tbuckley/cabot-search huggingface dataset:
PTU-089 Infliximab Down-regulates Stat 1, Alk And P44/42 Mapk Activation In Crohn’s Disease Biopsies Cultured<i>ex Vivo</i>
Authors: IM Bell, P Giuffrida, P Biancheri, F Ammoscato, T Macdonald
Journal: Gut (2014)

<h3>Introduction</h3> Crohn’s disease (CD) and ulcerative colitis (UC), the two main forms of inflammatory bowel disease, are characterised by increased mucosal activation of pro-inflammatory signalling molecules. The anti-tumour necrosis (TNF)-alpha monoclonal antibody infliximab is more effective in the treatment of CD than UC but its mechanism of action is still unknown. We therefore evaluated the effect of infliximab on the expression of a panel of phospho-proteins by inflamed CD and UC colonic biopsies cultured <i>ex vivo</i>. <h3>Methods</h3> Colonic biopsies were obtained from macroscopically inflamed areas of 5 patients with CD and 2 patients with UC, and were then cultured for 24 h in 300ul of serum-free HL-1 medium with infliximab (5ug/ml), or control IgG1 (5ug/ml). The biopsies were then snap frozen and later lysed to extract the protein. A Path Scan RTK signalling array kit from New England Biolabs was used to measure the expression of a panel of 39 phosphorylated proteins in the biopsy homogenates. <h3>Results</h3> Infliximab significantly reduced the expression of phosphorylated ALK, FLT3, EphB3,p44/42 MAPK, S6 Ribosomal Protein and Stat1 by over 40 fold compared to IgG1 in Crohn’s disease biopsies cultured <i>ex vivo</i>. In UC biopsies infliximab did not induce any significant change in phosphoprotein expression compared to IgG1 control except for a 10 fold reduction in phospho-VEGFR2. <h3>Conclusion</h3> Infliximab reduces the expression phospho-proteins Stat 1, ALK and p44/42 MAPK, which have a central role in sustaining the pro-inflammatory immune response. Differences in the effect of infliximab on the phosphorylation status of mucosal proteins may account for its different efficacy profile in CD and UC. <h3>Disclosure of Interest</h3> None Declared.
Regional prevalence of non-alcoholic fatty liver disease in Seoul and Gyeonggi-do, Korea
Authors: Eun Haeng Jeong, Dae Won Jun, Yong Kyun Cho, Young Gil Choe, Seungho Ryu, Seung Min Lee, Eun Chul Jang
Journal: Clinical and Molecular Hepatology (2013)

Background/Aims The prevalence of nonalcoholic fatty liver disease (NAFLD) in Korea has increased recently. The aim of the present study was to determine the regional differences in the prevalence and characteristics of NAFLD. Methods From January 2009 to December 2010, 161,891 Seoul and Gyeonggi-do residents receiving a health examination at our institution were enrolled in this cross-sectional study. After applying exclusion criteria, the data of 141,610 subjects (80,943 males, 60,667 females) were analyzed. The presence of NAFLD was established by ultrasound examination. Results The overall prevalence of NAFLD was 27.3% (38.3% in men, 12.6% in women). When standardized according to age, area, and sex, the prevalence of NAFLD was 25.2%. The age and area standardized prevalence of NAFLD was higher for men (34.4%) than for women (12.2%; P<0.001). The overall prevalence of NAFLD was higher in Gyeonggi-do (27.7%) than in Seoul (26.9%; P<0.001). Among the men, the prevalence of NAFLD was higher in Gyeonggi-do (39.2%) than in Seoul (37.4%; P<0.001), while for the women it was higher in Seoul (13.2%) than in Gyeonggi-do (12.0%; P<0.001). Conclusions The regional prevalence of NAFLD differed between Seoul and Gyeonggi-do. Further studies are needed to establish the etiology of this difference. Keywords: Non-alcoholic fatty liver disease; Body mass index; Prevalence
Cutting balloon angioplasty versus rotational atherectomy for treatment of diffuse in-stent restenosis: Multicenter registry in Japan
Authors: Sunao Nakamura, Eita Saito, Takanori Miyauchi, Jin Yokoyama, Akihiko Kanazawa, Yasufumi Hayama, Koji Hozawa, Shotaro Nakamura, Hitoshi Nakamura, Kazutoshi Yamamoto
Journal: Journal of the American College of Cardiology (2003)
Informed Consent in Randomized Quality Improvement Trials
Authors: Mark J. Pletcher, Bernard Lo, Deborah Grady
Journal: JAMA Internal Medicine (2014)

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 Internal Medicine HomeNew OnlineCurrent IssueFor Authors Podcast 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 Internal Medicine journal
Heterotrimeric G proteins regulate nitrogen-use efficiency in rice
Authors: Hongying Sun, Qian Qian, Kun Wu, Jijing Luo, Shuansuo Wang, Chengwei Zhang, Yanfei Ma, Qian Liu, Xianzhong Huang, Qingbo Yuan, Ruixi Han, Meng Zhao, Guojun Dong, Longbiao Guo, Xudong Zhu, Zhiheng Gou, Wen Wang, Yuejin Wu, Hongxuan Lin, Xiangdong Fu
Journal: Nature Genetics (2014)
Mouse Eotaxin Expression Parallels Eosinophil Accumulation during Lung Allergic Inflammation but It Is Not Restricted to a Th2-Type Response
Authors: J.-A Gonzalo, G-Q Jia, V Aguirre, D Friend, A.J Coyle, N.A Jenkins, G-S Lin, H Katz, A Lichtman, N Copeland, M Kopf, J.-C Gutierrez-Ramos
Journal: Immunity (1996)
Stress-Induced Reversible and Mild-to-Moderate Irreversible Thallium Defects
Authors: Anastasia N. Kitsiou, Gopal Srinivasan, Arshed A. Quyyumi, Ronald M. Summers, Stephen L. Bacharach, Vasken Dilsizian
Journal: Circulation (1998)

In patients with coronary artery disease, stress-redistribution-reinjection thallium scintigraphy provides important information regarding myocardial ischemia and viability. Although both reversible and mild-to-moderate irreversible thallium defects retain metabolically active, viable myocardium, we hypothesized that stress-induced reversible thallium defects may better differentiate reversible from irreversible regional left ventricular dysfunction after revascularization.Twenty-four patients with chronic coronary artery disease underwent prerevascularization and postrevascularization exercise-redistribution-reinjection thallium single photon emission CT, gated MRI, and radionuclide angiography. After revascularization, mean left ventricular ejection fraction increased from 30+/-9% to 37+/-13% at rest (P<0.001). Before revascularization, abnormal contraction at rest was observed in 56 of 110 reversible and 20 of 37 mild-to-moderate irreversible thallium defects (51% and 54%, respectively). After revascularization, regional contraction improved in 44 of 56 reversible compared with 6 of 20 mild-to-moderate irreversible thallium defects (79% and 30%, respectively; P<0.001). The final thallium content (maximum tracer uptake on redistribution-reinjection images) was significantly higher in regions with reversible defects that improved than in those that did not improve after revascularization (86+/-16% versus 66+/-9%, P<0.001). In contrast, final thallium content was similar in regions with mild-to-moderate irreversible defects that improved and in those that did not improve after revascularization (69+/-9% versus 65+/-10%, P=NS). Furthermore, when asynergic regions were grouped according to the final thallium content, at 60% threshold value, functional recovery was observed in 83% of regions with reversible defects compared with 33% of regions with mild-to-moderate irreversible defects (P<0.001).These findings suggest that although both reversible and mild-to-moderate irreversible thallium defects after stress retain viable myocardium, the identification of reversible thallium defect on stress in an asynergic region more accurately predicts recovery of function after revascularization. Even at a similar mass of viable myocardial tissue (as reflected by the final thallium content), the presence of inducible ischemia is associated with an increased likelihood of functional recovery.
THE LATE DR. HUGGARD OF DAVOS
Authors: H. Angst, A. F. Bill, J. M. Bruce, W. J. S. Emery, B. Hudson, G. F. M. Hogg, R. W. Perks, R. D. Powell, E. C. Simmons, D. A. F. Vesey, E. S. Woods, H. C. Wrinch
Journal: BMJ (1912)
Randomized Clinical Trials in Heart Disease
Authors: Antoni Basinski
Journal: JAMA (1989)

<h3>To the Editor.—</h3> A recent article in<i>JAMA</i>by Yusuf et al<sup>1</sup>reviewed a large number of trials of interventions for lowering cholesterol levels for the primary and secondary prevention of coronary heart disease. The article states that "there was no apparent heterogeneity in reduction of coronary heart disease observed in the drug or dietary intervention trials, in the primary prevention or secondary prevention trials, or on fatal or nonfatal coronary heart disease events." We are unable to comment fully on these assertions as the analysis on which they are based has not been published. However, there is evidence of clinically important differences between trials. For example, in a published work by Yusuf and Furberg,<sup>2</sup>the aggregate risk ratio for coronary heart disease mortality in trials of dietary intervention was 0.99, while aggregation of the trials of lipid-lowering pharmaceutical agents showed a reduction in cardiac mortality for treated
Poetry and Medicine
Authors: Judith Boudreaux
Journal: JAMA (1991)

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
VASO-DILATATION IN HAEMOPTYSIS
Authors: E. T. Smith
Journal: BMJ (1906)

The patient's condition rapidly improved, all pain and -tenderness soon disappearing.HIis temperature, however, -although norma.l in the mornings, persistently rose every evening to 1000.A week after the operation, as tllere seemed to be a little pocketinig of the discharge below the patella, I made a small incisioni at this poin-t oln onie.side -of the ligamenituni patellae unider eucaine.I think, though, nowv that tllis was ulmiiecessary, as it miiade no -difference at the time to the evening rise of temperature, whichl gradually fell some days later to normal.The side tubes were left out a little over a wveek from tlle operation, and the wounds soon liealed.Passive movements were beguni in about a fortniglht, anld diligently persisted in.Movement, lhowever, from the first was very good.The patient's condition six weeks after the operation -was excellenit.He could walk fairly well witlh tlle aid of .astick, and the range of movement in the joinlt was from 'tlhe straight position to a right angle.[We have now had an opportunity of examininig our ,patient six montlhs after operationi; the m--ovemenit ill the joint is perfect, and the lad is able to walk anld bicycle without the least difficulty.]
Intralesional Cidofovir for Treating Extensive Genital Verrucous Herpes Simplex Virus Infection
Authors: Karolyn A. Wanat, Rachel H. Gormley, Misha Rosenbach, Carrie L Kovarik
Journal: JAMA Dermatology (2013)

The patient was subsequently treated with IVIG, 0.4g/ kg/d, for 5 consecutive days for her newly diagnosed CVID, while local application of paraffin gauze dressing (Jelonet; Smith & Nephew) was maintained.Surprisingly, 3 weeks after this single cycle, all ulcerations had healed (Figure 2), and complete resolution of pain was reported.The immunoglobulin levels remained stable 3 months after IVIG treatment, and no further ulcerations were detected during a 2-year follow-up, and so the patient did not require additional therapy.Discussion | In our case, no significant success was observed in reduction of NL ulcers after administration of currently accepted treatments, the efficiency of which was known to be limited.Interestingly, treatment of the patient's CVID with IVIG appeared to heal the ulcers within 3 weeks.As the IVIG treatment showed a similar dramatic ulcer reduction within 2 weeks in a previous case 3 (where no investigation of associated hypogammaglobulinemia was performed), the immunologic aspect of NL appears of major importance in these patients.Because of its strong association with diabetes, NL has been postulated to arise due to microangiopathic vascular changes.Therefore, NL might be due to immunologically mediated vascular changes. 4,5In this context, measures of serum immunoglobulin levels and direct immunofluorescent histologic study might be recommended in NL.Our findings suggest that IVIG can be a successful option in the treatment of NL,
Letter: Stangulated ovary and tube in inguinal hernia in pregnancy.
Authors: J Kotowski
Journal: BMJ (1974)

A concentration of 15 pig/ml was arbitrarily taken as a level read.lyobtainable in h blood wiLh bo.h antibiotics.Th-19 strains resistant to penicillin and tetracycline only were resis:ant to tetracycline in con- centrations above 20 Ag/lml.This resis ance pattern occurs quite frequently in strains of S. aph.aureus isolated both from hospital patients and from the general comnnunity.It would appear therefore that any micro- biological advantage which minocycline may exert over other tetracyclines is due to its sup rior activity against strains of Staph.aureus which are resistant to tetracycline.' -I am, etc.,
N6-Methyl-Adenosine (m6A) in RNA: An Old Modification with A Novel Epigenetic Function
Authors: Yamei Niu, Xu Zhao, Yong-Sheng Wu, Ming-Ming Li, Xiu-Jie Wang, Yun-Gui Yang
Journal: Genomics Proteomics & Bioinformatics (2012)

Abstract N6-methyl-adenosine (m6A) is one of the most common and abundant modifications on RNA molecules present in eukaryotes. However, the biological significance of m6A methylation remains largely unknown. Several independent lines of evidence suggest that the dynamic regulation of m6A may have a profound impact on gene expression regulation. The m6A modification is catalyzed by an unidentified methyltransferase complex containing at least one subunit methyltransferase like 3 (METTL3). m6A modification on messenger RNAs (mRNAs) mainly occurs in the exonic regions and 3′-untranslated region (3′-UTR) as revealed by high-throughput m6A-seq. One significant advance in m6A research is the recent discovery of the first two m6A RNA demethylases fat mass and obesity-associated (FTO) gene and ALKBH5, which catalyze m6A demethylation in an α-ketoglutarate (α-KG)- and Fe2+-dependent manner. Recent studies in model organisms demonstrate that METTL3, FTO and ALKBH5 play important roles in many biological processes, ranging from development and metabolism to fertility. Moreover, perturbation of activities of these enzymes leads to the disturbed expression of thousands of genes at the cellular level, implicating a regulatory role of m6A in RNA metabolism. Given the vital roles of DNA and histone methylations in epigenetic regulation of basic life processes in mammals, the dynamic and reversible chemical m6A modification on RNA may also serve as a novel epigenetic marker of profound biological significances.
Metabolic Signatures Associated with a NAD Synthesis Inhibitor–Induced Tumor Apoptosis Identified by 1H-Decoupled-31P Magnetic Resonance Spectroscopy
Authors: Manickam Muruganandham, Alan A. Alfieri, Cornelia Matei, Yuchun Chen, George Sukenick, Isabel Schemainda, Max Hasmann, Leonard B. Saltz, Jason A. Koutcher
Journal: Clinical Cancer Research (2005)

Abstract Purpose: Attempts to selectively initiate tumor cell death through inducible apoptotic pathways are increasingly being exploited as a potential anticancer strategy. Inhibition of NAD+ synthesis by a novel agent FK866 has been recently reported to induce apoptosis in human leukemia, hepatocarcinoma cells in vitro, and various types of tumor xenografts in vivo. In the present study, we used 1H-decoupled phosphorus (31P) magnetic resonance spectroscopy (MRS) to examine the metabolic changes associated with FK866 induced tumor cell death in a mouse mammary carcinoma. Experimental Design: Induction of apoptosis in FK866-treated tumors was confirmed by histology and cytofluorometric analysis. FK866-induced changes in mammary carcinoma tumor metabolism in vivo were investigated using 1H-decoupled 31P MRS. To discern further the changes in metabolic profiles of tumors observed in vivo, high-resolution in vitro 1H-decoupled 31P MRS studies were carried out with perchloric acid extracts of mammary carcinoma tumors excised after similar treatments. In addition, the effects of FK866 on mammary carcinoma tumor growth and radiation sensitivity were studied. Results: Treatment with FK866 induced a tumor growth delay and enhanced radiation sensitivity in mammary carcinoma tumors that was associated with significant increases in the 31P MR signal in the phosphomonoester region and a decrease in NAD+ levels, pH, and bioenergetic status. The 31P MRS of perchloric acid extracts of treated tumors identified the large unresolved signal in the phosphomonoester region as the resultant of resonances originating from intermediates of tumor glycolysis and guanylate synthesis in addition to alterations in pyridine nucleotide pools and phospholipid metabolism. Conclusion: The present results suggest that FK866 interferes with multiple biochemical pathways that contribute to the increased cell death (apoptosis) and subsequent radiation sensitivity observed in the mammary carcinoma that could be serially monitored by 31P MRS.
Relationship of regional myocardial perfusion to segmental wall motion: a physiologic basis for understanding the presence and reversibility of asynergy.
Authors: B M Massie, E H Botvinick, B H Brundage, B Greenberg, D Shames, H Gelberg
Journal: Circulation (1978)

Experimental work has shown that even small reductions in myocardial perfusion impair contractile performance. We, therefore, studied the relationship between regional perfusion, assessed by thallium-201 scintigraphy and segmental wall motion, quantitated on biplane contrast ventriculograms, in patients with coronary artery disease. We evaluated 270 segments in 54 patients, including 27 without evidence of myocardial infarction. Most normally perfused regions (125 of 140) contracted normally, whereas those with scintigraphic defects at rest were usually asynergic (42 of 46). Surprisingly, 57% (48 of 84) of regions with exercise-induced perfusion defects were also asynergic, including 48% (25 of 52) of those in patients without myocardial infarction. In 22 patients who had intervention ventriculograms, improvement of perfusion abnormalities at rest correlated closely with reversibility of asynergy. Although there was an association between the location and severity of coronary artery stenosis and segmental wall motion, myocardial perfusion during exercise was a significantly better predictor of asynergy. These findings suggest that resting asynergy may occur even in patients without previous infarction, predominantly in regions with jeopardized perfusion. Asynergy in regions with exercise-induced perfusion abnormalities may, therefore, be an indicator of resting ischemia and may be reversible by coronary artery revascularization.
Resistance to type 1 diabetes induction in 12-lipoxygenase knockout mice
Authors: David Bleich, Songyuan Chen, Brian Zipser, Duxin Sun, Colin D. Funk, Jerry L. Nadler
Journal: Journal of Clinical Investigation (1999)

Leukocyte 12-lipoxygenase (12-LO) gene expression in pancreatic β cells is upregulated by cytotoxic cytokines like IL-1β. Recent studies have demonstrated that 12-LO inhibitors can prevent glutamate-induced neuronal cell death when intracellular glutathione stores are depleted. Therefore, 12-LO pathway inhibition may prevent β-cell cytotoxicity. To evaluate the role of 12-LO gene expression in immune-mediated islet destruction, we used 12-LO knockout (12-LO KO) mice. Male homozygous 12-LO KO mice and control C57BL/6 mice received 5 consecutive daily injections of low-dose streptozotocin to induce immune-mediated diabetes. Fasting serum glucose and insulin levels were measured at 7-day intervals, and the mice were followed up for 28 days. 12-LO KO mice were highly resistant to diabetes development compared with control mice and had higher serum insulin levels on day 28. Isolated pancreatic islets were treated with IL-1β, TNF-α, and IFN-γ for 18 hours. Glucose-stimulated insulin secretion in cytokine-treated islets from C57/BL6 mice decreased 54% from that of untreated islets. In marked contrast, the same cytokine mix led to only a 26% decrease in islets from 12-LO KO mice. Furthermore, cytokine-induced 12-hydroxyeicosatetraenoic acid (12-HETE) production was absent in 12-LO KO islets but present in C57/BL6 islets. Isolated peritoneal macrophages were stimulated for 48 hours with IFN-γ + LPS and compared for nitrate/nitrite generation. 12-LO KO macrophages generated 50% less nitrate/nitrite when compared with C57BL/6 macrophages. In summary, elimination of leukocyte 12-LO in mice ameliorates low dose streptozotocin–induced diabetes by increasing islet resistance to cytokines and decreasing macrophage production of nitric oxide.
Etretinate and visual function: a 1-year follow-up study
Authors: J. F. PITTS, RONA M. MACKIE, G. N. DUTTON, ELIZABETH A. MCCLURE, D. ALLAN
Journal: British Journal of Dermatology (1991)

Concern has been expressed in the literature that the drug etretinate may be potentially retinotoxic. Four patients are reported who have received long-term treatment with etretinate and who have undergone detailed evaluation for the development of visual dysfunction over a 1-year period. Despite prolonged treatment and high total doses no evidence of ocular toxicity attributable to the drug was found in any of the patients.