tbuckley/cabot-search huggingface dataset:
Effect of Dietary Omega-3 and Omega-6 Fatty Acids on Development of Azaserine-Induced Preneoplastic Lesions in Rat Pancreas
Authors: T. P. O'Connor, B. D. Roebuck, F. J. Peterson, B. Lokesh, J. E. Kinsella, T. C. Campbell
Journal: JNCI Journal of the National Cancer Institute (1989)

We examined the effect of varying the ratio of dietary omega-3 (ω3) to omega-6 (ω6) on the development of pancreatic preneoplastic lesions in male Wistar rats given azaserine at 14 days of age. As the ratio of dietary ω 3 to ω 6 fatty acids increased in a diet totaling 20% by weight of fat, the development of preneoplastic atypical acinar cell nodules (AACNs) at 4 months after dosing with azaserine decreased significantly. In addition, serum levels of prostaglandin thromboxane B2, prostaglandin E2, and 6-keto-prostaglandin F1α decreased significantly. The fatty acid composition of the rbc membrane was also significantly influenced by the ratio of dietary ω 3 to ω 6 fatty acids. In a second experiment, we examined the effect of dietary intervention with a different type of fat (corn oil or menhaden oil) 2 months into the 4-month postdosing period on AACN development at the end of the post-dosing period. Intervention of the ω 6 fatty acid-rich diet with the ω 3 fatty acid-rich diet significantly decreased focal development. The opposite was true when intervention involved substituting the ω 3 fatty acid-rich diet with the ω6 fatty acid-rich diet. [J Natl Cancer Inst 81:858–863, 1989]
Regulation of pulmonary fibrosis by chemokine receptor CXCR3
Authors: Dianhua Jiang, Jiurong Liang, Jennifer Hodge, Bao Lu, Zhou Zhu, Shuang Yu, Juan Fan, Yunfei Gao, Zhinan Yin, Robert Homer, Craig Gerard, Paul W. Noble
Journal: Journal of Clinical Investigation (2004)

CXC chemokine receptor 3 (CXCR3) is the receptor for the IFN-γ–inducible C-X-C chemokines MIG/CXCL9, IP-10/CXCL10, and I-TAC/CXCL11. CXCR3 is expressed on activated immune cells and proliferating endothelial cells. The role of CXCR3 in fibroproliferation has not been investigated. We examined the role of CXCR3 in pulmonary injury and repair in vivo. CXCR3-deficient mice demonstrated increased mortality with progressive interstitial fibrosis relative to WT mice. Increased fibrosis occurred without increased inflammatory cell recruitment. CXCR3 deficiency resulted in both a reduced early burst of IFN-γ production and decreased expression of CXCL10 after lung injury. We identified a relative deficiency in lung NK cells in the unchallenged CXCR3-deficient lung and demonstrated production of IFN-γ by WT lung NK cells in vivo following lung injury. The fibrotic phenotype in the CXCR3-deficient mice was significantly reversed following administration of exogenous IFN-γ or restoration of endogenous IFN-γ production by adoptive transfer of WT lymph node and spleen cells. Finally, pretreatment of WT mice with IFN-γ–neutralizing Ab's enhanced fibrosis following lung injury. These data demonstrate a nonredundant role for CXCR3 in limiting tissue fibroproliferation and suggest that this effect may be mediated, in part, by the innate production of IFN-γ following lung injury.
A Retinoic Acid—Rich Tumor Microenvironment Provides Clonal Survival Cues for Tumor-Specific CD8+ T Cells
Authors: Yanxia Guo, Karina Pino-Lagos, Cory A. Ahonen, Kathy A. Bennett, Jinshan Wang, Joseph L. Napoli, Rune Blomhoff, Shanthini Sockanathan, Roshantha A. Chandraratna, Ethan Dmitrovsky, Mary Jo Turk, Randolph J. Noelle
Journal: Cancer Research (2012)

While vitamin A has been implicated in host resistance to infectious disease, little is known about the role of vitamin A and its active metabolite, retinoic acid (RA) in host defenses against cancer. Here, we show that local RA production within the tumor microenvironment (TME) is increased up to 5-fold as compared with naïve surrounding tissue, with a commensurate increase in RA signaling to regionally infiltrating tumor-reactive T cells. Conditional disruption of RA signaling in CD8(+) T cells using a dominant negative retinoic acid receptor α (dnRARα) established that RA signaling is required for tumor-specific CD8(+) T-cell expansion/accumulation and protective antitumor immunity. In vivo analysis of antigen-specific CD8(+) T-cell responses revealed that early T-cell expansion was RA-independent; however, late T-cell expansion and clonal accumulation was suppressed strongly in the absence of RA signaling. Our findings indicate that RA function is essential for the survival of tumor-reactive CD8(+) T cells within the TME.
TRICHOMONIASIS AND THE DERMATOLOGIST
Authors: G.W. Csonka
Journal: British Journal of Dermatology (1974)

Journal Article TRICHOMONIASIS AND THE DERMATOLOGIST Get access G.W. Csonka G.W. Csonka Watford General Hospital, Shrodells Wing, Vicarage Road, Watford Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 90, Issue 6, 1 June 1974, Pages 713–714, https://doi.org/10.1111/j.1365-2133.1974.tb06703.x Published: 01 June 1974
Inhibition of mitochondrial permeability transition pore opening: translation to patients
Authors: L. Gomez, B. Li, N. Mewton, I. Sanchez, C. Piot, M. Elbaz, M. Ovize
Journal: Cardiovascular Research (2009)

A large body of experimental evidence indicates that during an acute myocardial infarction (AMI), tissue injury occurring after reperfusion represents a significant amount of the whole, irreversible damage. It is now recognized that mitochondrial permeability transition pore opening plays a crucial role in this specific component of myocardial infarction. Ischaemic postconditioning and cyclosporine A (CsA) have been shown to dramatically reduce infarct size in many animal species. Recent proof-of-concept clinical trials support the idea that lethal myocardial reperfusion injury is also of significant importance in patients with ongoing AMI, and that targeting mitochondrial permeability transition by either percutaneous coronary intervention postconditioning or CsA can reduce infarct size and improve the recovery of contractile function after reperfusion. Large-scale trials are ongoing to address whether these new treatments may improve clinical outcome in reperfused AMI patients.
Radiofrequency Ablation in Barrett's Esophagus with Dysplasia
Authors: Nicholas J. Shaheen, Prateek Sharma, Bergein F. Overholt, Herbert C. Wolfsen, Richard E. Sampliner, Kenneth K. Wang, Joseph A. Galanko, Mary P. Bronner, John R. Goldblum, Ana E. Bennett, Blair A. Jobe, Glenn M. Eisen, M. Brian Fennerty, John G. Hunter, David E. Fleischer, Virender K. Sharma, Robert H. Hawes, Brenda J. Hoffman, Richard I. Rothstein, Stuart R. Gordon, Hiroshi Mashimo, Kenneth J. Chang, V. Raman Muthusamy, Steven A. Edmundowicz, Stuart J. Spechler, Ali A. Siddiqui, Rhonda F. Souza, Anthony Infantolino, Gary W. Falk, Michael B. Kimmey, Ryan D. Madanick, Amitabh Chak, Charles J. Lightdale
Journal: New England Journal of Medicine (2009)

Barrett's esophagus, a condition of intestinal metaplasia of the esophagus, is associated with an increased risk of esophageal adenocarcinoma. We assessed whether endoscopic radiofrequency ablation could eradicate dysplastic Barrett's esophagus and decrease the rate of neoplastic progression.
Lysine-Specific Demethylase 1 Is Strongly Expressed in Poorly Differentiated Neuroblastoma: Implications for Therapy
Authors: Johannes H. Schulte, Soyoung Lim, Alexander Schramm, Nicolaus Friedrichs, Jan Koster, Rogier Versteeg, Ingrid Ora, Kristian Pajtler, Ludger Klein-Hitpass, Steffi Kuhfittig-Kulle, Eric Metzger, Roland Schüle, Angelika Eggert, Reinhard Buettner, Jutta Kirfel
Journal: Cancer Research (2009)

Aberrant epigenetic changes in DNA methylation and histone acetylation are hallmarks of most cancers, whereas histone methylation was previously considered to be irreversible and less versatile. Recently, several histone demethylases were identified catalyzing the removal of methyl groups from histone H3 lysine residues and thereby influencing gene expression. Neuroblastomas continue to remain a clinical challenge despite advances in multimodal therapy. Here, we address the functional significance of the chromatin-modifying enzyme lysine-specific demethylase 1 (LSD1) in neuroblastoma. LSD1 expression correlated with adverse outcome and was inversely correlated with differentiation in neuroblastic tumors. Differentiation of neuroblastoma cells resulted in down-regulation of LSD1. Small interfering RNA-mediated knockdown of LSD1 decreased cellular growth, induced expression of differentiation-associated genes, and increased target gene-specific H3K4 methylation. Moreover, LSD1 inhibition using monoamine oxidase inhibitors resulted in an increase of global H3K4 methylation and growth inhibition of neuroblastoma cells in vitro. Finally, targeting LSD1 reduced neuroblastoma xenograft growth in vivo. Here, we provide the first evidence that a histone demethylase, LSD1, is involved in maintaining the undifferentiated, malignant phenotype of neuroblastoma cells. We show that inhibition of LSD1 reprograms the transcriptome of neuroblastoma cells and inhibits neuroblastoma xenograft growth. Our results suggest that targeting histone demethylases may provide a novel option for cancer therapy.
Genomewide Association Analysis of Coronary Artery Disease
Authors: Nilesh J. Samani, Jeanette Erdmann, Alistair S. Hall, Christian Hengstenberg, Massimo Mangino, Bjoern Mayer, Richard J. Dixon, Thomas Meitinger, Peter Braund, H.-Erich Wichmann, Jennifer H. Barrett, Inke R. König, Suzanne E. Stevens, Silke Szymczak, David-Alexandre Tregouet, Mark M. Iles, Friedrich Pahlke, Helen Pollard, Wolfgang Lieb, Francois Cambien, Marcus Fischer, Willem Ouwehand, Stefan Blankenberg, Anthony J. Balmforth, Andrea Baessler, Stephen G. Ball, Tim M. Strom, Ingrid Brænne, Christian Gieger, Panos Deloukas, Martin D. Tobin, Andreas Ziegler, John R. Thompson, Heribert Schunkert
Journal: New England Journal of Medicine (2007)

Modern genotyping platforms permit a systematic search for inherited components of complex diseases. We performed a joint analysis of two genomewide association studies of coronary artery disease.
US physician group calls for expanded role for telemedicine in medical practice
Authors: Michael McCarthy
Journal: BMJ (2015)

The American College of Physicians (ACP) has strongly endorsed the use of telemedicine in clinical practice in a new position paper.1 “The use of these technologies has been shown to increase patient satisfaction while delivering care that is similar in quality to, and in some cases more efficient than, in-person care and support. Research shows that telemedicine can potentially reduce costs, improve health outcomes, and increase access to primary and specialty care,” the paper said.

The college, which represents internists and internal medicine sub-specialists, …
Chemokine drives tuberculosis
Authors: Heather L. Van Epps
Journal: The Journal of Experimental Medicine (2005)

High levels of the chemokine monocyte chemoattractant protein-1 (MCP-1) give tuberculosis (TB) the upper hand, according to a population study on page 1649. Flores-Villanueva and colleagues show that individuals whose cells are genetically programmed to produce copious amounts of MCP-1 are more likely to develop active disease when infected with Mycobacterium tuberculosis.






Figure 

Tuberculosis patients homozygous for the MCP-1 –2518G allele (GG) have the highest plasma levels of MCP-1.




Infections with M. tuberculosis, the causative agent of TB, are on the rise; an estimated eight million new infections and two million TB-induced deaths occur annually. But not all people who are exposed to M. tuberculosis become ill—a phenomenon largely attributed to genetic differences that make some individuals more susceptible to disease than others. Indeed, a recent study identified a region on chromosome 17 that was linked to increased susceptibility to active tuberculosis, although the exact gene(s) responsible for this effect was not identified.

Flores-Villanueva and colleagues now show that a polymorphism in the promoter of the MCP-1 gene, which resides on chromosome 17, is the likely culprit of this increased susceptibility. In a group of infected individuals from Mexico, this polymorphism (-2518G) was five times more prevalent in patients with active TB than in those who remained healthy. This polymorphism was previously shown to cause increased expression of the MCP-1 protein.

MCP-1 is an attractant for monocytes and T cells, two cell types that help to form the granulomas that contain the bacteria, and is thus thought to help orchestrate the initial response to M. tuberculosis infection. But extremely high levels of MCP-1 can inhibit the expression of interleukin (IL)-12, a cytokine primarily produced by dendritic cells and monocytes that is required to activate antibacterial effector cells. Indeed, monocytes isolated from patients homozygous for the -2518G allele produced high levels of MCP-1 and low levels of IL-12 when stimulated with M. tuberculosis extracts.

In an accompanying commentary (page 1617), Alcais and colleagues note that the presence of the -2518G susceptibility allele in approximately half of the Mexican population means that, in the absence of other genetic factors, the attributable risk of this mutation for developing disease could exceed 60%—the largest genetic impact on adult TB ever described.
Treatment of Experimental Asthma by Decoy-mediated Local Inhibition of Activator Protein-1
Authors: Christophe Desmet, Philippe Gosset, Emmanuelle Henry, Virginie Garzé, Pedro Faisca, Nanda Vos, Fabrice Jaspar, Dorothée Mélotte, Bart Lambrecht, Daniel Desmecht, Bernard Pajak, Muriel Moser, Pierre Lekeux, Fabrice Bureau
Journal: American Journal of Respiratory and Critical Care Medicine (2005)

Asthma is associated with increased expression of a typical array of genes involved in immune and inflammatory responses, including those encoding the prototypic Th2 cytokines interleukin (IL) 4, IL-5, and IL-13. Most of these genes contain binding sites for activator protein-1 (AP-1) within their promoter and are therefore believed to depend on AP-1 for their expression, suggesting that this transcription factor could be of particular importance in asthma pathophysiology.To clarify the role of AP-1 in the effector phase of pulmonary allergy.Ovalbumin (OVA)-sensitized mice were intratracheally given decoy oligodeoxyribonucleotides (ODNs) specifically directed to AP-1 or scrambled control ODNs before challenge with aerosolized OVA. Twenty-four hours after the last OVA challenge, airway hyperresponsiveness was measured and allergic airway inflammation was evaluated quantitatively. AP-1 decoys were localized using flow cytometry and immunohistochemistry. AP-1 activity in the lung was assessed using electrophoretic mobility shift assay.Intratracheally delivered AP-1 decoys efficiently targeted airway immune cells, thus precluding AP-1 activation on OVA challenge. Decoy-mediated local inhibition of AP-1 resulted in significant attenuation of all the pathophysiologic features of experimental asthma-namely, eosinophilic airway inflammation, airway hyperresponsiveness, mucous cell hyperplasia, production of allergen-specific immunoglobulins, and synthesis of IL-4, IL-5, and IL-13. Scrambled control ODNs had no detectable effects.Our results reveal a key role for AP-1 in the effector phase of pulmonary allergy and indicate that specific AP-1 inhibition in the airways may have therapeutic value in the control of established asthma.
PWE-073 Colonoscopy for a family history of colorectal cancer: are we screening “the worried well”?: Abstract PWE-073 Table 1
Authors: A K Hunt, S Qiu, Z Mohamed, I Beveridge, C E Collins, J Mawdsley, K Sundaram, K J Monahan
Journal: Gut (2012)

<h3>Introduction</h3> The British Society of Gastroenterology (BSG) updated guidelines for colonoscopic screening of people with family history (FH) of colorectal cancer (CRC) in 2010. In the UK, most patients anxious about their FH of CRC are referred by primary care doctors to non-specialist hospitals. Previous studies indicate guideline adherence is poor with significant clinical, medico-legal, and resource implications. <h3>Methods</h3> Our study analysed adherence to the 2010 BSG guidelines in a district general hospital (catchment population of 300 000). Observational data were collected from all colonoscopies in which FH was the primary indication over a 16-month period from guideline publication up to April 2011 at our centre. <h3>Results</h3> Of the 91 cases found (mean age 49.1 years, range 24.7–73.2), there were 11 high, 24 high moderate and 20 low moderate risk cases identified. 36 were low risk and did not fulfil criteria for initial colonoscopic screening. The 55 within guideline were screened on average 4.0 years early (p&lt;0.0002; paired T test; 0–24.2 years early), with 18 cases screened early. 17 of the 91 cases were offered unnecessary follow-up colonoscopies. Yield for polyps and CRC was significantly lower in screened individuals (16/91 (18%)) compared to patients offered colonoscopies for other indications during the same period (246/838 (25%); p=0.018; χ<sup>2</sup> test). Referrers recorded “reassurance” in 29 cases as a factor for screening. <h3>Conclusion</h3> The BSG guidelines are based on robust evidence. Despite this, many patients (40%) undergoing screening in our centre do not meet guideline criteria. Some (33%) were screened too early, and others (19%) had unnecessary follow-up. Therefore, some patients are exposed to the risk of colonoscopy decades younger than recommended without justifiable benefits. This is reflected in similar data from other centres. Non-adherence to guideline occurs at multiple levels from referral and beyond. Clinicians often feel compelled to offer screening against guidelines for the reassurance of anxious patients. Our study identifies multiple opportunities where intervention could result in better adherence to guidelines; interventions such as the development of family cancer clinics outside clinical genetics centres to improve management of these patients. <h3>Competing interests</h3> None declared.
Human lower oesophageal sphincter relaxation is associated with raised cyclic nucleotide content.
Authors: M S Barnette, F C Barone, P J Fowler, M Grous, W J Price, H S Ormsbee
Journal: Gut (1991)

Increases in cyclic adenosine monophosphate and cyclic guanosine monophosphate content accompany relaxation of isolated strips of opossum and canine lower oesophageal sphincter muscle. The aim of this investigation was to characterise these responses in isolated muscle from the human lower oesophageal sphincter. Electrical stimulation of enteric neurons produced a frequency dependent relaxation of the human lower oesophageal sphincter that was sensitive to tetrodotoxin. Furthermore, as previously shown in the opossum and canine lower oesophageal sphincter, cyclic guanosine monophosphate content was significantly raised in muscle strips frozen during maximum electrical field stimulation whereas cyclic adenosine monophosphate content was unchanged. In addition, sodium nitroprusside (EC50 = 0.1 microM) produced a concentration dependent relaxation of human lower oesophageal sphincter, significantly increased cyclic guanosine monophosphate content, but did not alter cyclic adenosine monophosphate content. Zaprinast (M&B 22948) and SK&F 94120, selective inhibitors of cyclic guanosine monophosphate and cyclic adenosine monophosphate phosphodiesterases, respectively, both relaxed human lower oesophageal sphincter with a potency similar to that seen in the dog or opossum lower oesophageal sphincter. Finally, the 8-bromo analogues of both cyclic adenosine monophosphate (EC50 = 420 microM) and cyclic guanosine monophosphate (EC50 = 100 microM) relaxed the human lower oesophageal sphincter. These studies suggest that in the human, as well as the canine and opossum lower oesophageal sphincter, increases in cyclic nucleotide content are associated with relaxation and increases in cyclic guanosine monophosphate are associated with the relaxation induced by stimulation of enteric neurons.
Genomics Identifies Medulloblastoma Subgroups That Are Enriched for Specific Genetic Alterations
Authors: Margaret C. Thompson, Christine Fuller, Twala L. Hogg, James Dalton, David Finkelstein, Ching C. Lau, Murali Chintagumpala, Adekunle Adesina, David M. Ashley, Stewart J. Kellie, Michael D. Taylor, Tom Curran, Amar Gajjar, Richard J. Gilbertson
Journal: Journal of Clinical Oncology (2006)

Purpose Traditional genetic approaches to identify gene mutations in cancer are expensive and laborious. Nonetheless, if we are to avoid rejecting effective molecular targeted therapies, we must test these drugs in patients whose tumors harbor mutations in the drug target. We hypothesized that gene expression profiling might be a more rapid and cost-effective method of identifying tumors that contain specific genetic abnormalities. Materials and Methods Gene expression profiles of 46 samples of medulloblastoma were generated using the U133av2 Affymetrix oligonucleotide array and validated using real-time reverse transcriptase polymerase chain reaction (RT-PCR) and immunohistochemistry. Genetic abnormalities were confirmed using fluorescence in situ hybridization (FISH) and direct sequencing. Results Unsupervised analysis of gene expression profiles partitioned medulloblastomas into five distinct subgroups (subgroups A to E). Gene expression signatures that distinguished these subgroups predicted the presence of key molecular alterations that we subsequently confirmed by gene sequence analysis and FISH. Subgroup-specific abnormalities included mutations in the Wingless (WNT) pathway and deletion of chromosome 6 (subgroup B) and mutations in the Sonic Hedgehog (SHH) pathway (subgroup D). Real-time RT-PCR analysis of gene expression profiles was then used to predict accurately the presence of mutations in the WNT and SHH pathways in a separate group of 31 medulloblastomas. Conclusion Genome-wide expression profiles can partition large tumor cohorts into subgroups that are enriched for specific genetic alterations. This approach may assist ultimately in the selection of patients for future clinical trials of molecular targeted therapies.