tbuckley/cabot-search huggingface dataset:
Posterior Cingulate Glucose Metabolism, Hippocampal Glucose Metabolism, and Hippocampal Volume in Cognitively Normal, Late-Middle-Aged Persons at 3 Levels of Genetic Risk for Alzheimer Disease
Authors: Hillary D. Protas, Kewei Chen, Jessica B. S. Langbaum, Adam S. Fleisher, Gene E. Alexander, Wendy Lee, Daniel Bandy, Mony J. de Leon, Lisa Mosconi, Shannon Buckley, Diana Truran-Sacrey, Norbert Schuff, Michael W. Weiner, Richard J. Caselli, Eric M. Reiman
Journal: JAMA Neurology (2012)

<h3>Objective</h3>To characterize and compare measurements of the posterior cingulate glucose metabolism, the hippocampal glucose metabolism, and hippocampal volume so as to distinguish cognitively normal, late-middle-aged persons with 2, 1, or 0 copies of the apolipoprotein E (APOE) ϵ4 allele, reflecting 3 levels of risk for late-onset Alzheimer disease.<h3>Design</h3>Cross-sectional comparison of measurements of cerebral glucose metabolism using <sup>18</sup>F-fluorodeoxyglucose positron emission tomography and measurements of brain volume using magnetic resonance imaging in cognitively normal ϵ4 homozygotes, ϵ4 heterozygotes, and noncarriers.<h3>Setting</h3>Academic medical center.<h3>Participants</h3>A total of 31 ϵ4 homozygotes, 42 ϵ4 heterozygotes, and 76 noncarriers, 49 to 67 years old, matched for sex, age, and educational level.<h3>Main Outcome Measures</h3>The measurements of posterior cingulate and hippocampal glucose metabolism were characterized using automated region-of-interest algorithms and normalized for whole-brain measurements. The hippocampal volume measurements were characterized using a semiautomated algorithm and normalized for total intracranial volume.<h3>Results</h3>Although there were no significant differences among the 3 groups of participants in their clinical ratings, neuropsychological test scores, hippocampal volumes (P = .60), or hippocampal glucose metabolism measurements (P = .12), there were significant group differences in their posterior cingulate glucose metabolism measurements (P = .001). The APOE ϵ4 gene dose was significantly associated with posterior cingulate glucose metabolism (r = 0.29, P = .0003), and this association was significantly greater than those with hippocampal volume or hippocampal glucose metabolism (P &lt; .05, determined by use of pairwise Fisher z tests).<h3>Conclusions</h3>Although our findings may depend in part on the analysis algorithms used, they suggest that a reduction in posterior cingulate glucose metabolism precedes a reduction in hippocampal volume or metabolism in cognitively normal persons at increased genetic risk for Alzheimer disease.
SAT0290 Effect of tnf antagonists on radiographic progression in psoriatic arthritis: Systematic review and meta-analysis of randomized controlled trials
Authors: R. Goulabchand, G. Mouterde, T. Barnetche, J. Morel, B. Combe
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Psoriatic arthritis (PsA) can cause important structural damages which can lead to disability. TNF antagonists have shown their clinical efficacy in PsA, but only a few data are available regarding their structural effect. <h3>Objectives</h3> To determine whether TNF antagonists have an effect on radiographic progression in patients with PsA by performing a systematic review and meta-analysis based on data from randomized controlled trials (RCTs) versus placebo. To check if the combination with methotrexate (MTX) is superior to monotherapy. <h3>Methods</h3> A systematic review of literature was performed until March 2011. Bibliographic references were selected from Embase and Medline databases, and from the two last EULAR and the ACR annual meetings. Radiographs progression were scored by Sharp method modified for PsA (mTSS). Primary endpoint was the proportion of patients with no radiographic progression at week 24 (defined by a mTSS variation score ≤0.5). Secondary end point included the proportion of non progressors at week 48 and mean variation of mTSS at week 24. The Mantel-Haenszel method was used to provide a common odds-ratio (OR) estimate and 95% confidence interval (CI) in TNF antagonists (+/– DMARDs) versus placebo (+/– DMARDs) treated patients for infliximab, etanercept, adalimumab and golimumab RCTs. Statistical heterogeneity was assessed on the Q test (χ<sup>2</sup>), using a significance level of 0.05. OR and 95% CI were shown on forest plots. <h3>Results</h3> Search found out 206 articles and 3 abstracts. Retrieved data allowed meta-analysis on 4 articles and 1 abstract for the proportion of non progressors at week 24. 1110 patients were included, 484/584 (82,9%) were considered as non-progressors at week 24 in the TNF antagonists group versus 362/526 (68,8%) in the placebo group (OR=2.68 [1.99; 3.60] p&lt;0.0001) without heterogeneity (I<sup>2</sup>=3%;p=0.39) (<i>figure 1</i>). Based on 3 studies, same results were found at week 48 in favor of TNF antagonists group (OR=2.42 [1.57;3.71] I<sup>2</sup>=0%;p=0.91). Among 533 patients receiving TNF antagonists versus 454 receiving placebo in 3 studies (4 comparisons), the mean change of the mTSS at week 24 was lower in the TNF antagonist group versus placebo (Mean difference= -0,69 [-1.12; -0.27], with heterogeneity (I<sup>2</sup>=76%;p=0.006). Only two RCTs provided datas on the combination with MTX: the mean or median change of the mTSS was similar in adalimumab or infliximab subgroups, irrespective of the MTX use. <h3>Conclusions</h3> This meta-analysis of RCTs showed that all TNF antagonists lead to a better control of structural damages of the PsA than a placebo after 24 and 48 weeks of treatment. The respective role of DMARDS was not determined due to a lack of data. <h3>Disclosure of Interest</h3> None Declared
Localized oncolytic virotherapy inflames distant tumors and synergizes with immune checkpoint blockade leading to systemic tumor rejection
Authors: Dmitriy Zamarin, Rikke Holmgaard, Sumit Subudhi, Mena Mansour, Peter Palese, Taha Merghoub, Jedd D Wolchok, James P Allison
Journal: Journal for ImmunoTherapy of Cancer (2013)

Meeting abstracts Preexistent tumor inflammation is associated with superior clinical benefit from immunotherapies targeting immune checkpoints, calling for development of strategies that can induce tumor immune infiltration. To this end, therapy with oncolytic viruses (OV) presents an attractive
Cytosine Methylation Profiles as a Molecular Marker in Non–Small Cell Lung Cancer
Authors: Mathias Ehrich, John K. Field, Triantafillos Liloglou, George Xinarianos, Paul Oeth, Matthew R. Nelson, Charles R. Cantor, Dirk van den Boom
Journal: Cancer Research (2006)

Abstract Aberrant promoter methylation is frequently observed in different types of lung cancer. Epigenetic modifications are believed to occur before the clinical onset of the disease and hence hold a great promise as early detection markers. Extensive analysis of DNA methylation has been impeded by methods that are either too labor intensive to allow large-scale studies or not sufficiently quantitative to measure subtle changes in the degree of methylation. We used a novel quantitative DNA methylation analysis technology to complete a large-scale cytosine methylation profiling study involving 47 gene promoter regions in 96 lung cancer patients. Each individual contributed a lung cancer specimen and corresponding adjacent normal tissue. The study identified six genes with statistically significant differences in methylation between normal and tumor tissue (P &amp;lt; 10−6). We explored the quantitative methylation data using an unsupervised hierarchical clustering algorithm. The data analysis revealed that methylation patterns differentiate normal from tumor tissue. For validation of our approach, we divided the samples to train a classifier and test its performance. We were able to distinguish normal from lung cancer tissue with &amp;gt;95% sensitivity and specificity. These results show that quantitative cytosine methylation profiling can be used to identify molecular classification markers in lung cancer. (Cancer Res 2006; 66(22): 10911-8)
Antigranulocyte antibodies and deranged immune function associated with phenytoin‐induced serum sickness
Authors: Jay E. Menitove, Anne L. Rassiga, Gordon D. McLaren, Thomas M. Daniel, Adel A. F. Mahmoud
Journal: American Journal of Hematology (1981)

A phenytoin-associated serum-sickness-like syndrome was followed by severe pancytopenia in a 17-year-old female. Serum obtained during the acute phase of her illness contained antibodies against homologous eosinophils and neutrophils, antibodies against autologous neutrophils, and antibodies to phenytoin. The serum also inhibited bone marrow granulocyte colon formation in vitro. Lymphocyte transformation by pokeweed mitogen was impaired and, after recovery, the patient's lymphocytes were transformed in vitro by the addition of phenytoin. These data demonstrate that profound derangements of immunity can be associated with a phenytoin-induced serum-sickness-like illness.
<i>Escherichia coli</i> Nissle 1917 Facilitates Tumor Detection by Positron Emission Tomography and Optical Imaging
Authors: Peter Brader, Jochen Stritzker, Christopher C. Riedl, Pat Zanzonico, Shangde Cai, Eva M. Burnazi, E.Rashid Ghani, Hedvig Hricak, Aladar A. Szalay, Yuman Fong, Ronald Blasberg
Journal: Clinical Cancer Research (2008)

Abstract Purpose: Bacteria-based tumor-targeted therapy is a modality of growing interest in anticancer strategies. Imaging bacteria specifically targeting and replicating within tumors using radiotracer techniques and optical imaging can provide confirmation of successful colonization of malignant tissue. Experimental Design: The uptake of radiolabeled pyrimidine nucleoside analogues and [18F]FDG by Escherichia coli Nissle 1917 (EcN) was assessed both in vitro and in vivo. The targeting of EcN to 4T1 breast tumors was monitored by positron emission tomography (PET) and optical imaging. The accumulation of radiotracer in the tumors was correlated with the number of bacteria. Optical imaging based on bioluminescence was done using EcN bacteria that encode luciferase genes under the control of an l-arabinose–inducible PBAD promoter system. Results: We showed that EcN can be detected using radiolabeled pyrimidine nucleoside analogues, [18F]FDG and PET. Importantly, this imaging paradigm does not require transformation of the bacterium with a reporter gene. Imaging with [18F]FDG provided lower contrast than [18F]FEAU due to high FDG accumulation in control (nontreated) tumors and surrounding tissues. A linear correlation was shown between the number of viable bacteria in tumors and the accumulation of [18F]FEAU, but not [18F]FDG. The presence of EcN was also confirmed by bioluminescence imaging. Conclusion: EcN can be imaged by PET, based on the expression of endogenous E. coli thymidine kinase, and this imaging paradigm could be translated to patient studies for the detection of solid tumors. Bioluminescence imaging provides a low-cost alternative to PET imaging in small animals.
ADP Regulates SNF1, the Saccharomyces cerevisiae Homolog of AMP-Activated Protein Kinase
Authors: Faith V. Mayer, Richard Heath, Elizabeth Underwood, Matthew J. Sanders, David Carmena, Rhonda R. McCartney, Fiona C. Leiper, Bing Xiao, Chun Jing, Philip A. Walker, Lesley F. Haire, Roksana Ogrodowicz, Stephen R. Martin, Martin C. Schmidt, Steven J. Gamblin, David Carling
Journal: Cell Metabolism (2011)

The SNF1 protein kinase complex plays an essential role in regulating gene expression in response to the level of extracellular glucose in budding yeast. SNF1 shares structural and functional similarities with mammalian AMP-activated protein kinase. Both kinases are activated by phosphorylation on a threonine residue within the activation loop segment of the catalytic subunit. Here we show that ADP is the long-sought metabolite that activates SNF1 in response to glucose limitation by protecting the enzyme against dephosphorylation by Glc7, its physiologically relevant protein phosphatase. We also show that the regulatory subunit of SNF1 has two ADP binding sites. The tighter site binds AMP, ADP, and ATP competitively with NADH, whereas the weaker site does not bind NADH, but is responsible for mediating the protective effect of ADP on dephosphorylation. Mutagenesis experiments suggest that the general mechanism by which ADP protects against dephosphorylation is strongly conserved between SNF1 and AMPK.
Convergence of oncogenic and hormone receptor pathways promotes metastatic phenotypes
Authors: Michael A. Augello, Craig J. Burd, Ruth Birbe, Christopher McNair, Adam Ertel, Michael S. Magee, Daniel E. Frigo, Kari Wilder-Romans, Mark Shilkrut, Sumin Han, Danielle L. Jernigan, Jeffry L. Dean, Alessandro Fatatis, Donald P. McDonnell, Tapio Visakorpi, Felix Y. Feng, Karen E. Knudsen
Journal: Journal of Clinical Investigation (2012)

Cyclin D1b is a splice variant of the cell cycle regulator cyclin D1 and is known to harbor divergent and highly oncogenic functions in human cancer. While cyclin D1b is induced during disease progression in many cancer types, the mechanisms underlying cyclin D1b function remain poorly understood. Herein, cell and human tumor xenograft models of prostate cancer were utilized to resolve the downstream pathways that are required for the protumorigenic functions of cyclin D1b. Specifically, cyclin D1b was found to modulate the expression of a large transcriptional network that cooperates with androgen receptor (AR) signaling to enhance tumor cell growth and invasive potential. Notably, cyclin D1b promoted AR-dependent activation of genes associated with metastatic phenotypes. Further exploration determined that transcriptional induction of SNAI2 (Slug) was essential for cyclin D1b–mediated proliferative and invasive properties, implicating Slug as a critical driver of disease progression. Importantly, cyclin D1b expression highly correlated with that of Slug in clinical samples of advanced disease. In vivo analyses provided strong evidence that Slug enhances both tumor growth and metastatic phenotypes. Collectively, these findings reveal the underpinning mechanisms behind the protumorigenic functions of cyclin D1b and demonstrate that the convergence of the cyclin D1b/AR and Slug pathways results in the activation of processes critical for the promotion of lethal tumor phenotypes.
Preoperative Differentiation between Carcinoma of the Pancreas and Chronic Pancreatitis: The Contribution of Cytology
Authors: D.R. Hunt, L.H. Blumgart
Journal: Endoscopy (1982)

In a prospective study of 54 consecutive patients where carcinoma of the pancreas was suspected, a simple protocol was employed. Each patient had duodenoscopy and pancreatic juice cytology. Those patients with jaundice had cholangiography by percutaneous or endoscopic retrograde technique. Patients who were not jaundiced had endoscopic retrograde cholangiopancreatography. Malignancy, confirmed by histology, was diagnosed in 25 patients. Patients diagnosed to have benign disease have been followed for two years and in none has the diagnosis changed to malignancy. Twenty-one of those with carcinoma were correctly diagnosed on the basis of cholangiograms or pancreatograms but there were three false-positive diagnoses of malignancy. Cytology identified 15 of the 25 with carcinoma; there were no false positive diagnoses. Pancreatic cytology is highly specific for the diagnosis of carcinoma and should be used early. In patients with negative cytology, an acceptable level of accuracy can be achieved by a combination of endoscopy and radiology.
Leukopenia in Still's Disease
Authors: Michael Calmes
Journal: JAMA (1985)

To the Editor.—  We read with interest the article entitled Leukopenia in Still's Disease by Scopelitis et al,1which described two patients with fevers, polyarthritis, adenopathy, splenomegaly, and an erythematous rash. Both developed leukopenia during their illness, and one had thrombocytopenia. In addition, one patient developed pleural effusion and pulmonary infiltrates. Reported test results for antinuclear antibodies (ANA) were negative.  This certainly represents an interesting finding of cytopenia with Still's disease, since leukocytosis has previously been one of the hallmarks of Still's disease, as mentioned by the authors. However, from the data presented, we do not feel the diagnosis of systemic lupus can be totally excluded. There are numerous reports in the literature of the disease entity, ANA-negative SLE (systemic lupus erythematosus). In one series of 66 patients with ANA-negative SLE,362% were found to have anti-Ro antibodies, which now have been shown to be immunologically identical to
The Incidence of Transfusion-Associated Hepatitis G Virus Infection and Its Relation to Liver Disease
Authors: Harvey J. Alter, Yoshiyuki Nakatsuji, Jacqueline Melpolder, John Wages, Robert Wesley, J. Wai-Kuo Shih, Jungsuh P. Kim
Journal: New England Journal of Medicine (1997)

The role of hepatitis G virus (HGV) in transfusion-associated infection and its relation to liver disease are not well understood.
Benefit of Combined Resynchronization and Defibrillator Therapy in Heart Failure Patients With and Without Ventricular Arrhythmias
Authors: Claudia Ypenburg, Lieselot van Erven, Gabe B. Bleeker, Jeroen J. Bax, Marianne Bootsma, Maurits C. Wijffels, Ernst E. van der Wall, Martin J. Schalij
Journal: Journal of the American College of Cardiology (2006)
Endoscopic Transgastric Debridement and Drainage for Splenic Necrosis Following an Acute Episode in Chronic Alcoholic Pancreatitis
Authors: J. Binek, C. Fretz, C. Meyenberger
Journal: Endoscopy (2006)

Management of the complications and sequelae of acute and chronic pancreatitis is a clinical challenge. We report a case of successful transgastric drainage of splenic necrosis after occlusion of the splenic vessels during an acute episode in chronic pancreatitis.
Intestinal arteriolar responses to mucosal and serosal applications of adenosine analogues.
Authors: K G Proctor
Journal: Circulation Research (1987)

Adenosine or its synthetic analogues were topically applied to the intestinal jejunum while steady-state blood flow was calculated in submucosal arterioles using video microscopy. Blood flow increased (220 or 130% of control) with the serosal application of 10(-6) M N-ethyl carboxamido adenosine (NECA, A2-selective agonist) or 2-chloro adenosine (2CA, nonselective agonist) but not with cyclohexyl adenosine (CHA, A1-selective agonist). The nonselective competitive antagonist, 8-phenyl theophylline, attenuated the response evoked by NECA. The mucosal application of 10(-6) M CHA caused blood flow decreases (81% of control), but neither NECA nor 2CA evoked a response. These observations suggest a mucosal diffusion barrier, so the concentrations of the analogues were raised one hundredfold. Serosal 10(-4) M CHA or NECA caused blood flow increases, but the effects were negligible with mucosal application, suggesting that the mucosa was indeed impermeable to these compounds. The responses evoked by 10(-4) M 2CA were similar on the serosa or mucosa (200-220% of control), submaximal (maximum = 400% of control at 10(-3) M), and not antagonized by 8-phenyl theophylline or by the cellular uptake inhibitor, nitrobenzyl-6-thio guanosine. In context with earlier studies, greater than 10(-6) M 2CA probably evokes vasodilation that is not entirely mediated by extracellular receptors. Serosal adenosine (10(-4) M) caused submaximal blood flow increases (200% of control) that were not potentiated by nitrobenzyl-6-thio guanosine or another transport inhibitor, dipyridamole.(ABSTRACT TRUNCATED AT 250 WORDS)
TRACHOMA, ITS RELATIVE INFREQUENCY IN SOUTHERN CALIFORNIA.
Authors: H. BERT. ELLIS
Journal: JAMA (1898)

Although there is not a perfect agreement among pathologists as to the identity or non-identity of follicular conjunctivitis and trachoma (that is, as to whether they are independent affections), still the recent text-books on ophthalmology are almost unanimous in making a clinical if not a pathologic distinction between these manifestations. It is not my intention, nor is it necessary in a paper of this description, and on such an occasion, to enter into a dissertation giving the details of the arguments that have been, and are still being brought forward to prove the sameness or dissimilarity of these diseases. It is sufficient for the purposes of this article to state my own position in the controversy without giving the reasons for "the faith that is in me," and thus prevent any misunderstanding of terms. "Granular lids" is a phrase that I but rarely use, and then always as a synonym
IgE antibodies to animal‐derived lipocalin, kallikrein and secretoglobin are markers of bronchial inflammation in severe childhood asthma
Authors: B. Nordlund, J. R. Konradsen, I. Kull, M. P. Borres, A. Önell, G. Hedlin, H. Grönlund
Journal: Allergy (2012)

Abstract Background: Component‐resolved allergy diagnostics enables the detection of crossreactive or species‐specific allergen components. This study analysed Immunoglobulin E ( I g E ) profiles to single allergen components in relation to bronchial inflammation in severe childhood asthma. Methods: Ninety‐five schoolchildren were assessed, 39 with controlled mild‐to‐moderate asthma and 56 uncontrolled severe asthmatics. Allergen components ( n = 111) of food allergens, pollen and perennial aeroallergens were analysed using an immunosolid‐phase allergen chip. Blood eosinophils (10 9 × l −1 ), bronchial inflammation ( F e NO , ppb), lung function ( FEV 1 %) and bronchial hyper‐responsiveness ( BHR ) (dose–response slope of methacholine challenge) were measured. Results: A specific I g E response to more than three animal‐derived components – lipocalin ( nM us m 1, rE qu c 1, Fel d 4, rC an f 1, 2), kallikrein ( rC an f 5) and secretoglobin ( rF el d 1) – was more common among severe asthmatics compared to children with controlled asthma ( n = 14 vs n = 3, P = 0.030). These subjects also displayed higher blood eosinophils (0.65 vs 0.39, P = 0.021), higher Fractional exhaled nitric oxide (38 ppb vs 25 ppb, P = 0.021) and increased BHR (112 vs 28, P = 0.002) compared to other severe asthmatics positive to fewer lipocalin/kallikrein/secretoglobin components. Among all sensitized subjects, there were correlations between specific Ig E levels for rF el d 4 and nM us m 1 ( r = 0.751, P ≤ 0.001) and for rF el d 4 and rE qu c 1 ( r = 0.850, P ≤ 0.001). Conclusion: Multi‐sensitization towards lipocalin, kallikrein and secretoglobin components is associated with increased bronchial inflammation in severe asthmatics. In addition, crossreactive patterns were observed between different lipocalin components.
The presence of a microsomal UDP-glucuronyl transferase for bilirubin in homozygous jaundiced gunn rats and in the crigler-najjar syndrome
Authors: Gerard B. Odell, Julio O. Cukier, Glenn R. Gourley
Journal: Hepatology (1981)

The infusion of a closely related derivative of bilirubin, its dimethyl diester (DME), into jaundiced (jj) Gunn rats was associated with biliary excretion of mono-and diglucuronides of bilirubin. In vitro incubation of DME with liver microsomes from jj rats demonstrated sequential demethylation and glucuronidation of DME. Liver microsomes from a patient with the Crigler-Najjar syndrome were unable to form glucuronides of bilirubin in vitro unless DME was used as substrate. The results suggest that the deficiency in Gunn rats and in the Crigler-Najjar syndrome may be due to a structural defect in the microsomal matrix which contains glucuronyl transferase. This interpretation envisions a microenvironment of the transferase enzyme which is either impermeable to bilirubin or induces conformational changes which interfere with glucuronidation.