tbuckley/cabot-search huggingface dataset:
Large-scale data integration framework provides a comprehensive view on glioblastoma multiforme
Authors: Kristian Ovaska, Marko Laakso, Saija Haapa-Paananen, Riku Louhimo, Ping Chen, Viljami Aittomäki, Erkka Valo, Javier Núñez-Fontarnau, Ville Rantanen, Sirkku Karinen, Kari Nousiainen, Anna-Maria Lahesmaa-Korpinen, Minna Miettinen, Lilli Saarinen, Pekka Kohonen, Jianmin Wu, Jukka Westermarck, Sampsa Hautaniemi
Journal: Genome Medicine (2010)

Coordinated efforts to collect large-scale data sets provide a basis for systems level understanding of complex diseases. In order to translate these fragmented and heterogeneous data sets into knowledge and medical benefits, advanced computational methods for data analysis, integration and visualization are needed.We introduce a novel data integration framework, Anduril, for translating fragmented large-scale data into testable predictions. The Anduril framework allows rapid integration of heterogeneous data with state-of-the-art computational methods and existing knowledge in bio-databases. Anduril automatically generates thorough summary reports and a website that shows the most relevant features of each gene at a glance, allows sorting of data based on different parameters, and provides direct links to more detailed data on genes, transcripts or genomic regions. Anduril is open-source; all methods and documentation are freely available.We have integrated multidimensional molecular and clinical data from 338 subjects having glioblastoma multiforme, one of the deadliest and most poorly understood cancers, using Anduril. The central objective of our approach is to identify genetic loci and genes that have significant survival effect. Our results suggest several novel genetic alterations linked to glioblastoma multiforme progression and, more specifically, reveal Moesin as a novel glioblastoma multiforme-associated gene that has a strong survival effect and whose depletion in vitro significantly inhibited cell proliferation. All analysis results are available as a comprehensive website.Our results demonstrate that integrated analysis and visualization of multidimensional and heterogeneous data by Anduril enables drawing conclusions on functional consequences of large-scale molecular data. Many of the identified genetic loci and genes having significant survival effect have not been reported earlier in the context of glioblastoma multiforme. Thus, in addition to generally applicable novel methodology, our results provide several glioblastoma multiforme candidate genes for further studies.Anduril is available at http://csbi.ltdk.helsinki.fi/anduril/The glioblastoma multiforme analysis results are available at http://csbi.ltdk.helsinki.fi/anduril/tcga-gbm/
Circumscribed palmar or plantar hypokeratosis: A distinctive epidermal malformation of the palms or soles
Authors: Amparo Pérez, Arno Rütten, Reinhard Gold, Francisco Urbina, Carlos Misad, Maria José Izquierdo, Celia Requena, Adolfo Aliaga, Heinz Kutzner, Luis Requena
Journal: Journal of the American Academy of Dermatology (2002)
NOTES OF CASES ILLUSTRATING THE USE OF ADRENALIN CHLORIDE IN OPHTHALMIC, NASAL, AND AURAL SURGERY
Authors: A. S. Green
Journal: BMJ (1902)

and a certain amount of constipation which may or may not have been due to the use of this drug, the patient suffered no ill-effects, even after taking it for three or four weeks.This means of increasing the coagulability of the blood was adopted in a puerperal case reported in the BRITISH MEDICAL JOURNAL in May, I90I, but, as far as I am aware, has not hitherto been employed as a preventive measure against the excessive haemorrhages of haemophilia, which are so trouble- some and often serious in persons of this diathesis after the -extraction of teeth.
11q Deletions Identify a New Subset of B-Cell Chronic Lymphocytic Leukemia Characterized by Extensive Nodal Involvement and Inferior Prognosis
Authors: Hartmut Döhner, Stephan Stilgenbauer, Michael R. James, Axel Benner, Traudel Weilguni, Martin Bentz, Konstanze Fischer, Werner Hunstein, Peter Lichter
Journal: Blood (1997)
Does RAGE protect smokers from COPD?
Authors: R.P. Young, B.A. Hay, R.J. Hopkins
Journal: European Respiratory Journal (2011)

To the Editors:

We read with interest the article by Smith et al . [1], which showed a positive correlation between plasma soluble receptor for advanced glycation end-products (sRAGE) and forced expiratory volume in 1 s (FEV1) in patients with chronic obstructive pulmonary disease (COPD). Here, we outline the results of recent genetic epidemiological studies that suggest the advanced glycosylation end product-specific receptor ( AGER ) gene, which encodes sRAGE, may also have a role in the development of COPD.

Two recent large genome-wide association (GWA) studies conclude that a locus on chromosome 6p21 is associated with lung function (FEV1 and FEV1/forced vital capacity) [2, 3], directly implicating the AGER gene, which is known to be expressed in alveolar epithelial cells [2]. However, this association was made in populations dominated by nonsmokers and did not specifically examine the effect in chronic smokers. We and others have …
RENAL HYPERTENSION PRODUCED BY AN AMINO ACID
Authors: Richard J. Bing, Marjorie B. Zucker
Journal: The Journal of Experimental Medicine (1941)

Acute renal hypertension is produced by the injection of the amino acid dopa (l-dihydroxyphenylalanine) into the partially or completely ischemic kidney of the cat. Evidence is presented suggesting that the rise in blood pressure following the injection of dopa is caused by its conversion into hydroxytyramine, a pressor amine. Kidneys with normal blood flow fail to transform dopa into a pressor substance.
Frequency of Distinguishing Clinical Features in Vogt-Koyanagi-Harada Disease
Authors: Narsing A. Rao, Amod Gupta, Laurie Dustin, Soon Phaik Chee, Annabelle A. Okada, Moncef Khairallah, Bahram Bodaghi, Phuc Lehoang, Massimo Accorinti, Manabu Mochizuki, Tisha Prabriputaloong, Russell W. Read
Journal: Ophthalmology (2009)
Soil Contamination from PCB-Containing Buildings
Authors: Robert F. Herrick, Daniel J. Lefkowitz, George A. Weymouth
Journal: Environmental Health Perspectives (2006)

BackgroundPolychlorinated biphenyls (PCBs) in construction materials, such as caulking used around windows and expansion joints, may constitute a source of PCB contamination in the building interiors and in surrounding soil. Several studies of soil contamination have been conducted around buildings where the caulking has been removed by grinding or scraping. The PCBs in soil may have been generated in the process of removing the caulking, but natural weathering and deterioration of the caulking may have also been a source.ObjectivesThe objectives of this study were to measure PCB levels in soil surrounding buildings where PCB-containing caulk was still in place, and to evaluate the mobility of the PCBs from caulking using the Toxicity Characteristic Leaching Procedure (U.S. Environmental Protection Agency Method 1311).DiscussionWe found soil PCB contamination ranging from 3.3 to 34 mg/kg around buildings with undisturbed caulking that contained 10,000–36,200 mg/kg PCBs. The results of the Toxicity Characteristic Leaching Procedure (leachate concentrations of 76–288 mg PCB/L) suggest that PCBs in caulking can be mobilized, apparently as complexes with dissolved organic matter that also leach off the caulking material.Conclusions and RecommendationsAlthough these new findings are based on a small sample size, they demonstrate the need for a national survey of PCBs in building materials and in soil surrounding these buildings. Because the buildings constructed during the time the PCB caulking was in use (1960s and 1970s) include schools, hospitals, and apartment buildings, the potential for exposure of children is a particular concern. It is necessary to reconsider the practice of disposing of old PCB caulking removed during building renovations in conventional landfills, given the apparent mobility of PCBs from the caulking material. Disposal of some caulking material in nonhazardous landfills might lead to high PCB levels in landfill leachate.
Spontaneous disappearance of intraepidermal type VII collagen in a patient with dystrophic epidermolysis bullosa
Authors: N. HATTA, M. TAKATA, H. SHIMIZU
Journal: British Journal of Dermatology (1995)

Journal Article Spontaneous disappearance of intraepidermal type VII collagen in a patient with dystrophic epidermolysis bullosa Get access N. HATTA, N. HATTA Department of Dermatology, Kanazawa University School of Medicine, Kanazawa 920, Japan Search for other works by this author on: Oxford Academic Google Scholar M. TAKATA, M. TAKATA Department of Dermatology, Kanazawa University School of Medicine, Kanazawa 920, Japan Search for other works by this author on: Oxford Academic Google Scholar H. SHIMIZU H. SHIMIZU Department of Dermatology, Keio University School of Medicine, Tokyo 160, Japan Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 133, Issue 4, 1 October 1995, Pages 619–624, https://doi.org/10.1111/j.1365-2133.1995.tb02716.x Published: 01 October 1995 Article history Accepted: 12 November 1994 Published: 01 October 1995
Increased lung neutrophil apoptosis and inflammation resolution
Authors: C. G. A. Persson, L. Uller
Journal: European Respiratory Journal (2012)

onset respiratory distress with cough, tachypnoea, retraction and diffuse crackles on auscultation in infants ,12 months of age [2].Another strength of our study is that we also assayed nasal washes simultaneously for 14 different respiratory viruses, rather than just including infants with respiratory syncytial virus bronchiolitis.
Direct demonstration that cytotoxic T lymphocytes recognize conformational determinants and not primary amino acid sequences.
Authors: L P De Waal, S G Nathenson, C J Melief
Journal: The Journal of Experimental Medicine (1983)

The bm 1 H-2Kb mutant differs from the parental strain C57BL/6 (B6) only at amino acid (AA) positions 152, 155, and 156 of the H-2K molecule. The H-2Ld molecule is structurally identical with the H-2 Kbm1 molecule from positions 146-162, thus including all three AA substitutions in Kbm1. In direct lysis and monolayer adsorption studies, B6 anti-bml cytotoxic T lymphocytes (CTL) were shown to include at least five distinct CTL subsets of the following specificities. (a) Uniquely reactive with Kbm1; (b) cross-reactive with Kk; (c) cross-reactive with Dk; (d) cross-reactive with H-2d minus Ld, and (e) cross-reactive with Ld. If B6 anti-bm1 CTL were directed against the primary AA-sequence difference, then all five subsets are expected to react with Ld. However, four out of five CTL subsets including a major population uniquely directed against Kbm1 failed to react with Ld. These findings strongly strengthen the notion that CTL recognize conformational determinants and not primary AA sequences.
Sclerotic (hypocellular) fibromas of the skin
Authors: P. Donati, A. Amantea, M. Carducci, L. Balus
Journal: British Journal of Dermatology (1991)

Journal Article Sclerotic (hypocellular) fibromas of the skin Get access P. Donati, P. Donati Laboratorio di Istopatologia, Istituto San Gallicano, Via di S Gallicano 25/A, 00100 Roma, Italy Search for other works by this author on: Oxford Academic Google Scholar A. Amantea, A. Amantea Laboratorio di Istopatologia, Istituto San Gallicano, Via di S Gallicano 25/A, 00100 Roma, Italy Search for other works by this author on: Oxford Academic Google Scholar M. Carducci, M. Carducci Laboratorio di Istopatologia, Istituto San Gallicano, Via di S Gallicano 25/A, 00100 Roma, Italy Search for other works by this author on: Oxford Academic Google Scholar L. Balus L. Balus Laboratorio di Istopatologia, Istituto San Gallicano, Via di S Gallicano 25/A, 00100 Roma, Italy Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 124, Issue 4, 1 April 1991, Pages 395–396, https://doi.org/10.1111/j.1365-2133.1991.tb00612.x Published: 01 April 1991
A Synthetic Matrix with Independently Tunable Biochemistry and Mechanical Properties to Study Epithelial Morphogenesis and EMT in a Lung Adenocarcinoma Model
Authors: Bartley J. Gill, Don L. Gibbons, Laila C. Roudsari, Jennifer E. Saik, Zain H. Rizvi, Jonathon D. Roybal, Jonathan M. Kurie, Jennifer L. West
Journal: Cancer Research (2012)

Abstract Better understanding of the biophysical and biochemical cues of the tumor extracellular matrix environment that influence metastasis may have important implications for new cancer therapeutics. Initial exploration into this question has used naturally derived protein matrices that suffer from variability, poor control over matrix biochemistry, and inability to modify the matrix biochemistry and mechanics. Here, we report the use of a synthetic polymer-based scaffold composed primarily of poly(ethylene glycol), or PEG, modified with bioactive peptides to study murine models of lung adenocarcinoma. In this study, we focus on matrix-derived influences on epithelial morphogenesis of a metastatic cell line (344SQ) that harbors mutations in Kras and p53 (trp53) and is prone to a microRNA-200 (miR-200)–dependent epithelial–mesenchymal transition (EMT) and metastasis. The modified PEG hydrogels feature biospecific cell adhesion and cell-mediated proteolytic degradation with independently adjustable matrix stiffness. 344SQ encapsulated in bioactive peptide-modified, matrix metalloproteinase–degradable PEG hydrogels formed lumenized epithelial spheres comparable to that seen with three-dimensional culture in Matrigel. Altering both matrix stiffness and the concentration of cell-adhesive ligand significantly influenced epithelial morphogenesis as manifest by differences in the extent of lumenization, in patterns of intrasphere apoptosis and proliferation, and in expression of epithelial polarity markers. Regardless of matrix composition, exposure to TGF-β induced a loss of epithelial morphologic features, shift in expression of EMT marker genes, and decrease in mir-200 levels consistent with EMT. Our findings help illuminate matrix-derived cues that influence epithelial morphogenesis and highlight the potential utility that this synthetic matrix-mimetic tool has for cancer biology. Cancer Res; 72(22); 6013–23. ©2012 AACR.
Risk Stratification and Outcome of Patients With Hypertrophic Cardiomyopathy ≥60 Years of Age
Authors: Barry J. Maron, Ethan J. Rowin, Susan A. Casey, Tammy S. Haas, Raymond H.M. Chan, James E. Udelson, Ross F. Garberich, John R. Lesser, Evan Appelbaum, Warren J. Manning, Martin S. Maron
Journal: Circulation (2012)

Background— Hypertrophic cardiomyopathy (HCM) is prominently associated with risk for sudden death and disease progression, largely in young patients. Whether patients of more advanced age harbor similar risks is unresolved, often creating clinical dilemmas, particularly in decisions for primary prevention of sudden death with implantable defibrillators. Methods and Results— We studied 428 consecutive HCM patients presenting at ≥60 years of age and followed for 5.8±4.8 years; 53% were women. Of the 428 patients, 279 (65%) survived to 73±7 years of age (range, 61–96 years), most (n=245, 88%) with no/mild symptoms, including 135 with ≥1 conventional sudden death risk factors and 50 (37%) with late gadolinium enhancement. Over follow-up, 149 (35%) died at 80±8 years of age, mostly from non–HCM-related causes (n=133, 31%), including a substantial proportion from noncardiac disease (n=54). Sixteen patients (3.7%) had HCM-related mortality events (0.64%/y), including embolic stroke (n=6), progressive heart failure or transplantation (n=3), postoperative complications (n=2), and arrhythmic sudden death events (n=5, 1.2% [0.20%/y]). All-cause mortality was increased in HCM patients ≥60 years of age compared with an age-matched US general population, predominantly as a result of non–HCM-related diseases ( P &lt;0.001; standard mortality ratio, 1.5). Conclusions— HCM patients surviving into the seventh decade of life are at low risk for disease-related morbidity/mortality, including sudden death, even with conventional risk factors. These data do not support aggressive prophylactic defibrillator implantation at advanced ages in HCM. Other cardiac or noncardiac comorbidities have a greater impact on survival than HCM in older patients.
Genome-wide review of transcriptional complexity in mouse protein kinases and phosphatases.
Authors: Alistair RR Forrest, Darrin F Taylor, Mark L Crowe, Alistair M Chalk, Nic J Waddell, Gabriel Kolle, Geoffrey J Faulkner, Rimantas Kodzius, Shintaro Katayama, Christine Wells, Chikatoshi Kai, Jun Kawai, Piero Carninci, Yoshihide Hayashizaki, Sean M Grimmond
Journal: Genome biology (2006)

Abstract Background Alternative transcripts of protein kinases and protein phosphatases are known to encode peptides with altered substrate affinities, subcellular localizations, and activities. We undertook a systematic study to catalog the variant transcripts of every protein kinase-like and phosphatase-like locus of mouse http://variant.imb.uq.edu.au . Results By reviewing all available transcript evidence, we found that at least 75% of kinase and phosphatase loci in mouse generate alternative splice forms, and that 44% of these loci have well supported alternative 5' exons. In a further analysis of full-length cDNAs, we identified 69% of loci as generating more than one peptide isoform. The 1,469 peptide isoforms generated from these loci correspond to 1,080 unique Interpro domain combinations, many of which lack catalytic or interaction domains. We also report on the existence of likely dominant negative forms for many of the receptor kinases and phosphatases, including some 26 secreted decoys (seven known and 19 novel: Alk, Csf1r, Egfr, Epha1, 3, 5,7 and 10, Ephb1, Flt1, Flt3, Insr, Insrr, Kdr, Met, Ptk7, Ptprc, Ptprd, Ptprg, Ptprl, Ptprn, Ptprn2, Ptpro, Ptprr, Ptprs, and Ptprz1) and 13 transmembrane forms (four known and nine novel: Axl, Bmpr1a, Csf1r, Epha4, 5, 6 and 7, Ntrk2, Ntrk3, Pdgfra, Ptprk, Ptprm, Ptpru). Finally, by mining public gene expression data (MPSS and microarrays), we confirmed tissue-specific expression of ten of the novel isoforms. Conclusion These findings suggest that alternative transcripts of protein kinases and phosphatases are produced that encode different domain structures, and that these variants are likely to play important roles in phosphorylation-dependent signaling pathways.
Steroid Sulfatase and Estrogen Sulfotransferase in Human Endometrial Carcinoma
Authors: Hiroki Utsunomiya, Kiyoshi Ito, Takashi Suzuki, Takako Kitamura, Chika Kaneko, Taisuke Nakata, Hitoshi Niikura, Kunihiro Okamura, Nobuo Yaegashi, Hironobu Sasano
Journal: Clinical Cancer Research (2004)

Abstract Purpose: Intratumoral metabolism and synthesis of estrogens are considered to play important roles in the pathogenesis and/or development of human endometrial carcinoma. Steroid sulfatase hydrolyzes biologically inactive estrogen sulfates to active estrogens, whereas estrogen sulfotransferase sulfonates estrogens to estrogen sulfates. However, the status of steroid sulfatase and/or estrogen sulfotransferase in human endometrial carcinoma has not been examined. Experimental Design: We first examined the expression of steroid sulfatase and estrogen sulfotransferase in 6 normal endometrium and 76 endometrial carcinoma using immunohistochemistry to elucidate the possible involvement of steroid sulfatase and estrogen sulfotransferase. We then evaluated the enzymatic activity and the semiquantitative analysis of mRNA using reverse transcription-PCR in 21 endometrial carcinomas. We correlated these findings with various clinicopathological parameters including the expression of aromatase, 17β-hydroxysteroid dehydrogenase type 1 and type 2. Results: Steroid sulfatase and estrogen sulfotransferase immunoreactivity was detected in 65 of 76 (86%) and 22 of 76 (29%) cases, respectively. Results of immunoreactivity for steroid sulfatase and estrogen sulfotransferase were significantly correlated with those of enzymatic activity and semiquantitative analysis of mRNA. No significant correlations were detected among the expression of the enzymes involved in intratumoral estrogen metabolism. There was a significant correlation between steroid sulfatase/estrogen sulfotransferase ratio and clinical outcomes of the patients. However, there were no significant differences between steroid sulfatase or estrogen sulfotransferase and estrogen receptor, progesterone receptor, Ki67, histologic grade, or clinical outcomes of the patients. Conclusions: Results of our study demonstrated that increased steroid sulfatase and decreased estrogen sulfotransferase expression in human endometrial carcinomas may result in increased availability of biologically active estrogens and may be related to estrogen-dependent biological features of carcinoma.
A Homozygous Frameshift Mutation in LRAT Causes Retinitis Punctata Albescens
Authors: Karin W. Littink, Maria M. van Genderen, Mary J. van Schooneveld, Linda Visser, Frans C.C. Riemslag, Jan E.E. Keunen, Bjorn Bakker, Marijke N. Zonneveld, Anneke I. den Hollander, Frans P.M. Cremers, L. Ingeborgh van den Born
Journal: Ophthalmology (2012)
Mechanism of endothelin-1-induced pulmonary vasoconstriction.
Authors: M J Horgan, J M Pinheiro, A B Malik
Journal: Circulation Research (1991)

Endothelins are endothelial cell-derived peptides with potent vasoconstrictor properties. We investigated the actions of porcine/human endothelin-1 (ET-1) on the microvasculature of the guinea pig lung perfused at constant flow with Ringers-albumin. We measured the perfusion pressure, distribution of pulmonary vascular resistance (using the double occlusion method), lung weight change, and the pulmonary capillary filtration coefficient. At concentrations of greater than or equal to 10(-10) M, ET-1 produced dose-dependent increases in mean pulmonary artery pressure (EC50, approximately 10(-9.5) M), which were rapid in onset and biphasic (first phase peaking at 1-2 minutes; second phase peaking at 10-15 minutes) up to 60 minutes of the perfusion period. The vasoconstrictor response was sustained for the 60-minute perfusion period. The pulmonary vasoconstriction was inhibited by pretreatment with indomethacin (10(-5) M), the thromboxane A2 receptor antagonist SQ-29,548 (4 x 10(-6) M), or papaverine (10(-5) M). Nifedipine (10(-5) or 10(-7) M) had no effect on the first phase but prevented the second phase of the vasoconstriction. The vasoconstriction was primarily the result of a 10-fold increase in pulmonary venous resistance. Pulmonary edema developed after ET-1 challenge because of the venoconstriction and the resultant pulmonary capillary hypertension. However, the pulmonary capillary filtration coefficient was unchanged, indicating that pulmonary vascular permeability did not increase. ET-1 also had no effect on transendothelial 125I-albumin flux. The results indicate that ET-1 is a potent thromboxane-dependent venoconstrictor in the guinea pig lung.(ABSTRACT TRUNCATED AT 250 WORDS)