tbuckley/cabot-search huggingface dataset:
A novel recurrent NPM1-TYK2 gene fusion in cutaneous CD30-positive lymphoproliferative disorders
Authors: Thirunavukkarasu Velusamy, Mark J. Kiel, Anagh A. Sahasrabuddhe, Delphine Rolland, Catherine A. Dixon, Nathanael G. Bailey, Bryan L. Betz, Noah A. Brown, Alexandra C. Hristov, Ryan A. Wilcox, Roberto N. Miranda, L. Jeffrey Medeiros, Yoon K. Jeon, Kedar V. Inamdar, Megan S. Lim, Kojo S. J. Elenitoba-Johnson
Journal: Blood (2014)
RELATIVE VALUE OF SURGICAL AND MEDICAL TREATMENT OF GASTRIC AND DUODENAL ULCER
Authors: ARTHUR DEAN BEVAN
Journal: JAMA (1922)

During the last ten years or more I have had the opportunity of making, with my medical colleagues at the Presbyterian Hospital, a combined study from both the medical and surgical points of view of the subject of peptic ulcer. I believe that we have approached this matter with open minds and have attempted, in this clinical research, first, to establish the relationship between the clinical picture and the pathologic anatomy, and, secondly, to determine the value of both the medical and the surgical treatment and the indications for each. During this period of ten years, of course, similar researches have been made in a large number of clinics, both in this country and abroad; notably by workers in the Mayo Clinic at Rochester; by the Leeds group in England, headed by Moynihan; by von Eiselsberg and his assistants, Haberer and Clairmont, and by Schmieden, who was formerly with Bier
Cost-effectiveness of Air Bags in Motor Vehicles
Authors: G. L. Larkin
Journal: JAMA (1998)

We used industry-based cost estimates4 that were lower for seat belts and higher for installed air bags than those used in the study by Graham et al. Air bag component and installation costs vary, but are generally higher than the $278 estimate used by Graham et al (who did not include installation). It also was unclear why the cost of all seat belts in the vehicle ($57) was included together instead of using the cost of each belt in the individual front seats ($30). We feel the latter may be more appropriate, because the analysis is highly sensitive to costs of equipment.
Pathway-specific dopaminergic deficits in a mouse model of Angelman syndrome
Authors: Thorfinn T. Riday, Elyse C. Dankoski, Michael C. Krouse, Eric W. Fish, Paul L. Walsh, Ji Eun Han, Clyde W. Hodge, R. Mark Wightman, Benjamin D. Philpot, C.J. Malanga
Journal: Journal of Clinical Investigation (2012)

Angelman syndrome (AS) is a neurodevelopmental disorder caused by maternal deletions or mutations of the ubiquitin ligase E3A (UBE3A) allele and characterized by minimal verbal communication, seizures, and disorders of voluntary movement. Previous studies have suggested that abnormal dopamine neurotransmission may underlie some of these deficits, but no effective treatment currently exists for the core features of AS. A clinical trial of levodopa (l-DOPA) in AS is ongoing, although the underlying rationale for this treatment strategy has not yet been thoroughly examined in preclinical models. We found that AS model mice lacking maternal Ube3a (Ube3am–/p+ mice) exhibit behavioral deficits that correlated with abnormal dopamine signaling. These deficits were not due to loss of dopaminergic neurons or impaired dopamine synthesis. Unexpectedly, Ube3am–/p+ mice exhibited increased dopamine release in the mesolimbic pathway while also exhibiting a decrease in dopamine release in the nigrostriatal pathway, as measured with fast-scan cyclic voltammetry. These findings demonstrate the complex effects of UBE3A loss on dopamine signaling in subcortical motor pathways that may inform ongoing clinical trials of l-DOPA therapy in patients with AS.
Abstract 5535: Availability of a newly designed technique, triple-combination array analysis: Identification of estrogen receptor 1 gene in hepatocellular carcinoma using this method
Authors: Mitsuhiro Hishida, Shuji Nomoto, Yoshikuni Inokawa, Masamichi Hayashi, Yasuhiro Kodera
Journal: Cancer Research (2012)

Abstract Background: Hepatocellular carcinoma (HCC) is one of the top five causes of cancer-related deaths worldwide. Recent developments in the treatment of HCC have failed to treat completely or prevent HCC. Genome-wide gene-expression profile analyses can now detect many candidate genes that are modified by HCC. We have developed a new technique to identify suppressor genes of HCC: triple-combination array analysis. Methods: Triple-combination array analysis, which combines gene expression profiles, single nucleotide polymorphism arrays and methylation arrays, was performed on each HCC tissue sample. Subsequently, samples from 48 HCC patients were subjected to quantitative real-time reverse-transcriptase polymerase chain reaction (PCR) and methylation-specific PCR. Results: Using this method, estrogen receptor 1 (ESR1) was detected as a candidate suppressor gene. Of the 48 clinical samples, 40 (83.3%) showed ESR1 promoter hypermethylation. In 24 (50%) HCC samples, the expression level of ESR1 gene was decreased by &amp;gt;90%, which was significantly related to hepatitis B virus, high liver damage score, and pathological invasion of the intrahepatic portal vein. Conclusions: The present study indicates that triple-combination array is an available and convenient technique for detecting the genes with altered expression in disease, and we suggest that the ESR1 gene acts as a suppressor gene in HCC. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5535. doi:1538-7445.AM2012-5535
[372] ALPHA-LIPOIC ACID ENHANCES CHOLINE DEFICIENT DIET-INDUCED FATTY LIVER AND STEATOHEPATITIS, AND PROMOTES THE GROWTH OF PRENEOPLASTIC LESIONS IN RAT LIVER
Authors: A. Perra, G. Simbula, M. Pibiri, P. Sulas, G.M. Ledda-Columbano, A. Columbano
Journal: Journal of Hepatology (2007)
THE TRANSMISSION OF DISEASE BY THE MOSQUITO.
Authors: JOHN R. TAYLOR
Journal: JAMA (1905)

The study of the life and habits of mosquitoes, not only in their adult stage, but in their cycle of development from the egg to the mosquito, is one of the most fascinating subjects that a person who has the time could possibly take up. Not only is the subject fascinating, but it is also of great importance that the life history of all species of mosquitoes should be understood, as they have been proved beyond a doubt to play a prominent part in the transmission of disease to human beings and animals, and more especially is this true of malaria, yellow fever and filariasis. Mosquitoes belong to the order of<i>Diptera</i>, of the family<i>Culicidæ.</i>They are differentiated from other insects which simulate them by, 1. The piercing mouth. 2. The scales on the veins of the wings. 3. The particular venation of the wings. There are four stages
Abstract 1600: Endogenous Nox4 Is Protective During Ischemia/reperfusion In The Heart
Authors: Tetsuro Ago, Junya Kuroda, Chiao-Po Hsu, Peiyong Zhai, Jayashree Pain, Junichi Sadoshima
Journal: Circulation (2008)

Although excessive production of reactive oxygen species (ROS) causes cellular injuries, ROS also act as signaling molecules and regulate physiological cellular functions. ROS are extensively generated during ischemia/reperfusion (I/R) and cause tissue damages. The NAD(P)H oxidases are major sources of ROS in the cardiovascular system. Among NAD(P)H oxidase proteins, Nox4 is expressed in the heart and cultured cardiac myocytes. To test whether ROS derived from Nox4 induce tissue damage following I/R in the heart, we made mice on FVB background with cardiac-specific overexpression of wild-type Nox4 (Tg-Nox4) and catalytically inactive Nox4 (Tg-DN-Nox4 (P437H)) in which NADPH is unable to bind to Nox4. We confirmed that ROS generation and oxidative stress in the heart are greater in Tg-Nox4 and is lower in Tg-DN-Nox4, compared with non-transgenic mice (NTg), as determined by dihydroethidium fluorescence and 8-hydroxyguanosine staining, respectively. Neither Tg-Nox4 nor Tg-DN-Nox4 exhibited obvious baseline phenotype at 3 months of age. Tg-Nox4, Tg-DN-Nox4, and NTg (n=5, each) at 3 months old were subjected to 45 minutes ischemia, by ligating the left anterior descending artery, followed by 24 hours reperfusion. Unexpectedly, myocardial infarction (MI) size/area at risk (AAR) determined by TTC staining was significantly greater in Tg-DN-Nox4 than in NTg (67% vs 30 %, p&lt;0.05). On the other hand, MI size/AAR in Tg-Nox4 (35 %) was comparable to that in NTg. To elucidate the mechanism by which suppression of Nox4 deteriorates I/R injury, we examined expression of proteins involved in cardiac metabolism. We found that expression levels of peroxisome proliferator-activated receptor α (PPARα), an important transcription factor stimulating mitochondrial fatty acid oxidation, remained high in Tg-DN-Nox4 during I/R (3.0 fold vs NTg), whereas it was suppressed in NTg and Tg-Nox4. Consistently, overexpression of DN-Nox4 enhanced transcriptional activity of PPARα by 2-fold, as determined by a luciferase assay, in cultured myocytes. Taken together, endogenous Nox4 may protect the heart from I/R injury by suppressing fatty acid oxidation through downregulation of PPARα which would otherwise lead to excess ROS generation after I/R.
Feasibility of T-Cell-Based Adoptive Immunotherapy in the First 12 Patients with Advanced Urothelial Urinary Bladder Cancer. Preliminary Data on a New Immunologic Treatment Based on the Sentinel Node Concept
Authors: Amir Sherif, Mudhar N. Hasan, Per Marits, Mona Karlsson, Ola Winqvist, Magnus Thörn
Journal: European Urology (2009)
Abstract 1650: Overview of the clinical ELLIPSE (ELucidating Loci Involved in Prostate cancer SuscEptibility) Consortium (CEC)
Authors: Chee L. Goh, Fredrick Schumacher, Zsofia Kote-Jarai, Peter Kraft, Douglas Easton, Brian Henderson, Rosalind Eeles
Journal: Cancer Research (2012)

Abstract Background The inherited link of prostate cancer (PrCa) has led to large scale Genome Wide Association Studies (GWASs), which aim to identify susceptibility loci associated with PrCa. Currently, these Single Nucleotide Polymorphisms (SNPs) have only been evaluated against overall PrCa risk and several disease parameters. The challenge now is to translate these genetic risk algorithms into the clinical setting. This has led to NIH (National Institute of Health) funded post-GWAS initiatives in PrCa and the establishment of the Clinical ELLIPSE Consortium (CEC) to harmonise genetic, clinical and epidemiological data from existing consortia around the world. This will provide the necessary guidance in developing useful and powerful risk prediction models for PrCa risk, including screening outcome and treatment effects. These risk prediction models may have an immediate public health impact by providing clinicians with the necessary tools to improve clinical decision making. Methods Several projects are currently underway including the analysis of Active Surveillance outcomes against these SNPs, and the analysis of the PRACTICAL (PRostate cancer AssoCiation group To Investigate Cancer Associated aLterations in the genome) consortium cohort, looking at the association of these SNPs with disease parameters. Collaborations have been established with ERSPC (European Randomized Study of Screening for Prostate Cancer), STAMPEDE (Systemic Therapy in Advanced or Metastatic Prostate cancer: Evaluation of Drug Efficacy) and RAPPER (radiogenomic) consortia, to analyse these SNPs’ role in screening and treatment outcomes. Results An inventory collected across the consortium showed that there are 59688 cases and 191698 controls with clinical data. There were also large numbers of tumour (11982 samples) and blood (43624 samples) available. These figures are very encouraging and discussions are currently underway to access and combine data across the groups for analyses. Conclusion The CEC provides the necessary framework needed to foster successful collaborations and begin the transition from ‘bench-side’ research to ‘bed-side’ care. Acknowledgments This project is supported by The NIH grant: No. 1 U19 CA 148537-01 and Cancer Research UK. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1650. doi:1538-7445.AM2012-1650
A Rapid Method for Retrovirus-Mediated Identification of Complementation Groups in Fanconi Anemia Patients
Authors: Saurabh Chandra, Orna Levran, Ingrid Jurickova, Chiel Maas, Rick Kapur, Detlev Schindler, Rashida Henry, Kelly Milton, Sat Dev Batish, Jose A. Cancelas, Helmut Hanenberg, Arleen D. Auerbach, David A. Williams
Journal: Molecular Therapy (2005)

Fanconi anemia (FA) is a rare autosomal recessive disorder that results from mutations in at least 11 different genes. Recent studies have demonstrated that clinical progression of the disease may be influenced by inter- and intragenic variations, emphasizing the importance of identifying the complementation groups. In the present study we have employed bicistronic retrovirus vectors that coexpress FA-specific cDNAs for complementation groups A, C, F, and G, together with the enhanced green fluorescence protein (EGFP), allowing for specific analysis of transduced EGFP+ cells within bulk cultures by flow cytometry. In addition, the assay relies on the correction of the characteristic FA-associated G2/M arrest after treatment of cells with DNA-damaging agents, which is analyzed by flow cytometry. Results obtained with this assay matched the complementation groups known for 12 control lymphoblast cell lines tested. We report here the results obtained for 48 FA patients with unknown complementation groups using this new assay. Complementation groups were identified for 24 patients. We have identified mutations in the genes corresponding to the assigned complementation group in 23 samples. This assay has now been established in a standardized fashion for complementation assignments in FA patients and the subsequent directing of rapid mutation analysis in those patients.
Abstract 12658: Humoral Activation in Decompensated Heart Failure with Preserved or Reduced Ejection Fraction
Authors: Kalkidan G Bishu, Barry A Borlaug, Horng H Chen, Martin M LeWinter, Anita Deswal, Mark J Semigran, Gregory D Lewis, Steven McNulty, Adrian F Hernandez, Eugene Braunwald, Margaret M Redfield
Journal: Circulation (2010)

Introduction: Heart failure (HF) may be associated with preserved (HFpEF) or reduced (HFrEF) ejection fraction. Acute HF decompensation (AHF) is associated with impaired renal hemodynamics and acti...
Mass Psychogenic Illness Attributed to Toxic Exposure at a High School
Authors: Timothy F. Jones, Allen S. Craig, Debbie Hoy, Elaine W. Gunter, David L. Ashley, Dana B. Barr, John W. Brock, William Schaffner
Journal: New England Journal of Medicine (2000)

Mass psychogenic illness may be difficult to differentiate from illness caused by bioterrorism, rapidly spreading infection, or toxic substances. We investigated symptoms attributed to exposure to toxic gas at a high school in Tennessee. In November 1998, a teacher noticed a 'gasoline-like' smell in her classroom, and soon thereafter she had a headache, nausea, shortness of breath, and dizziness. The school was evacuated, and 80 students and 19 staff members went to the emergency room at the local hospital; 38 persons were hospitalized overnight. Five days later, after the school had reopened, another 71 persons went to the emergency room. An extensive investigation was performed by several government agencies.We were unable to find a medical or environmental explanation for the reported illnesses. The persons who reported symptoms on the first day came from 36 classrooms scattered throughout the school. The most frequent symptoms (in this group and the group of people who reported symptoms five days later) were headache, dizziness, nausea, and drowsiness. Blood and urine specimens showed no evidence of carbon monoxide, volatile organic compounds, pesticides, polychlorinated biphenyls, paraquat, or mercury. There was no evidence of toxic compounds in the environment. A questionnaire administered a month later showed that the reported symptoms were significantly associated with female sex, seeing another ill person, knowing that a classmate was ill, and reporting an unusual odor at the school.The illness attributed to toxic exposure had features of mass psychogenic illness - notably, widespread subjective symptoms thought to be associated with environmental exposure to a toxic substance in the absence of objective evidence of an environmental cause. Alleviation of the anxiety surrounding an episode of mass psychogenic illness requires prompt recognition and a detailed investigation.
Community physicians and NHS reorganisation in England.
Authors: D P Miles
Journal: BMJ (1981)

Throughout our research we have been aware of the danger of looking at a limited number of specialties?for example, the danger of not recognising the relevance of a particular expenditure head. The benefit of our research, however, is that it has illustrated to us that progress may be made in improving the NHS financial and non-financial information systems. Problems will be encountered. One is the regular compilation of certain statistical information?for example, work measure? ment, arrangement of sessions, numbers and types of tests, drug issues, etc. This is particularly the case where there are multispecialty wards, theatres, etc. Another problem is promotion of the sense of need for the information in the various departments. This is particularly important if accurate informa? tion is to be collected. The reorganised NHS structure offers an ideal opportunity to improve the information systems so that management has information relevant to decisions and in particular so that clinicians can redirect resources to meet changing circumstances. Undoubtedly it will be argued that there are more pressing operational and organisational problems to be faced in the DHAs but we would counter that this is shortsighted and in any case is there ever a right time for a change ?
Abstract 5777: EMD 1214063, an exquisitely selective c-Met kinase inhibitor in clinical phase 1
Authors: Oliver Schadt, Friedhelm Bladt, Andree Blaukat, Dieter Dorsch, Manja Friese-Hamim, Claus Fittschen, Ulrich Graedler, Michael Meyring, Wilfried Rautenberg, Frank Stieber, Claudia Wilm
Journal: Cancer Research (2010)

Abstract The role of the receptor tyrosin kinase c-Met in tumor progression, metastasis and aggressiveness has been convincingly demonstrated in preclinical and early clinical settings. Several compounds with different selectivity profiles inhibiting c-Met are currently under preclinical/clinical investigation and might emerge as valuable cancer therapeutics in the future. During an HTS run N-(3-(3,6-Dihydro-5-(3,4-dimethoxyphenyl)-2-oxo-2H-1,3,4-thiadiazin-3-ylmethyl)-phenyl)-carbaminic acid-(3-(N,N-diethylamino)-propylester) (1) was identified as an attractive lead structure with an interesting overall profile (clogD (7.4): 2.5, S (pH 7.4): &amp;gt;100 µg/ml, IC50 (c-Met in vitro): 30 nM, IC50 (c-Met cellular): 800 nM) providing a valid starting point for lead optimization. The co-crystal structure of 1 revealed the binding mode and the essential structural features. The initial HTS hit was bound in a DFG-in conformation interacting namely with the main chain nitrogen atom of methionine 1160 within the hinge region and with the main chain nitrogen of aspartic acid 1222. After subsequent optimization of potency, efficacy, PK properties and the safety profile of thiadiazinone 1, EMD1214063 was identified as candidate for further development and is currently investigated in a phase 1 clinical trial. The pyridazinone EMD1214063 inhibits enzymatic and cellular c-Met kinase activity with IC50 values in the low nanomolar range. This compound displayed an exquisite selectivity when tested in vitro against a panel of more than 250 potential off-targets, including kinases, GPCRs, ion channels, transporters and various enzymes and demonstrated excellent anti-tumor activity in vivo in a variety of xenograft models. Depending on the particular model, complete regressions were observed with doses as low as 6 mg/kg/d administered per os. The overall profile of EMD1214063 including first time disclosure of the precise structure, synthesis, structure activity relationships, in vitro potency, selectivity profile, pharmacokinetic and in vivo data will be discussed. Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 5777.
Characterization of Complex Coronary Artery Stenosis Morphology by Coronary Computed Tomographic Angiography
Authors: Brett M. Wertman, Victor Y. Cheng, Saibal Kar, Heidi Gransar, Ryan A. Berg, Hursh Naik, Rajendra Makkar, John D. Friedman, Jay N. Schapira, Daniel S. Berman
Journal: JACC. Cardiovascular imaging (2009)
General practitioners and skin biopsy.
Authors: F. H. Rampen
Journal: BMJ (1992)

between subjects with Alzheimer's disease, subjects with multi-infarct dementia, and controls (identified clinically with the criteria of the National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association3 and the Diagnostic and Statistical Manual of Mental Disorders ThirdEdition, Revised (DSM-III-R).4We found that magnetic resonance imaging had a blind agreement with clinical diagnosis in 14 (61%) of 23 cases, and single photon emission tomography in 24 (77%) of 31 cases.5Furthermore, all 22 subjects with dementia tolerated single photon emission tomography whereas six were unable to tolerate magnetic resonance imaging.For single photon emission tomography we used a gammacamera with three detectors with a total acquisition time of only 15 minutes.It thus seems that single photon emission tomo- graphy with hexamethylpropyleneamineaxime labelledwithtechnetium-99misnotonlyaclinically useful tool separating these disorders but the procedure best tolerated by elderly and demented subjects.
Prostaglandins I2 and E2 have a synergistic role in rescuing epithelial barrier function in porcine ileum.
Authors: A T Blikslager, M C Roberts, J M Rhoads, R A Argenzio
Journal: Journal of Clinical Investigation (1997)

Prostaglandins (PG) are cytoprotective for gastrointestinal epithelium, possibly because they enhance mucosal repair. The objective of the present studies was to assess the role of prostaglandins in intestinal repair. Intestinal mucosa from porcine ileum subjected to 1 h of ischemia was mounted in Ussing chambers. Recovery of normal transepithelial electrical resistance occurred within 2 h, and continued to increase for a further 2 h to a value twice that of control. The latter response was blocked by inhibition of prostaglandin synthesis, and restored by addition of both carbacyclin (an analog of PGI2) and PGE2, whereas the addition of each alone had little effect. Histologically, prostaglandins had no effect on epithelial restitution or villous contraction, indicating that elevations in transepithelial resistance were associated with increases in paracellular resistance. Furthermore, prostaglandin-stimulated elevations in resistance were inhibited with cytochalasin D, an agent known to stimulate cytoskeletal contraction. Synergistic elevations in transepithelial resistance, similar to those of carbacyclin and PGE2, were also noted after treatment with cAMP and A23187 (a calcium ionophore). We conclude that PGE2 and PGI2 have a synergistic role in restoration of intestinal barrier function by increasing intracellular cAMP and Ca2+, respectively, which in turn signal cytoskeletal-mediated tight junction closure.