tbuckley/cabot-search huggingface dataset:
THU0399 Is pernio a microvascular disease?
Authors: M. Ozmen, V. Kurtoglu, G. Can, E.F. Tarhan, D. Soysal, S.L. Aslan
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Pernio is a disorder that affects unprotected skin regions of the individuals who are exposed to nonfreezing, damp cold. Various hypotheses such as abnormal vasoconstriction, vasculitis, and hyperviscosity have been proposed as the underlying pathophysiology. Nailfold video capillaroscopy demonstrates organic or functional changes in the microcirculation. <h3>Objectives</h3> The purpose of this study was to examine nailfold capillaries by the video capillaroscopy and evaluate the vascular involvement in patients with idiopathic pernio. <h3>Methods</h3> 53 patients with idiopathic pernio (male: female 35:18, mean age 25±9 years) who had consulted the rheumatology outpatient clinic between 2008 and 2011, and age- and sex-matched 38 healthy volunteers (male: female 30:8, mean age 24±4 years) were included in the study. 47 of the patients and all the healthy volunteers were evaluated by the nailfold video capillaroscopy. During the examination, architectural derangement, tortuosity, avascular areas and hemorrhages were investigated and capillary and apical capillary diameters were measured. <h3>Results</h3> In the patient group, the mean capillary diameter and the mean apical capillary diameters were 56±15μm and 24±7μm, respectively. The mean capillary diameter and the mean apical capillary diameter were 37±8 μm and 15±4μm in the control group, respectively (both p&lt;0.001). Tortuosity was found in 28 of the patients (60%) and 7 of the healthy volunteers (18%) (p&lt;0.001). All of these differences were independent of the disease activity, smoking and the number of episodes. There were no architectural derangements, avascular areas or hemorrhages. <h3>Conclusions</h3> In the present study, increased nailfold capillary diameter, increased apical capillary diameter and the presence of tortuosity were found in patients with pernio regardless of the disease activity. These findings suggest organic damage of the microcirculation. <h3>Disclosure of Interest</h3> None Declared
Abstract 5439: Developmental checkpoint function of Δ40p53.
Authors: Piyan Zhang, Heidi Scrable
Journal: Cancer Research (2013)

Abstract Δ40p53, an N-terminally truncated p53 isoform, is predominantly expressed in embryonic stem cells (ESCs) and during early post-implantation embryogenesis in the mouse. We have discovered that Δ40p53 controls the switch from pluripotency to differentiation by regulating IGF signaling in ESCs. Our studies revealed this isoform of p53 inhibits retinoic acid-induced differentiation and subsequent epithelial-mesenchymal transition (EMT). As ESCs differentiate, Δ40p53 cannot activate the expression of some important developmental genes, such as p21, FGF10, DKK1, lamin A and ZO-1, coincident with decreasing Erk signaling and an enhanced Wnt/β-catenin pathway. ChIP assays suggested that p21, FGF10 and ZO-1 are inhibited at the elongation step. To distinguish between the transcription regulation functions of full-length p53 and Δ40p53, we generated stable HeLa cell lines transfected with Flag-tagged p53 and Δ40p53. qPCR and ChIP assays confirmed that Δ40p53, but not full-length p53, represses gene elongation, with a concomitant decrease in acetylation of histone H4 and H3 in the promoter region. Our studies reveal that Δ40p53, but not p53, is able to block ESC differentiation by regulation of specific gene expression at the elongation step during mouse development. Citation Format: Piyan Zhang, Heidi Scrable. Developmental checkpoint function of Δ40p53. [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 5439. doi:10.1158/1538-7445.AM2013-5439
The ERS Research Agency: the beginning
Authors: Joan B. Soriano, James Paton, Fernando Martin Burrieza, Werner Bill, Carine Pannetier, Stefano Aliberti, Ian M. Adcock, Scott Wagers, Giovanni Battista Migliori
Journal: European Respiratory Journal (2016)

There is at the current time a significant opportunity for the ERS to leverage its experience and reputation as an international umbrella organisation to promote high-quality, multinational respiratory research with the goal of improving the health of respiratory patients. This editorial proposes a model for the role and structure of an ERS Research Agency. It is based upon research, implicit knowledge and explicit feedback from ERS members and selected external individuals and organisations.As with any new endeavour there are challenges and threats. Building a Research Agency will be a major undertaking that will require significant organisational planning, resources, effort and commitment.Organisations with multiple stakeholders tend to have a status quo inertia that has to be overcome for any significant new endeavour. The ERS Research Agency could be an investment in the future of respiratory research.
Arginase 1 is an innate lymphoid-cell-intrinsic metabolic checkpoint controlling type 2 inflammation
Authors: Laurel A Monticelli, Michael D Buck, Anne-Laure Flamar, Steven A Saenz, Elia D Tait Wojno, Naomi A Yudanin, Lisa C Osborne, Matthew R Hepworth, Sara V Tran, Hans-Reimer Rodewald, Hardik Shah, Justin R Cross, Joshua M Diamond, Edward Cantu, Jason D Christie, Erika L Pearce, David Artis
Journal: Nature Immunology (2016)
TCT-537 12-Month Primary Patency Rates of Contemporary Endovascular Device Therapy for Femoro-Popliteal Occlusive Disease in 6024 Patients: Beyond Balloon Angioplasty
Authors: Konstantinos Marmagkiolis, Malek Al-Hawwas, Massoud A. Leesar, Mehmet Cilingiroglu
Journal: Journal of the American College of Cardiology (2014)
Abstract B16: Tumor suppressive functions by ATF2/7 transcription factors in a cMyc-driven B-cell lymphoma model
Authors: Jacek Walczvnski, Nic Jones, Wolfgang Breitwieser
Journal: Cancer Research (2011)

Abstract ATF2 and the highly homologous ATF7 are members of the AP-1 transcription factor family which regulate expression of genes involved in development and stress response. In cancer, ATF2 has been reported to function both as a tumor suppressor and tumor promoter. The aim of the project was to investigate the possible roles of ATF2/7 in cMyc-driven B-cell lymphoma development and to characterize their interaction with the cMyc oncogene. Previously, cMyc, which is frequently deregulated in Burkitt's lymphoma (Rabbitts et al, 1984), was shown to prolong the half-life and induce phosphorylation of ATF2 (Miethe et al, 2001). In addition, the MAP kinase JNK and its substrate ATF2 are frequently found upregulated in B-cell lymphomas (Kersten et al, 2004; Gururajan et al, 2005). We established a mouse B-cell lymphoma model by crossing B-cell specific knockouts of Atf2/7 (Atf2ΔBC, Atf7−/−) with Eμ-Myc transgenic animals. Eμ-Myc mice express the cMyc proto-oncogene driven by the immunoglobulin heavy chain enhancer (Eμ) and develop B-cell lymphomas with high frequency. We compared timing of tumor onset between Eμ-myc, Atf2ΔBC, Atf7−/− Eμ-myc, Atf2ΔBC/+, Atf7−/−, and Eμ-myc, Atf7−/−. In addition, we derived cell lines fom Eμ-Myc-driven lymphomas and characterized growth, apoptosis, and drug sensitivity in the presence or absence of functional Atf2/7. Atf2 and its phosphorylated (activated) form were found to be upregulated in cells obtained from tumor samples from Eμ-Myc mice in comparison to normal B lymphocytes. Analysis of tumor-free survival showed that Eμ-myc, AtfΔBC, Atf7−/− develop B-cell lymphomas at significantly faster rates than controls. In vitro deletion of Atf2 in cell lines derived from cMyc-driven lymphomas resulted in a marked reduction in the basal levels of apoptosis. Furthermore, Atf2/7-deficient Eμ-myc tumor cells were significantly more resistant to genotoxic stress (e.g., doxorubicin) induced apoptosis. Gene expression analysis identified proapoptotic members of the Bcl-2 family as possible transcriptional targets of Atf2. In this study, we show a novel tumor suppressive role of ATF2 in cMyc-induced lymphomagenesis and suggest the potential functions of ATF2 in regulating programmed cell death. The results also imply that the evaluation of levels of activated ATF2 in clinical samples of B-cell lymphoma may give an indication of their sensitivity to chemotherapeutic agents. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the Second AACR International Conference on Frontiers in Basic Cancer Research; 2011 Sep 14-18; San Francisco, CA. Philadelphia (PA): AACR; Cancer Res 2011;71(18 Suppl):Abstract nr B16.
Infection with the Virus of Herpes Simplex
Authors: T. F. McNair Scott
Journal: New England Journal of Medicine (1954)

THE virus of herpes simplex, which is primarily a parasite of man, by a process of adaptation through the ages has achieved an enviable relation with its host so that in most cases the two live together almost in a state of symbiosis. However, clinicians are concerned with the relatively uncommon situations in which this ideal arrangement fails and the host responds to the entrance of the parasite with an illness that is sometimes violent.In the course of the last fifteen years, a good deal of information on the host-parasite relation of this virus (Table 1) has been gathered. . . .
Skeletal Metastases Mimicking a Bilateral “Delta Sign” on Tc-99m MDP Bone Scintigraphy
Authors: SEOK TAE LIM, MYUNG-HEE SOHN, JAE-YONG KWAK, CHANG-YEOL YIM
Journal: Clinical Nuclear Medicine (2001)

TAE LIM, SEOK M.D.; SOHN, MYUNG-HEE M.D.; KWAK, JAE-YONG M.D.; YIM, CHANG-YEOL M.D. Author Information
Colonic Uptake of Tc-99m MDP in Pseudomembranous Colitis
Authors: ERIC M. ROHREN, SALVADOR BORGES-NETO
Journal: Clinical Nuclear Medicine (2002)

From the Department of Radiology, Duke University Medical Center, Durham, North Carolina Received for publication November 26, 2001. Revision accepted March 7, 2002. Correspondence: Eric M. Rohren, Department of Radiology, Box 3949, Duke University Medical Center, Erwin Road, Durham, North Carolina 27710. E-mail: [email protected]
Hemosuccus pancreaticus caused by in situ carcinoma of the pancreas
Authors: H. Inoue, M. Katurahara, Y. Hamada, K. Ninomiya, S. Tano, R. Takayama, K. Nojiri, M. Tameda, N. Horiki, Y. Takei
Journal: Endoscopy (2012)

A-77-year-old-woman was referred to our hospital because of dilatation of the main duct in the pancreatic body, as seen on transabdominal ultrasonography. The patient had experienced several episodes of acute pancreatitis in the previous 2 years. Laboratory tests showed mild anemia (hemoglobin 11.7 g/dL; reference range: 12 – 16 g/dL). Levels of serum amylase, carcinoembryonic antigen, and carbohydrate antigen 19–9 were within normal limits. Computed tomography and magnetic resonance cholangiopancreatography revealed mild dilatation of the main pancreatic duct and demonstrated lack of a mass lesion. Endoscopic retrograde cholangiopancreatography (ERCP) showed stricture of the main duct in the head of the pancreas ([Fig. 1]). Cytological analysis of the pancreatic juice showed no malignancy. During ERCP, a side-viewing upper endoscope showed blood oozing from the major papilla ([Fig. 2]). Bleeding was intermittent and stopped after ERCP. Endoscopic ultrasonography (EUS) showed a small vague hypoechoic area adjacent to the stenotic duct of the pancreas.
P2-06-04: Phosphatidylinositol-3-Kinase Pathway Mutations Are Common in Breast Columnar Cell Lesions.
Authors: ML Troxell, AL Brunner, K Montgomery, SX Zhu, T Neff, A Warrick, C Beadling, CL Corless, RB West
Journal: Cancer Research (2011)

Abstract The phosphatidylinositol-3-kinase pathway is one of the most commonly mutated in invasive breast carcinoma, with PIK3CA mutations present in ∼25% of invasive carcinomas, and AKT1 mutations identified in up to 5%. Several studies have demonstrated the same complement of mutations in ductal carcinoma in-situ (DCIS), as well as benign papillomas. We sought to investigate whether PIK3CA mutations occur in breast columnar cell lesions (CCL). Twenty-five breast resection specimens containing CCL (including columnar cell change, columnar cell hyperplasia, and flat epithelial atypia) were identified from the files of Stanford University Pathology; 15 of these had associated invasive carcinoma (IDC) or carcinoma in situ. DNA was prepared from punches of formalin-fixed paraffin-embedded tissue blocks using standard methods. DNA extracts were screened for a panel of point mutations using a multiplex PCR panel with a mass-spectroscopy readout (Sequenom MassARRAY). The panel covers 321 mutations in 30 genes, including ABL, AKT1/2/3, BRAF, CDK4, CTNNB1, EGFR1, ERBB2, FBX4, FBXW7, FGFR1/2/3, FLT3, GNAQ, HRAS, JAK2, KIT, KRAS, MAPK2K1/2, MET, NRAS, PDGFRA, PIK3CA, PTPN11, RET, SOS1, and TP53. The majority of mutations were confirmed by Sanger sequencing. PIK3CA mutations were identified in 12/25 CCL (48%); paired normal breast tissue was tested in 21 cases and was negative for mutations in all but one case. In associated DCIS, 4/8 (50%) harbored PIK3CA mutations, while 3/9 IDC had mutations (33%, 2 PIK3CA, 1 AKT1). The mutation status of CCL and carcinomas was frequently discordant. Of 15 cases, only 6 demonstrated the same genotype in matched samples of CCL and carcinoma (5 wildtype, 1 PIK3CA H1047R). Interestingly, 5 patients had mutations in CCL with wildtype DCIS or IDC; 2 patients had different point mutations in CCL and carcinoma, including one patient with discordant mutant DCIS and wildtype IDC. Only 3 cases had wildtype CCL and mutated carcinoma. The nearly 50% PIK3CA mutation prevalence in CCL is greater than reported in most studies of invasive breast cancer. Further, CCL and carcinoma were frequently discordant for PIK3CA/AKT1 mutation status; most commonly the CCL harbored a PIK3CA mutation, while the associated carcinoma was wildtype. Although these findings need validation in a larger study, they raise interesting questions as to the role of PIK3CA/AKT pathway in breast carcinogenesis, and as to the biologic/precursor potential of CCL. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P2-06-04.
Delayed perforation 10 days after endoscopic hemostasis using hemostatic forceps for a bleeding Dieulafoy lesion
Authors: S. Ninomiya, H. Shiroshita, T. Bandoh, W. Soma, H. Abe, T. Arita
Journal: Endoscopy (2013)

To our knowledge, there have been no reports in the English literature of cases of delayed perforation occurring more than 2 days after hemostasis for gastrointestinal bleeding, including bleeding related to endoscopic submucosal dissection. Additionally, according to previous reports [1] [2], in patients with delayed perforation, surgery was often required to improve their clinical course. We report a rare case of successful conservative treatment for delayed perforation occurring 10 days after endoscopic hemostasis using hemostatic forceps for a bleeding Dieulafoy lesion.
Abstract C40: Salicylic acid-based small molecule inhibitors of Stat3 show potent and selective activity in a variety of human cancer cell lines
Authors: Brent D. G. Page, Steven Fletcher, Aaron Schimmer, James Turkson, Patrick T. Gunning
Journal: Cancer Research (2009)

Abstract Signal transducer and activator of transcription 3 (Stat3) protein is an oncogenic transcription factor that exhibits aberrant functioning in many types human cancer. Constitutive Stat3 activation causes over-expression of anti-apoptotic proteins and makes cancer cells resistant to natural apoptotic processes. Inhibiting Stat3 reduces the expression of anti-apoptotic proteins and can selectively kill cancerous cells. We have identified several salicylic acid based inhibitors of Stat3 that show potent activity in vitro and in whole cell assays. In silico docking studies have revealed S3I-201, a known Stat3 inhibitor, exhibits incomplete occupation of Stat3's SH2 domain. A thorough structure activity relationship study has provided a series of compounds that more completely occupy Stat3's SH2 domain and show potent and highly selective activity against Stat3 and a variety of human cancers. Inhibitor design, synthesis, in vitro and in vivo assays and preliminary metabolic studies will be discussed. Citation Information: Cancer Res 2009;69(23 Suppl):C40.
Reversible Cardiac Dysfunction (Hibernation) from Ischemia Due to Compression of the Coronary Arteries by a Pseudoaneurysm
Authors: William B. Baker, Milton S. Klein, Michael J. Reardon, Mario S. Verani, William A. Zoghbi
Journal: New England Journal of Medicine (1991)

THE term hibernating myocardium was coined by Rahimtoola1 to describe persistent cardiac dysfunction due to chronic ischemia that is at least partially reversible if the severity of ischemia is reduced. Myocardial hibernation has most often been reported in patients with severe atherosclerotic coronary artery disease who are undergoing revascularization procedures. We describe a case of myocardial hibernation due to pulsatile compression of the coronary arteries by a ventricular pseudoaneurysm complicating mitral-valve replacement. After the pseudoaneurysm was repaired, ventricular function gradually returned to normal. Case Report A 67-year-old woman was admitted to our hospital for evaluation of a four-month history of . . .
Small rise in rubella cases triggers warning
Authors: J. Wise
Journal: BMJ (2013)

Last year saw the highest number of rubella cases in England and Wales since 1999. Although numbers are still small there is some concern that the disease could start to circulate more widely.

Health Protection Agency figures show that there were 65 laboratory confirmed cases of rubella in England and Wales in 2012,1 up from six confirmed cases in 2011, 12 in 2010, and nine in 2009. Fifty of the 65 cases in 2012 were reported from the south east of England, with most cases among recent immigrants. Data for 2013 are not yet available. The last large outbreak of rubella was in 1996, when close to 4000 cases were reported in England and Wales.

Pat Tookey, who leads the national congenital rubella surveillance programme at University College London’s Institute for Child Health, told the BMJ that the current outbreaks of measles in England and Wales …
Abstract 2386: Overexpression of 14-3-3ζ in mouse mammary gland promotes mammary tumor development and progression by enhancing multiple tumor-associated properties
Authors: Shau-Hsuan Li, Shannon L. Wyszomierski, Ping Li, Qingfei Wang, Sumaiyah K. Rehman, Yan Xiong, Jun Yang, Hua Guo, Siyuan Zhang, Dexing Fang, Daniel Medina, William J. Muller, Dihua Yu
Journal: Cancer Research (2011)

Abstract The 14-3-3 proteins are a family of evolutionarily conserved proteins ubiquitously expressed in eukaryotic organisms. 14-3-3 proteins interact with and regulate many different target proteins including oncoproteins and tumor suppressors. Previously, we found that 14-3-3ζ was overexpressed in &amp;gt;40% of human breast cancers and associated with poor clinical outcome of patients. We also showed that 14-3-3ζ contributed to the transformation of MCF10A non-transformed human mammary epithelial cells and multiple breast cancer cells in vitro. Here, to assess the oncogenic capacity of 14-3-3ζ in vivo, we generated transgenic mice with HA-tagged 114-3-3ζ overexpressed in the mammary epithelium, driven by either the whey acidic protein promoter (WAP-HA-14-3-3ζ) or the MMTV- LTR promoter (MMTV-HA-14-3-3ζ). Multiparous WAP-HA-14-3-3ζ transgenic mice developed hyperplastic lesions and showed an increased susceptibility to the induction of mammary tumors by the carcinogen, DMBA. Remarkably, MMTV-HA-14-3-3ζ mice developed mammary tumors with a median tumor latency of 662 days without DMBA treatment. WAP-HA-14-3-3ζ and MMTV-HA-14-3-3ζ mice crossed with MMTV-neu transgenic mice (WAP-ζ.neu and and MMTV-ζ.neu) exhibited accelerated neu-mediated mammary tumorigenesis and metastasis. Compared to the mammary tumors of MMTV-neu mice, 14-3-3ζ overexpression in bitransgenic mice tumors further increased cell proliferation, reduced apoptosis and enhanced angiogenesis. These data indicate that 14-3-3ζ overexpression in the mouse mammary gland promotes the development and progression of mammary tumors and that 14-3-3ζ, in cooperation with other oncogenic events, plays a causal role in mammary tumorigenesis and metastasis. 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 2386. doi:10.1158/1538-7445.AM2011-2386
PTU-193 A Novel, Rational Approach to Treating Primary Bile Acid Diarrhoea: a Proof of Concept Study of the FXR Agonist Obeticholic Acid
Authors: I Johnston, J D Nolan, T Dew, D Shapiro, J R Walters
Journal: Gut (2013)

<h3>Introduction</h3> Primary (idiopathic) bile acid diarrhoea (PBAD) is a common chronic diarrhoeal condition, affecting ~1% of the population, and a large proportion of patients otherwise diagnosed with IBS-D. We showed that the ileal hormone Fibroblast Growth Factor 19 (FGF19), which decreases hepatic bile acid (BA) synthesis, is reduced in this condition, resulting in excess BA production and faecal BA loss. FGF19 is secreted in response to the natural farnesoid X receptor (FXR) agonist chenodeoxycholic acid (CDCA). Obeticholic acid (OCA), 6-ethyl CDCA, is a semi-synthetic derivative with ~100x greater FXR agonist potency. We aim to determine the FGF19, BA and clinical response to OCA in PBAD patients. <h3>Methods</h3> After a 2-week run in period, 10 patients (7F:3M, median age 47, range 24–74) with PBAD (SeHCAT 7d retention &lt; 10%, median 4.8%), received oral OCA 25mg daily, for 2 weeks. Bile acid sequestrants were discontinued; loperamide was allowed as rescue therapy. Patients completed symptom diaries including stool frequency and Bristol Stool-form Scale (BSFS); a diarrhoea index ([stool frequency * mean BSFS] + loperamide use [weekly mg*3]) was calculated. Fasting serum FGF19 and total BA were measured before the first dose of OCA and after 2w treatment. Postprandial FGF19 and BA (6h area-under-curve, AUC) were determined after the first and last OCA dose. Data (expressed as medians) were analysed by Wilcoxon paired tests and Spearman correlation. <h3>Results</h3> OCA increased fasting FGF19 from 133 to 237 pg/ml (p = 0.007) at 2w. Most patients had an increase &gt; 60% in fasting FGF19 and a large OCA first dose/postprandial response. Fasting BA reduced from 1.5 to 0.9 µmol/l (p = 0.13) and postprandial BA AUC was lower after the 2 w OCA treatment (from 4.9 to 3.0 µmol/l, p = 0.02). Clinical improvements were found in all patients, including in stool frequency (23 to 14/wk, p = 0.02), BSFS (5.15 to 4.34, p = 0.05) and the diarrhoea index (113 to 76, p = 0.005). The reduction in BA AUC (p = 0.02) and the increase in fasting FGF19 (p = 0.03) both correlated with the reduction in stool frequency. Symptoms of abdominal pain, urgency and bloating also tended to be less on OCA treatment. OCA was well tolerated and no adverse events were reported of clinical concern. <h3>Conclusion</h3> This study has shown for the first time that rational therapy with the FXR agonist OCA in PBAD is well tolerated and effective, stimulating serum FGF19 and reducing postprandial BA, resulting in clinical improvements in stool frequency and type. We propose larger, randomised, controlled trials of OCA. [EudraCT 2011–003777–28] <h3>Disclosure of Interest</h3> None Declared.
Massive Cardiac Ga-67 Uptake in a Child With Pulmonary Hypertension, Heart Failure, and Bleeding
Authors: MOZAFAREDDIN K. KARIMEDDINI, MIGUEL A. SERPA, RICHARD P. SPENCER
Journal: Clinical Nuclear Medicine (1997)

A 3.5-year-old boy, who had hemoptysis and pulmonary hypertension, had massive radiogallium accumulation in the heart wall. The known causes of Ga-67 cardiomyopathic process uptake were reviewed.