tbuckley/cabot-search huggingface dataset:
Diversion of intestinal flow decreases the numbers of interleukin 4 secreting and interferon gamma secreting T lymphocytes in small bowel mucosa
Authors: A Schmit
Journal: Gut (2000)

The intestinal immune system faces large amounts of antigens, and its regulation is tightly balanced by cytokines. In this study, the effect of intestinal flow diversion on spontaneous secretion of interleukin (IL)-4 and interferon (IFN)- gamma was analysed.Eight patients (two with Crohn's disease, four with ulcerative colitis, and two with previous colon cancer) carrying a double lumen small bowel stoma after a total colectomy procedure were included in the study. For each patient, eight biopsy samples were taken endoscopically from both the diverted and non-diverted part of the small bowel. Intraepithelial lymphocytes (IELs) and lamina propria lymphocytes (LPLs) were isolated separately and assayed for numbers of cells spontaneously secreting IL-4 and/or IFN-gamma by an ELISPOT technique.Compared with the non-diverted mucosa, a significant decrease in the number of spontaneously IFN-gamma secreting CD3 lymphocytes was observed in the diverted small bowel mucosa among both IELs (p = 0.008) and LPLs (p = 0.007). The same results, although less significant, were obtained for IL-4, especially in LPLs (p = 0.01).The intestinal content influences the spontaneous secretion of IFN-gamma and IL-4 by intestinal lymphocytes. These results could help to elucidate the anti-inflammatory role of split ileostomy in patients suffering from inflammatory bowel diseases.
Allergy gap between Finnish and Russian Karelia on increase
Authors: T. Laatikainen, L. von Hertzen, J.-P. Koskinen, M. J. Mäkelä, P. Jousilahti, T. U. Kosunen, T. Vlasoff, M. Ahlström, E. Vartiainen, T. Haahtela
Journal: Allergy (2011)

To cite this article: Laatikainen T, von Hertzen L, Koskinen J-P, Mäkelä MJ, Jousilahti P, Kosunen TU, Vlasoff T, Ahlström M, Vartiainen E, Haahtela T. Allergy gap between Finnish and Russian Karelia on increase. Allergy 2011; 66: 886–892. Background: Multinational time-trend analyses of atopic disease have shown that the East–West gradients in prevalence are shrinking. We set out to clarify whether the disparities in the occurrence of atopy and atopic diseases in Finnish and Russian Karelia during the past 10 years have diminished and how the prevalence of atopy has evolved with successive years of birth. Methods: Two surveys with identical methodology were performed in 1997/1998 and 2007. The study population comprised randomly selected adults, aged 25–54 years, from Finnish and Russian Karelia. Serum samples were collected for total and specific IgE measurements. Clinical data were obtained by questionnaires. Results: Sensitization rates to birch pollen increased from 7.8% to 14.8% (P < 0.001) and to cat from 6.1% to 10.8% (P < 0.001) in Finland. In Russia, no significant increase was found. Contrary to this, total IgE remained stable in Finland but decreased significantly (P < 0.001) in Russia. Analyses based on years of birth revealed that the prevalence of sensitization to allergens increased with successive birth years in Finland, but remained stable in Russia. Over the 10 years, self-reported physician-diagnosed asthma increased from 5.5% to 8.1% (P = 0.05) and hay fever from 8.1% to 13.2% (P < 0.001) in Finland. Conclusions: Disparities in the prevalence of atopy and atopic disease between Finnish and Russian Karelia have further grown. The 'allergy epidemic' continues in Finland and is mainly attributable to the years of birth effect shown in atopy prevalence. In Russia, no signs of the epidemic are discernible, although the decrease in total IgE may indicate a change in environmental exposure.
Saturated Fats Versus Polyunsaturated Fats Versus Carbohydrates for Cardiovascular Disease Prevention and Treatment
Authors: Patty W. Siri-Tarino, Sally Chiu, Nathalie Bergeron, Ronald M. Krauss
Journal: Annual Review of Nutrition (2015)

The effects of saturated fatty acids (SFAs) on cardiovascular disease (CVD) risk are modulated by the nutrients that replace them and their food matrices. Replacement of SFAs with polyunsaturated fatty acids has been associated with reduced CVD risk, although there is heterogeneity in both fatty acid categories. In contrast, replacement of SFAs with carbohydrates, particularly sugar, has been associated with no improvement or even a worsening of CVD risk, at least in part through effects on atherogenic dyslipidemia, a cluster of traits including small, dense low-density lipoprotein particles. The effects of dietary SFAs on insulin sensitivity, inflammation, vascular function, and thrombosis are less clear. There is growing evidence that SFAs in the context of dairy foods, particularly fermented dairy products, have neutral or inverse associations with CVD. Overall dietary patterns emphasizing vegetables, fish, nuts, and whole versus processed grains form the basis of heart-healthy eating and should supersede a focus on macronutrient composition.
Optogenetic Brain Interfaces
Authors: Ramin Pashaie, Polina Anikeeva, None Jin Hyung Lee, Rohit Prakash, Ofer Yizhar, Matthias Prigge, Divya Chander, Thomas J. Richner, Justin Williams
Journal: IEEE Reviews in Biomedical Engineering (2014)

The brain is a large network of interconnected neurons where each cell functions as a nonlinear processing element. Unraveling the mysteries of information processing in the complex networks of the brain requires versatile neurostimulation and imaging techniques. Optogenetics is a new stimulation method which allows the activity of neurons to be modulated by light. For this purpose, the cell-types of interest are genetically targeted to produce light-sensitive proteins. Once these proteins are expressed, neural activity can be controlled by exposing the cells to light of appropriate wavelengths. Optogenetics provides a unique combination of features, including multimodal control over neural function and genetic targeting of specific cell-types. Together, these versatile features combine to a powerful experimental approach, suitable for the study of the circuitry of psychiatric and neurological disorders. The advent of optogenetics was followed by extensive research aimed to produce new lines of light-sensitive proteins and to develop new technologies: for example, to control the distribution of light inside the brain tissue or to combine optogenetics with other modalities including electrophysiology, electrocorticography, nonlinear microscopy, and functional magnetic resonance imaging. In this paper, the authors review some of the recent advances in the field of optogenetics and related technologies and provide their vision for the future of the field.
Cancer-Associated Adipocytes Exhibit an Activated Phenotype and Contribute to Breast Cancer Invasion
Authors: Béatrice Dirat, Ludivine Bochet, Marta Dabek, Danièle Daviaud, Stéphanie Dauvillier, Bilal Majed, Yuan Yuan Wang, Aline Meulle, Bernard Salles, Sophie Le Gonidec, Ignacio Garrido, Ghislaine Escourrou, Philippe Valet, Catherine Muller
Journal: Cancer Research (2011)

Abstract Early local tumor invasion in breast cancer results in a likely encounter between cancer cells and mature adipocytes, but the role of these fat cells in tumor progression remains unclear. We show that murine and human tumor cells cocultivated with mature adipocytes exhibit increased invasive capacities in vitro and in vivo, using an original two-dimensional coculture system. Likewise, adipocytes cultivated with cancer cells also exhibit an altered phenotype in terms of delipidation and decreased adipocyte markers associated with the occurrence of an activated state characterized by overexpression of proteases, including matrix metalloproteinase-11, and proinflammatory cytokines [interleukin (IL)-6, IL-1β]. In the case of IL-6, we show that it plays a key role in the acquired proinvasive effect by tumor cells. Equally important, we confirm the presence of these modified adipocytes in human breast tumors by immunohistochemistry and quantitative PCR. Interestingly, the tumors of larger size and/or with lymph nodes involvement exhibit the higher levels of IL-6 in tumor surrounding adipocytes. Collectively, all our data provide in vitro and in vivo evidence that (i) invasive cancer cells dramatically impact surrounding adipocytes; (ii) peritumoral adipocytes exhibit a modified phenotype and specific biological features sufficient to be named cancer-associated adipocytes (CAA); and (iii) CAAs modify the cancer cell characteristics/phenotype leading to a more aggressive behavior. Our results strongly support the innovative concept that adipocytes participate in a highly complex vicious cycle orchestrated by cancer cells to promote tumor progression that might be amplified in obese patients. Cancer Res; 71(7); 2455–65. ©2011 AACR.
Exercise Provides Direct Biphasic Cardioprotection via Manganese Superoxide Dismutase Activation
Authors: Nobushige Yamashita, Shiro Hoshida, Kinya Otsu, Michio Asahi, Tsunehiko Kuzuya, Masatsugu Hori
Journal: The Journal of Experimental Medicine (1999)

Epidemiologic investigations have shown that exercise reduces morbidity and mortality from coronary artery disease. In this study, using a rat model, we attempted to determine whether exercise can reduce ischemic injury to the heart and elucidate a mechanism for the cardioprotective effect of exercise. Results showed that exercise significantly reduced the magnitude of a myocardial infarction in biphasic manner. The time course for cardioprotection resembled that of the change in manganese superoxide dismutase (Mn-SOD) activity. The administration of the antisense oligodeoxyribonucleotide to Mn-SOD abolished the expected decrease in infarct size. We showed that the level of tumor necrosis factor alpha (TNF-alpha) and interleukin 1beta (IL-1beta) increased after exercise. The simultaneous administration of the neutralizing antibodies to the cytokines abolished the exercise-induced cardioprotection and the activation of Mn-SOD. Furthermore, TNF-alpha can mimic the biphasic pattern of cardioprotection and activation of Mn-SOD. An antioxidant completely abolished cardioprotection and the activation of Mn-SOD by exercise or the injection of TNF-alpha as well as exercise-induced increase in TNF-alpha and IL-1beta. The production of reactive oxygen species and endogenous TNF-alpha and IL-1beta induced by exercise leads to the activation of Mn-SOD, which plays major roles in the acquisition of biphasic cardioprotection against ischemia/reperfusion injury in rats.
EpiExplorer: live exploration and global analysis of large epigenomic datasets
Authors: Konstantin Halachev, Hannah Bast, Felipe Albrecht, Thomas Lengauer, Christoph Bock
Journal: Genome biology (2012)

Epigenome mapping consortia are generating resources of tremendous value for studying epigenetic regulation. To maximize their utility and impact, new tools are needed that facilitate interactive analysis of epigenome datasets. Here we describe EpiExplorer, a web tool for exploring genome and epigenome data on a genomic scale. We demonstrate EpiExplorer's utility by describing a hypothesis-generating analysis of DNA hydroxymethylation in relation to public reference maps of the human epigenome. All EpiExplorer analyses are performed dynamically within seconds, using an efficient and versatile text indexing scheme that we introduce to bioinformatics. EpiExplorer is available at http://epiexplorer.mpi-inf.mpg.de.
Atypical carcinoid tumours of the lung: prognostic factors and patterns of recurrence
Authors: M A Cañizares, J M Matilla, A Cueto, J Algar, I Muguruza, N Moreno-Mata, R Moreno-Balsalobre, R Guijarro, R Arrabal, E Garcia-Fontan, A Gonzalez-Piñeiro, M Garcia-Yuste, Emetne-Separ Members
Journal: Thorax (2014)

<h3>Background</h3> Atypical carcinoids (AC) of the lung are rare intermediate-grade neuroendocrine neoplasms. Prognostic factors for these tumours are undefined. <h3>Methods</h3> Our cooperative group retrieved data on 127 patients operated between 1980 and 2009 because of an AC. Several clinical and pathological features were studied. <h3>Results</h3> In a univariable analysis, T-status (p=0.005), N-status (p=0.021), preoperative M-status (previously treated) (p=0.04), and distant recurrence developed during the outcome (p&lt;0.001) presented statistically significant differences related to survival of these patients. In a multivariable analysis, only distant recurrence was demonstrated to be an independent risk factor for survival (p&lt;0.001; HR: 13.1). During the monitoring, 25.2% of the patients presented some kind of recurrence. When we studied recurrence factors in a univariable manner, sublobar resections presented significant relationship with locoregional recurrence (p&lt;0.001). In the case of distant recurrence, T and N status presented significant differences. Patients with preoperative M1 status presented higher frequencies of locoregional and distant recurrence (p=0.004 and p&lt;0.001, respectively). In a multivariable analysis, sublobar resection was an independent prognostic factor to predict locoregional recurrence (p=0.002; HR: 18.1). <h3>Conclusions</h3> Complete standard surgical resection with radical lymphadenectomy is essential for AC. Sublobar resections are related to locoregional recurrence, so they should be avoided except for carefully selected patients. Nodal status is an important prognostic factor to predict survival and recurrence. Distant recurrence is related to poor outcome.
Comparison of detection and miss rates of narrow band imaging, flexible spectral imaging chromoendoscopy and white light at screening colonoscopy: a randomised controlled back-to-back study
Authors: Su Jin Chung, Donghee Kim, Ji Hyun Song, Hae Yeon Kang, Goh Eun Chung, Jeongmin Choi, Young Sun Kim, Min Jung Park, Joo Sung Kim
Journal: Gut (2013)

Virtual chromoendoscopy (CE) is expected to enhance adenoma yield and reduce variation in performance between colonoscopists. This study aimed to compare the efficacy of narrow band imaging (NBI), flexible spectral imaging CE (FICE) and white light (WL) colonoscopy and their impact for less experienced endoscopists.We performed a randomised tandem colonoscopy trial controlling for withdrawal time and bowel preparation. Average-risk adults undergoing screening colonoscopy were enrolled and randomly assigned to first withdrawal with one of the three imaging modalities (NBI (NBI-WL group), FICE (FICE-WL group) and WL (WL-WL group)). Eight colonoscopists were categorised into expert and non-expert subgroups.1650 subjects (mean age 51.4 years, 63.9% men) were included (550 in each group). Compared with WL, neither NBI nor FICE increased the mean number of adenomas detected per patient (0.37 vs 0.35 and 0.36; p=0.591) or the percentage of patients with adenoma (25.3% vs 24.5% and 23.6%; p=0.753). For all three modalities, expert subgroups had higher yields of adenomas than non-expert subgroups. Learning curves were observed only for non-expert subgroups with all three modalities. The percentage of missed adenomas did not differ between the three groups (20.8% by WL vs 22.9% by NBI and 26.0% by FICE, p=0.300) and was not affected by endoscopists' expertise.Neither NBI nor FICE improved adenoma detection or miss rates, with no difference in diagnostic efficacy between the two systems. Virtual CE had no additional benefits over WL for non-experts.KCT0000570.
Phase III Trial Comparing Three Doses of Docetaxel for Second-Line Treatment of Advanced Breast Cancer
Authors: Vernon Harvey, Henning Mouridsen, Vladimir Semiglazov, Erik Jakobsen, Edouard Voznyi, Bridget A. Robinson, Vanina Groult, Michael Murawsky, Soeren Cold
Journal: Journal of Clinical Oncology (2006)

Purpose To evaluate whether a relationship exists between docetaxel dose and clinical response in the treatment of patients with advanced breast cancer. Patients and Methods Patients whose cancer had progressed after one prior chemotherapy regimen for advanced breast cancer or had recurred during or within 6 months of adjuvant chemotherapy were randomly assigned to docetaxel 60, 75, or 100 mg/m 2 intravenously every 3 weeks. Results Five hundred twenty-seven patients were randomly assigned (intent to treat [ITT]), and 524 were assessable for toxicity. In the population assessable for efficacy (n = 407), logistic regression analysis showed that increasing docetaxel dose was significantly associated with higher response rate (P = .007) and improved time to progression (TTP; P = .014). In the ITT analysis, a significant dose-response relationship was observed for tumor response (P = .026) but not for TTP (P = .067). The incidences of most hematologic and nonhematologic toxicities were related to increasing dose, with grade 3 to 4 neutropenia occurring in 76.4%, 83.7%, and 93.4% and febrile neutropenia occurring in 4.7%, 7.4%, and 14.1% of patients administered the 60, 75, and 100 mg/m 2 doses, respectively. One death was considered treatment related. Conclusion A relationship between increasing dose of docetaxel and increased tumor response was observed across the dose range of 60 to 100 mg/m 2 every 3 weeks. Toxicities were related to increasing dose. Depending on the therapy goal, any of the doses studied may be appropriate for second-line treatment of advanced breast cancer.
Vascular endothelial growth factor (VEGF) expression is not associated with prognosis in patients with radically resected ampullary carcinoma
Authors: D. Santini, B. Vincenzi, G. Perrone, C. Rabitti, D. Borzomati, S. Valeri, R. Coppola, P. Magistrelli, G. Tonini
Journal: Annals of Oncology (2005)
Evaluation of diaphragmatic fatigue in obstructive sleep apnoeas during non-REM sleep
Authors: F. Cibella, G. Cuttitta, S. Romano, V. Bellia, G. Bonsignore
Journal: Thorax (1997)

Resistive load applied to the airways may induce diaphragmatic fatigue, and hypoxaemia has been shown to predispose to the development of fatigue. Inspiratory muscle fatigue may occur in patients with obstructive sleep apnoea syndrome (OSAS), as these patients repetitively develop both inspiratory loading and hypoxaemia. The results of previous studies on this topic are inconclusive, probably because of the methodological approaches used.Six obese patients with OSAS underwent a polysomnographic study. The diaphragmatic pressure time index (PTI) was evaluated as an indicator of diaphragmatic contraction, and the mean frequency of the diaphragmatic electromyogram power spectrum (Fm) and the maximum relaxation rate of transdiaphragmatic pressure (MRR) as indices of a fatiguing diaphragm. A total of 119 randomly selected apnoeas (each including 5-13 occluded efforts) were analysed throughout the night in non-REM sleep to assess possible muscle fatigue due to the high pressure generation in each apnoea. A breath-by-breath within-apnoea analysis was performed on the first three pre-apnoeic breaths, on all the occluded efforts, and on the first three unoccluded breaths following the apnoea interruption. Possible fatigue development due to the cumulative effect of apnoeas over the night was also evaluated.A progressive increase of Fm and MRR was found during the obstructive phase in all the subjects in the within-apnoea analysis. The overnight analysis did not show a reduction in either PTI, Fm, or MRR secondary to recurrent upper airway obstruction during the night.No evidence of diaphragmatic fatigue or impaired diaphragmatic contraction was found either within each apnoea or throughout the whole night, despite the generation of high PTI values during the apnoeic occluded phases. It is concluded that diaphragmatic fatigue does not occur in OSAS during non-REM sleep.
Explanations for the clinical and microscopic localization of lesions in pemphigus foliaceus and vulgaris
Authors: My G. Mahoney, Zhihong Wang, Kyle Rothenberger, Peter J. Koch, Masayuki Amagai, John R. Stanley
Journal: Journal of Clinical Investigation (1999)

Patients with pemphigus foliaceus (PF) have blisters on skin, but not mucous membranes, whereas patients with pemphigus vulgaris (PV) develop blisters on mucous membranes and/or skin. PF and PV blisters are due to loss of keratinocyte cell–cell adhesion in the superficial and deep epidermis, respectively. PF autoantibodies are directed against desmoglein (Dsg) 1; PV autoantibodies bind Dsg3 or both Dsg3 and Dsg1. In this study, we test the hypothesis that coexpression of Dsg1 and Dsg3 in keratinocytes protects against pathology due to antibody-induced dysfunction of either one alone. Using passive transfer of pemphigus IgG to normal and DSG3null neonatal mice, we show that in the areas of epidermis and mucous membrane that coexpress Dsg1 and Dsg3, antibodies against either desmoglein alone do not cause spontaneous blisters, but antibodies against both do. In areas (such as superficial epidermis of normal mice) where Dsg1 without Dsg3 is expressed, anti-Dsg1 antibodies alone can cause blisters. Thus, the anti-desmoglein antibody profiles in pemphigus sera and the normal tissue distributions of Dsg1 and Dsg3 determine the sites of blister formation. These studies suggest that pemphigus autoantibodies inhibit the adhesive function of desmoglein proteins, and demonstrate that either Dsg1 or Dsg3 alone is sufficient to maintain keratinocyte adhesion.
197 TRANSJUGULAR INTRAHEPATIC PORTOSYSTEMIC SHUNTS FOLLOWING LIVER TRANSPLANTATION CAN BE ASSOCIATED WITH A GOOD PROGNOSIS: A SINGLE CENTRE EXPERIENCE
Authors: B.J. Hogan, D. Thorburn, D. Sharma, B. Davidson, J.P. O'Beirne, A.K. Burroughs, D. Yu, D.W. Patch
Journal: Journal of Hepatology (2012)
Cure Models as a Useful Statistical Tool for Analyzing Survival
Authors: Megan Othus, Bart Barlogie, Michael L. LeBlanc, John J. Crowley
Journal: Clinical Cancer Research (2012)

Abstract Cure models are a popular topic within statistical literature but are not as widely known in the clinical literature. Many patients with cancer can be long-term survivors of their disease, and cure models can be a useful tool to analyze and describe cancer survival data. The goal of this article is to review what a cure model is, explain when cure models can be used, and use cure models to describe multiple myeloma survival trends. Multiple myeloma is generally considered an incurable disease, and this article shows that by using cure models, rather than the standard Cox proportional hazards model, we can evaluate whether there is evidence that therapies at the University of Arkansas for Medical Sciences induce a proportion of patients to be long-term survivors. Clin Cancer Res; 18(14); 3731–6. ©2012 AACR.