tbuckley/cabot-search huggingface dataset:
Conservation and Innovation of APOBEC3A Restriction Functions during Primate Evolution
Authors: Richard N. McLaughlin, Jacob T. Gable, Cristina J. Wittkopp, Michael Emerman, Harmit S. Malik
Journal: Molecular Biology and Evolution (2016)

LINE-1 (long interspersed element-1) retroelements are the only active autonomous endogenous retroelements in human genomes. Their retrotransposition activity has created close to 50% of the current human genome. Due to the apparent costs of this proliferation, host genomes have evolved multiple mechanisms to curb LINE-1 retrotransposition. Here, we investigate the evolution and function of the LINE-1 restriction factor APOBEC3A, a member of the APOBEC3 cytidine deaminase gene family. We find that APOBEC3A genes have evolved rapidly under diversifying selection in primates, suggesting changes in APOBEC3A have been recurrently selected in a host–pathogen "arms race." Nonetheless, in contrast to previous reports, we find that the LINE-1 restriction activity of APOBEC3A proteins has been strictly conserved throughout simian primate evolution in spite of its pervasive diversifying selection. Based on these results, we conclude that LINE-1s have not driven the rapid evolution of APOBEC3A in primates. In contrast to this conserved LINE-1 restriction, we find that a subset of primate APOBEC3A genes have enhanced antiviral restriction. We trace this gain of antiviral restriction in APOBEC3A to the common ancestor of a subset of Old World monkeys. Thus, APOBEC3A has not only maintained its LINE-1 restriction ability, but also evolved a gain of antiviral specificity against other pathogens. Our findings suggest that while APOBEC3A has evolved to restrict additional pathogens, only those adaptive amino acid changes that leave LINE-1 restriction unperturbed have been tolerated.
Transcatheter Therapies for Treating Tricuspid Regurgitation
Authors: Josep Rodés-Cabau, Rebecca T. Hahn, Azeem Latib, Michael Laule, Alexander Lauten, Francesco Maisano, Joachim Schofer, Francisco Campelo-Parada, Rishi Puri, Alec Vahanian
Journal: Journal of the American College of Cardiology (2016)
CYP2C19 LOSS-OF-FUNCTION ALLELE GENOTYPING COMBINED WITH THROMBELASTOGRAPH PLATELET-MAPPING ASSAY IS AN INDEPENDENT PREDICTOR OF ADVERSE CARDIOVASCULAR OUTCOMES IN CHINESE PATIENTS TREATED WITH CLOPIDOGREL UNDERGOING CORONARY STENTING
Authors: Xiao-Fang Tang, Yue-Jin Yang, Jin-Qing Yuan, Jue Chen, Jia-Hui Zhang, Zhan Gao, Run-Lin Gao
Journal: Journal of the American College of Cardiology (2014)
Breast epithelial differentiation is altered in BRCA1mut/+ carriers prior to the onset of cancer and contributes to the basal tumor phenotype.
Authors: P Keller, PB Gupta, I Klebba, H Gilmore, S Come, S Schnitt, ES Lander, C Kuperwasser
Journal: Cancer Research (2009)

Abstract Abstract #3083 Human breast tumors are broadly divided into either luminal-like or basal-like cancers. This distinction is significant since basal-like tumors are more aggressive and afford a poor patient prognosis relative to luminal-like tumors. For reasons that are unclear, germline mutations in BRCA1 strongly predispose for poor prognosis basal-like tumors. The predisposition for basal-like tumors in BRCA1mut/+ patients could be due to (1) differences in underlying target cell populations between BRCA1mut/+ and BRCA1+/+ women or (2) differences in the genetic mutations arising within a single shared target cell type. This basic question has remained unresolved due to a lack of experimental models in which it can be addressed. We describe here a novel in vivo breast cancer system that enables the generation of tumors by introducing oncogenes into normal breast epithelium derived directly from human breast tissue. This system is unique in that it enables human-derived epithelial cells to be sorted for cell surface markers and transformed without requiring in vitro culture prior to implantation in vivo. Using this experimental system, we show that epithelial cells from BRCA1mut/+ patients give rise to tumors that exhibit multiple features of basal differentiation, in contrast to epithelial cells transformed with identical oncogenes from BRCA1+/+ patients. We show further that non-cancerous epithelial cells from BRCA1mut/+ patients already exhibit atypical differentiation even prior to the onset of cancer, in contrast to cells from BRCA1+/+ women. Remarkably, some of these differences are observable in the context of unperturbed breast tissue obtained from disease-free BRCA1mut/+ and BRCA1+/+ patients. Collectively, these findings show that the increased incidence of basal-like tumors in BRCA1mut/+ patients is a reflection of the altered differentiation of breast epithelial cells in BRCA1mut/+ patients. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 3083.
Abstract 3027: A novel function of EGFR in epigenetic modulation via hMOF in breast cancer .
Authors: Seung-Oe Lim, Chia-Wei Li, Shih-Shin Chang, Jia Shen, Mien-Chie Hung
Journal: Cancer Research (2013)

Abstract The epidermal growth factor receptor (EGFR) is aberrantly active in breast cancer, initiates and drives tumorigenic pathways, and has been implicated in multiple tumorigenic processes including hyperplasia, chemo-resistance and metastasis. Histone lysine modifications directly influence activation and repression of transcription. MYST family acetyltransferase, human males absent on the first (hMOF), plays an important role in transcription activity through histone H4K16 acetylation. Loss of hMOF and subsequently the absence of H4K16 acetylation have been shown to be a common feature in human cancer including breast cancer. However, the regulation of hMOF remains largely unknown. Recently, we have discovered the acetylation of EGFR in human breast cancer cells. Thus, we screened a set of EGFR-interacting acetyltransferases using co-immunoprecipitation analysis and ingenuity pathway analysis (IPA). Here, we found that EGFR directly interacts with and phosphorylates hMOF. EGFR-induced phosphorylation hMOF was significantly reduced in the hMOF YF mutant. Indeed, hMOF YF mutant showed a higher histone acetyltransferase (HAT) activity compare to wild type hMOF. In addition, tyrosine kinase inhibitor (TKI) also enhanced the HAT activity of wild type hMOF. Furthermore, we found that EGFR modulates acetylation status of histone H4K16 via phosphorylating hMOF. We anticipate our study of EGFR and hMOF to be of therapeutic relevance, possibly leading to novel discovery in drug development targeting the receptor tyrosine kinase and the acetylation process. Citation Format: Seung-Oe Lim, Chia-Wei Li, Shih-Shin Chang, Jia Shen, Mien-Chie Hung. A novel function of EGFR in epigenetic modulation via hMOF in breast cancer . [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3027. doi:10.1158/1538-7445.AM2013-3027
SAT0180 Cardiovascular Risk in Granulomatosis with Polyangiitis (Wegener’S) of Different Severity and Duration
Authors: E. Kuznetsova, P. Novikov, S. Moiseyev
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Persistent inflammation and immunosupressive treatment predispose patients (pts) with rheumatic diseases to early atherosclerosis. The risk of cardiovascular (CV) events in GPA is not well studied. <h3>Objectives</h3> To evaluate the prevalence of CV risk factors, subclinical carotid atherosclerosis and CV outcomes in pts with GPA. <h3>Methods</h3> 94 pts with GPA were enrolled (53 females, 41 males; mean age 54.0±14.9) in the stude. Diagnosis was established according to ACR criteria and CHCC2012. Mean value of Vasculitis Damage Index (VDI) was 1,8±1,9; VDI was &lt;5 in 59 pts (mean age 51±14,8, 26 males, 33 females) and ≥5 (mean age 55±13,9, 15 males, 20 females) in 31 pts. Mean duration of GPA was 7±6,4 years. It was &lt;5 лет in 47 pts (mean age 51±13,7, 24 males, 23 females) and ≥5 лет in 47 pts (mean age 55±14,7, 18 males, 29 females). Localized, early systemic and generalized disease was established in 29, 24 and 41 pts, respectively. ANCA, mainly to PR3, were positive in 69 pts. We studied the traditional CV risk factors and outcomes (stroke, myocardial infarction [MI], revascularization procedures). Subclinical atherosclerosis was evaluated using carotid US (TIM and plaques). <h3>Results</h3> We revealed high prevalence of CV risk factors in GPA: dyslipidemia – 68%, hypertension – 74%, overweight – 63%. Carotid US showed increased TIM and plaques in 63% and 27%, respectively. 10 pts (11%) had history of CV events: MI (n=4), stroke (n=3) and revascularization procedures (n=3). Prevalence of CV risk factors and subclinical atherosclerosis was similar in patients with VDI &lt;5 и ≥5; the incidence of CV events was higher in patients with VDI ≥5 (20% vs 5%, р&lt;0,05). The influence of GPA duration on prevalence of traditional risk factors, subclinical atherosclerosis and CV events was not established. The prevalence of CV risk factors, subclinical atherosclerosis, CV events was similar in pts with local, early systemic and generalized GPA. The prevalence of CV risk factors and subclinical atherosclerosis was similar in ANCA(+) and ANCA(–) pts. The rate of CV events was insignificantly higher in ANCA(+) pts (p=0.19) <h3>Conclusions</h3> The pts with GPA have high prevalence of CV risk factors, subclinical carotid atherosclerosis and increased risk of CV events. Severity of disease contributes to increased risk of CV events while duration of GPA has no effect. <h3>Disclosure of Interest</h3> None Declared
Incidental Finding of F-18 FDG Skin Uptake in a Patient With Psoriasis During the Evaluation of a Recurrent Papillary Thyroid Carcinoma
Authors: Claire Bruna-Muraille, Jean-Marie Pochart, Dimitri Papathanassiou, Renaud Guedec-Ghelfi, Amélie Cuif-Job, Jean-Claude Liehn
Journal: Clinical Nuclear Medicine (2010)

We report the case of a patient, referred in our institution for a PET/CT for a suspected recurrence of papillary thyroid carcinoma. An intense cutaneous uptake of FDG was seen in the upper neck region. The clinical examination showed an indurate and thickened red descamative plaque evocative of psoriasis, and the patient reported a long history of psoriatic lesions of the skin, evolving for many years. This case illustrates an incidental finding which must be recognized, and not confounded with other causes of skin uptake. The FDG image is not surprising, as FDG uptake is expected in active inflammatory disease.
The Importance of Morphine-Augmented Cholescintigraphy for the Diagnosis of a Subtle Cholecystocolic Fistula
Authors: JOSEPH W. SAM, NASRIN GHESANI, ABASS ALAVI, STEPHEN E. RUBESIN, BERNARD A. BIRNBAUM
Journal: Clinical Nuclear Medicine (2001)

SAM, JOSEPH W. M.D., Ph.D.; GHESANI, NASRIN M.D.; ALAVI, ABASS M.D.; RUBESIN, STEPHEN E. M.D., AND; BIRNBAUM, BERNARD A. M.D. Author Information
Non-insulin dependent diabetes mellitus and non-Hodgkin's lymphoma
Authors: J. I Brody
Journal: BMJ (1995)

ED1TOR,-We agree with Helen Ward and John S Yudkin that diabetic retinopathy should not be a contraindication to the use of thrombolysis in myocardial infarction.'In September 1991 one of us (RCW) expressed concern locally that the practical difficulty of excluding diabetic retino- pathy could easily lead to diabetic patients being denied thrombolysis.The need for a rapid decision, often without the benefit of case notes and after opiate analgesia, posed particular problems for the receiving team.Subsequently, discussion took place in Mersey region among diabetologists, ophthalmologists, and cardiologists in their respective subcommittees of the regional medical committee.It was agreed that diabetic retinopathy should no longer be regarded as a contraindication to thrombolysis for two reasons: firstly, the potential benefits of a
TCT-561 Safety and Efficacy of Carotid Stenting in the Treatment of Carotid Artery Stenosis: Immediate Results and Long Term Follow-up
Authors: Cinzia Moncalvo, Vincenzo Puma, Giuseppe Celano, Mario Caprile, Angelo Laurenza, Giuseppe Carosio, Paolo Cioffi
Journal: Journal of the American College of Cardiology (2014)
Abstract 1723: The BH4 domain of Bcl-2 is sufficient to induce RNA expression profile changes in human prostate cancer cell lines.
Authors: Jennifer R. Cohen, Simon A. Williams
Journal: Cancer Research (2013)

Abstract Bcl-2 is the archetypal gene and first characterized member of the family bearing its name. Prostate cancer was the first solid tumor malignancy in which an elevation of cellular Bcl-2 levels was associated with advanced disease. It is thought that the anti-apoptotic activity of Bcl-2 contributes to the uniformly lethal nature of castration-resistant advanced prostate cancer. Bcl-2 is a validated target for cancer therapies. Current small molecule drug inhibitors mimic the BH3 domain of pro-apoptotic Bcl-2 family members, binding to a pocket composed mainly of Bcl-2 homology (BH) domains 1-3, and only partially BH4. Surprisingly, while these agents are effective inducers of apoptosis, they do not inhibit the oncogenic functions of the BH4 domain. The BH4 domain is essential for the antiapoptotic functions of Bcl-2, and appears to mediate interactions with proteins not part of the Bcl-2 family. This explains the small but significant body of evidence supporting an oncogenic signaling role for Bcl-2 driven by the BH4 domain. The full extent of the non-apoptotic roles of Bcl-2, including the contribution of the BH4 domain, has yet to be clarified. Our work aims to address this in prostate cancer cells, developing and utilizing a system that will implicate both the full length gene product and the BH4 domain. Eukaryotic expression constructs were designed to contain the full length Bcl-2 gene built to co-express with GFP, or a fusion gene composed of the Bcl-2 BH4 domain, GFP, and the Bcl-2 C-terminal transmembrane domain. These plasmids were then transfected into the 22Rv1, LNCaP, and LAPC4 human prostate cancer cell lines to generate stable expression clones. The clones were validated for protein expression by western blot prior to a determination of classical functionality by treatment with apoptosis-inducing agents. RNA was then isolated from the clones for expression array analysis. We successfully generated human prostate cancer cells stably overexpressing Bcl-2 and the Bcl-2 BH4 domain. These clones displayed enhanced resistance to apoptosis induction. Bcl-2 overexpression also induced expression profile changes in these clones. This was mimicked by expression of the BH4 domain alone. We have developed a useful system to help enhance our understanding of Bcl-2 by highlighting changes in RNA expression profiles induced by the gene's overexpression. We also show that the BH4 domain drives much of this function. The mechanisms responsible for these Bcl-2/BH4-induced changes warrant further investigation. Citation Format: Jennifer R. Cohen, PhD, Simon A. Williams, PhD. The BH4 domain of Bcl-2 is sufficient to induce RNA expression profile changes in human prostate cancer cell lines. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1723. doi:10.1158/1538-7445.AM2013-1723
PWE-277 Fracture prevalence and vitamin D status in primary biliary cirrhosis: the Leicestershire experience
Authors: R Krishnamoorthy, A Grant, P Sheldon, T Delahooke
Journal: Gut (2012)

<h3>Introduction</h3> Metabolic bone disease is a recognised complication in Primary Biliary Cirrhosis (PBC) and increases the risk of developing fractures. Although osteoporosis is the major contributor, Vitamin D (25- hydroxy- vitamin- D3) deficiency due to fat-soluble vitamin malabsorption is also a contributing factor for bone disease in PBC. Our objective was to assess the prevalence of fractures and vitamin D deficiency in PBC patients. <h3>Methods</h3> Patients with diagnosed with PBC between the years 1994 and 2011 were retrospectively identified from the hepatology outpatients. Fracture data were collected from the x-ray reports in the radiology software. Biochemical data including AMA titres and Vitamin D status were retrospectively identified and entered using the pathology database. The grading for Vitamin D levels were as follows: severely deficient- 20 mg/l or &gt;50 nmol/l. Available Bone Mineral Density (BMD) data in patients who had a Dual-emission x-ray absorptiometry (DEXA) scan was studied. <h3>Results</h3> Among 209 patients (179 female, median age 68 years, 168 AMA positive with median AMA titre of 1 in 256) with PBC, 27 patients (12.9%, 25 females, median age 74) had sustained a fracture during their clinical course. 33 fracture episodes were identified. Femur/hip fractures were the commonest (9/33, 27%), followed by hand (5/33, 15%). DEXA scans were performed in 39 patients, with a median T score of −2.2. Vitamin D levels were available in 91 patients (44%), the levels being adequate in only 27 patients (29.6%), reflecting the magnitude of the Vitamin D status. 38 patients were insufficient (41.7%), 17 were deficient (18.6%) and 9 were severely deficient (0.09%). <h3>Conclusion</h3> Fracture prevalence and vitamin D deficiency is high in PBC patients. Assessing Vitamin D status is a useful measure to improve bone health and reduce the burden of metabolic bone disease. <h3>Competing interests</h3> None declared. <h3>Reference</h3> 1. <b>Solaymani-Dodaran M</b>, Card TR, Aithal GP, <i>et al.</i> Fracture risk in people with primary biliary cirrhosis: a population-based cohort study. <i>Gastroenterology</i> 2006;<b>131</b>:1752.
LATE DIFFERENCE OF CLINICAL OUTCOME BETWEEN ZOTAROLIMUS VERSUS EVEROLIMUS ELUTING CORONARY STENTS IN AN ISOLATED PROXIMAL LEFT ANTERIOR DESCENDING ARTERY LESION
Authors: Nikolaos Anousakis-Vlachochristou, Konstantinos Toutouzas, Chrysoula Patsa, Andreas Synetos, George Latsios, Eleftherios Tsiamis, Komatanou Efmorfia, Ioannis Matsoukis, Anastasios Spanos, Dimitris Tousoulis
Journal: Journal of the American College of Cardiology (2015)
1121 PHENOTYPE AND EXPRESSION QTL ANALYSES OF HEPATOCELLULAR DAMAGE IN VITRO AND FIBROGENESIS IN VIVO IN BXD MICE IDENTIFY EXTRACELLULAR PROTEINASE INHIBITOR (Expi) AS CANDIDATE GENE
Authors: R. Liebe, R. Hall, S. Dooley, F. Lammert
Journal: Journal of Hepatology (2013)
Abstract 4105: Hedgehog inhibition promotes type I TRAIL cytotoxicity in human cholangiocarcinoma cells
Authors: Satoshi Kurita, Justin L. Mott, Martin E. Fernandez-Zapico, Steve F. Bronk, Maria E. Guicciardi, Lewis R. Roberts, Toshifumi Hibi, Gregory J. Gores
Journal: Cancer Research (2011)

Abstract [Background and Aim] TRAIL is a promising therapeutic agent for human malignancies that can activate apoptosis via mitochondria-independent (Type I) or mitochodria-dependent (Type II) death receptor signaling. However, many malignant cells are resistant to TRAIL cytotoxicity and fail to trigger Type I or Type II killing. Using cholangiocarcinoma cells, we identified a role for Hedgehog signaling via GLI transcription factors in the regulation of TRAIL cytotoxicity, and provide new mechanistic insights whereby Hedghog inhibition increases apoptosis. [Materials and Methods] The human cholangiocarcinoma cell lines KMCH, HuCCT-1, and Mz-ChA-1 were employed. Hedgehog signaling was inhibited with cyclopamine or an shRNA construct targeting smootherned (SMO). Type II TRAIL signaling was inhibited with shRNA constructs for Bid or Bim and siRNA for Bax and Bak. Antiapoptotic mediators including Inhibitor of Apoptosis Proteins (IAPs) and Bcl-2 family proteins were examined by immunoblot analysis and/or real time RT-PCR. Apoptosis was quantified morphologically by DAPI and fluorescence microscopy, and biochemically by caspase-3/7 activity. GLI transcription factor binding to the XIAP promoter was examined by EMSA and chromatin immuneprecipitation (ChIP) assay. [Results] Pharmacologic or genetic inhibition of Hedgehog signaling down-regulates both XIAP and cIAP-1 mRNA and protein expression. Knockdown of XIAP, but not cIAP-1, by small-interfering RNA markedly sensitized cells to TRAIL-induced apoptosis, suggesting XIAP is the functional target. Putative GLI-binding sites were identified in the XIAP promoter, and EMSA and ChIP assays demonstrated direct binding by GLI proteins. Sensitization to TRAIL-induced apoptosis was not altered by knockdown of the BH3-only proteins Bim and Bid, or by knockdown of Bax plus Bak, implicating a mitochondria-independent Type I pathway of apoptosis. [Conclusion] These data provide evidence for up-regulation of XIAP by an oncogenic Hedgehog pathway and demonstrate that Hedgehog inhibition sensitizes cells to TRAIL via decreasing XIAP levels. Hedgehog inhibition thereby promotes Type I death receptor signaling and sensitizes cells to apoptosis, which suggests Hedgehog and XIAP inhibition may be a therapeutic approach for TRAIL-resistant neoplasms. 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 4105. doi:10.1158/1538-7445.AM2011-4105
The Risk of Subarachnoid and Intracerebral Hemorrhages in Blacks as Compared with Whites
Authors: Joseph P. Broderick, Thomas Brott, Thomas Tomsick, Gertrude Huster, Rosemary Miller
Journal: New England Journal of Medicine (1992)

Stroke is an important cause of death among blacks, and intracerebral and subarachnoid hemorrhages account for nearly half of all early deaths from stroke. The present study investigates whether blacks and whites differ in their risk of having either intracerebral or subarachnoid hemorrhage.
Whole-Body Bone Scan Findings in X-Linked Hypophosphatemia
Authors: C. Van De Wiele, R. A. Dierckx, L. Weynants, M. Simons, J. M. Kaufman
Journal: Clinical Nuclear Medicine (1996)

X-linked hypophosphatemia, also called phosphate diabetes, is the most frequent form of inherited rickets in North American. In a series of 38 untreated adult X-linked hypophosphatemia patients, Hardy et al suggested that scintigraphic findings may be attributed solely to degenerative arthritis. However, the authors present a 31-year old, drug-free, X-linked hypophosphatemia patient, in whom bone scan findings were more compatible with osteomalacia and secondary degenerative arthritis, rather than with isolated degenerative arthritis. These findings are in agreement with the biochemical and histologic proof of active osteomalacia in untreated adult X-linked hypophosphatemia patients, provided by Reid et al. The first whole-body bone images of X-linked hypophosphatemia are presented.