tbuckley/cabot-search huggingface dataset:
Abstract 2726: Haplotype Sharing Test as a Tool to Map Genes for Familial Cardiomyopathy
Authors: Frans Gerbens, Peter van Tintelen, Paul A van der Zwaag, Ludolf G Boven, Jasper J van der Smagt, Richard N Hauer, Robert M Hofstra, Gerard J te Meerman
Journal: Circulation (2007)

Background: In Mendelian diseases, such as arrhythmogenic right ventricular and dilated cardiomyopathies (ARVC and DCM), chromosomal regions identical-by-descent (IBD) from a common founder can be ascertained both by pedigree analysis and by haplotype-sharing methods. Finding shared haplotypes is greatly facilitated with the currently available high-density SNP arrays. However, determining which of the shared haplotypes is IBD and contains the disease-associated mutation, and which are identical-by-state (IBS) and are shared by chance, is difficult. An additional criterion is needed to indicate the region containing the disease mutation. The probability for shared haplotypes to be IBD rather than IBS increases with an increasing number of SNPs. We hypothesized that the largest shared haplotype is the most likely region to hold the causative disease mutation. Methods: The Haplotype-Sharing Test (HST) was designed, using SNP genotyping data from isolated patients and parent-offspring pairs and trios to identify the largest possibly shared haplotypes between patients that are members of a (large but unobserved) pedigree. We applied the HST to: three distantly related families each with at least one ARVC patient using 10K SNP genotyping arrays, and a large family with 5 DCM patients using 250K SNP arrays. Results: In pedigree A a haplotype run of 118 SNPs spanning 32 MB on chromosome 12p12.3-q13.13 was identified. This haplotype is substantially larger than any other area that is shared due to random effects. Screening of the PKP2 gene, located in this region, revealed a pathogenic splice-site mutation that was segregating with the disease. In family B (DCM) the largest shared haplotype was 178 SNPs, spanning 3.5 MB on chromosome 15. Sequencing of potential candidate genes (including alpha Tropomyosin and Integrin alpha 1) is pending. Conclusions: Our identification of the causative founder mutation in pedigree A in the largest shared region shows that our hypothesis, though heuristic in character, was correct. More importantly, haplotype sharing is a powerful tool for identifying disease-causing genes in single and extended families when an insufficient number of meioses are present to perform classic linkage analysis.
Risk factors for recurrent primary sclerosing cholangitis after liver transplantation
Authors: Reena Ravikumar, Emmanuel Tsochatzis, Sophie Jose, Michael Allison, Anuja Athale, Felicity Creamer, Bridget Gunson, Vikram Iyer, Mansoor Madanur, Derek Manas, Andrea Monaco, Darius Mirza, Nicola Owen, Keith Roberts, Gourab Sen, Parthi Srinivasan, Stephen Wigmore, Giuseppe Fusai, Bimbi Fernando, Andrew Burroughs
Journal: Journal of Hepatology (2015)
Pankreas Kistik Lezyonları Olan Hastalarda Pankreas Kanseri: 197 Hastayı Kapsayan Prospektif Bir Çalışma
Authors: Minoru Tada, Takao Kawabe, Masatoshi Arizumi, Osamu Togawa, Saburo Matsubara, Natsuyo Yamamoto, Yosuke Nakai, Naoki Sasahira, Kenji Hirano, Takeshi Tsujino, Keisuke Tateishi, Hiroyuki Isayama, Nobuo Toda, Haruhiko Yoshida ve Masao Omata
Journal: Clinical Gastroenterology and Hepatology (2006)
Detection of Duffy Antigen in the Plasma Membranes and Caveolae of Vascular Endothelial and Epithelial Cells of Nonerythroid Organs
Authors: Asok Chaudhuri, Søren Nielsen, Marie-Louise Elkjaer, Valerie Zbrzezna, Fang Fang, A. Oscar Pogo
Journal: Blood (1997)
Why do babies cry?
Authors: I. Choonara
Journal: BMJ (1999)

Paper p 1393

Parents know that babies cry because they are either in pain or distressed They also know that babies cry to attract their attention so that they can comfort them. Pain is a subjective experience so one cannot prove that a newborn baby is in pain. One can, however, confirm that the baby is exhibiting signs of distress, probably caused by a painful procedure (such as venepuncture). Parents know that a crying baby needs comforting and will hold the infant close. Breast feeding mothers will give their infants the opportunity to breast feed, even if they are not hungry.

The study by Carbajal et al in this week's issue confirms that these actions of mothers are appropriate (p 1393).1 This is important not because parents are likely to …
Colocutaneous Fistula as Late Complication of Total Hip Replacement in Rheumatoid Arthritis
Authors: M G Ridley, T R Price, R Grahame, M Jourdan, M Watson
Journal: Journal of the Royal Society of Medicine (1985)

Late complications affecting various intrapeivic structures may occur following total hip replacement in association with medial displacement of bone cement into the pelvis. We describe here what we believe to be the first report of a colocutaneous fistula occurring as a result of this problem, and discuss the possible causes.
Out of the Theoretical Cul-de-sac (Commentary)
Authors: Ralph Hertwig, Annika Wallin
Journal: Behavioral and Brain Sciences (2004)

A key premise of the heuristics-and-biases program is that heuristics are “quite useful.” Let us now pay more than lip service to this premise, and analyse the environmental structures that make heuristics more or less useful. Let us also strike from the long list of biases those phenomena
that are not biases and explore to what degree those that remain are adaptive or can be understood as by-products of adaptive mechanisms.
Improved stoves, electricity, water and floor for better health in Peruvian rural households: An approximation
Authors: Roberto Accinelli, Lidia Lòpez, Julio Aguirre
Journal: European Respiratory Journal (2014)

Background:  Poverty conditions are related to higher prevalence of diseases, particularly infectious ones. In developing countries such as Peru, there are interventions trying to improve the households9 living conditions.  Objectives:  To assess the impact of rural electrification on health.  Population of study:  We carried out a secondary analysis of Survey of Rural Household Energy Use 2013. The dataset included electrified and no electrified Peruvian rural households. 1015 heads families were interviewed but we removed 28 because of missing information, leaving 987householders as the final sample.  Methods: The survey had 912 questions about household composition, demographics and economic indicators, energy sources, consumption patterns and including 12 questions about health status and respiratory and ocular symptoms. Statistical analysis was performed using Stata V.12. Multiple logistic regression analysis was used to assess the associations between health status and respiratory and ocular symptoms with electricity.  Results:  Users of improved stoves were healthier (8.64%) and more of them did not have chronic cough (4.88%). More users of improved stoves and electricity did not have rheum (11.2%). Also householderswith concrete or hardwood floor were healthier (8.58%) and more of them did not have red eyes (20.4%) or rheum (7.23%). More people with electricity or improved stoves did not have cough (8.69% and 8.53%, respectively).  Conclusions:  Providing connection to electricity, water and sanitation networks in Peruvian rural households have less impact on health than providing them with improved stoves and concrete or hardwood floor.
Sputum neutrophil differential cell count in health and relationship to disease severity in asthma
Authors: Clair Barber, Scott Elliott, Jon Ward, Laurie Lau, Kerry Gove, Tom Brown, Hitasha Rupani, Tim Hinks, Ratko Djukanovic, Ramesh Kurukuaaratchy, Anoop Chauhan, Peter Howarth
Journal: European Respiratory Journal (2014)

Rationale: Sputum inflammometry has been used to phenotype asthma, with eosinophilic, neutrophilic, mixed granulocytic and paucicellular sub-groups described. Both ≥40% and ≥61% have been used as criteria to define sputum neutrophilia.

Methods: As part of the Wessex Severe Asthma Cohort study, induced sputum was obtained from healthy non-asthmatic controls (HC, n=67), non-steroid treated asthmatics (MA , n=44), steroid treated (step 2/3) asthmatics (ModA, n=44) and those with severe (step 4/5 treated)asthma (SA, n=246) and differential cell counts obtained. Sputum neutrophil counts were not normally distributed and group comparisons were undertaken using non-parametric statistical analysis.

Results: Median [1QR] sputum neutrophil % was significantly greater (p<0.001) in the SA (51.0 [38.7] than either HC (19.3 [31.50], p<0.0001), MA (25.40 [31.37], p<0.0001) or ModA (31.05 [41.70], p=0.005). ModA neutrophil % was significantly higher than HC (p<0.02) but not MA. The respective proportion of subjects (%) with neutrophil % of ≥40% and ≥61% was: SA (65.4 and 39.4), ModA (43.2 and 22.7), MA (31.8 and 15.9), HC (25.4 and 12.9). In SA neutrophil% in sputum was independent of smoking history, atopic status or oral steroid use and very weakly correlated with age and FEV1% predicted (inverse) (each R2 = 0,031, p=0.005). Sputum eosinophilia (≥2%) was evident in 34.8% and 29.9% of those with≥40% and ≥61%sputum neutrophilia respectively.

Conclusion: Neutrophilic asthma is a prominent phenotype in severe asthma with approximately one third also having co-existent airway eosinophilic inflammation independent of the definition.

Funding: WSAC was funded by the Medical Research Council UK.
Randomized trial of the cardioprotective agent ICRF-187 in pediatric sarcoma patients treated with doxorubicin.
Authors: L H Wexler, M P Andrich, D Venzon, S L Berg, L Weaver-McClure, C C Chen, V Dilsizian, N Avila, P Jarosinski, F M Balis, D G Poplack, M E Horowitz
Journal: Journal of Clinical Oncology (1996)

PURPOSE We conducted an open-label, randomized trial to determine whether ICRF-187 would reduce doxorubicin-induced cardiotoxicity in pediatric sarcoma patients. METHODS Thirty-eight patients were randomized to receive doxorubicin-containing chemotherapy (given as an intravenous bolus) with or without ICRF-187. Resting left ventricular ejection fraction (LVEF) was monitored serially with multigated radionuclide angiography (MUGA) scan. The two groups were compared for incidence and degree of cardiotoxicity, response rates to four cycles of chemotherapy, event-free and overall survival, and incidence and severity of noncardiac toxicities. RESULTS Eighteen ICRF-187-treated and 15 control patients were assessable for cardiac toxicity. ICRF-187-treated patients were less likely to develop subclinical cardiotoxicity (22% v 67%, P &lt; .01), had a smaller decline in LVEF per 100 mg/m2 of doxorubicin (1.0 v 2.7 percentage points, P = .02), and received a higher median cumulative dose of doxorubicin (410 v 310 mg/m2, P &lt; .05) than did control patients. Objective response rates were identical in the two groups, with no significant differences seen in event-free or overall survival. ICRF-187-treated patients had a significantly higher incidence of transient grade 1 serum transaminase elevations and a trend toward increased hematologic toxicity. CONCLUSION ICRF-187 reduces the risk of developing short-term subclinical cardiotoxicity in pediatric sarcoma patients who receive up to 410 mg/m2 of doxorubicin. Response rates to chemotherapy, event-free and overall survival, and noncardiac toxicities appear to be unaffected by the use of ICRF-187. Additional clinical trials with larger numbers of patients are needed to determine if the short-term cardioprotection afforded by ICRF-187 will reduce the incidence of late cardiac complications in long-term survivors of childhood cancer.
Genes encoding tumor-specific antigens are expressed in human myeloma cells
Authors: N. Van Baren, F. Brasseur, D. Godelaine, G. Hames, A. Ferrant, F. Lehmann, M. Andre, C. Ravoet, C. Doyen, G.c. Spagnoli, Marleen Bakkus, Kris Thielemans, Thierry Boon
Journal: Blood (1999)
EDIL3 is a novel regulator of epithelial-mesenchymal transition controlling early recurrence of hepatocellular carcinoma
Authors: Hongping Xia, Jianxiang Chen, Ming Shi, Hengjun Gao, Karthik Sekar, Veerabrahma Pratap Seshachalam, London Lucien P.J. Ooi, Kam M. Hui
Journal: Journal of Hepatology (2015)
A novel method for harvesting and culturing airway epithelial cells from neonates
Authors: David Miller, Graham Devereux, Steve Turner, Daniella Spiteri-Cornish, Peter Danielian, Alison Scaife, Garry Walsh
Journal: European Respiratory Journal (2012)

Introduction: The airway epithelium is considered important in the pathogenesis of several respiratory conditions including asthma.While studies of airway epithelial cell(AEC) cultures obtained from adults and children have provided valuable insight into the role of these cells in airway disease, little is known about how neonatal AEC phenotype impacts on respiratory disease in later life.We describe a novel method for culturing nasal AEC within days of birth.   Methods: AEC were sampled from healthy, unsedated infants within 72 hours of birth by gently brushing both nostrils with an interdental brush. Brushes were agitated in specialised AEC growth media and primary cell monolayers grown to confluence before sub-culture.IL-8 concentrations were measured in supernatants from tertiary passage AEC monolayers at rest and after exposure to IL-1β & TNF-α(both at 10ng/ml).   Results: Sampling was acceptable to parents and there were no adverse effects. Primary cultures were successfully established in 74(82%) of 90 neonates sampled. Epithelial lineage of the cells was confirmed by morphological analysis and positive immunostaining for cytokeratin 19 and negative staining for potentially contaminating cell types.Constitutive IL-8 secretion was observed and was upregulated by cytokine stimuli.   Conclusion: We describe a safe, minimally invasive and reproducible method of culturing AEC from neonates suitable for functional cell analysis and amenable to large population based studies.This novel technique offers a unique opportunity to study “naive” AEC not yet exposed to the confounding effects of environmental pollutants and pathogens and may prove useful in elucidating the early origins of respiratory disease.
Abstract 1618: Role of Nitric Oxide in Regulation of Myocardial Glucose Metabolism; A Potential Mechanism of Cardioprotection
Authors: Karin Kaiserova, Yiru Guo, Roberto Bolli, Aruni Bhatnagar
Journal: Circulation (2008)

Ischemia induces a switch in myocardial substrate utilization from fatty acids to glucose and stimulates nitric oxide (NO) production. Although increased NO synthesis can ameliorate ischemic injury, mechanism by which NO confers cardioprotection remains unclear. Based on our recent observation that increased NO production contributes to ischemic activation of aldose reductase (AR), we tested the hypothesis that NO prevents ischemic injury by increasing reduction of glucose to sorbitol via polyol pathway over its oxidation to lactate in glycolysis, that could prevent acidosis. Our data show that in isolated mouse hearts subjected to 30 min of ischemia, sorbitol levels increased from 43.2 ± 2.4 to 68.7 ± 4.6 nmol/mg (n=6; P &lt; 0.05) and returned to pre-ischemic levels after 30 min of reperfusion. Treatment with eNOS agonist, bradykinin (10 μM), prior to ischemia, increased AR activity from 27.5 ± 0.7 to 35.9 ± 1.4 mU/mg (n=6; P &lt; 0.01) and decreased lactate levels from 3.7 ± 0.6 to 1.5 ± 0.4 mM (n=6; P &lt; 0.05) upon reperfusion. Bradykinin also decreased creatine kinase (CK) and lactate dehydrogenase (LDH) release by 65 ± 7% and 85 ± 9%, respectively. In contrast, NOS inhibitor, L-NAME (0.1 mM) decreased AR activity (22.4 ± 2.0 mU/mg), but increased the activity of glyceraldehyde-3-phosphate dehydrogenase (from 2.4 ± 0.1 to 3.5 ± 0.2 U/mg) and lactate production (5.8 ± 0.9 mM). AR inhibitor, sorbinil (0.1 mM) increased lactate production (5.9 ± 0.1 mM) and exacerbated ischemic injury. Pretreatment with bradykinin normalized lactate levels and reduced injury caused by sorbinil. To examine whether upregulation of AR is sufficient to confer cardioprotection, cardio-specific AR transgenic mice were generated. Echocardiography confirmed, that these mice had normal myocardial function and when subjected to 30 min of coronary occlusion followed by 24 h of reperfusion displayed reduced myocardial infarct size (49.6 ± 4.1 vs 64.6 ± 3.5 % of the area at risk; transgenic vs wild type; n=7; P &lt; 0.01). Collectively, these results show that NO mediates cardioprotection by increasing glucose flux via polyol pathway, which may represent an adaptive mechanism protecting the heart from ischemic injury. This research has received full or partial funding support from the American Heart Association, AHA Great Rivers Affiliate (Delaware, Kentucky, Ohio, Pennsylvania &amp; West Virginia).
Abstract 2431: Left Ventricular Scar Burden Predicts Life-Threatening Arrhythmia in Recipients of Implantable Cardioverter Defibrillilators
Authors: Pavlo I Netrebko, Vitaly Geyfman, Louis A Nassef, Randle H Storm, Jess W Oren, Vlad Cotarlan, Pugazhendi Vijayaraman, Jamshid Shirani
Journal: Circulation (2007)

Objective. Implantable cardioverter defibrillators (ICD) reduce arrhythmic deaths and are implanted based on LV ejection fraction (LVEF) and symptoms. Myocardial scar is a substrate for ventricular tachyarrhythmia (VT). We aimed to assess if number of LV scar segments [#SS, by cardiac magnetic resonance (CMR)] would predict life-threatening VT in recipient of ICD. Methods. Among 722 recipients of ICD (2002–2006), 54 [age 32– 84 (mean 63±12) years, 89% men, 76% ischemic, LVEF ≤35%] had CMR with delayed gadolinium enhancement prior to ICD. Using a 17-segment LV model, presence of scar was determined. End point was defined as confirmed VT requiring termination by anti-tachycardia pacing or shock. Results. At a mean follow-up of 15 (median 11.5) months, 12 (22%) patients reached end point. Univariate analysis identified LVEF and #SS as predictors whereas age, coronary artery disease, diabetes, hypertension, medications (anti-arrhythmic, beta-blocker, angiotensin-converting enzyme inhibitor, statin), creatinine, LV end-diastolic volume or LV mass were not predictive. #SS was higher in those who reached endpoint (8.5±1.2 vs 5.2±0.7, p=0.03). By receiver operator curve, a cut-off of ≥7 scarred segments identified those at high risk for VT (Graph - open circles are those with &lt;7 scarred segments). By logistic regression, after control for EF, #SS remained significant (P 0.03) with 1.3 times higher incidence of VT per added scarred segment. LVEF and #SS did not correlate (p=0.07). Conclusion. Presence of large scar burden predicts VT in patients with advanced LV dysfunction. Assessment of myocardial scar burden by CMR may improve risk stratification prior to ICD implantation.
Abstract 1506: Targeting of CaV1.2 Channels to Caveolae Requires CaV{beta} Subunit Association with Caveolin-3 in the Cardiomyocytes
Authors: Ravi C Balijepalli, Jason D Foell, Jing Wang, Jabe M Best, Timothy J Kamp
Journal: Circulation (2008)

Cavβ subunits regulate the function and membrane trafficking of Cav1.2 channels. Previously we have shown that Cavβ subunit isoforms show different subcellular distribution in ventricular myocytes ...
Neonatal encephalopathies
Authors: A D Edwards, K B Nelson
Journal: BMJ (1998)

Papers pp 1549,1544 

Neonatal encephalopathy is a significant problem. The United States collaborative perinatal project studied 39 000 infants born with birth weights greater than 2500 g and found that 70% of the infants who showed early neonatal depression and encephalopathy died or were disabled.1 For many years it was accepted that fetal asphyxia during labour was the major cause of both neonatal encephalopathy and cerebral palsy. However, the evidence for this is surprisingly thin. Diagnosis of cerebral hypoxia-ischaemia during labour is difficult and is usually inferred from non-specific signs, such as low Apgar scores or seizures observed after delivery. More precise assessment using specialist technologies like magnetic resonance is possible but not widely available,2 and a working diagnosis of hypoxic-ischaemic encephalopathy may sometimes be applied with less than irrefutable proof of its presence. Nevertheless, several large studies have been unable to show significant perinatal asphyxia in most children who develop cerebral palsy1; indeed, a growing number of …
Abstract SY09-04: Cancer crosstalk: miR-200-containing extracellular vesicles promote breast cancer cell metastasis
Authors: Judy Lieberman, Minh Le
Journal: Cancer Research (2015)

Abstract Metastasis is the major cause of death of breast cancer patients. Not all cancer cells within a tumor are capable of metastasizing. The microRNA-200 (miR-200) family, which regulates the mesenchymal-to-epithelial transition, is enriched in the serum of patients with metastatic cancers. Ectopic expression of miR-200 can confer metastatic ability to poorly metastatic tumor cells in some settings. Here, we investigated whether metastatic capability could be transferred between metastatic and nonmetastatic cancer cells via extracellular vesicles. miR-200 was secreted in extracellular vesicles from metastatic murine and human breast cancer cell lines, and miR-200 levels were increased in sera of mice bearing metastatic tumors. In culture, murine and human metastatic breast cancer cell extracellular vesicles transferred miR-200 microRNAs to nonmetastatic cells, altering gene expression and promoting mesenchymal-to-epithelial transition. In murine cancer and human xenograft models, miR-200-expressing tumors and extracellular vesicles from these tumors promoted metastasis of otherwise weakly metastatic cells either nearby or at distant sites and conferred to these cells the ability to colonize distant tissues in a miR-200-dependent manner. Together, our results demonstrate that metastatic capability can be transferred by the uptake of extracellular vesicles. Citation Format: Judy Lieberman, Minh Le. Cancer crosstalk: miR-200-containing extracellular vesicles promote breast cancer cell metastasis. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr SY09-04. doi:10.1158/1538-7445.AM2015-SY09-04