tbuckley/cabot-search huggingface dataset:
AB0477 Ocular manifestations in patients with behçet’s disease
Authors: S. Toujani, L. Metoui, F. Ajili, I. Gharsallah, N. Ben Abdelhafidh, B. Louzir, S. Othmani
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Ocular complications of Behçet's disease are considered one of the major criteria upon which the diagnosis is based. <h3>Objectives</h3> The purpose of this study is to analyze clinical manifestations, treatment and prognosis of ocular Behçet's disease. <h3>Methods</h3> This retrospective study concerned 81 cases of Behçet's disease followed by internal diseases department. An ophtalmologic examination was practiced in all cases including visual acuity, fluorescein angiography and use of slit lamp biomicroscopy. <h3>Results</h3> Ocular manifestations was observed in 23 patients (28%). There were 21 men and 2 women. The mean age at onset was 26,7 years. Ocular involvment was the first manifestation of Behçet's disease in 11 cases (48%) but the mean Behçet's disease duration before ocular manifestations onset was 4 years and 3 months. The most common ocular manifestation was panuveitis noted in 10 cases, followed by anterior uveitis in 2 cases (associated with hypopyon in 1 case) and retinal vasculitis in 17 cases (74%). Before treatment, ocular complications were observed in 30% of patients dominated by catarct in 3 cases, retinal atrophy in 2 cases and ocular hypertension in 2 other cases. All patients were treated with oral corticoids. An initial high dose intravenous corticosteroid were indicated in 82%, immunosuppressive drugs in 52% (Cyclophosphamide in 11 cases, Ciclosporine in 6 cases and Azathioprine in 1 case) and biotherapy in 21% of cases (Infliximab and Rituximab). A decline in the ocular involvment of Behçet's disease was observed after a mean duration of 50,63 months. The incidence rate of ocular inflammatory attack was 1,5 per year and one case of death occured two months after the diagnosis. However, 16 affected eyes had an improvement of visual acuity with a mean of 5/10. <h3>Conclusions</h3> The ocular manifestations of Behçet's disease are one of the major criteria of both diagnosis and prognosis. It usually requires systemic medications including corticosteroids and immunosuppressive drugs. <h3>Disclosure of Interest</h3> None Declared
Dietary glycemic factors, insulin resistance, and adiponectin levels in acne vulgaris
Authors: Aslı Aksu Çerman, Ezgi Aktaş, İlknur Kıvanç Altunay, Janset Erkul Arıcı, Aysın Tulunay, Feyza Yener Ozturk
Journal: Journal of the American Academy of Dermatology (2016)
P5-02-03: Lipid Raft Disruption by Docosahexaenoic Acid Induces Apoptosis in Transformed Human Mammary Luminal Epithelial Cells Harboring HER-2 Overexpression.
Authors: GR Ravacci, None Tharcisio, T Junior, AF Logullo, RS Torrinhas, MM Brentani, DL Waitzberg
Journal: Cancer Research (2011)

Abstract Background, In HER-2 overexpressing breast cells, HER-2 receptors exist on the cell surface as monomers, homodimers and heterodimers with EGFR and HER-3. For signal activation and transduction to occur, the HER-2 receptors must be located in lipid rafts. Therefore, HER-2 overexpression must be accompanied by increased lipid rafts on the cell membrane to ensure constant signal transmission. Methods, To test this hypothesis, we used HB4a — untransformed human mammary epithelial cell strain — and HB4aC5.2 cells — HB4a cells co-transfected with ErbB-pJ5E.c-2 (normal full length human HER-2 cDNA). We analyzed the lipid rafts, cholesterol and fatty acids from cell membrane by confocal microscopy and gas chromatography. The proteins associated to HER-2 activity and lipid rafts formation, such as Akt, ERK ½ and FASN were analyzed by western blotting. To evaluate the lipid rafts importance for HER-2 signaling, we treated cells with docosahexaenoic acid (DHA) to disrupt the lipid rafts. Thereby, all analysis was repeated and cells death and apoptosis were analyzed by flow cytometry. Values were obtained by the mean and standard deviation of five independent experiments and developed in triplicate, by using one-way analysis of a variance (ANOVA) test, followed by Bonferroni post-test, to identify significant (p&amp;lt;0.05) differences between cell lines and results with different concentrations of DHA treatment. Results, HB4aC5.2 cells have five copies of pJ5E.c-ErbB-2 inserted into their genome and express approximately 900 times more HER-2 than HB4a cells. HER-2 overexpression in HB4aC5.2 cells was accompanied by increased lipid rafts in cell membranes, hyperactivation of downstream Akt and ERK1/2 proteins, and rate of cell growth increase as compared to the HB4a strain. In addition, HER-2 overexpression was associated to increased activation of FASN, a key enzyme involved in cellular lipogenesis. The final product of FASN activation, palmitate, is used to synthesize saturated phospholipids, necessary to form lipid rafts. Treatment of HB4aC5.2 cells with DHA, an omega-3 fatty acid, disrupted the lipid rafts by its increased incorporation into the cell membrane; inhibited HER-2 activation by decreasing Akt, ERK1/2, and FASN proteins; and induced apoptosis. The same treatment maintained the structure of HB4a cell lipid rafts, accompanied by a low percentage of DHA-induced apoptosis. Conclusion, Although little is yet known about lipid rafts, our data support the theory that disturbances in these micro-domains may represent a useful tool in controlling cell signaling triggered by HER-2 receptors and contribute to a better understanding of the role of this receptor in HER-2 positive breast cancer. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P5-02-03.
AB0184 Thrombospondin 1, an Antiangiogenic and Proapoptotic Factor, is Elevated in the Plasma of Patients with Antiphospholipid Syndrome
Authors: M.D. Patsouras
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Antiphospholipid syndrome (APS) is an acquired thombophillia characterized by recurrent thromboembolism and pregnancy morbidity. Thrombospondin (TSP-1) is a matricellular glycoprotein secreted by platelets upon activation with antiangiogenic and proapoptotic properties. Thrombospondin exerts its actions on endothelian cells through its receptors CD47 and CD36. The latter has already been shown to be involved in the activation of monocytes by antiphospholipid antibodies <h3>Objectives</h3> To investigate the involvement of thrombospondin 1 in the Antiphospholipid syndrome <h3>Methods</h3> The study involved patients fulfilling the diagnostic criteria of APS, a healthy control (n=46) and a disease control goup (SLE n=26). Plasma, serum and platelets were isolated from the above groups. Plasma and platelet intracellular TSP-1 levels were determined using an ELISA. <h3>Results</h3> APS patients had higher plasma levels of TSP-1 than the healthy control group and the SLE patients (APS: mean 390.0 ng/ml intarquartile range 95.90-437.7 ng/ml versus HC: 185.3 [46.3-236.6 ng/ml], p&lt;0.0001 and versus SLE: 153.0 [8.2-267.2 ng/ml], p=0.029). Moreover the plasma to intacellular levels ratio between APS and HC is not different suggesting not only platelet degranulation but overexpression as well. Regarding the clinical aspects of APS there was no statistically significant difference between patients with thromboembosism and pregnancy morbidity or between venous and arterial events. However, there was significant difference between the patients who had experienced miscarriages only (403.2 ng/ml) and those had both misacarriages and thrombosis (130.1 ng/ml). <h3>Conclusions</h3> Preliminary results suggest that APS patients have higher levels of TSP-1 in plasma and platelets overexpress TSP-1 suggesting a possible involment in thrombus formation and inhibition of angiogenesis that needs to be clarified. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.5473
FRI0032 Tophus formation limits neutrophil-induced inflammation
Authors: C. Schorn, Y. Zhao, C. Janko, G. Schett, M. Herrmann
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> In the presence of sodium uric acid precipitates as monosodium urate (MSU)<sup>1</sup>. In kidney and joints MSU induces renal calculi and gouty arthritis, respectively. The latter is characterized by red, hot and swollen arthritic joints and can be used as a model for neutrophil-mediated inflammation. After migration into the joint space and the synovial membrane neutrophil ingest MSU crystals and secret chemotactic mediators, intensifying the inflammation<sup>2</sup>. <h3>Objectives</h3> In our assays we compared the effect of monosodium urate crystals (MSU) on low density cell cultures, typical for the initial phase of tissue infiltration, with high density cell cultures, a hallmark for the late phase of tissue infiltration. <h3>Methods</h3> Human PMN (polymorphonuclear cells) were incubated with MSU crystals and analysed by fluorescence microscopy (DAPI). For measurements of reactive oxygen species (ROS) anticoagulated human blood was incubated with 10 μM DCFH-DA. After erythrocyte lysis the intracellular DCF-fluorescence of the leukocytes was recorded by flow cytometry. The cytokine production in culture supernatants of low density cell cultures (1-5 Mio/ml) and high density cell cultures (100 Mio/ml) was analysed by multiplex bead technology and quantified by cytofluorometry. Moreover, tophi were generated <i>in vitro</i> by incubation of high density cell culture of PMN with MSU for 30 minutes at 37°C. In addition, mice were treated intraperitoneally with MSU crystals resulting in generation of gouty tophi. Paraffin sections of murine and human tophi were analysed by nuclear staining and immunohistology. <h3>Results</h3> In the <i>in vitro</i> low density cell cultures (5 Mio/ml) we observed the ROS-dependent NETting of neutrophils induced by MSU crystals with massive cytokine and chemokine release. In contrast, in high density cell cultures (100 Mio/ml) and after <i>in vivo</i> injection of MSU into the peritoneum of mice gouty tophi are formed. The formation of the tophus <i>in vitro</i> is inhibited by DNase- 1 and EDTA treatment. Interleukin (IL)-8 and IL-1RA are released by the tophi whereas other cytokines and chemokines, exogenously added to the medium, are sequestered and degraded by the tophus. The disappearance of cytokines and chemokines is inhibited by PMSF, a serine protease inhibitor, and reduced by proteinase 3 inhibitors. <h3>Conclusions</h3> We conclude that individual NETting neutrophils act as pro-inflammatory stimulus by massive cytokine release, whereas tophi formed in areas of massive NETting are cytokine sinks that contribute to the resolution of inflammation by proteases. <h3>References</h3> Schorn, C., et al. Sodium overload and water influx activate the NALP3 inflammasome. J Biol Chem 286, 35-41 (2011) Ryckman, C., et al. Monosodium urate monohydrate crystals induce the release of the proinflammatory protein S100A8/A9 from neutrophils. J Leukoc Biol 76, 433-440 (2004). <h3>Disclosure of Interest</h3> None Declared
IMPACT OF CANGRELOR OVERDOSING ON BLEEDING COMPLICATIONS IN PATIENTS UNDERGOING PERCUTANEOUS CORONARY INTERVENTION: INSIGHTS FROM THE CHAMPION TRIALS
Authors: Dominick J. Angiolillo, Deepak Bhatt MD, Philippe Steg, Gregg Stone, Harvey White, C. Michael Gibson, Christian Hamm, Matthew Price, Jayne Prats, Tiepu Liu, Jonathan Day, Kenneth Mahaffey, Robert Harrington
Journal: Journal of the American College of Cardiology (2015)
Combinations of Antimicrobial Drugs: Trimethoprim-Sulfamethoxazole
Authors: Maxwell Finland
Journal: New England Journal of Medicine (1974)

The controversy over the use of multiple antimicrobial drugs has centered primarily on combinations supplied by pharmaceutical manufacturers in predetermined and fixed ratios and in dosage forms intended for systemic use. The subject has been discussed on several occasions by the American Medical Association's Council on Drugs1 , 2 and in these editorial columns,3 4 5 particularly since 1956. At that time a concerted effort was made by some manufacturers, with strong support from the then head of the Division of Antibiotics of the Food and Drug Administration,6 , 7 to promote certain antibiotic combinations, and this was openly and vigorously opposed by nearly all the . . .
CLINICAL OUTCOMES AFTER SINGLE CROSS-OVER BIORESORBABLE SCAFFOLD IMPLANTATION WITH OR WITHOUT SIDE BRANCH STRUTS DILATATION
Authors: Akihito Tanaka, Richard Jabbour, Hiroyoshi Kawamoto, Alaide Chieffo, Mauro Carlino, Matteo Montorfano, Azeem Latib, Antonio Colombo
Journal: Journal of the American College of Cardiology (2016)
The Sources of the SGR “Hole”
Authors: Ali Alhassani, Amitabh Chandra, Michael E. Chernew
Journal: New England Journal of Medicine (2011)

Interview with Michael Chernew on Medicare’s physician-payment system and the sustainable growth rate (SGR) formula. (00:00)Download In the sustainable growth rate system, Medicare physician-payment cuts apply evenly to all states, specialties, and services, though they've contributed differentially to service-volume increases. Which states and specialties have added the most to the SGR deficit?
Health minister will meet the BMA on staff shortages GP leaders want more doctors involved in commissioning Tobacco firms sign new deal on sports sponsorship MPs review how choices are made in the NHS
Authors: L. Beecham
Journal: BMJ (1995)

# Health minister will meet the BMA on staff shortages {#article-title-2}

Mr Gerald Malone, the minister for health, has agreed to meet representatives of the BMA to discuss the difficulties many hospitals face in recruiting sufficient junior hospital staff. The main difficulty is in accident and emergency departments. Some hospitals have asked patients to stay away unless absolutely necessary or to consult their general practitioners while others have warned that patients could expect long waits or that the casualty unit would have to close at night. In order to keep its casualty department open Peterborough NHS Trust is offering local general practitioners pounds sterling50 a hour—five times the rate that junior doctors would receive—to work in the department.

There are several reasons for the shortage of staff. The closure of some units, such as at St Bartholomew's Hospital in London, means more pressure on the units taking the extra patients. The Royal College of Surgeons has dropped accident and emergency as a specialty for the fellowship examination and junior doctors are choosing other specialties. At the end of 1994 the maximum number of contracted hours that junior doctors could work was reduced from 83 to 72, although the BMA believes that many junior doctors are still working more than 72hours. Junior doctors traditionally change jobs every February and August which has aggravated the problem.

Although the health minister said that the number of junior doctors had increased from 23875 in 1991 to over 27100, the Medical Manpower Standing Advisory Committee, chaired by Professor Sir Colin Campbell, is expected to report shortly that one in five junior doctors was not in practice five years after qualifying. One reason is the …
The Association between On-Site Cardiac Catheterization Facilities and the Use of Coronary Angiography after Acute Myocardial Infarction
Authors: Nathan R. Every, Eric B. Larson, Paul E. Litwin, Charles Maynard, Stephan D. Fihn, Mickey S. Eisenberg, Alfred P. Hallstrom, Jenny S. Martin, W. Douglas Weaver
Journal: New England Journal of Medicine (1993)

During the past decade the use of coronary angiography after acute myocardial infarction has substantially increased. Among the possible contributing factors, the increasing availability of cardiac catheterization facilities was the focus of our investigation.
Abstract 3426: A signature for epithelial to mesenchymal transition in lung adenocarcinoma
Authors: Mark Schliekelman, Ayumu Taguchi, Hong Wang, Qing Zhang, Chee-Hong Wong, Alice Chin, Adi Gazdar, Samir Hanash
Journal: Cancer Research (2011)

Abstract Identification of a molecular signature associated with epithelial to mesenchymal transition (EMT) may provide insight into the potential of a tumor to metastasize. To this effect we have undertaken a systems approach to understanding EMT with transcript and proteomic profiling of 30 lung adenocarcinoma cell lines. In-depth proteomic profiling was performed on conditioned media, cell surface and whole cell lysates from lung adenocarcinoma cell lines, allowing characterization as epithelial or mesenchymal based on their levels of E-cadherin and Vimentin, as well as cell morphology. Gene and protein expression from five cell lines that exhibited mesenchymal features were compared with five cell lines that exhibited epithelial features to identify proteins specifically associated with either a mesenchymal or epithelial phenotype. We identified protein signatures specific for mesenchymal or epithelial cells in the whole cell lysates, cell surface and conditioned media, with secreted proteins in the conditioned media representing the most distinct signature based on cluster analysis of protein expression. A much larger number of proteins were specific for epithelial cells than for mesenchymal, suggesting tighter regulation of expression in the epithelial cells. Networks of proteins associated with cell motion, extracellular matrix and growth regulation were identified that were distinct for mesenchymal cell lines while epithelial cell lines exhibited networks of proteins associated with metabolism and cell adhesion. Gene expression analysis of these cell lines supports the observations of tighter gene regulation in epithelial cells as well as the identified protein networks. Identification of a protein signature for EMT provides further understanding of a critical step in tumor progression and has the potential to yield biomarkers to assess likelihood of tumor metastasis in lung adenocarcinoma. 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 3426. doi:10.1158/1538-7445.AM2011-3426
Abstract 4767: C6 ceramide sensitizes multiple aggressive pancreatic cancer cell lines to gemcitabine, paclitaxel and cetuximab mediated anti tumor effects <i>in vivo</i> and <i>in vitro</i>
Authors: Harold J. Wanebo, Shan Lu, Cao Cong, David Shrayer, Yinsheng Wan, Wayne Bowen
Journal: Cancer Research (2011)

Abstract Introduction: Pancreatic adenocarcinoma continues to be a highly lethal malignancy (5 yr survival 5%) poorly responsive to all chemo radiation therapies, with only modest improvement with Gemcitabine the current “main line” drug. We have previously demonstrated the C6 Ceramide chemo enhancement of Gemcitabine and other pancreatic chemo agents. The current study explores the mechanism of C6 Ceramide effects on pancreatic chemo resistance pathways – pro-survival and ras-signaling in pancreatic cancer cells. Methods: In vivo: 2-3 month SCID male mice with pancreatic (pan) tumor implants (2 × 106 L3.6 cells) received intraperitoneal (I.P.) injections (3x/wk) of Paclitaxel (Pax) (3.0mg/gm), Gemcitabine (Gem, 10mg/gm) with/without C6 ceramide (10mg/ml) and were observed 6 weeks and tumor response/survival recorded. In vitro: Drug dose Pax 3 ug/ml, Gem 3 ug/ml, C6 Ceramide 10 ug/ml. The MTT anti tumor response was measured in 3 pancreatic lines L3.6, PANC-1, and MIA (Kras mutated). Signaling activation by Western blot utilized antibodies: LY294002, and Wortmannin to block PI3K/AKT pathway, U0126 and PD 98059 to block ERK pathway and Rapamycin to block mTORC1 pathway. Results: Combined therapy with C6 Ceramide induced significant inhibition of exponential tumor growth and prolonged survival by Gem and Pax. Administration of Gem or Pax with C6 Ceramide induced a significant increase in cell death and apoptosis in pancreatic cancer cells (L3.6, PANC-1 and MIA PaCa-2) which were associated with inhibiting perturbations of cell signaling pathways including pro-survival PI3K/Akt/mTOR, and ERK/MAPK, Ras signaling pathways. Pharmacological inhibition with specific signaling pathway inhibitors enhanced cytotoxicity by Gem or Pax, suggesting that survival pathway inhibition might be the key mechanism contributing to C6 Ceramide synergism of Pax or Gem anti-tumor effects. We also showed C6 ceramide potentiation of Cetuximab anti tumor effects on Kras mutant MIA cells thus overcoming (EGFR mAb) resistance by inhibiting pro-survival PI3K/AKT/mTOR pathways and bypassing K-RAS mutant Ras-ERK pathways. Conclusion: C6 Ceramide an apoptosis signal potentiates the anti tumor effects of chemo agents Gemcitabine and Paclitaxel and the biologic EGFR Inhibitor Cetuximab against 3 aggressive pancreatic cancer cell lines by apparent inhibition of the pro-survival PI3K/AKT/mTOR pathways and the Kras mutated ERK/MAPK pathway. 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 4767. doi:10.1158/1538-7445.AM2011-4767
Abstract 4542: The design, synthesis and <i>in vitro</i> evaluation of selective FR α and β and PCFT substrates with potent GARFTase inhibitory activity as antitumor agents
Authors: Aleem Gangjee, Lei Wang, Christina Cherian, Sita Kugel Desmoulin, Zhanjun Hou, Roy L. Kisliuk, Larry H. Matherly
Journal: Cancer Research (2010)

Abstract Three folate transporters, the reduced folate carrier (RFC), folate receptors (FR) and the proton-coupled folate transporter (PCFT) account for most of the folate influx activity in mammalian cells. Lack of selectivity for folate transporters is one of the major causes of chemotherapy failure with antifolate drugs. We recently reported the potent glycinamideribonucleotide formyltransferase (GARFTase) inhibitory activity of a series of classical 2-amino-4-oxo-6-substituted pyrrolo[2,3-d]pyrimidines with a thienoyl for benzoyl-substituted side chain with FR and PCFT specificity over RFC. In an attempt to optimize for selective transport by FR and PCFT, and GARFTase inhibitory activity, a furan for benzoyl-substituted side chain analog with a 4-carbon bridge was synthesized. The target compound was tested against KB human tumor cells that express FR alpha, human RFC, and human PCFT using a fluorescence-based cytotoxicity screen, and showed remarkably potent subnanomolar inhibitory activity (IC50 of 0.29 nM). The furan analog was further tested in isogenic Chinese hamster ovary sublines, engineered to express human FR alpha (RT-16), FR beta (D4), hRFC (pC43-10), or hPCFT (R2/hPCFT4). The furan side chain compound again showed a subnanomolar IC50s for both FR alpha and FR beta expressing cells (IC50 of 0.16 nM for RT16, and 0.92 nM for D4). Thus, in comparison with the lead thienoyl side chain compound (IC50 of 2 nM for RT16, and 0.75 nM for D4), the furan analog exhibited similar activities toward FR beta, but a 12.5-fold increased activity toward FR alpha. For PCFT-expressing R2/hPCFT4 cells, the furan side chain compound (IC50 of 439 nM) was about 10-fold less potent than the thienoyl analog (IC50 of 43.4 nM). The furan analog was inactive against human dihydrofolate reductase (hDHFR) or human thymidylate synthase (hTS) (IC50 &amp;gt;10−5 M), suggesting that neither hDHFR nor hTS is a principal target. Metabolite protection from in vitro cytotoxicity in KB cells showed that thymidine (10 μM) did not affect the growth inhibitory effects of the furan analog whereas adenosine (60 μM) and 5-amino-4-imidazolecarboxamide (320 μM) were completely protective, identifying GARFTase as the likely intracellular target. Our results indicate that the side chain heterocyclic ring may control the transport selectivity for both FR and PCFT of the pyrrolo[2,3-d]pyrimidines. 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 4542.