tbuckley/cabot-search huggingface dataset:
Assessing <i>BRCA</i> Carrier Probabilities in Extended Families
Authors: Carlos H. Barcenas, G.M. Monawar Hosain, Banu Arun, Jihong Zong, Xiaojun Zhou, Jianfang Chen, Jill M. Cortada, Gordon B. Mills, Gail E. Tomlinson, Alexander R. Miller, Louise C. Strong, Christopher I. Amos
Journal: Journal of Clinical Oncology (2006)

Purpose Carrier prediction models estimate the probability that a person has a BRCA mutation. We evaluated the accuracy of the BOADICEA model and compared its performance with that of other models (BRCAPRO, Myriad I and II, Couch, and Manchester Scoring System). We also studied the effect of extended family information on risk estimation using BOADICEA. Methods We compared the area under receiver operating characteristic curves generated from 472 families with one member tested for BRCA mutations. We calculated sensitivity, specificity, and predictive values at an estimated probability of 10% and explored the biases of carrier prediction. Results BOADICEA performed better than the other models in Ashkenazi Jewish (AJ) families, BRCAPRO performed slightly better in non-AJ families, and Myriad II performed comparably well in both groups. Including extended family information in BOADICEA yielded slightly better performance than did limiting the information to second-degree relatives. Using a 10% cutoff point, BOADICEA and Myriad II were most sensitive in predicting BRCA1/2 mutations in AJ families, and Myriad II was most sensitive in non-AJ families. The Manchester Scoring System was the most sensitive and least specific in a subgroup of non-AJ families. BOADICEA and BRCAPRO tended to underestimate the observed risk at low estimated probabilities and overestimate it at higher probabilities. Conclusion The BOADICEA, BRCAPRO, and Myriad II models performed similarly. Including second-degree relatives slightly improved carrier prediction by BOADICEA. The Myriad II model was the easiest to implement.
Spiny Follicular Hyperkeratosis Eruption: A New Cutaneous Adverse Effect of Sorafenib
Authors: Nathalie Franck, Stéphane Barete, Philippe Moguelet, Benoît Blanchet, Agnès Carlotti, Stanislas Ropert, Marie Françoise Avril, Camille Francès, Bertrand Billemont, François Goldwasser
Journal: Journal of Clinical Oncology (2010)
dsRNA activation of endothelin-1 and markers of vascular activation in endothelial cells and fibroblasts
Authors: Giuseppina Farina, Michael York, Cindy Collins, Robert Lafyatis
Journal: Annals of the Rheumatic Diseases (2010)

In patients with systemic sclerosis (SSc), the relationship between innate immune activation, represented by increased expression of interferon (IFN)-regulated genes, and vascular injury/activation, manifest by increased endothelin-1 (ET-1), endothelin converting enzyme-1 (ECE1) and intercellular adhesion molecule-1, is uncertain.To investigate the potential roles of innate immune ligands in both these pathogenic pathways.The effect of known Toll-like receptor (TLR) ligands was tested in vitro on dermal microvascular and pulmonary arterial endothelial cells, and on dermal fibroblasts cultured from healthy controls and patients with SSc. To test the effect of double-stranded RNA (dsRNA) on vascular activation/injury in vivo, polyinosinic/polycytidylic acid (poly(I:C)) was administered continuously over 7 days by subcutaneous osmotic pump.dsRNA/poly(I:C), but not other TLR ligands, highly stimulated ET-1 protein and mRNA (EDN1), as well as intercellular adhesion molecule-1 (ICAM-1) and IFN-regulated MX2, by endothelial cells and dermal fibroblasts. Poly(I:C) induced EDN1, ECE1, and ICAM-1 mRNA expression in poly(I:C) treated skin. Poly(I:C)-induced EDN1, ECE1 and MX2 was not blocked in mice with the type I IFN receptor deleted. However, poly(I:C)-induced EDN1 and ECE1, but not poly(I:C)-induced ICAM-1 expression was blocked in mice with the TLR3 signalling protein TRIF/TICAM-1 deleted.Together these data show that the dsRNA can regulate genes associated with vascular activation, as seen in SSc, that type I IFNs do not mediate these effects, and that EDN1 and ECE1 but not ICAM-1 activation is mediated by TLR3.
Angiopoietin-like 4 Protein Elevates the Prosurvival Intracellular O2−:H2O2 Ratio and Confers Anoikis Resistance to Tumors
Authors: Pengcheng Zhu, Ming Jie Tan, Royston-Luke Huang, Chek Kun Tan, Han Chung Chong, Mintu Pal, Chee Ren Ivan Lam, Petra Boukamp, Jiun Yit Pan, Suat Hoon Tan, Sander Kersten, Hoi Yeung Li, Jeak Ling Ding, Nguan Soon Tan
Journal: Cancer Cell (2011)
Interleukin 1 induces cultured human endothelial cell production of granulocyte-macrophage colony-stimulating factor.
Authors: C A Sieff, S Tsai, D V Faller
Journal: Journal of Clinical Investigation (1987)

Monokine-stimulated endothelial cells are known to produce both burst- and colony-stimulating activities, but neither the nature of the monokine nor the hematopoietic growth factor(s) produced is known. We show by mRNA analysis that an immortalized line of human endothelial cells constitutively produce granulocyte-macrophage colony-stimulating factor. Furthermore, interleukin 1 and tumor necrosis factor induce early passage human umbilical endothelial cells to produce the same growth factor.
Exercise training reduces pulmonary ischaemia-reperfusion-induced inflammatory responses
Authors: R. K. Mussi, E. A. Camargo, T. Ferreira, C. De Moraes, M. A. Delbin, I. F. C. Toro, S. Brancher, E. C. T. Landucci, A. Zanesco, E. Antunes
Journal: European Respiratory Journal (2007)

Physical exercise reduces the deleterious effects of cardiovascular and inflammatory disorders. The purpose of the present study was to evaluate the beneficial effects of physical training on the inflammatory responses following lung ischaemia–reperfusion (IR) in rats. Male Wistar rats were divided into sham-operated animals and sedentary and trained animals submitted to lung IR. The run training programme consisted of 5 sessions·week<sup>−1</sup>, each lasting 60 min·day<sup>−1</sup>, at 66% of maximal oxygen consumption for 8 weeks. The left pulmonary artery, bronchus and pulmonary vein were occluded for 90 min and reperfused for 2 h. Lung protein extravasation was measured as <sup>125</sup>I-human albumin accumulation, whereas lung neutrophil infiltration was measured as myeloperoxidase activity. Lung IR in sedentary rats resulted in marked increases in protein extravasation and neutrophil influx, and in significant elevations of serum tumour necrosis factor (TNF)-α and interleukin (IL)-1β levels. Physical preconditioning attenuated the increased IR-induced protein leakage without affecting neutrophil influx. It also reduced serum TNF-α (and IL-1β) levels, but had no effect on IL-10 levels. Plasma superoxide dismutase activity was significantly increased in trained IR rats. The present data show that physical preconditioning protects the rat lung from ischaemia–reperfusion injury by attenuating the pulmonary vascular permeability that may be a consequence of reduced levels of tumour necrosis factor-α and interleukin-1β and elevated superoxide dismutase activity.
A Comparison Between the Effects of Hexamethonium and Atropine in Combination and of Vagotomy with Gastrojejunostomy on Human Gastric Secretion
Authors: J. McArthur, H. I. Tankel, A. W. Kay
Journal: Gut (1960)

This study records the gastric secretory response, using the Kay augmented histamine test, and compares "medical" vagotomy with atropine and hexamethonium with "surgical" vagotomy. The results suggest that it may be of value in predicting the effect of vagotomy with gastrojejunostomy.
Abstract 4486: Stromal depletion by a docetaxel nanoparticle for enhanced therapy of breast and pancreatic cancer
Authors: Mark Ernsting, Mami Murakami, Elijus Undzys, Shyh-Dar Li
Journal: Cancer Research (2014)

Abstract Tumor stroma consists of genetically normal cells that express abnormal phenotype in the tumor microenviroment, and are drivers of tumor cell proliferation and migration processes. Stromal cells can represent a significant fraction of tumor mass, and represent a barrier to drug delivery, given that stromal fibroblasts exert contractile forces which reduce vascular perfusion and increase interstitial fluid pressure. In the field, the stroma is widely recognized as a target for therapy, both to normalize the reactive microenvironment, and to reduce drug delivery barriers, but with limited clinical success. We have developed a nanoparticle delivery system for docetaxel (Cellax), a conjugate of carboxymethylcellulose and PEG, which condenses into well defined 120 nm particles suitable for intravenous administration. In addition to enhanced pharmacokinetics, 5-10X improved tumor uptake, and enhanced anti-tumor efficacy compared to approved taxanes such as native DTX (Taxotere) and nab-PTX (an albumin-paclitaxel nano-formulation, Abraxane), we have observed an anti-stromal effect in breast and pancreatic models. In a 4T1 orthotopic breast cancer model in mice, 85% of Cellax particles were taken up by cancer-associated fibroblasts (CAF), a major component of stroma. Further, in 4T1 and MDA-MB-231 breast models, Cellax treatments reduced CAF by 82 and 70% respectively, while native DTX and Nab-paclitaxel exerted no anti-stromal activity. Concomitant effects were ∼70-fold increased perfusion, ∼3-fold decreased interstitial fluid pressure (IFP), and a 7-24 fold reduction in lung metastases. In a primary human pancreatic xenograft model (OCIP19), we measured a 50% reduction in αSMA+ cells (activated pancreatic stellate cells) and macrophage within 1 day of Cellax treatment, while nab-PTX only decreased the macrophage population 3-7 days post therapy. In addition, vascular perfusion in the Cellax treated pancreatic tumor was increased 12X relative to nab-PTX and control treatment groups, with significantly reduced metastases. Preliminary mechanistic studies indicate that albumin absorbs to Cellax particles, promoting interaction with SPARC-expressing stromal cells, leading to stroma-specific activity. Citation Format: Mark Ernsting, Mami Murakami, Elijus Undzys, Shyh-Dar Li. Stromal depletion by a docetaxel nanoparticle for enhanced therapy of breast and pancreatic cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4486. doi:10.1158/1538-7445.AM2014-4486
Forced Expression of α-Myosin Heavy Chain in the Rabbit Ventricle Results in Cardioprotection Under Cardiomyopathic Conditions
Authors: Jeanne James, Lisa Martin, Maike Krenz, Carmen Quatman, Fred Jones, Raisa Klevitsky, James Gulick, Jeffrey Robbins
Journal: Circulation (2005)

The biochemical differences between the 2 mammalian cardiac myosin heavy chains (MHCs), alpha-MHC and beta-MHC, are well described, but the physiological consequences of basal isoform expression and isoform shifts in response to altered cardiac load are not clearly understood. Mature human ventricle contains primarily the beta-MHC isoform. However, the alpha-MHC isoform can be detected in healthy human ventricle and appears to be significantly downregulated in failing hearts. The unique biochemical properties of the alpha-MHC isoform might offer functional advantages in a failing heart that is expressing only the beta-MHC isoform. This hypothesis cannot be tested in mice or rats because both species express alpha-MHC as the predominant isoform.To test the effects of persistent alpha-MHC expression on the background of beta-MHC, we made transgenic (TG) rabbits that expressed rabbit alpha-MHC cDNA in the ventricle so that the endogenous myosin was partially replaced by the transgenically encoded species. Molecular, histological, and functional analyses showed no significant baseline effects in the TG rabbits compared with nontransgenic (NTG) littermates. To determine whether alpha-MHC expression afforded any advantages to stressed myocardium, a cohort of TG and NTG rabbits was subjected to rapid ventricular pacing. Although both the TG and NTG rabbits developed dilated cardiomyopathy, the TG rabbits had a higher shortening fraction, less septal thinning, and more normal +/-dP/dt than paced NTG rabbits.Transgenic expression of alpha-MHC does not have any apparent detrimental effects under basal conditions and is cardioprotective in experimental tachycardia-induced cardiomyopathy.
Longitudinal Follow-up Study of Smoking-induced Lung Density Changes by High-resolution Computed Tomography
Authors: KENZO SOEJIMA, KAZUHIRO YAMAGUCHI, EIICHI KOHDA, KEI TAKESHITA, YOKO ITO, HIROAKI MASTUBARA, TSUYOSHI OGUMA, TAKASHI INOUE, YASUYUKI OKUBO, KAZUHISA AMAKAWA, HIROKI TATENO, TETSUYA SHIOMI
Journal: American Journal of Respiratory and Critical Care Medicine (2000)

To evaluate the ability of high-resolution computed tomography (HRCT) to detect longitudinal changes in structural abnormalities caused by smoking, HRCT and pulmonary function tests were used to examine nonsmokers, current smokers, and past smokers annually for 5 yr. Inspiratory HRCT was taken for the upper, middle, and lower lung fields, while expiratory images were obtained for the upper and lower lung fields only. We estimated the three quantitative CT parameters including MLD (mean CT value), HIST (CT value with the most frequent appearance), and %LAA (relative area of low attenuation with CT values less than -912 HU). Most of the pulmonary function tests, excepting FEV(1), did not change annually, whereas many of the inspiratory HRCT parameters did. In nonsmokers, only %LAA in the middle or lower lung fields exhibited an annual increase. In current smokers, %LAA in the upper lung field was augmented, while inspiratory MLD or HIST in the middle or lower lung field became more positive. In past smokers, %LAA in any lung field examined increased. The annual change in %LAA in the upper lung field was larger for past smokers than nonsmokers, with little difference between past and current smokers. Expiratory CT parameters showed few annual changes in all groups. In conclusion, (1) aging increases airspace abnormalities, mainly in the lower lung field; (2) although continuous smoking worsens airspace abnormalities mainly in the upper portion of the lung, this trend does not seem to slow down even after smoking cessation; and (3) inspiratory HRCT images are superior to expiratory images for longitudinal estimation of structural abnormalities caused by aging and smoking.
Rethinking “Cancer as a Dynamic Developmental Disorder” a Quarter Century Later
Authors: Harry Rubin
Journal: Cancer Research (2009)

In a Perspectives article of 1985 in Cancer Research, I discussed evidence for a nonmutational origin of teratocarcinoma, and cited related claims in liver carcinogenesis, which I later broadened to include spontaneous transformation in cell culture. Further research on spontaneous transformation cast doubt on that interpretation, and motivated re-examination of the cases for teratocarcinomas and liver cancer. This re-examination led to the conclusion that mutation and selection underlie the development of neoplasia in all three cases. At the same time, it affirmed the primary role of hierarchical tissue structure and intercellular relations in maintaining homeostasis, which was the major theme of the 1985 article. Tumor promotion disrupts intercellular relations to allow progressively selective proliferation of initiated cells and accompanying clonal accumulation of genetic change.
Peripheral Nerve Function Is Increasingly Impaired During Puberty in Adolescents With Type 1 Diabetes
Authors: Päivi H. Riihimaa, Kalervo Suominen, Uolevi Tolonen, Ville Jäntti, Mikael Knip, Päivi Tapanainen
Journal: Diabetes Care (2001)

OBJECTIVE—To evaluate the impact of puberty on peripheral nerve function in adolescents with type 1 diabetes. RESEARCH DESIGN AND METHODS—Of 138 eligible patients with type 1 diabetes, 100 patients (age &amp;gt;9 years and diabetes duration &amp;gt;2 years) attending an outpatient diabetes clinic and 100 age- and sex-matched healthy control subjects took part in this cross-sectional study. Peripheral motor and sensory nerve conduction tests, cardiovascular reflex tests on the autonomic nervous system, and measurements of vibration-perception threshold (VPT) were performed. RESULTS—Nerve conduction velocity (NCV) in the distal motor and sensory nerves, the motor nerve distal latency, and the sensory nerve action potential (SNAP) amplitude were impaired in the adolescent patients with type 1 diabetes. The deterioration in motor NCV, H-reflex latency, and SNAP amplitude became more conspicuous in late puberty and postpuberty and was related to poor metabolic control. A total of 10 patients had distal diabetic polyneuropathy (DP) neurophysiologically, and these patients had significantly lower heart-rate variation in the deep breathing test than the other patients. Three of the patients with DP had peripheral neurological signs or symptoms. A slight difference in the VPT between the patients and control subjects was observed after puberty. CONCLUSIONS—Increasing subclinical motor nerve impairment can be detected during late puberty and after puberty, and sensory NCV and SNAP amplitude are reduced in adolescents with type 1 diabetes. Poor metabolic control during puberty appears to induce deteriorating peripheral neural function in young patients with type 1 diabetes.
IFN-γ–Mediated Downregulation of LXA4 Is Necessary for the Maintenance of Nonresolving Inflammation and Papilloma Persistence
Authors: Chunhui Wang, Mingjie Xiao, Xiaoman Liu, Chen Ni, Jianhong Liu, Ulrike Erben, Zhihai Qin
Journal: Cancer Research (2013)

Nonresolving inflammation is a hallmark of many types of tumors and the molecular mechanisms maintaining this inflammation are still largely unknown. In a two-stage carcinogenesis model, we observed here that the lack of IFN-γ receptor or neutralization of IFN-γ accelerated spontaneous papilloma regression in mice. The impaired maintenance of local inflammation was associated with reduced IFN-γ and enhanced biosynthesis of proresolution lipid mediator lipoxin A4 (LXA4). Interestingly, blocking LXA4 eliminated the effect of anti-IFN-γ, whereas treatment of mice with a therapeutic dose of LXA4 accelerated papilloma regression in an IFN-γ-independent manner. These results link for the first time a cytokine-dependent maintenance of inflammation with a downregulated production of proresolution lipid mediators. Strategies promoting spontaneous resolution of chronic inflammation by blocking IFN-γ and/or increasing LXA4 may be useful for the treatment of inflammation-associated tumors.
Feature learning, multiresolution analysis, and symbol grounding
Authors: Karl F. MacDorman
Journal: Behavioral and Brain Sciences (1998)

Cognitive theories based on a fixed feature set suffer from frame and symbol grounding problems. Flexible features and other empirically acquired constraints (e.g., analog-to-analog mappings) provide a framework for letting extrinsic relations influence symbol manipulation. By offering a biologically plausible basis for feature learning, nonorthogonal multiresolution analysis and dimensionality reduction, informed by functional constraints, may contribute to a solution to the symbol grounding problem.
Fetal Growth Spurt and Pregestational Diabetic Pregnancy
Authors: Shell Fean Wong, Fung Yee Chan, Jeremy J.N. Oats, David H. McIntyre
Journal: Diabetes Care (2002)

To assess the timing of fetal growth spurt among pre-existing diabetic pregnancies (types 1 and 2) and its relationship with diabetic control. To correlate fetal growth acceleration with factors that might influence fetal growth.This retrospective study involved all pregestational diabetic pregnancies delivered at a tertiary obstetric hospital in Australia between 1 January 1994 and 31 December 1999. Pregnancies with major congenital fetal anomalies, multiple pregnancies, small-for-gestational-age pregnancies (<10th centile), and those that were terminated before 20 weeks were excluded. In this cohort, pregnancies delivered at term had at least four ultrasound scans performed. The first scans were performed before 14 weeks of gestation and were regarded as dating scans. Abdominal circumference measurements were retrieved from the ultrasound reports. The z-scores for abdominal circumferences, according to the gestational age, were calculated. The gestations when the ultrasound scans were performed were stratified at four weekly intervals beginning at 18 weeks and continuing through the rest of the study. Majority of these diabetic pregnancies had ultrasound scans performed at 18, 28, 32, and 36 weeks. The abdominal circumference z-scores for pregnancies with large-for-gestational-age (LGA) babies (>90th centile for gestation) were compared with babies with normal birth weights.A total of 101 diabetic pregnancies were included. Diabetic mothers, who had LGA babies, had significantly higher prepregnancy body weight and BMI (P < 0.05). There were no differences in maternal age or parity among the two groups. There were also no differences in the first-, second-, and third-trimester HbA(1c) levels between the two groups. The abdominal circumference z-scores were significantly higher for LGA babies from 18 weeks and thereafter. The differences increased progressively as the gestation advanced. Maximum difference was noted in the third trimester (30-38 weeks).Fetal growth acceleration in LGA fetuses of diabetic mothers starts in the second trimester, from as early as 18 weeks. In this study, glucose control did not appear to have a direct effect on the incidence of LGA babies, and such observation might result from the effects of other confounding factors.
Linear IgA disease with haemorrhagic pompholyx and dapsone-induced neutropenia
Authors: P. DUHRA, R. CHARLES-HOLMES
Journal: British Journal of Dermatology (1991)

Journal Article Linear IgA disease with haemorrhagic pompholyx and dapsone‐induced neutropenia Get access P. DUHRA, P. DUHRA South Warwickshire Hospital, Warwick, U.K. Dr P.Duhra. Skin Department, St Marks Annexe, Coventry and Warwickshire Hospital. Stoney Stanton Road, Coventry CV1 4FH. U.K. Search for other works by this author on: Oxford Academic Google Scholar R. CHARLES‐HOLMES R. CHARLES‐HOLMES South Warwickshire Hospital, Warwick, U.K. Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 125, Issue 2, 1 August 1991, Pages 172–174, https://doi.org/10.1111/j.1365-2133.1991.tb06066.x Published: 01 August 1991