tbuckley/cabot-search huggingface dataset:
Role of antioxidant vitamins in prevention of cardiovascular diseases
Authors: A. Ness, M. Egger, G. D. Smith, E. Lonn, S. Yusuf
Journal: BMJ (1999)

Trust wants help in formulating system to recognise performance of salaried GPsEditor-General practitioners (academic and non-academic) are still excluded from the merit award arrangements for consultants.We are therefore asking readers to help us formulate a system to recognise progress and performance for salaried general practitioners in our trust.We currently employ several general practitioners on the NHS consultant salary scale.They take part in the discretionary points system, but we would like now to develop detailed proposals by which they could progress through enhanced payments-wholly funded by the trustagainst meritorious criteria, which would be widely recognised and acknowledged.This would give them similar opportunities for recognition to those
Overproduction of IL-18 in the lungs induces IL-13 and IFN-g producing CD4+ T cell in the lungs, and results in airway hyperresponsiveness in Balb/c mice
Authors: Masanori Sawada, Tomoaki Hoshino, Yuki Sakazaki, Hanako Oda, Shinich Takenaka, Takashi Kinoshita, Haruki Imaoka, Tomotaka Kawayama, Hisamichi Aizawa
Journal: European Respiratory Journal (2011)

We newly established Balb/c background IL-18 transgenic (TG) mice using the human surfactant protein C promoter to drive expression of mature mouse IL-18 cDNA in the lungs. After sensitization on days 0 and 5 with ovalbumin (OVA), mice were challenged with OVA aerosol on day 19. Pulmonary inflammations and airway hyperresponsiveness (AHR) were examined on day 20. We previously reported that constitutive mouse mature IL-18 overproduction in the lungs of C57BL/6 mice induces emphysema (Am J Respir Crit Care Med 2007, 176:49-62). In contrast to C57BL/6 IL-18 TG mice, emphysematous changes were not observed in the lungs of Balb/c IL-18 TG mice. AHR to inhaled acetylcholine were not induced in non-treated Balb/c IL-18 TG mice. However, AHR and airway inflammation accompanied with CD4+ T cells, eosinophils and neutrophils were significantly and greatly increased in OVA-sensitized/challenged Balb/c IL-18 TG mice, when compared with OVA-sensitized/challenged WT Balb/c mice. Moreover, levels of IFN-g and IL-13 in the bronchoalveolar lavage fluid of OVA-sensitized/challenged Balb/c IL-18 TG mice were significantly elevated when compared with OVA-sensitized/challenged WT Balb/c mice. We used anti-CD4 mab or Balb/c IL-18 TG/IL-13 KO mice to examine the role of CD4+ T cells and IL-13 in this Balb/c IL-18 TG mouse. Anti-CD4 mab decrease the level of IL-13 and IFN-g. AHR and pulmonary inflammations were decreased in anti-CD4 mab or Balb/c IL-18 TG/IL-13 KO mice. This study suggested that overproducing IL-18 proteins in the lungs of Balb/c mice induce IL-13 and CD4+ T cells which may involve in the pathogenesis of asthma.
Long-term Use of Aspirin and Risk of Colorectal Cancer
Authors: Gregory C Vachon
Journal: JAMA (2005)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Potent inhibition of arterial intimal hyperplasia by TIMP1 gene transfer using AAV vectors
Authors: Genaro A Ramirez Correa, Serena Zacchigna, Nikola Arsic, Lorena Zentilin, Alessandro Salvi, Gianfranco Sinagra, Mauro Giacca
Journal: Molecular Therapy (2004)

Seminal to the process of arterial restenosis after balloon angioplasty is extracellular matrix degradation by metalloproteinases (MMPs); activity of these proteins is strongly inhibited by the tissue inhibitors of MMPs (TIMPs). Here we exploit gene transfer using an adeno-associated virus (AAV) for TIMP1 gene delivery in a rat model of intimal hyperplasia. High-titer AAV-Timp1 efficiently transduced human coronary artery smooth muscle cells (SMCs) in vitro and inhibited the capacity of these cells to migrate through a Matrigel barrier. In injured rat carotid arteries, AAV vectors were found to transduce SMCs efficiently and to maintain transgene expression for several weeks in vivo. In AAV-Timp1-transduced animals, the intima:media ratio of injured carotids was significantly reduced by 70.5% after 2 weeks, by 58.5% after 1 month, and by 52.4% after 2 months from treatment. The decrease in intimal hyperplasia was paralleled by a significant inhibition of collagen accumulation and by increased elastin deposition in the neointima, two findings that relate to the inhibition of MMP activity. These results indicate that AAV vectors are efficient tools for delivering genes to the arterial wall and emphasize the importance of MMPs for the generation of intimal hyperplasia. Local TIMP1 gene transfer might thus represent an efficient strategy to prevent restenosis.
Ireland's junior doctors urged to accept pay deal
Authors: Doug Payne
Journal: BMJ (2000)

The Irish Medical Organisation is urging non-consultant hospital doctors to accept a pay package that could be worth an additional £Ir20 000 (£15 900; $23 900) to each of the country's 3000 junior doctors.

The £Ir60m package includes £Ir45m to cover a new agreement on overtime. Until now, junior doctors have seen the rate they were paid decline in inverse proportion to the hours they worked. Under …
Abstract 414: Aberrant DNA methylation and expression of mRNA in EGFR-mutant lung cancer cell line with long-term exposure to gefitinib
Authors: Hideki Terai, Kenzo Soejima, Katsuhiko Naoki, Hiroyuki Yasuda, Takashi Sato, Daisuke Arai, Keiko Ohgino, Kota Ishioka, Aoi Kuroda, Tetsuo Tani, Ayano Ohashi, Makoto Nishino, Masayoshi Miyawaki, Junko Hamamoto, Tomoko Betsuyaku
Journal: Cancer Research (2014)

Abstract Many of the patients with non-small cell lung cancer (NSCLC) who initially responded well to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) will eventually relapse. The mechanisms of resistance to EGFR-TKIs is not yet fully clarified. The suppression of genes by DNA methylation is reported to be involved in the mechanism of tolerance to cytotoxic drugs. The purpose of this study is to identify epigenetically regulated genes and to clarify the contribution of epigenetic alteration to the acquired resistance to EGFR-TKI. We established gefitinib-resistant PC-9, which was originally gefitinib-sensitive lung cancer cell line, by serial long term exposure to gefitinib. We collected RNA and DNA from both gefitinib-sensitive and -resistant PC-9 cells and performed comprehensive analysis for DNA methylation and mRNA expression using infinium array and cDNA microarray, respectively. We identified 640 genes those DNA methylations were increased in gefitinib-resistant cell line compared to parental cell line. Then, we selected 29 candidate genes those mRNA expression were decreased in resistant PC-9. We are currently underway to elucidate the specific function of each gene and updated data will be presented at the meeting. Citation Format: Hideki Terai, Kenzo Soejima, Katsuhiko Naoki, Hiroyuki Yasuda, Takashi Sato, Daisuke Arai, Keiko Ohgino, Kota Ishioka, Aoi Kuroda, Tetsuo Tani, Ayano Ohashi, Makoto Nishino, Masayoshi Miyawaki, Junko Hamamoto, Tomoko Betsuyaku. Aberrant DNA methylation and expression of mRNA in EGFR-mutant lung cancer cell line with long-term exposure to gefitinib. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 414. doi:10.1158/1538-7445.AM2014-414
Arteriography for Lower Gastrointestinal Hemorrhage
Authors: Christina L. Jacovides, Gregory Nadolski, Steven R. Allen, Niels D. Martin, Daniel N. Holena, Patrick M. Reilly, Scott Trerotola, Benjamin M. Braslow, Lewis J. Kaplan, Jose L. Pascual
Journal: JAMA Surgery (2015)

Optimizing the nature and sequence of diagnostic imaging when managing lower gastrointestinal hemorrhage may reduce subsequent morbidity and mortality.To determine if preceding visceral arteriography with computed tomographic angiography (CTA) in acute lower gastrointestinal hemorrhage increases hemorrhage identification and localization and to determine if CTA was superior to nuclear scintigraphy when used as a pre-angiogram test.Analysis was conducted of prospectively acquired data from an interventional radiology database and of individual electronic medical records from an academic tertiary medical center. On January 1, 2009, a new, evidence-based, institutional protocol that formally incorporated CTA to manage acute lower gastrointestinal hemorrhage was launched after multidisciplinary consultation. All records of patients who underwent visceral angiography (VA) for acute lower gastrointestinal hemorrhage from January 1, 2005, to December 31, 2012, were evaluated.Imaging, procedural, and operative details were abstracted from the medical records of all patients who underwent VA for lower gastrointestinal hemorrhage.Visceral angiography results and efficacy were compared in patients before and after protocol implementation and compared based on which imaging method was used prior to angiography.A total of 161 angiographic procedures were performed during the study period (78 before and 83 after protocol implementation). Use of CTA increased from 3.8% to 56.6%, and use of nuclear scintigraphy decreased from 83.3% to 50.6% following protocol implementation (P < .001). Preceding angiography with CTA resulted in similar angiography contrast administration (mean [SD] amount for CTA prior to VA, 135 [63] vs 160 [77] mL; P = .18) and fluoroscopy time (mean [SD], 26.3 [16.8] vs 32.2 [34.9] minutes; P = .34). Although nuclear scintigraphy and CTA had similar sensitivity and specificity, localization of hemorrhage site by CTA was more precise and consistent with angiography findings. As a pre-angiography test, compared with nuclear scintigraphy, CTA reduced overall the number of imaging studies required (mean [SD] number per patient admission, 2.1 [0.3] vs 2.5 [0.8]; P = .005) and resulted in administration of more overall contrast (mean [SD], 220 [80] vs 130 [70] mL; P < .001) without worsening renal function.Preceding VA with a diagnostic study improves positive localization of the site of lower gastrointestinal hemorrhage compared with VA alone. Increasing the use of CTA for pre-angiography imaging may reduce overall imaging studies while appearing to increase positive yield at VA. Computed tomographic angiography can be used as part of a lower intestinal hemorrhage management algorithm and does not appear to worsen renal function despite the additional contrast load.
Impact of Intraprocedural Stent Thrombosis During Percutaneous Coronary Intervention
Authors: Philippe Généreux, Gregg W. Stone, Robert A. Harrington, C. Michael Gibson, Ph. Gabriel Steg, Sorin J. Brener, Dominick J. Angiolillo, Matthew J. Price, Jayne Prats, Laura LaSalle, Tiepu Liu, Meredith Todd, Simona Skerjanec, Christian W. Hamm, Kenneth W. Mahaffey, Harvey D. White, Deepak L. Bhatt
Journal: Journal of the American College of Cardiology (2013)
Molecular epidemiology of paediatric invasive pneumococcal disease in southern Spain after the introduction of heptavalent pneumococcal conjugate vaccine
Authors: I. Obando, L.A. Arroyo, D. Sánchez-Tatay, D. Tarragó, D. Moreno, W.P. Hausdorff, A.B. Brueggemann
Journal: Clinical Microbiology and Infection (2006)
Abstract 11558: Sitagliptin Attenuated Brain Damage and Cognitive Impairment in Mice With Chronic Cerebral Hypo-Perfusion Through Suppressing Oxidative Stress and Inflammatory Reaction
Authors: Tzu -Hsien Tsai, Sarah Chua, Jiunn-Jye Sheu, Steve Leu, Hon Kan Yip
Journal: Circulation (2014)

Background: Sitagliptin, a new anti-diabetic drug that inhibits dipeptidyl peptidase (DPP)-4 enzyme activity, has been reported to possess neuroprotective property. We tested the protective effect of sitagliptin against chronic cerebral hypoperfusion (CHP) in mice after bilateral carotid artery stenosis (BCAS). Methods: Thirty C57BL/6 mice were divided into three groups: Sham control (SC) (n=10), CHP (n=10), CHP-sitagliptin (orally 600mg/kg/day) (n=10). Working memory was assessed with novel-object recognition test. Magnetic resonance imaging (MRI) was performed at day 0 and day 90 after BCAS procedure prior to sacrifice. Results: Immunohistochemical (IHC) staining showed significantly enhanced microglia activation, astrocytosis, and demyelinating change of white matter in CHP group than in SC but the changes were significantly suppressed after sitagliptin treatment (all p&lt;0.01). The mRNA expressions of inflammatory (TNF-α, MCP-1and MMP-2) and apoptotic (Bax) biomarkers showed an identical pattern, whereas the anti-inflammatory (IL-10) and anti-apoptotic (Bcl-2) biomarkers showed an opposite pattern compared to that of IHC among all groups (all p&lt;0.01). The protein expressions of oxidative stress (NOX-I, NOX-II, nitrotyrosin, oxidized protein), inflammatory (NF-κB, TNF-α and MMP-2), apoptotic (mitochondrial Bax, cleaved PARP), and DNA-damage (γ-H2AX) markers showed an identical pattern, while expression pattern of anti-apoptotic marker (Bcl-2) was opposite to that of IHC (all p&lt;0.01). Glycogen-like peptide-1 receptor protein expression progressively increased from SC to CHP-sitagliptin (p&lt;0.01). The short-term working-memory loss and cortical-matter reduction on MRI-T2 showed a pattern identical to that of IHC in all groups (all p&lt;0.01). Conclusion: Sitagliptin protected against cognitive impairment and brain damage in a murine CHP model. Key words: chronic cerebral hypoperfusion, sitagliptin, oxidative stress inflammation
Abstract 1735: Discovery of novel and selective reversible inhibitors of EGFR containing the T790M drug resistance mutation with activity in vitro and in vivo
Authors: Gabriele Schaefer, Emily J. Hanan, Emily Chan, Lily Shao, Yuan Chen, Jamie Knight, Robert L. Yauch, Stephen Schmidt, Steven Sideris, Shiva Malek, Timothy P. Heffron
Journal: Cancer Research (2014)

Abstract Activating mutations in the epidermal growth factor receptor (EGFR) characterize a subset of non-small cell lung cancers (NSCLC) with exquisite sensitivity to tyrosine kinase inhibitors like erlotinib or gefitinib. However, after an initial dramatic response, patients harboring these mutations progress within 8-14 months on therapy. In approximately 60% of patients, the resistance to TKIs is associated with the acquisition of a secondary mutation within the EGFR kinase domain. The mutation in the kinase domain leads to the substitution of a bulky methionine for threonine at position 790 (T790M) also referred to as the gatekeeper residue. Using structure based-design we identified and optimized a series of non-covalent, and highly selective pyridinyl-aminopyrimidine inhibitors of EGFR containing the T790M drug resistant mutation that spared the wild-type EGFR enzyme. These pyridinyl-aminopyrimidine compounds potently inhibited phosphorylation of T790M containing EGFR in enzymatic assays and cell based assays. Strong inhibition of enzyme activity resulted in anti-proliferative activity in H1975 and PC9 erlotinib resistant cells but treatment with these molecules did not affect cell lines containing wild-type EGFR. Moreover, oral dosing of mice bearing either H1975 or PC9_erlotinib resistant xenograft tumors resulted in robust inhibition of tumor growth that was accompanied by profound and dose-dependent inhibition of EGFR activity as well as downstream signaling molecules such as ERK1/2 and AKT. These results suggest that these pyridinyl-aminopyrimidine inhibitors have the potential to benefit NSCLC patients who have developed resistance to first-generation EGFR inhibitors due to the acquisition of the T790M mutation, without the skin rash and gastrointestinal toxicity associated with wild-type EGFR inhibition. *EJH and GS contributed equally to this work. Citation Format: Gabriele Schaefer, Emily J. Hanan, Emily Chan, Lily Shao, Yuan Chen, Jamie Knight, Robert L. Yauch, Stephen Schmidt, Steven Sideris, Shiva Malek, Timothy P. Heffron. Discovery of novel and selective reversible inhibitors of EGFR containing the T790M drug resistance mutation with activity in vitro and in vivo. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1735. doi:10.1158/1538-7445.AM2014-1735
Abstract 14911: Development and Implantation of Tissue Engineered Self expandable Aortic Stent Grafts (bio Stent Grafts) Using In-body Tissue Architecture Technology in Beagles
Authors: Hidetake Kawajiri, Takeshi Mizuno, Takeshi Moriwaki, Ryosuke Iwai, Keiichi Kanda, Hitoshi Yaku, Yasuhide Nakayama
Journal: Circulation (2014)

Background:  Endovascular aortic repair became important treatment option, among aortic surgery with excellent outcomes. Although, endoleaks and migration remains as an issue to be mortified, and stent graft which assimilates to native aorta is desirable. We have developed autologous prosthetic tissues using “in-body tissue architecture” technology, which is a novel and practical approach based on the tissue encapsulation phenomenon of foreign materials in living bodies. Using this technology, we have fabricated the connective tissue covered stent grafts (bio stent grafts;BSGs), which is expected to show good biocompatibility.   Materials and Methods:  The preparation mold was assembled by insertion of an acryl rod (diameter: 8.6 mm, length: 40 mm) into a self-expanding nitinol stent (diameter: 9.0 mm, length: 35 mm). The molds (n=9) were embedded into the subcutaneous pouches of 3 beagles for 4 weeks. Upon trimming the excessive tissue and removing each rod, BSGs were obtained. Of 9 stent grafts, 3 were implanted to infrarenal abdominal aorta of the beagles via femoral artery. Aortogram and examination of aortic specimen was performed 30 days after implantation.   Results:  The stent strut was completely surrounded by the connective tissue membrane. (Fig. A) The graft wall of the BSG possessed an elastic modulus that was almost two times higher than that of the native beagle aorta. BSGs were delivered accurately to beagle’s abdominal aorta. After 30 days, stent graft assimilated to the native aorta, and neoendothelialization had occurred in all the luminal surface (Fig. B and C). In α-SMA staining of sections from the grafts, a number of SMA-positive cells (cherry red) were observed in the BSG wall and neointima(Fig.D).   Conclusions:  We developed and implanted a stent grafts (BSGs) using the in body tissue architecture technology. This BSG is expected to exhibit excellent biocompatibility after being implanted in the aorta, which might reduce the risk of endoleaks or migration.
Abstract 814: Novel aspirin based selenium compounds as therapy against pancreatic cancer
Authors: Deepkamal N. Karelia, Manoj K. Pandey, Daniel Plano, Shantu Amin, Arun K. Sharma
Journal: Cancer Research (2014)

Abstract Inflammation plays an important role in tumor growth promotion and has been linked to several human cancers. Evidences have demonstrated that inflammation has a high correlation with pancreatic cancer (PC) growth and promotion. An important mediator of inflammatory process is Cyclooxygenase 2 (COX-2) protein, which has been shown to be over-expressed in PC. Another major pathway which is crucial for inflammatory responses, cell proliferation, and resistance to apoptosis is the nuclear factor κB (NF-κB) pathway. It has been demonstrated that NF-κB pathway is responsible for drug resistance in PC. Aspirin, a well-known non-steroidal anti-inflammatory drug (NSAID), has been shown to have anti-cancer effects against PC. The mechanism of action of aspirin against PC is partially dependent on COX inhibition, as well as COX independent mechanism. Through extensive structure-activity relationship studies on Se-NSAID compounds, we have recently identified two Se-Aspirin compounds, ASD-43 and ASD-49, designed by incorporating selenium (Se) into salicylic acid structure, rendering it lethal to cancer cells. Previously, we had reported that Se-aspirin hybrid compounds were effective in different cancers, including PC. In this study we sought to evaluate the mechanism of action of these compounds in inhibiting the growth of PC. Since aspirin induces its effect partially by inhibiting COX, we hypothesized that these agents (ASD-43 and ASD-49) showed their anti-cancer activity by potently inhibiting COX activity as well as by modulating the inflammatory NF-κB pathway. Our studies, in Panc-1 cells, have shown that both ASD-43 and ASD-49 inhibited the degradation of IκB-alpha, which inhibits NF-κB from going into the nucleus, in presence of tumor necrosis factor (TNF). Upon treatment with ASD-43 and ASD-49, NF-κB regulated proteins like survivin and Bcl-xL expression was down regulated. Furthermore, a dose dependent induction of apoptosis in these cells was detected by activation of caspase-3 and PARP cleavage. Taken together, these results suggest that both ASD-43 and ASD-49 may represent potentially promising therapeutic agents for PC that induce apoptosis via the inhibition of COX and NF-κB pathways. Detailed investigations regarding the efficacy and mechanism of action of these compounds will be presented. Citation Format: Deepkamal N. Karelia, Manoj K. Pandey, Daniel Plano, Shantu Amin, Arun K. Sharma. Novel aspirin based selenium compounds as therapy against pancreatic cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 814. doi:10.1158/1538-7445.AM2014-814
Effects of Oral Salicylate on Serum Uric Acid Levels
Authors: G E PRICE, D K FORD
Journal: JAMA (1963)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal