tbuckley/cabot-search huggingface dataset:
Experimental studies on the value of the reference substances polyethyleneglycol, bromsulphthalein, and 51-Cr as indicators of the fluid content in the intestinal lumen.
Authors: H Worning, E Amdrup
Journal: Gut (1965)

EDITORIAL SYNOPSIS These studies have shown that calculation of total intestinal content based on the concentration of non-absorbable markers in the aspirate may give values which are up to 50 % too high.Experimental and clinical studies on the function of the liver, the bile ducts, and the pancreas, together with studies on the motility and absorptive function of the small intestine, are generally based on intestinal intubation combined with aspiration at various levels of the intestinal content using different techniques (Blankenhorn, Hirsch, and Ahrens, 1955).In the interpretation of the results obtained in a number of these studies the aspiration of the intestinal content has been assumed to be of a quantitative nature (Lagerlof, 1942; Dreiling and Janowitz, 1962), but apparently such an assumed requirement is not always fulfilled and recent investigations of the motility and absorptive capacity of the small intestine have been based on the application of non-absorbable (reference) substances.Infusion into the intestinal canal of these markers, uniformly mixed with the intestinal content, is assumed to provide a standard of the total intestinal content, or rather an expression of the quantity of fluid which, within the experimental period, passes through a certain section of the intestine.In most of these investigations polyethyleneglycol has served as marker (Shaffer and Critchfield, 1947;
Promoter Hypermethylation and BRCA1 Inactivation in Sporadic Breast and Ovarian Tumors
Authors: M. Esteller
Journal: JNCI Journal of the National Cancer Institute (2000)

Inherited mutations in the BRCA1 gene may be responsible for almost half of inherited breast carcinomas. However, somatic (acquired) mutations in BRCA1 have not been reported, despite frequent loss of heterozygosity (LOH or loss of one copy of the gene) at the BRCA1 locus and loss of BRCA1 protein in tumors. To address whether BRCA1 may be inactivated by pathways other than mutations in sporadic tumors, we analyzed the role of hypermethylation of the gene's promoter region.Methylation patterns in the BRCA1 promoter were assessed in breast cancer cell lines, xenografts, and 215 primary breast and ovarian carcinomas by methylation-specific polymerase chain reaction (PCR). BRCA1 RNA expression was determined in cell lines and seven xenografts by reverse transcription-PCR. P values are two-sided.The BRCA1 promoter was found to be unmethylated in all normal tissues and cancer cell lines tested. However, BRCA1 promoter hypermethylation was present in two breast cancer xenografts, both of which had loss of the BRCA1 transcript. BRCA1 promoter hypermethylation was present in 11 (13%) of 84 unselected primary breast carcinomas. BRCA1 methylation was strikingly associated with the medullary (67% methylated; P =.0002 versus ductal) and mucinous (55% methylated; P =.0033 versus ductal) subtypes, which are overrepresented in BRCA1 families. In a second series of 66 ductal breast tumors informative for LOH, nine (20%) of 45 tumors with LOH had BRCA1 hypermethylation, while one (5%) of 21 without LOH was methylated (P =.15). In ovarian neoplasms, BRCA1 methylation was found only in tumors with LOH, four (31%) of 13 versus none of 18 without LOH (P =.02). The BRCA1 promoter was unmethylated in other tumor types.Silencing of the BRCA1 gene by promoter hypermethylation occurs in primary breast and ovarian carcinomas, especially in the presence of LOH and in specific histopathologic subgroups. These findings support a role for this tumor suppressor gene in sporadic breast and ovarian tumorigenesis.
"Annoyance" of genital warts
Authors: C. O'Mahony
Journal: BMJ (2008)

As Hammond said,1 and my website shows in the wart section (www.chestersexualhealth.co.uk), genital warts are not just an annoying nuisance. Both human papillomavirus (HPV) vaccines are so far equally effective for HPV 16 and 18, but it …
The Simulation of Smiles (SIMS) model: Embodied simulation and the meaning of facial expression
Authors: Paula M. Niedenthal, Martial Mermillod, Marcus Maringer, Ursula Hess
Journal: Behavioral and Brain Sciences (2010)

Abstract Recent application of theories of embodied or grounded cognition to the recognition and interpretation of facial expression of emotion has led to an explosion of research in psychology and the neurosciences. However, despite the accelerating number of reported findings, it remains unclear how the many component processes of emotion and their neural mechanisms actually support embodied simulation. Equally unclear is what triggers the use of embodied simulation versus perceptual or conceptual strategies in determining meaning. The present article integrates behavioral research from social psychology with recent research in neurosciences in order to provide coherence to the extant and future research on this topic. The roles of several of the brain's reward systems, and the amygdala, somatosensory cortices, and motor centers are examined. These are then linked to behavioral and brain research on facial mimicry and eye gaze. Articulation of the mediators and moderators of facial mimicry and gaze are particularly useful in guiding interpretation of relevant findings from neurosciences. Finally, a model of the processing of the smile, the most complex of the facial expressions, is presented as a means to illustrate how to advance the application of theories of embodied cognition in the study of facial expression of emotion.
A strong correlation between expression of Wntless and of human epidermal growth factor receptor 2 in gastric, ovarian, and breast cancers suggests a novel-signalling pathway involving NFκB and STAT3
Authors: Jonathan Stewart, Jacqueline James, Glenn McCluggage, Stephen McQuaid, David Boyle, Kenneth Arthur, Paul Mullan, Claire Kidson, Nuala McCabe, Richard Kennedy, Darragh McArt, Anne Carson, Benedict Yan, Lei Zhengdeng, Patrick Tan, David Virshup, Manuel Salto-Tellez
Journal: The Lancet (2013)
Oropharyngeal carriage and lower airway colonisation/infection in 45 tracheotomised children
Authors: P Morar
Journal: Thorax (2002)

A study was undertaken to determine the oropharyngeal carrier state of potentially pathogenic microorganisms (PPM) and the magnitude of colonisation and infection rates of the lower airways with these PPM in children requiring long term ventilation first transtracheally and afterwards via a tracheotomy.A 5 year, prospective, observational cohort study was undertaken in 45 children (33 boys) of median age 6.4 months (range 0-180) over a 5 year period at the Royal Liverpool Children's NHS Trust of Alder Hey, a university affiliated tertiary referral centre. The children were first admitted to the 20-bed paediatric intensive care unit (PICU) and, following placement of a tracheotomy, they were transferred to a four bedded respiratory ward. The two main indications were neurological disorders and airway obstruction. All children were ventilated transtracheally for a median period of 12 days (range 0-103) and, after placement of the tracheotomy, for a similar period of 12 days (range 1-281). Surveillance cultures of the oropharynx were taken on admission to the PICU and on the day of placement of the tracheotomy. Throat swabs were taken twice weekly during ventilation, both transtracheal and via the tracheotomy. Tracheal aspirates were taken once weekly and when clinically indicated (in cases where the lower airway secretions were turbid).Twenty five patients (55%) had abnormal flora, mainly aerobic Gram negative bacilli (AGNB), particularly Pseudomonas aeruginosa, while the community PPM Staphylococcus aureus was present in the oropharynx of 37% (17/45) of the study population. The lower airways were sterile in six children; the other 39 patients (87%) had a total of 82 episodes of colonisation. "Community" PPM significantly increased once the patients received a tracheotomy, independent of the number of patients enrolled, episodes of colonisation/infection, and the number of colonised/infected patients. "Hospital" PPM significantly decreased after tracheotomy only when episodes were compared.While P aeruginosa present in the admission flora caused primary endogenous colonisation/infection during mechanical ventilation on the PICU, S aureus not carried in the throat was responsible for the exogenous colonisation/infection once the patients had a tracheotomy. This is in sharp contrast to adult studies where exogenous infections are invariably caused by AGNB. This discrepancy may be explained by chronic underlying conditions such as diabetes, alcoholism, and chronic obstructive pulmonary disease which promote AGNB, whereas the children were recovering following tracheotomy.
FKBP12 Is a Critical Regulator of the Heart Rhythm and the Cardiac Voltage-Gated Sodium Current in Mice
Authors: Mitsunori Maruyama, Bai-Yan Li, Hanying Chen, Xuehong Xu, Long-Sheng Song, Silvia Guatimosim, Wuqiang Zhu, Weidong Yong, Wenjun Zhang, Guixue Bu, Shien-Fong Lin, Michael C. Fishbein, W. Jonathan Lederer, John H. Schild, Loren J. Field, Michael Rubart, Peng-Sheng Chen, Weinian Shou
Journal: Circulation Research (2011)

FK506 binding protein (FKBP)12 is a known cis-trans peptidyl prolyl isomerase and highly expressed in the heart. Its role in regulating postnatal cardiac function remains largely unknown.We generated FKBP12 overexpressing transgenic (αMyHC-FKBP12) mice and cardiomyocyte-restricted FKBP12 conditional knockout (FKBP12(f/f)/αMyHC-Cre) mice and analyzed their cardiac electrophysiology in vivo and in vitro. A high incidence (38%) of sudden death was found in αMyHC-FKBP12 mice. Surface and ambulatory ECGs documented cardiac conduction defects, which were further confirmed by electric measurements and optical mapping in Langendorff-perfused hearts. αMyHC-FKBP12 hearts had slower action potential upstrokes and longer action potential durations. Whole-cell patch-clamp analyses demonstrated an ≈ 80% reduction in peak density of the tetrodotoxin-resistant, voltage-gated sodium current I(Na) in αMyHC-FKBP12 ventricular cardiomyocytes, a slower recovery of I(Na) from inactivation, shifts of steady-state activation and inactivation curves of I(Na) to more depolarized potentials, and augmentation of late I(Na), suggesting that the arrhythmogenic phenotype of αMyHC-FKBP12 mice is attributable to abnormal I(Na). Ventricular cardiomyocytes isolated from FKBP12(f/f)/αMyHC-Cre hearts showed faster action potential upstrokes and a more than 2-fold increase in peak I(Na) density. Dialysis of exogenous recombinant FKBP12 protein into FKBP12-deficient cardiomyocytes promptly recapitulated alterations in I(Na) seen in αMyHC-FKBP12 myocytes.FKBP12 is a critical regulator of I(Na) and is important for cardiac arrhythmogenic physiology. FKPB12-mediated dysregulation of I(Na) may underlie clinical arrhythmias associated with FK506 administration.
MicroRNA-375 Is Downregulated in Gastric Carcinomas and Regulates Cell Survival by Targeting PDK1 and 14-3-3ζ
Authors: Yoshiyuki Tsukamoto, Chisato Nakada, Tsuyoshi Noguchi, Masato Tanigawa, Lam Tung Nguyen, Tomohisa Uchida, Naoki Hijiya, Keiko Matsuura, Toshio Fujioka, Masao Seto, Masatsugu Moriyama
Journal: Cancer Research (2010)

We investigated expression profiles of microRNA (miRNA) in gastric carcinomas by use of a miRNA microarray platform covering a total of 470 human miRNAs. We identified 39 differentially expressed miRNAs in gastric carcinoma, of which six were significantly downregulated and the other 33 were upregulated. We found that miRNA-375 (miR-375) was the most downregulated and that its ectopic expression in gastric carcinoma cells markedly reduced cell viability via the caspase-mediated apoptosis pathway. Interestingly, we found that expression of miR-375 inhibited expression of PDK1, which is a direct target of miR-375, followed by suppression of Akt phosphorylation. Further analysis by gene expression microarray revealed that 14-3-3zeta, a potent antiapoptotic gene, was significantly downregulated at both the mRNA and protein levels in cells transfected with miR-375. The activity of a luciferase reporter containing the miR-375 binding sequence at the 3' untranslated region (UTR) of 14-3-3zeta mRNA was repressed by the ectopic expression of miR-375, suggesting that miR-375 targets the 3' UTR of 14-3-3zeta. In addition, knockdown of either PDK1 or 14-3-3zeta in gastric carcinoma cells induced caspase activation, which was also observed in miR-375-transfected cells, suggesting that miR-375 may exert its proapoptotic function, at least in part, through the downregulation of PDK1 and 14-3-3zeta. Taken together, we propose that miR-375 is a candidate tumor suppressor miRNA in gastric carcinoma.
Diversity of the Immune Repertoire and Immunoregulation
Authors: Robert S. Schwartz
Journal: New England Journal of Medicine (2003)

ince the midpoint of the 20th century, medical advances in economically developed countries have exceeded all expectations.In 1950, the year I entered medical school, the average life expectancy in the United States was 68 years.By 2000, it was 77 years (80 years for women). 1 In 1957, when I began my fellowship in hematology, there was no combination chemotherapy, the choice of antibiotics was limited, computed tomography and magnetic resonance imaging did not exist, and most neoplasms were incurable.And in 1958, the year I began my research on immunosuppressive drugs, the role of the lymphocyte was unclear, and successful organ and bone marrow transplantation lay in the future.This is not a comprehensive review, but rather a personal reflection on some aspects of immunology with clinical relevance.My main point is that the immune system's enormous repertoire of antigen receptors allows reactivity not only against pathogens, but also against autoantigens.This potential disadvantage is countered, however, by potent regulatory mechanisms that reduce the risk of harm.Research on these mechanisms has changed clinical practice by uncovering new ways of controlling autoimmune diseases and preventing graft rejection.Rearranged DNA Rearranged DNA mRNA Light-Chain Genes V3 L V3 Cm V8 V1 V2 V3 V2 Vn J1 J2 Jn Ck (1) Ck Ck L J1 V8 Ck L J1 V8 Ck Cd Cm Cx Cd
Reflectance confocal microscopy in the diagnosis of solitary pink skin tumours: review of diagnostic clues
Authors: C. Longo, E. Moscarella, G. Argenziano, A. Lallas, M. Raucci, G. Pellacani, A. Scope
Journal: British Journal of Dermatology (2015)

Reflectance confocal microscopy (RCM) is a noninvasive tool that can be helpful in the diagnosis of nonpigmented skin tumours. As RCM enables visualization of architectural and cytological structures at near-histological resolution, it can improve the diagnostic accuracy of dermoscopically equivocal solitary pink neoplasms. For management decisions, it is important to identify specific morphological clues that allow bedside classification of nonpigmented skin neoplasms into benign vs. malignant and melanocytic vs. nonmelanocytic. More specifically, the presence of a nested melanocytic proliferation at the dermoepidermal junction or dermis level permits the clinician to ascribe a given lesion as melanocytic; the identification of basaloid bright tumour islands is a key RCM feature for the diagnosis of basal cell carcinoma; and the presence of disarrayed epidermis along with small demarcated papillae is suggestive for the diagnosis of squamous cell carcinoma. The present review offers a comprehensive description of the main RCM diagnostic clues for solitary pink neoplasms that direct clinicians to the correct diagnosis and that may serve as groundwork for future prospective studies.
Performance of an NIDDM Screening Questionnaire Based on Symptoms and Risk Factors
Authors: Johannes B Ruige, J Nico D de Neeling, Pieter J Kostense, Lex M Bouter, Robert J Heine
Journal: Diabetes Care (1997)

OBJECTIVE To investigate to what extent a short questionnaire on symptoms and risk factors can be used to identify people at increased risk for undiagnosed NIDDM. RESEARCH DESIGN AND METHODS A general population sample of 2,364 Caucasian subjects, age 50–74 years, not known to have diabetes, completed a questionnaire on diabetes-related symptoms and risk factors. Subsequently, they underwent an oral glucose tolerance test. A backward stepwise multiple logistic regression was carried out with the absence or presence of newly detected diabetes as the dependent variable and the items from the questionnaire as the independent variables. The selected items were included in a new symptom risk questionnaire, which was evaluated in a different population sample of 786 subjects, age 45–74 years, not known to have diabetes and compared with existing questionnaires. RESULTS The newly developed symptom-risk questionnaire contains questions concerning the following items, which were independently and significantly (P &amp;lt; 0.05) associated with the presence of previously undiagnosed diabetes: pain during walking with need to slow down, shortness of breath when walking with people of the same age, frequent thirst, age, sex, obesity, parent or sibling with diabetes, use of antihypertensive drugs, and reluctance to use a bicycle for transportation. The 1993 American Diabetes Association questionnaire, the 1995 Herman et aL (17) questionnaire, and the newly developed symptom-risk questionnaire had sensitivities of 59, 72, and 72%; specificities of 57, 55, and 56%; positive predictive values of 5.6, 6.4, and 6.5%; and negative predictive values of 97, 98, and 98%, respectively. CONCLUSIONS The newly developed symptom-risk questionnaire has good performance characteristics, and the advantage of a variable cutoff makes it a useful screening tool for NIDDM in general practice.
Polycyclic Aromatic Hydrocarbon–DNA Adducts in Prostate and Biochemical Recurrence after Prostatectomy
Authors: Benjamin A. Rybicki, Christine Neslund-Dudas, Cathryn H. Bock, Andrew Rundle, Adnan T. Savera, James J. Yang, Nora L. Nock, Deliang Tang
Journal: Clinical Cancer Research (2008)

Abstract Purpose: DNA adduct levels may be influenced by metabolic activity, DNA repair capabilities, and genomic integrity, all of which play a role in cancer progression. Experimental Design: To determine if elevated DNA adducts are a marker for prostate cancer progression, we measured polycyclic aromatic hydrocarbon–DNA adducts by immunohistochemistry in prostate cells of 368 surgical prostate cancer patients treated at the Henry Ford Hospital in Detroit, Michigan, between September 1999 and July 2004. Patients were followed up to 5 years after surgery with relative risk for biochemical recurrence (BCR) estimated with a Cox proportional hazards model that adjusted for standard clinical risk factors. Results: At 1 year of follow-up, patients with adduct levels above the median in tumor cells [hazard ratio (HR), 2.40; 95% confidence interval (95% CI), 1.10-5.27] and nontumor cells (HR, 3.22; 95% CI, 1.40-7.39) had significant increased risk of BCR, but these HRs decreased to 1.12 (95% CI, 0.68-1.83) and 1.46 (95% CI, 0.89-2.41) in tumor and nontumor cells at 5 years postsurgery. When we restricted our analysis to patients with advanced-stage (III+) disease, those with high adduct levels in either tumor (53.5% versus 30.2%; P = 0.07) or nontumor (55.2% versus 28.6%; P = 0.02) cells had BCR rates almost 2-fold higher. In race-stratified analyses, the greatest risk of BCR associated with high adduct levels (in nontumor cells) was for African American patients younger than 60 years old (HR, 3.79; 95% CI, 1.01-14.30). Conclusions: High polycyclic aromatic hydrocarbon–DNA adduct levels in nontumor prostate cells are most strongly associated with BCR between 1 and 2 years after surgery and in patient subsets defined by younger age, advanced tumor stage, and African American race.
S51 Circulating Desmosine Relates To Cardiovascular Comorbidity, Coronary Artery Calcification Score (cacs), Systemic Inflammation And Mortality In Patients With Copd
Authors: R. A. Rabinovich, B. E. Miller, K. Wrobel, G. Choudhury, K. Ranjit, E. M. Drost, L. D. Edwards, D. A. Lomas, S. I. Rennard, A. Agusti, R. Tal-Singer, J. Vestbo, E. Wouters, E. V. Beek, J. T. Murchison, W. MacNee, J. T. Huang
Journal: Thorax (2014)

<h3>Introduction</h3> COPD is a risk factor for cardiovascular comorbidities. Elastin degradation represents a shared mechanism for the pulmonary and vascular features. <h3>Methods and Results</h3> Plasma desmosine (pDES), a marker of elastin degradation, was measured in 955 COPD patients (609 male, age 63.1 ± 7.2 years, FEV<sub>1</sub> 50.6 ± 15.1%predicted) by an isotope dilution LC-MS/MS method. Coronary artery calcification (CACS), a surrogate of atherosclerosis, was assessed in 440 standard CT scan images (low 1000 AU). <h3>Results</h3> pDES was elevated in patients with cardiovascular comorbidities (p &lt; 0.01) and correlated with FEV<sub>1</sub> (r = 0.39, p &lt; 0.0001), MMRC (r = 0.16, p &lt; 0.0001), 6MWD (r=-0.16, p &lt; 0.0001), BODE index (r = 0.10, p &lt; 0.005), fibrinogen, IL6, IL8, CCL18, and SPD but not with emphysema. These variables showed significant higher values in the patients in the highest pDES quartile. pDES was elevated in patients with very high CACS in comparison with patients with lower CACS (<b>Figure 1</b>) and in patients that died during a 3 year follow-up (p &lt; 0.0001). <h3>Conclusion</h3> pDES relates to lung function, systemic inflammation, cardiovascular comorbidities, and CACS in patients with COPD. pDES is a predictor of all cause overall mortality. The ECLIPSE study (GSK Study No. SCO104960, NCT00292552) was sponsored by GlaxoSmithKline.
Expression of Hepatoma-Derived Growth Factor Is Correlated with Lymph Node Metastasis and Prognosis of Gastric Carcinoma
Authors: Shinji Yamamoto, Yasuhiko Tomita, Yoshihiko Hoshida, Shuji Takiguchi, Yoshiyuki Fujiwara, Takushi Yasuda, Yuichiro Doki, Kenya Yoshida, Katsuyuki Aozasa, Hideji Nakamura, Morito Monden
Journal: Clinical Cancer Research (2006)

Hepatoma-derived growth factor (HDGF) is a unique nuclear/growth factor and might play an important role in the development and progression of carcinomas. In the present study, association of HDGF expression with recurrence and prognosis of gastric carcinoma was examined.HDGF expression in 317 patients with gastric carcinoma (233 males and 84 females) with ages ranging from 26 to 81 years (median, 60 years) was analyzed by immunohistochemistry. Samples with >90% of tumor cells to express positive immunoreactivity similar to or stronger than that in endothelial cells both for nucleus and cytoplasm were regarded as HDGF index level 2, and others as HDGF index level 1.One hundred and eighty-two cases showed level 1 HDGF expression, whereas 135 cases showed level 2 HDGF expression. Patients with level 2 expression showed higher rates of proximal tumor location (P < 0.0001), large tumor size (P < 0.0001), infiltrative tumor growth (P < 0.0001), presence of vascular and lymphatic invasion (P < 0.0001 for both), presence of lymph node metastasis (P < 0.0001), deep tumor invasion (P < 0.0001), and poorer disease-free and overall survival (P < 0.0001 for both) compared to those with level 1 expression. Multivariate analysis revealed HDGF expression level as an independent prognosticator for disease-free and overall survival.HDGF expression level was shown to be a prognostic factor for gastric carcinoma.