tbuckley/cabot-search huggingface dataset:
MODEL OF END-STAGE LIVER DISEASE EXCLUDING INR (MELD-XI) SCORING SYSTEM PROVIDES THE ADDITIONAL LONG-TERM PROGNOSTIC INFORMATION TO ADHERE RISK LEVEL IN PATIENTS ADMITTED WITH ACUTE DECOMPENSATED HEART FAILURE
Authors: Takahisa Yamada, Takashi Morita, Yoshio Furukawa, Shunsuke Tamaki, Yusuke Iwasaki, Masato Kawasaki, Atsushi Kikuchi, Takumi Kondo, Tatsuhisa Ozaki, Yoshihiro Sato, Masahiro Seo, Iyo Ikeda, Eiji Fukuhara, Masatake Fukunami
Journal: Journal of the American College of Cardiology (2016)
P427Endonuclease G-like-1 (EXOG), a mitochondrial endo/exonuclease has a role in mitochondrial function and ROS mediated cardiomyocyte hypertrophy.
Authors: W Tigchelaar, H Yu, WH Van Gilst, RA De Boer, HHW Sillje
Journal: Cardiovascular Research (2014)

Purpose: The heart is one of the most energy consuming organs. This energy is used to maintain proper contractile function and is produced mainly in the mitochondria by oxidative phosphorylation (OXPHOS). The production of reactive oxygen species (ROS) is an unavoidable byproduct of OXPHOS. Increased ROS production has detrimental effects on the cells, inducing DNA damage and apoptosis. EndonucleaseG-like-1 (EXOG) and EndonucleaseG are mitochondrial endo/exonucleases with poorly investigated functions in the heart. Whereas EXOG has been implicated in mitochondrial DNA repair, EndonucleaseG appears to play a role in apoptosis, but a recent study in cardiomyocytes showed its importance in mitochondrial function and cardiac hypertrophy. Whether EXOG has additional functions as well, is not clear, but it is interesting to note that EXOG is present in a human genomic locus linked to cardiovascular disease. The goal of this study was to elucidate the role of EXOG in mitochondrial function in cardiomyocytes. Methods: EXOG adenoviral mediated knock-down was performed in neonatal rat cardiomyocytes. The Seahorse XF24 Extracellular Flux Analyzer was used to measure bio-energetic functions, including OCR (oxygen consumption rate). Mitochondrial parameters including citrate synthesis, mtDNA amount, mtDNA damage and reactive oxygen species (ROS) production were determined. Hypertrophy was assessed by 3H-leucine incorporation and cell surface measurements. Results: Knock-down of EXOG did not induce mtDNA damage in neonatal cardiomyocytes. Mitochondrial respiration was improved and revealed a 2.4 fold increase in basal mitochondrial OCR (n=6, P< 0.05). Moreover, the ATP-linked OCR was 5.2 fold higher. Western blotting did not showed changes in components of the OXPHOS complex and no changes in mitochondrial biogenesis were observed, suggesting that specific activities in the mitochondria are modulated. Also the membrane potential was not altered, but mitochondrial specific ROS production was strongly increased (5.4 fold) indicating that proper electron transport chain (ETC) flux was impaired. These changes were accompanied by an increase in cellular growth. Interestingly, this hypertrophic response could be attenuated by specific mitochondrial ROS scavengers. Conclusion: In cardiomyocytes EXOG silencing did not have a direct effect on mitochondrial DNA integrity. However, absence of EXOG increased mitochondrial activity and ROS production, which could be linked to cardiomyocyte hypertrophy.
Abstract LB-277: Dynamic functional analysis of the response of cancer cell lines to the drug UNBS1450
Authors: Michael L. Bittner, Edward Smith, Jianping Hua, Sima Chao, Milana Cypert, Gerald Gooden, Sonsoles Shack, Lalitamba Alla, Claudia Cerella, Marc Diederich, Steven Weitman
Journal: Cancer Research (2011)

Abstract The analysis of the dynamics of cellular responses to drugs is currently bounded by inherent limitations of the methods most often used to assess levels of promoter activity and protein abundance or activation. The sensitivity of these assays is limited by the averaging of analyte over many cells, which can produce an average that is not accurately descriptive of the wide range of activities of members of the population examined. The ability of these assays to indicate the trajectory of the various responses is limited by a very infrequent sampling rate, frequently 2–4 time points spread over many hours. These limits are further exacerbated by populations of treated cells' inhomogeneity in the timing of their own response to the drugs. To improve the determination of the functional dynamics of cells' responses to drugs, PBS-Bio has developed technology that allows gathering data from living cells using fluorescent reporter technology. This technology allows measurements to be made serially on single populations of cells at the individual cell level, providing both high sensitivity in terms of when even a small fraction of the cells exhibit significant shifts of a particular activity, the rate of shift of cells in the population to this different activity and the ability to temporally order the timing of events relative to each other. Experimentation on two cell lines, A549 and PC3, using a variety of drugs that affect different cellular processes and a set of fluorescent reporters that provide information on a variety of cellular processes it was possible to show that the modified cardenolide drug, UNBS1450 (Unibioscreen), provoked a very early reduction in the expression of the MCL1 and MYC genes, followed by induction of a strong apoptotic response in both cell lines. As loss of MCL1 provoked by other means has been shown to be sufficient to induce apoptosis in both these lines, a very strong case can be made for UNBS1450's ability to provoke Mcl1 protein reduction as the drug's mode of apoptotic induction. This finding would also implicate Mcl1 as a useful biomarker of the possible efficacy of UNBS1450. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr LB-277. doi:10.1158/1538-7445.AM2011-LB-277
AB0644 Cardiovascular risk factors and carotid intima-media thickness in systemic lupus erythematosus
Authors: C.-H. Suh, B.-R. Koh, H.-A. Kim, S.-S. Kim
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Systemic lupus erythematosus (SLE) is a prototypical autoimmune disorder, which is known to have accelerated atherosclerosis, such as myocardial infarction. <h3>Objectives</h3> We have investigated accelerated subclinical atherosclerosis in SLE patients using carotid intima-media thickness (IMT) and carotid plaque, and tried to determine traditional cardiovascular risk factors. <h3>Methods</h3> One hundred-nine female Korean SLE patients and 52 age- and sex-matched normal controls (NC) were included. B-mode ultrasonography was used to measure carotid IMT and carotid plaque. Traditional risk factors for atherosclerosis and disease-related factors were recorded. <h3>Results</h3> The age of SLE patients were 38.8±7 year-old, which was not different from the NC (36.9±5.5 year-old). The SLE was mild disease activity (SLE disease activity index (SLEDAI) 4.28±3.11) with relative short disease duration (6.43±4.45 years). The carotid IMT of SLE was 0.411±0.083 mm, which was thicker than that of NC (0.322±0.081 mm, p&lt;0.01). However, the carotid IMT of Korean SLE is lower than that of Caucasian SLE (0.68∼0.71 mm) (ref. 1). Also, there was no carotid plaque in the Korean SLE and NC. A significant correlation was found between carotid IMT and each of age (r=0.36, p&lt;0.001), body mass index (BMI, r=0.2, p=0.036), and SLEDAI (r=0.21, p=0.013) in SLE patients. Also, it was significantly lower in SLE patients taking aspirin (0.364±0.09 vs. 0.416±0.089, p=0.015). <h3>Conclusions</h3> Subclinical atherosclerosis occurs relatively rare in Korean SLE patients; however the carotid IMT of them is higher than Korean healthy controls. This subclinical accelerated atherosclerosis was correlated with traditional risk factor and lupus disease activity. <h3>References</h3> Roman MJ, Shanker BA, Davis A, et al. Prevalence and correlates of accelerated atherosclerosis in systemic lupus erythematosus. New Engl J Med 2003;349:2399-406 <h3>Disclosure of Interest</h3> None Declared
P622 MODELLING HCV REPLICATION IN AN INFLAMED LIVER ENVIRONMENT: A NEW ROLE FOR STROMAL EXPRESSED VAP-1 TO REGULATE VIRAL REPLICATION
Authors: S.K. Galsinh, C. Weston, A. Barnes, I.A. Rowe, G. Muirhead, D. Smith, D. Adams, C. Buckley, B. Peter, J.A. McKeating
Journal: Journal of Hepatology (2014)
Human enamel thickness and ENAM polymorphism
Authors: Diane M Daubert, Joanna L Kelley, Yuriy G Udod, Carolina Habor, Chris G Kleist, Ilona K Furman, Igor N Tikonov, Willie J Swanson, Frank A Roberts
Journal: International Journal of Oral Science (2016)

The tooth enamel development gene, enamelin (ENAM), showed evidence of positive selection during a genome-wide scan of human and primate DNA for signs of adaptive evolution. The current study examined the hypothesis that a single-nucleotide polymorphism (SNP) C14625T (rs7671281) in the ENAM gene identified in the genome-wide scan is associated with a change in enamel phenotype. African Americans were selected as the target population, as they have been reported to have a target SNP frequency of approximately 50%, whereas non-Africans are predicted to have a 96% SNP frequency. Digital radiographs and DNA samples from 244 teeth in 133 subjects were analysed, and enamel thickness was assessed in relation to SNP status, controlling for age, sex, tooth number and crown length. Crown length was found to increase with molar number, and females were found to have thicker enamel. Teeth with larger crowns also had thicker enamel, and older subjects had thinner enamel. Linear regression and generalized estimating equations were used to investigate the relationship between enamel thickness of the mandibular molars and ENAM SNP status; enamel in subjects with the derived allele was significantly thinner (P=0.040) when the results were controlled for sex, age, tooth number and crown length. The derived allele demonstrated a recessive effect on the phenotype. The data indicate that thinner dental enamel is associated with the derived ENAM genotype. This is the first direct evidence of a dental gene implicated in human adaptive evolution as having a phenotypic effect on an oral structure.
Pernicious Anemia in Childhood
Authors: O. Ross McIntyre, Louis W. Sullivan, Graham H. Jeffries, Randall H. Silver
Journal: New England Journal of Medicine (1965)

PERNICIOUS anemia in childhood is a rare disorder. Only 25 definitely proved cases have been reported in the medical literature.1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 To establish this diagnosis, other causes of megaloblastic anemia — folic acid deficiency and vitamin B12 deficiency due to a general or specific intestinal absorptive defect — must be excluded. Thus, the diagnostic criteria include a megaloblastic anemia, absence of intrinsic factor from the gastric juice and impaired vitamin B12 absorption (corrected by the administration of intrinsic factor). Cases in which a clinical diagnosis of pernicious anemia had been made without the demonstration of the absence of intrinsic . . .
Case 51-1990
Authors: Richard C. Cabot, Robert E. Scully, Eugene J. Mark, William F. McNeely, Betty U. McNeely, Vincent Agnello, Robert B. Colvin
Journal: New England Journal of Medicine (1990)

Presentation of CaseA 57-year-old man with hepatic cirrhosis and ascites was admitted to the hospital because of the recent onset of proteinuria and microhematuria.The patient was a construction laborer who was disabled by degenerative joint disease of the lumbosacral spine. Five years before admission he came to this hospital because of a nonpruritic rash on his legs that he first noticed three years previously. The patient had emigrated from Italy several years earlier. He had had jaundice at the age of 20 years and gave a long history of alcohol abuse that involved 3 gal (11 liters) of . . .
Postvaccinal Encephalitis with Pre-Existing Focal Cerebral Seizures
Authors: Donald S. Bickers
Journal: New England Journal of Medicine (1952)

THE occasional incidence of acute encephalitis following vaccination against smallpox may be as old as the procedure itself. Ranque, a French physician writing in 1801 (cited by Gorter1), mentioned fever, convulsions and coma as a sequel to vaccination. It was more than a century before sporadic cases began to be noted in the literature.2 , 3 Lucksch,2 in 1924, described the pathological findings in 3 cases in children. Though he erred in holding the pathological picture to be identical with that of encephalitis lethargica, his report served to focus attention on the disease. The excellent report of Turnbull and McIntosh3 established . . .
Anomalous Postural Aldosterone Response in Glucocorticoid-Suppressible Hyperaldosteronism
Authors: Arunabha Ganguly, Clarence E. Grim, Myron H. Weinberger
Journal: New England Journal of Medicine (1981)

IN normal persons the plasma aldosterone concentration rises with assumption of upright posture in response to activation of the renin-angiotensin system and to decreased metabolic clearance of aldosterone resulting from reduced hepatic blood flow.1 In contrast, patients with primary aldosteronism due to an adrenal adenoma have a paradoxical fall in plasma aldosterone after four hours of upright posture.2 3 4 5 This response is thought to be due to the ACTH-mediated modulation of aldosterone secretion combined with the normal diurnal rhythm of ACTH secretion, and it has been useful in differentiating unilateral from bilateral forms of the disease.2 3 4 5 6 We report a similar, anomalous . . .
P1000 CLINICAL OUTCOMES AND SAFETY PROFILE OF TRANSARTERIAL CHEMOEMBOLIZATION FOR HEPATOCELLULAR CARCINOMA WITH SMALL (70–150 µM, M1) DRUG ELUTING BEADS: A PHASE I STUDY
Authors: C. Spreafico, C. Sposito, T. Cascella, A. Facciorusso, M. Bongini, S. Bhoori, V. Mazzaferro
Journal: Journal of Hepatology (2014)
IS INFLUENZA TRANSMISSIBLE DURING THE PERIOD OF INCUBATION?
Authors: Cornelius Van Zwalenburg
Journal: JAMA (1918)

<h3>To the Editor:</h3> —Sherman Institute is a United States government school for Indian boys and girls under the United States Indian Service, at Riverside, Calif. It is a boarding school, drawing pupils from the western United States, between the ages of 8 and 20, the average being about 15. The entire expense is borne by the United States Indian. Service. All of the pupils and about sixty employees are housed in dormitories on the campus, an eighth of a mile square, in an orange-growing district in the city of Riverside, 6 miles from the business center. September 28, there arrived at the school, in care of a matron, seven Navajo boys and five girls from the San Juan Reservation at Ship Rock, N. M. En route, coming through Arizona, they encountered a woman manifestly ill with influenza. They traveled for several hours in the same sleeper with her. Monday, September
Retroperitoneal schwannoma diagnosed by endoscopic ultrasound-guided fine-needle aspiration
Authors: César Lopes, Manuela Zereu, Roque Furian, Bianca Furian, Tiago Remonti
Journal: Endoscopy (2014)

A 59-year-old white man was referred for evaluation of epigastric pain that was radiating to his back and a 5-kg weight loss over 6 months. A computed tomography (CT) scan revealed a heterogeneous low-attenuation tumor, measuring 5 cm in size, adjacent to the celiac artery and the pancreatic body ([Fig. 1]). Sectorial endoscopic ultrasound (GF-UCT140-AL5; Olympus America Inc., New York, USA), coupled to an ultrasound unit (Prosound alfa-5 SX; Aloka), detected a retroperitoneal well-circumscribed, hypoechoic mass, which measured 5 × 4 cm and was located immediately above the celiac tripod ([Fig. 2]).
Abstract PR01: Structural mechanism of sequence-specific 5-methylcytosine (5mC) recognition by AP-1 transcription factors
Authors: Samuel Hong, Xiaodong Cheng
Journal: Cancer Research (2016)

Abstract DNA methylation is generally known to inhibit transcription factor binding. However, this notion has been challenged with identifications of several transcription factors that preferentially activate methylated promoters in specific sequences. AP-1 transcription factor (c-Jun/c-Fos heterodimer), a master regulator of a wide range of cancer-related genes, has been shown to bind a novel consensus sequence (5'-TGACTCG-3') in CpG methylation-dependent manner. In the fluorescence polarization-based DNA binding assay, both c-Jun/c-Fos heterodimer and c-Jun/c-Jun homodimer preferentially bind DNA containing the methylated consensus sequence compared to DNA with unmethylated sequence. Using a homodimer of c-Jun/c-Jun basic leucine zipper (bZIP) DNA binding domain, we have solved the X-ray structure of AP-1 in complex with an oligonucleotide containing the methylated consensus sequence. The structure reveals that a common motif conserved among bZIP proteins is involved in the specific recognition of methylated CpG by one monomer and TpG by the other monomer. Like 5mC, thymine (5-methyluracil) contains a methyl group at C5 position, and the similarity imposed by the methyl C5 preserves key structural features of DNA sequence recognized by AP-1. Our in vitro finding resonates with previous studies of AP-1-like transcription factors that preferentially bind methylated response elements. In light of such evidence, our characterization of AP-1 as a sequence-specific 5mCpG and TpG reader suggests a novel way in which DNA methylation may function to activate transcription in a methylation-dependent manner. Citation Format: Samuel Hong, Xiaodong Cheng. Structural mechanism of sequence-specific 5-methylcytosine (5mC) recognition by AP-1 transcription factors. [abstract]. In: Proceedings of the AACR Special Conference on Chromatin and Epigenetics in Cancer; Sep 24-27, 2015; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2016;76(2 Suppl):Abstract nr PR01.
P2-05-02: PGC1, Peroxisome Proliferator Activated Receptor-gamma (PPAR-gamma) Coactivator-1, Is Necessary in PPAR-gamma Modulated Angiogenesis.
Authors: WG Jiang, X Li, RE Mansel
Journal: Cancer Research (2011)

Abstract Background. Peroxisome proliferator activated receptor- gamma (PPAR-gamma), a nuclear hormone receptor, has been shown to be an important regulator of gene expression. PPAR-gamma agonists have been shown to have anti-cancer properties by ways of inducing expression of tumour suppressor genes. It has been indicated that this action of PPAR-gamma is manifested by forming a complex with the PPAR-gamma coactivators (PGC1 &amp;2) and in association with other transcription factors such as SRC-1 and CREB binding proteins. Both PPAR-gamma and PGC-1 have been shown to be aberrantly expressed in human cancer including human breast cancer (1). PPAR-gamma also plays a role in regulating angiogenesis and that PPAR-gamma agonists have been shown to have anti-angiogenic functions. In the present study, we investigated the role of PGC-1 in PPAR-gamma mediated actions on vascular endothelial cells. Materials and methods. Mammalian expression systems for human full length PGC-1 ereonstructed. Anti-PGC-1 transgenes were constructed again using human mammalian expression vector in order to knock down PGC-1 transcript from the cells. Human vascular endothelial cell, HECV, was used in the study. Cell functions linked to angiogenesis including cell adhesion and cellular migration was evaluated using the electric cell impedance sensing method. PPAR-gamma agonists and antagonists were used in the cell models during the analyses. Results. HECV cells weakly expressed PGC-1 and PPAR-gamma. Using the transgenes created, sublines over-expressing PGC1 (HECVPGC1exp) or with PGC-1 expression knockdown (HECVPGC1KD) were established. Loss of PGC1 showed marked increase in both adhesion and cellular migration, opposite was true forHECVPGC1exp cells. PPAR-gamma agonist, pioglitizone and ciglitizone, reduced the adhesion of control cells. In contrast, PPAR-gamma antagonist SR202 exhibited a concentration dependent stimulation of both adhesion and migration of the control cells. Knocking down PGC1 in endothelial cells rendered cells lost response to SR202. Conclusions. PGC-1 is essential in during the modulation of endothelial cells by PPAR-gamma. Together with the aberrant expression of both PPAR-gamma and PGC-1 in breast cancer, it is concluded that PGC-1 is a central player in PPAR-gamma mediated action in both cancer cells and angiogenesis. 1. Jiang WG, Douglas-Jones A, Mansel RE. Expression of peroxisome-proliferator activated receptor-gamma (PPARgamma) and the PPARgamma co-activator, PGC-1, in human breast cancer correlates with clinical outcomes. Int J Cancer. 2003, 106(5):752–757. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P2-05-02.
F-18 DEOXYGLUCOSE (FDG) AND TC-99M-MDP SIMULTANEOUS WHOLE BODY SPECT IMAGING IN THE DETECTION AND LOCALIZATION OF TUMORS.
Authors: A D Waxman, G A Francken, C C Chau, H G Gabbie, B B Woods, D R Chapman
Journal: Clinical Nuclear Medicine (1998)

s Presented At The 22Nd Annual Western Regional Meeting Of The Society Of Nuclear Medicine October 1997
Abstract P6-14-17: <i>In Vitro</i> Evaluation of the Anti-EGFR Antibody Cetuximab and the Anti-HER2 Antibody Trastuzumab in a Panel of Human Tumor Cell Lines
Authors: KF Marcoe, Y Ovechkina, R Keyser, K Bernards, J Chestnut-Speelman, K Yoshino, C. O'Day
Journal: Cancer Research (2010)

Abstract The epidermal growth factor receptors, EGFR (erbB-1) and HER2 (erbB-2), and their down stream signaling events promote tumor growth and survival in a variety of epithelial tumors. Current treatment strategies used to target these receptors include mAbs directed against their extracellular domains and small molecule inhibitors of their tyrosine kinase activities. The efficacy of these types of therapeutics is increasingly being found to be contingent on the genotype of the targeted cancer. In vitro evaluation of mAbs is reliant on selection of tumor cell lines driven by the specific antigen proteins of interest and their associated pathways. We selected a panel of eight human tumor cell lines, six breast cancer (BT474, SK-BR-3, MDA-MB-453, MDA-MB-231, MDA-MB-468 and MCF-7), one colon (SW48) and one skin (A431) with varying levels of HER2, EGFR and EGFR/HER2 expression to evaluate the mAbs cetuximab and trastuzumab for antiproliferative effects, ability to induce apoptosis and the ability to block cell cycle. These findings were compared to results obtained after treatment with lapatinib, erlotinib, Ly294002 and Tamoxifen. The BT474 and SK-BR-3 breast cancer cell lines with HER2 amplified expression demonstrated cytostatic antiproliferative and G1/S cell cycle block sensitivity to the anti-HER2 antibody trastuzumab. The more prominent inhibitory effects observed in the BT474 cell line were further confirmed by measurable induced decreased levels of phospho-Akt and increased levels of the CDK2 inhibitor p27Kip1 following treatment with trastuzumab, lapatinib and Ly294002. The SW48 colon and A431 skin cancer cell lines with EGFR mutations and EGFR over expression, respectively, demonstrated cytostatic antiproliferative sensitivity to the anti-EGFR antibody cetuximab. This in vitro cell-based multiplexed approach for assessment of oncology therapeutics based on genetically directed cell line selection, demarcation of cytostatic and cytotoxic cell proliferation inhibition and assessment of receptor down stream signaling biomarkers offers greater predictive efficacious value and can be used to identify optimal candidates for combination therapies. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P6-14-17.