (2014)

In the present issue of the European Respiratory Journal , Courand et al. [1] report on the prognostic relevance of radionuclide angiography of the right ventricle (RV) in a cohort of 100 patients with idiopathic, heritable or drug-related pulmonary arterial hypertension (PAH). Patients with a baseline RV ejection fraction (RVEF) >25% had better survival than those with a RVEF <25%. Furthermore, patients with a stable or increased RVEF at 3–6 months had a trend to better overall survival and a significantly lower cardiovascular mortality. These results are in keeping with recently demonstrated prognostic relevance of baseline and follow-up RVEF, but measured by magnetic resonance imaging (MRI) in PAH patients [2]. A striking finding in both studies was the dissociation between RVEF and pulmonary vascular resistance (PVR). Thus, a decreased PVR under targeted therapies could be associated with either deterioration or improvement in RV function [1, 2]. The notion emerges that PAH is a disease of RV–arterial uncoupling rather than only of pathological pulmonary vascular remodelling [3]. Decreased RVEF and PVR is associated with a decreased survival rate in PAH patients under targeted therapies <http://ow.ly/EBK8U>
Phase III Randomized Trial Assessing Rofecoxib in the Adjuvant Setting of Colorectal Cancer: Final Results of the VICTOR Trial
Authors: Rachel S. Midgley, Christopher C. McConkey, Elaine C. Johnstone, Janet A. Dunn, Justine L. Smith, Simon A. Grumett, Patrick Julier, Claire Iveson, Yoko Yanagisawa, Bryan Warren, Michael J. Langman, David J. Kerr
Journal: Journal of Clinical Oncology (2010)

Laboratory and case-control studies suggest a pivotal role for the cyclooxygenase-2 (COX-2) pathway in colorectal carcinogenesis. The purpose of this study was to test whether the COX-2 inhibitor rofecoxib could reduce recurrence and improve survival when administered in the adjuvant setting of colorectal cancer (CRC).Patients who had undergone potentially curative surgery and completion of adjuvant therapy for stage II and III CRC were randomly assigned to receive rofecoxib (20 mg daily) or placebo. The primary end point was overall survival (OS). Where formalin-fixed paraffin-embedded tumor tissue samples were available, COX-2 expression was evaluated by immunohistochemistry and correlated with clinical outcome.Two thousand four hundred thirty-four patients were entered onto the study. The trial was terminated early because of the worldwide withdrawal of rofecoxib. At this point, 1,167 patients had received rofecoxib and 1,160 patients had received placebo for median treatment durations of 7.4 and 8.2 months, respectively. For the rofecoxib and placebo arms, median follow-up times were 4.84 and 4.85 years, with 241 and 246 deaths and 297 and 329 recurrences, respectively. No difference was demonstrated in OS (hazard ratio [HR] = 0.97; 95% CI, 0.81 to 1.16; P = .75) or recurrence (HR = 0.89; 95% CI, 0.76 to 1.04; P = .15) comparing the two groups. Tumor COX-2 expression by immunohistochemistry was assessed for 871 patients, but neither prognostic nor predictive effects were observed.In this study of abbreviated therapy in the adjuvant setting of CRC, rofecoxib did not improve OS or protect from recurrence in unselected patients. In addition, COX-2 expression did not correlate with prognosis overall or predict effectiveness of COX-2 inhibitors.
The morphine prostigmine provocation (Nardi) test for sphincter of Oddi dysfunction: results in healthy volunteers and in patients before and after transduodenal sphincteroplasty and transampullary septectomy
Authors: D N Lobo, A S Takhar, A Thaper, M G Dube, B J Rowlands
Journal: Gut (2007)

<h3>Objectives</h3> Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). To further assess the potential role of Janus kinase inhibition in the development of malignancies, we performed an integrated analysis of data from the tofacitinib RA clinical development programme. <h3>Methods</h3> Malignancy data (up to 10 April 2013) were pooled from six phase II, six Phase III and two long-term extension (LTE) studies involving tofacitinib. In the phase II and III studies, patients with moderate-to-severe RA were randomised to various tofacitinib doses as monotherapy or with background non-biological disease-modifying antirheumatic drugs (DMARDs), mainly methotrexate. The LTE studies (tofacitinib 5 or 10 mg twice daily) enrolled patients from qualifying prior phase I, II and III index studies. <h3>Results</h3> Of 5671 tofacitinib-treated patients, 107 developed malignancies (excluding non-melanoma skin cancer (NMSC)). The most common malignancy was lung cancer (n=24) followed by breast cancer (n=19), lymphoma (n=10) and gastric cancer (n=6). The rate of malignancies by 6-month intervals of tofacitinib exposure indicates rates remained stable over time. Standardised incidence ratios (comparison with Surveillance, Epidemiology and End Results) for all malignancies (excluding NMSC) and selected malignancies (lung, breast, lymphoma, NMSC) were within the expected range of patients with moderate-to-severe RA. <h3>Conclusions</h3> The overall rates and types of malignancies observed in the tofacitinib clinical programme remained stable over time with increasing tofacitinib exposure.
Correlation between EGFR mutations and emphysematous changes in heavy smokers with lung cancer
Authors: Shizuka Ito, Kenichi Takeda, Yuji Kawasaki, Hiroki Izumi, Tomohiro Sakamoto, Hirokazu Touge, Masahiro Kodani, Shingo Matsumoto, Kunio Araki, Akira Yamasaki, Tadashi Igishi, Eiji Shimizu
Journal: European Respiratory Journal (2013)

Background: Demographic and clinical analyses have shown that smoking is predictive of the frequency on epidermal growth factor receptor (EGFR) mutations. We examines whether there was a clinical difference between heavy smokers with adenocarcinomas with wild-type and mutated EGFR status.

Methods: EGFR mutations status was determined. The records of 179 patients with lung adenocarcinoma were retrospectively reviewed. All patients were heavy smokeres, >10 pack years, the male/female ratio was 162/17, and the average age was 70 years, EGFR mutation status was wild-type in 133 individuals (74%) and mutated in 46 (36%). Two expert chest radiologists classified the patients into 2 groups on the basis of computed tomography morphological findings: the non-emphysema and emphysema groups. We compared EGFR status in these groups with each clinical factor.

Results: The cumulative smoking dose was higher (p=0.0003), and the forced expiratory volume/forced vital capacity ratio (FEV1/FVC) was lower (p=0.021) in the wild-type EGFR group than in the mutated EGFR group. Interestingly, the rate of emphysema was lower in the mutated EGFR group (p=0.0008), and the presence of emphysematous changes was an independent risk factor for reduced frequency of EGFR mutations in multivariate analysis (odds ration 3.47, p=0.005).

Conclusion: Tumores from patients with no or low emphysematous changes in the lungs had a higher rate of EGFR mutations than those with severe emphysematous changes, although the pathological diagnosis in both cases was of adenocarcinoma. These data suggest that oncogene or driver mutations causing lung cancer in smokers could be different between the emphysema and non-emphysema groups.