tbuckley/cabot-search huggingface dataset:
Sickle-Cell Trait and Splenic Infarction Associated with High-Altitude Flying
Authors: Harold O. Conn
Journal: New England Journal of Medicine (1954)

THE danger of high-altitude flying to patients with sicklemia, until lately, has been more theoretical than.real. As recently as 1951 Margolies1 said that "the sickle cell trait is not a contraindication to high altitude flying." This statement was based principally on studies by Henderson and Thornell2 and Findlay, Boulter and MacGibbon,3 as well as on the fact that few published reports linked sickle-cell crisis with airplane flights.Sullivan4 (1950) described a young sicklemic patient who apparently had episodes of splenic infarction after each of two airplane flights over the Rocky Mountains; this was regarded as a chance occurrence. Recently, however, . . .
Case 15-2011
Authors: W.D. Francois Venter, Thumbi Ndung'u, Quarraisha Abdool Karim
Journal: New England Journal of Medicine (2011)

A 19-year-old woman was seen in a clinic in South Africa because of headache, fatigue, sore throat, anorexia, and vaginal discharge. She had no history of STIs. Rapid testing for HIV-1 was negative. The initial symptoms resolved, but a painful genital ulcer developed.
EG-04 * DEVELOPMENT OF HIGHLY POTENT, SELECTIVE BET BROMODOMAIN INHIBITORS THAT ARE CNS PENETRANT AND EFFECTIVE IN RODENT MODELS OF BRAIN CANCER
Authors: S. Johnstone, A. Johhnsone, C. Penas, V. Stathias, S. Brothers, N. Ayad, C. Wahlestedt, J. Albert
Journal: Neuro-Oncology (2014)

BRD2, BRD3, and BRD4 are members of the BET family of bromodomain inhibitors that have received intense current interest as novel treatments for cancer. The BET proteins function as epigenetic modulators that recognize specifically marked regions of histones and thereby influence gene transcription. Numerous highly potent, highly selective BET inhibitors have emerged and some (e.g. IBET-762) have advanced to clinical trials. We aimed to develop BET inhibitors as drug for untreatable forms of brain cancer including GBM (glioblastoma multiforme) and metastatic brain cancer. Unfortunately, we found that they are poorly suited as drugs for any indications that require high CNS drug exposure because they have high susceptibility to efflux transporters and low passive cellular permeability. To improve CNS penetration, we employed a structure-based design approach that involved (1) disrupting key transporter pharmacophore points and (2) altering the physical properties to improve cellular permeability. In this manner we have identified EP11313 which has strong potency (BRD4 IC50 7 nM), low efflux (ER <2), high passive cellular permeability (Papp 13.3 × 10−6 cm/s), moderate oral bioavailability in mouse (59%) and high CNS exposure. EP11313 (after daily drug administration for 3 weeks) shows antiproliferative effects in TMZ-resistant cancer patient stem cell lines and dose-dependent tumor reduction in nu/nu mice that were centrally transplanted with luciferase-expressing GBM cell xenografts.
Abstract 5529: Silencing H-ferritin by siRNA delivered by cationic liposomes increases chemotherapeutic sensitivity for treating malignant tumor
Authors: Xiaoli Liu, A.b. Madhankumar, Becky Slagle-Webb, Jonas M. Sheehan, Nodar Surguladze, James R. Connor
Journal: Cancer Research (2010)

Abstract Cancer cells have a robust appetite for iron to support their rapid growth and high metabolic rates. The high levels of iron uptake require a mechanism to limit iron induced oxidative damage. This function is the responsibility of ferritin; an intracellular iron storage protein. Ferritin has been found in the nucleus of tumor cells where it appears to protect DNA from iron induced oxidative damage and promote transcription. Therefore, we hypothesized that silencing H-ferritin gene expression could increase the sensitivity of malignant tumors to radiation and chemotoxins. Potentially targets of H-ferritin disrupted iron homeostasis in tumor cells result in proving effective at negatively affecting tumor growth. To test our hypothesis, H-ferritin siRNA was delivered to U251 human astrocytoma cells, malignant peripheral nerve sheath tumor (MPNST) cells and a breast cancer cell line (MCF-7) via our cationic liposomes. Western immunoblotting analysis demonstrated that the siRNA delivered in this manner decreased H-ferritin protein expression by 70 to 80% in all three cell lines within 48 hours. The results from SRB assay displayed decrease H-ferritin was associated with a decrease in the LD50 for carmustine (BCNU) from greater than 100 µM to 40 μM in the U251 cells, 30 µM in MCF7 cells and 18 µM in MPNST cells. In addition, the results of MTS assay revealed the presence of H-ferritin siRNA was associated with a 50% increase in cell death of U251 cells at 20 Gy of radiation. The in vivo efficacy of siRNA delivered by cationic-liposomes was tested in the Athymic nude mice subcutaneous glioma tumor model. Intratumoral injections of cationic liposomes containing H-ferritin siRNA reduced the required effective dose of BCNU for tumor suppression by more than 50%. The interaction of H-ferritin with DNA was investigated in vitro by supercoil relaxation assay, which demonstrated that H-ferritin maintained DNA in a relaxed form that would promote transcription of DNA even in the presence of radiation and chemotoxins. The outcome of study for Caspase-3 activity exposed that transfection with H-ferritin siRNA was associated with activation of apoptotic caspase pathway. Overall, our data demonstrated that silencing the H-ferritin gene appears to be an effective way to sensitize tumors to radiation and chemotherapy. As importantly, we have demonstrated that siRNA can be delivered effectively by cationic liposomes in an in vivo tumor model. 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 5529.
The sensorimotor and social sides of the architecture of speech
Authors: Giovanni Pezzulo, Laura Barca, Alessando D'Ausilio
Journal: Behavioral and Brain Sciences (2014)

Speech is a complex skill to master. In addition to sophisticated phono-articulatory abilities, speech acquisition requires neuronal systems configured for vocal learning, with adaptable sensorimotor maps that couple heard speech sounds with motor programs for speech production; imitation and self-imitation mechanisms that can train the sensorimotor maps to reproduce heard speech sounds; and a "pedagogical" learning environment that supports tutor learning.
Reply to Külling et al.
Authors: B. Walder, A. Riphaus, J. Dumonceau
Journal: Endoscopy (2011)

We thank Külling et al. for their interest in the Guidelines on nonanesthesiologist administration of propofol (NAAP) for gastrointestinal endoscopy, issued by the European Society of Gastrointestinal Endoscopy, the European Society of Gastroenterology and Endoscopy Nurses and Associates, and the European Society of Anaesthesiology [1] [2] [3].
Patients' Vs Oncologists' Perception of Supportive Care in Cancer: Results of the French National Panach Survey
Authors: J. Phelip, L. Vanlemmens, M.S. Dilhuydy, P. Artru, T. Bouillet, C. Audigier-Valette, F. Caroli-Bosc, H. Curé, G.M. Ganem, L. Greillier, P. Laplaige, A. Marre, P. Quittet, P. Rouby, F. Scotte
Journal: Annals of Oncology (2014)
FDG Uptake in a Huge Uterine Myoma
Authors: CHIA-HUNG KAO
Journal: Clinical Nuclear Medicine (2003)

From the Department of Nuclear Medicine and PET Center, China Medical College Hospital, Taichung, Taiwan Received for publication August 19, 2002. Accepted September 16, 2002. Reprint requests: Chia-Hung Kao, Department of Nuclear Medicine and PET Center, China Medical College Hospital, No. 2, Yuh-Der Road, Taichung 404, Taiwan. E-mail: [email protected]http://www.cmch.org.tw
Ga-67 Scan Findings in Bone Marrow Involvement with Plasmablastic Myeloma and Corresponding Tc-99m MIBI Images
Authors: WAN-YU LIN, SHYH-JEN WANG
Journal: Clinical Nuclear Medicine (2001)

From the Department of Nuclear Medicine, Taichung Veterans General Hospital, Taichung, Taiwan, Republic of China Received for publication March 5, 2001. Accepted June 18, 2001. Correspondence: Wan-Yu Lin, Department of Nuclear Medicine, Taichung Veterans General Hospital, 160 Taichung Harbor Road, Section 3, Taichung 40705, Taiwan. E-mail: [email protected]
A3.5 IL-13-mediated STAT6 dependant modulation of fibrosis and effects of MIR135B
Authors: S O’Reilly, M Chiechomska, F Oakley, J van Laar
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Background and objectives</h3> Systemic sclerosis is an autoimmune disease that is characterised by inflammation and fibrosis. Perivascular infiltrates of T cells are found in the skin and the T cell bias is predominantly Th2 with an increase of IL-13 in the skin and blood. We have found that Interleukin-13 (IL-13) is elevated and mediates increase deposition of ECM in SSc but the underlying molecular mechanism of IL-13 mediated ECM increases is unknown. The aim here was to investigate the molecular mechanism of IL-13 mediated ECM induction in dermal fibroblasts and to determine the role of miR135b, a miR with a putative role in IL-13 effects. <h3>Methods</h3> Dermal fibroblasts were taken from punch biopsies from healthy controls or SSc patients and cultured <i>in vitro</i> with or without the addition of recombinant IL-13. siRNA was carried out with 100nM of siRNA against STAT6 with scramble siRNA using DharmaFECT reagent. Collagen1A1, TIMP-1 and alphaSMa gene expression was analysed by qRT-PCR with 18S as the internal housekeeping gene for normalisation. miR135b mimics were transfected into dermal fibroblasts using DharmaFECT and a control miR was also transfected for comparison. Bleomycin was injected into mice to cause skin fibrosis or saline control for comparison and the mice were sacrificed and skin biopsies taken and immunohistochemistry was performed with specific IL-13 antibodies and florescent labelled secondary antibodies and imaged using confocal microscopy. <h3>Results</h3> IL-13 dose dependently increased the levels of collagen1A1 in dermal fibroblasts. However, there was no increase in the other pro fibrotic molecules TIMP-1 or the myofibroblast marker alpha smooth muscle actin by IL-13 by qPCR. Furthermore there was no increase in the pro fibrotic molecule TGF-β1. siRNA mediated silencing of STAT6 in dermal fibroblasts attenuated the induction of collagen1A1 mediated by IL-13 indicating STAT6 is crucial in this effect. Prediction software suggested that STAT6 has a binding site for miR135b in its 3'UTR and transfection of miR135b reduced STAT-6 mediated collagen induction in these cells. Measurement of miR135 post transfection confirmed that the miR was transfected into the cells. Bleomycin induced fibrosis in the mouse model was used and using immunohistochemistry it was found that in the skin IL-13 was elevated compared to vehicle treated mice, indicating T cell infiltration in this model of systemic sclerosis. <h3>Conclusions</h3> IL-13 utilises STAT6 to mediate induction of collagen in dermal fibroblasts. STAT6 is an important molecule in mediating fibrosis and is targeted by miR135b and elevated levels of miR135b diminishes STAT6-mediated effects in these cells. IL-13 from T cells is also elevated in bleomycin induced fibrosis models.
THE PROGNOSTIC VALUE OF PERCENTAGE TOTAL PLAQUE SCORE NORMALIZED TO AGE: A POTENTIAL MEASURE OF CORONARY ATHEROSCLEROSIS PROGRESSION
Authors: Chadi Ayoub, Yeung Yam, Li Chen, Punitha Arasaratnam, Siok Ping Lim, Graham Hillis, Clara Chow, Benjamin Chow
Journal: Journal of the American College of Cardiology (2015)
921 HEPATIC LYMPHOCYTE IMMUNOPHENOTYPING STUDIES IN PATIENTS WITH PRIMARY BILIARY CIRRHOSIS: IL-12 RECEPTOR-b2 EXPRESSION AND INFILTRATING INTRAHEPATIC T-REGULATORY CELLS
Authors: M. Blahova, S.M. Curbishley, D.H. Adams, G.M. Hirschfield
Journal: Journal of Hepatology (2013)
Abstract 3109: Wnt2 secreted by tumor fibroblasts promotes tumor growth and cell motility in esophageal carcinoma
Authors: Xin-Yuan Guan, Li Fu, Chunyu Zhang, Sui Sui Dong, Yan Li, Juan Chen
Journal: Cancer Research (2011)

Abstract Interaction between neoplastic and stromal cells plays an important role in the tumor progression. Recently, we found that Wnt2 was frequently overexpressed in fibroblasts isolated from tumor tissue (TFs) compared to fibroblasts from non-tumor tissue (NFs) in esophageal squamous cell carcinoma (ESCC). In the present study, we studied the effect of TF-secreted Wnt2 in ESCC development via the tumor-stroma interaction. Quantitative real-time PCR found that Wnt2 expression was about 4 folds higher in the TFs than the NFs. Interestingly, no visible protein expression of WNT2 was detected in all tested ESCC cancer cell lines and clinical ESCC samples. Immunohistochemistry study showed that WNT2(+) cells was were mainly detected in the boundary between stroma and tumor tissue or scattered within tumor tissue. Furthermore, Wnt2-positive ESCC (defined as 5 or more Wnt2(+) cells observed in 200× microscopy field) was detected in 22/51 cases, which was significantly associated with the lymph node metastases (P=0.001), advanced TNM stage (P=0.001) and disease-specific survival (P&amp;lt;0.0001). To further investigate the effect of secreted Wnt2 on ESCC cells, an in vitro Wnt2 secreting system was established using Chinese hamster ovary (CHO) cells and conditioned medium was collected for functional study. Functional assays demonstrated that secreted Wnt2 could promote cell growth and cell migration. Molecular study found that the cell growth promoting effect of Wnt2 was via activating Wnt/β-catenin signaling pathway and subsequently upregulating cyclin D1 and c-myc expression. Wnt2 could also induce epithelial-mesenchymal transition (EMT) and promote cell motility. In conclusion, our data demonstrate that TF-secreted Wnt2 can promote cell growth through activating the canonical Wnt/β-catenin signaling pathway and increase cell motility by inducing EMT in esophageal cancer cells. Further characterization of the effect of Wnt2 secreted by TF on cancer development and progression will reveal the molecular mechanisms of how TF provide cancer cells a suitable microenvironment and find new therapeutic targets for cancer treatment. 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 3109. doi:10.1158/1538-7445.AM2011-3109
Lifeline Wales: experience with a computerised kidney doner registry
Authors: J R Salaman, P J A Griffin, J Haines
Journal: BMJ (1994)

In the United Kingdom about 60 people per million of the population develop chronic renal failure each year and are accepted on to dialysis programmes, but barely half will receive kidney transplants.1 The shortage of donors is aggravated by the reluctance of relatives to consent to donation in one third of cases.2,3 Relatives seem unable to give consent when the donor's wishes are not known. To address this problem various attempts have been made within the United Kingdom to record the wishes of potential donors. Computer registries can retain such information long term and can operate as an extension to the donor card scheme without a change in the law. Lifeline Wales is the largest such scheme in the United Kingdom, and …
¿ES RENTABLE LA USE-PAAF EN TUMORES SUBMUCOSOS?, ¿DE QUE DEPENDE?
Authors: C Pons Vilardell, JB Gornals Soler, L Madrigal, C Consiglieri Alvarado, R Llatjos Sanuy, N Baixeras Gonzalez, I Catala Costa
Journal: Endoscopy (2013)

Introducción: El papel de la USE-PAAF en el manejo de los tumores submucosos o subepiteliales (TSM) sigue siendo controvertido por su limitada rentabilidad diagnóstica descrita en comparación con otras lesiones de distinta naturaleza. Objetivo: Evaluar el rendimiento diagnóstico de la USE-PAAF en los TSM y comparar los resultados según el calibre de agujas (22 o 19G) y tamaño de las lesiones. Material y Método: Revisión retrospectiva durante un periodo de 5 años, de pacientes con TSM que se realizó USE-PAAF en nuestra unidad. Variables analizadas: edad, sexo, características USE, número de pases, estudio cito y anatomopatológico. Se realizaron punciones con agujas 19G o 22G a criterio del ecoendoscopista. En el análisis de resultados citopatológicos se consideró: diagnóstico definitivo (IH), sugestivo (sin IH), satisfactorio (diagnóstico + sugestivo), no diagnóstico e insuficiente. Resultados: Se revisaron 62 pacientes (35 hombres; 65 ± 13.4 años). Seis excluidos por pérdida de seguimiento. Patrón de imagen USE: 7,1% hiperecoico, 42,9% isoecoico, 50% hipoecoico; 83,9% sin calcificaciones. Tamaño TSE: 19,6% < 20 mm. Aguja 19 G en 64,3%. Localización TSE: gástrico 73,2%, esófago 21,4%, duodeno 3,6%, recto1,8%. USE-PAAF diagnóstica en 51,8%, sugestivo en 17,9%, no diagnóstica en 30,4%. Representatividad de la lesión en 43/56. Número de pases: 1,75 (rango 1 – 3). Muestra satisfactoria en 58.9% con 19G, y 10,7% con 22G. Rentabilidad diagnóstica: 70,7% TSE gástricas y 75% esofágicas. Diagnóstico definitivo en 62,5% de TSM> 20 mm, siendo estadísticamente significativo en comparación al 7,1% de TSM < 20 mm (P = 0.021). En 16 casos se pudo comparar los resultados con la pieza quirúrgica o endoscópica, coincidiendo el diagnóstico en 13 (81,3%). Conclusiones: El rendimiento diagnóstico de la USE PAAF en TSM se incrementa en lesiones > 20 mm y con la utilización de agujas de mayor grosor.
PWE-020 Using microarray data to elucidate the molecular phenotype of a novel oncogene and identify a therapeutic strategy
Authors: C-A J Ong, N B Shannon, O M Rueda, R Hardwick, C Caldas, R C Fitzgerald
Journal: Gut (2012)

<h3>Introduction</h3> The incidence of esophageal and junctional adenocarcinoma has increased sixfold in the past 30 years. Despite aggressive chemotherapy and attempts at curative surgery, the 5-year survival rate remains at 20%. Unlike other epithelial cancers, targeted therapy is limited. We have identified TRIM44 as a putatative oncogene that is amplified in 8% of EA and 6% of breast cancers. <h3>Methods</h3> The aims of this project were to elucidate the molecular phenotype underlying the oncogenic role of TRIM44 as well as suggest ways to therapeutically target TRIM44 dysregulation. <h3>Results</h3> Using three microarray datasets representing EA (n=37, n=64) and breast (n=997) we performed gene set enrichment analysis to identify signalling pathways dysregulated with TRIM44 high expression (EA and breast) or amplification (breast only). High expression of TRIM44 was associated with over-enrichment of targets of the mTOR pathway consistent across all three data sets. This association was validated using expression microarrays in a cell line (HSC39) with amplification of TRIM44 treated with siRNA. Using phosphorylation of p70S6K as a readout of mTOR activity we validated the link between TRIM44 and the MTOR pathway; knockdown of TRIM44 using siRNA in HSC39 and a cell line with high expression of TRIM44 (JIMT-1) resulted in a decrease in pathway activity. The connectivity map (http://www.broadinstitute.org/cmap/), a collection of expression array data derived from lines treated with bioactive small molecules was queried using signatures generated from the microarray data representing genes positively or negatively associated with TRIM44 (breast, EA, HSC39+SiRNA datasets). The top consistent hits were sirolimus, an mTOR inhibitor and analogue of rapamycin and LY-294002, a PI3K inhibitor. These hits represent small molecules predicted to reverse the effects of high TRIM44 expression. Treatment with inhibitors in HSC39 and JIMT-1 demonstrated that these lines were highly sensitive (IC50&lt;30 nM) to rapamycin, but less sensitive to PI3K inhibition (IC50&gt;400 nM), consistent with a link at the level of mTOR. <h3>Conclusion</h3> We have demonstrated the ability to identify a previously unknown association between TRIM44 and the mTOR pathway using expression and copy number data. This phenotype was validated in cell line experiments and highlighted a potential therapeutic strategy using analogues of rapamycin, a small molecule inhibitor of the mTOR pathway, which are currently in clinical use as immunosuppressants and in clinical trials for other cancer types. <h3>Competing interests</h3> None declared.
298Myocardial fibrosis after acute myocardial infarction, a diffuse or a localized process? results in a swine model of reperfused anterior myocardial infarction
Authors: A Hervas, A Ruiz, E De Dios, MJ Forteza, C Bonanad, F Chaustre, C Gomez, G Minana, FJ Chorro, V Bodi
Journal: Cardiovascular Research (2014)

Purpose: Fibrosis plays a key role in the pathophysiology of left ventricular (LV) remodelling after myocardial infarction (MI). The dynamics of this process and whether it is a localized or diffuse phenomenon has not been totally clarified. We aimed to characterize these issues in a swine model of reperfused anterior MI. Methods: Swine were subjected by means of percutaneous balloon inflation to a transient 90-min occlusion of mid left anterior descending artery followed by 72-h (acute MI model) or 1-month (chronic MI model) reperfusion. The extent of fibrosis was macroscopically (triphenyltetrazolium staining, % of LV volume) and microscopically (Sirius red staining, % of field) quantified in the infarct, adjacent and remote areas as well as in controls. TGF-β1, collagen1-A1, A2 and 3A1 gene expression was determined. Results: Macroscopically, necrosis (16±5% in the acute MI model) and fibrosis (16±4% in the chronic MI model) were detected in all cases. Macroscopic fibrosis occurred in the infarct but not in the adjacent or remote areas (Figure). At microscopic level, in comparison with controls, fibrosis was only significantly increased in the chronic MI model at the infarct area (35±4%, p<0.001) but not in the acute MI model or in the adjacent and remote areas in the chronic MI model (<4% in all cases, p=ns, Figure). TGF-β1 (p<0.05, acute and chronic MI models, Figure) and collagen1-A1, A2 and 3A1 (p<0.001, chronic MI model) gene expression were significantly increased in the infarct but not in the adjacent or remote areas (p=ns).
What do directors of postgraduate education in general practice do?
Authors: J. Bahrami
Journal: BMJ (1999)

The regional adviser in general practice was born in about 1972,1and died, though not without a fight, in 1996. The sole intention of its creation was to supervise vocational training for general practice, a new system of training that had been introduced, amid much acrimony, to improve the quality of general practice. The regional adviser was seen as the key person to implement the voluntary scheme and influence the attitudes of those in general practice and hospitals who were less than enthusiastic about it. Indeed, it was not until 1981 that the voluntary vocational training became a mandatory requirement for entry into independent medical practice.

Did the regional advisers achieve what was expected of them? There is no doubt that, despite the absence of any tradition of structured training in general practice and sometimes hostile opinion of the profession, they succeeded in establishing a good foundation for today's vocational training.

Since 1972, the continual changes in practically every aspect of the NHS inevitably affected general practice education and training. These changes increased dramatically in the past decade, when the profession was suddenly faced with the paraphernalia of a market driven political ideology.2 In addition, the gradual changes in vocational training (dictated by the Joint Committee on Postgraduate Training for General Practice),3 emergence of higher professional education, work on reaccreditation and recertification, consequences of the General Medical Council's performance review procedure,4 and revised vocational training scheme regulations added to regional advisers” responsibilities. Not surprisingly, these new areas of responsibility affected the nature of the job …