tbuckley/cabot-search huggingface dataset:
Abstract 3136: Lipid-Lowering Medication Modifies The Gene-Diet Association Between 5-Lipoxygenase Promoter Polymorphisms And Carotid Artery Atherosclerosis
Authors: Nitzan C Roth, Susanna Vikman, Hooman Allayee, Wendy J Mack, Howard N Hodis
Journal: Circulation (2008)

Background: 5-Lipoxygenase (5-LOX) is the rate-limiting enzyme in the biosynthesis of leukotrienes from arachidonic acid (Ara), an n-6 polyunsaturated fatty acid (PUFA). Previous studies suggest that polymorphisms in the number of tandem Sp1 binding sites in the promoter of the 5-LOX gene may have an atherogenic effect due to a heightened inflammatory state when dietary Ara is high and dietary long-chain n-3 PUFAs (eicosapentaenoic acid, EPA, plus docosahexaenoic acid, DHA) are low. Methods: We determined 5-LOX genotypes in 1,663 adults participating in one of five randomized controlled atherosclerosis trials using carotid artery intima-media thickness (CIMT) as the outcome. Baseline data on participant characteristics and clinic and laboratory measurements, including fasting lipids and CIMT, were obtained using the same methods in all trials. Diet was measured using 3-day records and intake of each PUFA was categorized as above or below the median. We used linear regression to examine the cross-sectional associations between 5-LOX genotype, dietary PUFAs, and CIMT. Results: Alleles were classified as wild-type (W, with 5 repeats), deletion (D, with 2– 4 repeats), or addition (A, with 6–9 repeats). The frequencies of the six genotypes were: 60.6% WW, 27.1% WD, 4.9% WA, 4.9% DD, 2.2% DA, and 0.4% AA. Among participants using lipid-lowering medication, mean CIMT was significantly elevated by 79.1 μm (95% CI = 5.3–152.9) in DD individuals compared to WW individuals after adjustment for sex, race, age, trial, and BMI &gt;25 kg/m 2 . High dietary EPA+DHA blunted the gene-CIMT association (p for interaction = 0.007). In contrast, DD genotype was not associated with CIMT among non-users of lipid-lowering medication. Conclusion: The atherogenic effect of the shorter promoter alleles is modulated by dietary intake, especially in individuals using lipid-lowering medication, indicating a complex mechanism involving both inflammation and lipids.
Abstract 411: Endogenous miRNA Induced By Ischemic Preconditioning Reduces Myocardial Infarct Size following Ischemia/Reperfusion In Mice
Authors: Chang Yin, Fadi N Salloum, Rakesh C Kukreja
Journal: Circulation (2007)

BACKGROUND: Due to its short length (~24 nt) and non-coding nature, microRNA (miRNA) used to be regarded as “evolutionary transcriptional debris”. Recent evidence suggests that miRNA is a novel regulator for transcription and translation. It is known that brief episodes of ischemia during ischemic preconditioning (IPC) trigger complex genetic pro-survival program that results in modulation of several key proteins involved in protection against I/R injury. We hypothesized that miRNA synthesized during IPC is the potential mediator of such protection. METHODS / RESULTS : Hearts were isolated from 3 groups (n = 6/group) of adult ICR mice and subjected to the following treatments in Langendorff mode: 120 min of perfusion with Krebs-Henseleit buffer (control); 30 min global ischemia followed by 1 hr reperfusion (I/R); 2 cycles of 30 sec ischemia and 90 sec reperfusion followed by 30 min ischemia and 1 hr reperfusion (IPC). Infarct size (IS) was measured by triphenyl tetrazolium staining. IPC in the Langendorff model reduced IS from 29.7 ± 2.1% in the I/R hearts to 9.1 ± 1.8 % in the IPC group. This protection was associated with a significant induction of miRNA-1 (162 ± 13%), miRNA-21 (118 ± 6%), and miRNA-24 (46 ± 12%). To test its protective role, miRNA was extracted from 6 hearts following the IPC protocol; and then injected in vivo into the left ventricle wall in another group of 6 mice. Forty-eight hrs later, these mice were subjected to I/R injury in vivo by left coronary artery ligation for 30 min followed by reperfusion for 24 hr. In addition, a subset of mice was treated with miRNA inhibitors (methylated antisense miRNA) in conjunction with miRNA from IPC hearts. The results show that miRNA extracted from the IPC hearts reproduced a protective phenotype with significantly lower infarction (18.8 ± 2.5 %) in vivo as compared to saline-treated control (37.5 ± 2.2%). This protective effect was totally abolished by specific inhibitors of miRNA-1 and miRNA-21 (IS: 43.7 ± 2.1%). CONCLUSION : miRNA extracted from preconditioned hearts shows a protective role against I/R injury. The detection of miRNA in preconditioned hearts offers a novel strategy in cardioprotection. Further studies are needed to identify the gene targets by which miRNA generate protective phenotype.
Abstract 772: Anti-tumor efficacy of the selective pan-FGFR Inhibitor BAY 1163877 in preclinical squamous cell carcinoma models of different origin
Authors: Mélanie Héroult, Matthias Ocker, Charlotte Kopitz, Dieter Zopf, Andrea Hägebarth, Karl Ziegelbauer, Stuart Ince, Peter Ellinghaus
Journal: Cancer Research (2015)

Abstract Squamous cell carcinoma (SCC) is a common subtype of lung cancer and is strongly associated with smoking. In contrast to adenocarcinomas of the lung, SCCs do not significantly harbor epidermal growth factor (EGFR) mutations or ALK, ROS1 or RET translocations, which are therapeutically tractable. SCC of the lung and SCC of the head and neck region and esophagus not only share risk factors, morphologic features and mechanisms of tumorigenesis but also frequent fibroblast growth factor receptor 1 (FGFR1) gene alterations. In addition, we found that FGFR2 and FGFR3 expression were also altered in patient derived models of SCC of various origins. FGFRs may thus represent viable therapeutic targets for the treatment of SCC. BAY 1163877, an orally available and potent inhibitor of FGFR1, FGFR2 and FGFR3, inhibited SCC cell proliferation as well as downstream FGFR signaling in vitro. When applied in vivo, BAY 1163877 was able to reduce growth of a FGFR1-overexpressing lung SCC xenograft model, a FGFR1-overexpressing esophageal SCC xenograft model, and a FGFR3-overexpressing head and neck SCC xenograft model, achieving reductions in tumor growth by 67 to 92% as compared to the vehicle control. BAY 1163877 was very well tolerated in all models performed. These data suggest that selective inhibition of FGFR1 to 3 with BAY 1163877 might have therapeutic potential for the treatment of SCC malignancies. A phase I clinical trial (NCT01976741) to determine the safety, tolerability and recommended Phase 2 dose in advanced cancer patients is ongoing. Citation Format: Mélanie Héroult, Matthias Ocker, Charlotte Kopitz, Dieter Zopf, Andrea Hägebarth, Karl Ziegelbauer, Stuart Ince, Peter Ellinghaus. Anti-tumor efficacy of the selective pan-FGFR Inhibitor BAY 1163877 in preclinical squamous cell carcinoma models of different origin. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 772. doi:10.1158/1538-7445.AM2015-772
Effects of gender and diagnosis on growth hormone response to clonidine for major depression: a large-scale multicenter study
Authors: M Schittecatte, G Charles, R Machowski, F Dumont, J Garcia-Valentin, J Wilmotte, P Papart, W Pitchot, J Wauthy, M Ansseau
Journal: American Journal of Psychiatry (1994)

The authors' goal was to establish, in a large multicenter sample of patients classified according to gender and menopausal status, if the growth hormone (GH) response to clonidine discriminated patients with episodes of major depression from patients with episodes of minor depression.The GH response to intravenous clonidine administration (150 micrograms) was compared in 71 male and 140 female patients with major depressive episodes and 47 male and 53 female patients with minor depressive episodes. These patients were diagnosed according to Research Diagnostic Criteria.Differences in the GH response to clonidine between diagnostic groups occurred only between male patients. These results were found in the group as a whole and in each center. The GH responses to clonidine of premenopausal women differed significantly from those of postmenopausal women in each diagnostic group.These results confirm that gender and menopausal status are of the utmost importance in the interpretation of the clonidine GH test.
Abstract 14196: Evaluation of Isis Apo(a)Rx, an Antisense Inhibitor to Apolipoprotein(a), in Healthy Volunteers
Authors: Nick Viney, Mark Graham, Rosanne Crooke, Steve Hughes, Walter Singleton
Journal: Circulation (2013)

ISIS APO(a)Rx is an antisense oligonucleotide designed to specifically inhibit the expression of apolipoprotein(a) [apo(a)], a distinct protein component of lipoprotein(a) [Lp(a)]. Apo(a) is produc...
The Immune System
Authors: Peter J. Delves, Ivan M. Roitt
Journal: New England Journal of Medicine (2000)

Lymphocytes and Lymphoid TissueThe complexity of the cellular interactions that occur during acquired immune responses requires specialized microenvironments in which the relevant cells can collaborate efficiently. Because only a few lymphocytes are specific for a given antigen, T cells and B cells need to migrate throughout the body to increase the probability that they will encounter that particular antigen. In their travels, lymphocytes spend only about 30 minutes in the blood during each cycle around the body.56 Immune responses to blood-borne antigens are usually initiated in the spleen, and responses to microorganisms in tissues are generated in local lymph . . .
Abstract 472: Cardiac Fibroblasts Regulate Myocardial Proliferation and Ventricular Formation through {beta}1 Integrin Signaling
Authors: Masaki Ieda, Takatoshi Tsuchihashi, Kathryn Ivey, Deepak Srivastava
Journal: Circulation (2008)

Ventricular cardiomyocyte proliferation is essential to support increasing hemodynamic demands during late cardiogenesis. The increase in thickness of the ventricle is achieved by greater proliferation in the compact myocardium than in the trabecular myocardium. Disruption of this process leads to a disease known as ventricular non-compaction. Although epicardial-derived signals may contribute to the proliferative process, the factors and cell types responsible for development of the compact layer are unclear. In particular, the function of embryonic cardiac fibroblasts, derivatives from epicardium, and their secreted factors are largely unknown. By analyzing cell markers, we found that cardiac fibroblasts appeared in the compact myocardium at embryonic day 12.5 and increased in number coincident with growth of the compact myocardium. Using a novel co-culture system, we found that embryonic cardiac fibroblasts were much more effective in inducing cardiomyocyte proliferation than adult cardiac fibroblasts. A genome-wide screen and siRNA knockdown experiments revealed that fibronectin and collagen were embryonic cardiac fibroblast-specific signals that promoted cardiomyocyte proliferation through β1 integrin signaling in primary culture. In vivo, cardiomyocyte expression of β1 integrin was upregulated as cardiac fibroblasts appeared in the heart and secreted extracellular matrix proteins. In agreement with a critical role for β1 integrin, cardiomyocyte-specific deletion of β1 integrin in mice resulted in reduced myocardial proliferation and ventricular compaction, with downregulation of cyclinD1 and cyclinE1 and upregulation of cyclinG2 and p21, leading to prenatal death. These findings demonstrate that cardiac fibroblasts regulate cardiomyocyte proliferation and ventricular compaction through extracellular matrix/β1 integrin signaling.
Abstract 11336: Racial Differences in Resistance to P2Y12 Receptor Antagonists in Thrombin-Stimulated Diabetic Platelets
Authors: John H Cleator, Matthew T Duvernay, Michael Holinstat, Nancy E Colowick, Dana T Blakemore, Frank E Harrell, Heidi E Hamm
Journal: Circulation (2011)

Background: Thrombin mediates potent effects on platelet activation via Protease-Activated Receptors (PARs), PAR1 and PAR4. Thrombin stimulates feed forward release of the secondary agonist ADP, wh...
Novel Biological Effects and Distinct Patterns of Rhoa Mutations in Adult T-Cell Leukemia/Lymphoma and Angioimmunoblastic T Cell Lymphoma
Authors: Yasunobu Nagata, Terukazu Enami, Kenji Kontani, Keisuke Kataoka, Mamiko Sakata-Yanagimoto, Akira Kitanaka, Aiko Sato, Yuichi Shiraishi, Kenichi Chiba, Hiroko Tanaka, Yusuke Shiozawa, Tetsuichi Yoshizato, Ayana Kon, Kenichi Yoshida, Masashi Sanada, Ken Ishiyama, Shuichi Miyawaki, Ryohei Ishii, Osamu Nureki, Satoru Miyano, Kazuya Shimoda, Toshiki Watanabe, Toshiaki Katada, Shigeru Chiba, Seishi Ogawa
Journal: Blood (2014)
Physician-assisted suicide in Oregon : A bold experiment. by Ann Alpers and Bernard Lo
Authors: Ann Alpres, Bernard Lo
Journal: JAMA (1995)

tag=1 data=Physician-assisted suicide in Oregon : A bold experiment. by Ann Alpers and Bernard Lo

tag=2 data=Alpres, Ann%Lo, Bernard

tag=3 data=The Journal of the American Medical Association,

tag=4 data=274

tag=5 data=6

tag=6 data=9 August 1995

tag=7 data=483-487.

tag=8 data=EUTHANASIA

tag=10 data=This article analyses the provisions of this bold experiment, the wide discretion it gives to physicians, and specific questions for physicians raised by patient requests for assisted suicide.

tag=11 data=1995/1/8

tag=12 data=95/0388

tag=13 data=CAB
Abstract B24: Targeting pancreatic ductal adenocarcinoma acidic microenvironment
Authors: Zobeida Cruz-Monserrate, Christina L. Roland, Defeng Deng, Thiruvengadam Arumugam, Anna Moshnikova, Oleg A. Andreev, Yana Reshetnyak, Craig D. Logsdon
Journal: Cancer Research (2015)

Abstract Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer death in the USA, accounting for ~40,000 deaths annually. The dismal prognosis for PDAC is largely due to its late diagnosis. Currently, the most sensitive diagnosis of PDAC requires invasive procedures, such as endoscopic ultrasonography, which has inherent risks and accuracy that is highly operator dependent. Here we took advantage of a general characteristic of solid tumors, the acidic microenvironment that is generated as a by-product of metabolism, to develop a novel approach of using pH (Low) Insertion Peptides (pHLIPs) for imaging of PDAC. We show that fluorescently labeled pHLIPs can localize and specifically detect PDAC in human xenografts as well as PDAC and PanIN lesions in genetically engineered mouse models. This novel approach may improve detection, differential diagnosis and staging of PDAC Citation Format: Zobeida Cruz-Monserrate, Christina L. Roland, Defeng Deng, Thiruvengadam Arumugam, Anna Moshnikova, Oleg A. Andreev, Yana Reshetnyak, Craig D. Logsdon. Targeting pancreatic ductal adenocarcinoma acidic microenvironment. [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Innovations in Research and Treatment; May 18-21, 2014; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2015;75(13 Suppl):Abstract nr B24.
Elimination Rates of Dioxin Congeners in Former Chlorophenol Workers from Midland, Michigan
Authors: Lesa L. Aylward, James J. Collins, Kenneth M. Bodner, Michael Wilken, Catherine M. Bodnar
Journal: Environmental Health Perspectives (2012)

Exposure reconstructions and risk assessments for 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and other dioxins rely on estimates of elimination rates. Limited data are available on elimination rates for congeners other than TCDD.We estimated apparent elimination rates using a simple first-order one-compartment model for selected dioxin congeners based on repeated blood sampling in a previously studied population.Blood samples collected from 56 former chlorophenol workers in 2004-2005 and again in 2010 were analyzed for dioxin congeners. We calculated the apparent elimination half-life in each individual for each dioxin congener and examined factors potentially influencing elimination rates and the impact of estimated ongoing background exposures on rate estimates.Mean concentrations of all dioxin congeners in the sampled participants declined between sampling times. Median apparent half-lives of elimination based on changes in estimated mass in the body were generally consistent with previous estimates and ranged from 6.8 years (1,2,3,7,8,9-hexachlorodibenzo-p-dioxin) to 11.6 years (pentachlorodibenzo-p-dioxin), with a composite half-life of 9.3 years for TCDD toxic equivalents. None of the factors examined, including age, smoking status, body mass index or change in body mass index, initial measured concentration, or chloracne diagnosis, was consistently associated with the estimated elimination rates in this population. Inclusion of plausible estimates of ongoing background exposures decreased apparent half-lives by approximately 10%. Available concentration-dependent toxicokinetic models for TCDD underpredicted observed elimination rates for concentrations < 100 ppt.The estimated elimination rates from this relatively large serial sampling study can inform occupational and environmental exposure and serum evaluations for dioxin compounds.
Declining frequency of neuroleptic malignant syndrome in a hospital population
Authors: P E Keck, H G Pope, S L McElroy
Journal: American Journal of Psychiatry (1991)

The authors investigated trends in the frequency of neuroleptic malignant syndrome at their center over a period of 8 years and assessed possible reasons for these trends.They used previously defined operational criteria in conducting a prospective survey of cases of the syndrome among 2,695 neuroleptic-treated patients from Oct. 1, 1986, to Aug. 31, 1990. The frequency of neuroleptic malignant syndrome during this period was then compared with the frequency in a comparable period prior to October 1986. The investigators also assessed changes between the two periods in risk factors associated with the syndrome, including patients' mean age, sex ratio, diagnoses, and severity of illness; neuroleptic dosage, potency, and route of administration; concomitant use of lithium; and degree of agitation.Four cases of neuroleptic malignant syndrome were diagnosed during the more recent 47-month survey period, yielding a frequency of 0.15% +/- 0.05%. This represents a significant decline in the frequency of the syndrome from the estimate of 1.10% +/- 0.40% for the earlier survey period. Significantly fewer patients in the recent period had received intramuscular doses of neuroleptics.The frequency of neuroleptic malignant syndrome has declined significantly at this center. The decline appears to be attributable to increasing clinical awareness of the features of the syndrome, allowing early intervention and treatment, and to a reduction in risk factors, such as use of intramuscular neuroleptics.
Sexually transmitted infections in women who have sex with women
Authors: C. Ford, K. Clarke, G. Hughes, T. Lamagni, N. Macdonald, M. Catchpole
Journal: BMJ (1998)

Outcome of pregnancy in women with insulin dependent diabetes Centralisation of care leads to better outcomeEditor-The finding of a persistently poor outcome of pregnancy in women with insulin dependent diabetes in two (northern) English regions is an important statement of the problem. 1 2 Both studies provide figures and show outcomes that are no different from those widely reported in the past.Unfortunately, neither give evidence of any degree of centralisation of obstetric or diabetic care, with on-site neonatal intensive care, although this is a proved means of improving the outcome of pregnancy for diabetic mothers. 3 The St Vincent declaration guidelines on the outcome of pregnancy, referred to in the accompanying editorial (p 263), are based on the Scandinavian reports held up as examples of good practice and state that "an interdisciplinary team should provide centralized diabetic pregnancy care in a hospital treating at least 20-30 cases a year.Pregnant diabetic
Abstract 20791: An Evaluation of Re-Replacement of the Aortic Root with Coronary Reimplantation
Authors: Ismail El-Hamamsy, Michael Ibrahim, Herbert Witzke, Louis M Stevens, Magdi H Yacoub
Journal: Circulation (2010)

Background: Total aortic root replacement with coronary reimplantation provides good early- and mid-term results for patients with aortic valve disease. However, there is continuing concern about t...
Outbreaks of monophasic Salmonella enterica serovar 4,[5],12:i:- in Luxembourg, 2006
Authors: J Mossong, P Marques, C Ragimbeau, P Huberty-Krau, S Losch, G Meyer, G Moris, C Strottner, W Rabsch, F Schneider
Journal: Eurosurveillance (2007)

A monophasic Salmonella enterica serovar 4,[5],12:i:- phage type DT193 emerged as the dominant serovar in Luxembourg in 2006, when it caused two major outbreaks involving 133 laboratory-confirmed human cases, 24 hospitalisations, and one death. The outbreak strain had an uncommon pulsed-field gel electrophoresis pattern STYMXB.0031 and antibiotic resistance profile ASSuT. A high proportion of cases were clustered in institutions for the elderly and in day-care centers. Strains identical to the outbreak strain were recovered from two control meals, a nappy changing table, retail sausages and caecal porcine samples at an abattoir. Locally produced pork meat is strongly suspected to have been the vehicle for the outbreaks, although the precise mechanisms remain unclear.
Ursodeoxycholic acid inhibits oxidative stress induced by bile acids and gastric acid in esophageal cell lines: Relevance to Barrett’s esophagus pathogenesis
Authors: Katerina Dvorak, Melissa Chavarria, Claire Payne, Harris Bernstein, Carol Bernstein, Lois Ramsey, Hana Holubec, Barbora Dvorakova, Harinder Garewal
Journal: Cancer Research (2007)

1405    Objectives:  Barrett9s esophagus (BE) is a premalignant condition associated with elevated risk for the development of esophageal adenocarcinoma (ADCA). Previous studies indicated that oxidative damage contributes to the development of ADCA. We tested the hypothesis that bile acids and gastric acid, two components of refluxate, can induce oxidative stress and oxidative DNA damage. We speculate that effects of gastric acid and bile acids may be inhibited by treatment with the cytoprotective bile acid, ursodeoxycholic acid (UDCA).   Methods:  Oxidative stress was evaluated by staining with an antibody to 8-hydroxy-deoxyguanosine (8-OH-dG) in BE tissues with different degrees of dysplasia. The levels of 8-OH-dG were also evaluated  ex vivo  in BE tissues incubated for 10 minutes with control medium and medium acidified to pH 4 and supplemented with 0.5mM bile acid cocktail. Furthermore, three esophageal cell lines (BE cells, normal squamous esophageal HET-1A cells and adenocarcinoma Seg-1 cells) were exposed for 1-10 minutes to control media, media containing bile acid cocktail, media acidified to pH 4, and media at pH 4 supplemented with 0.1mM bile acid cocktail and evaluated for induction of reactive oxygen species (ROS). In addition, the cells were treated as above but with 0.1 mM UDCA added to the media.   Results:  Immunohistochemical analysis showed that 8-OH-dG is present at increased levels in epithelial cells of dysplastic BE. Incubation of BE tissues with a combination of a bile acid cocktail and low pH leads to the increased formation of 8-OH-dG. An increase in ROS occurs after exposure to pH 4 and a bile acid cocktail in all three cell lines and pH 4 treatment alone induced ROS in BE cells and HET-1A cells. These increases in ROS were inhibited by treatment with 0.1mM UDCA.   Conclusions:  Oxidative DNA damage is present at increased levels in dysplastic BE tissue. Oxidative stress can be induced in esophageal tissues and cells by short exposures to bile acids and low pH. These alterations may underlie the development of BE and tumor progression. UDCA treatment may inhibit oxidative damage induced by cytotoxic bile acids and gastric acid.