tbuckley/cabot-search huggingface dataset:
DRUG INTERACTION BETWEEN CLOPIDOGREL AND RANITIDINE OR OMEPRAZOLE IN PATIENTS WITH CORONARY HEART DISEASE: A DOUBLE-BLIND, DOUBLE-DUMMY, RANDOMIZED COMPARATIVE STUDY
Authors: Remo Holanda de Mendonca Furtado, Beatriz Tonon Freire, Celia Strunz, Carlos JDG Barbosa, André Franci, Flavia BB Arantes, Cyrillo C. Filho, Fernando R. Menezes, Elbio A. D'Amico, Jose Nicolau
Journal: Journal of the American College of Cardiology (2014)
Iron binding proteins of iron-absorbing rat intestinal mucosa.
Authors: G Johnson, P Jacobs, L R Purves
Journal: Journal of Clinical Investigation (1983)

The distribution and quantitation of the iron-binding proteins of rat small intestinal mucosa was studied, in iron-deficient and replete animals, to explore their role in the absorption of iron. Adsorption (mucosal uptake) of iron in in situ ligated loops of small intestinal mucosa was found to be uniform throughout the length of the small intestine whereas absorption (carcass uptake) showed a steep decreasing gradient from the duodenum to the ileum. The disrupted, in vivo labeled mucosal cells were fractionated by isopycnic centrifugation and transferrin and ferritin were quantitated by radioimmunoassay. Transferrin derived from mucosal cells was shown to have a higher affinity for the antibody than transferrin in serum. Of the transferrin present in the mucosal extract, only a portion could be accounted for by contamination from the serum; the proteolysis resistant and intrinsic transferrin may be mucosal cell specific. Transferrin was found in similar amounts in all regions of the small intestine, was not affected by iron loading but doubled in response to iron deficiency. Mucosal ferritin was found in greater amounts in the iron-absorbing areas of the intestine, increased in the duodenum of iron-loaded animals, and decreased in iron-deficient animals. The incorporation of newly absorbed radioiron into ferritin was only found in iron absorbing regions and was completely inhibited by colchicine and cytochalasin-B, suggesting that ferritin was loaded with iron at the point of iron absorption and that the process is associated with vesicle movement and not simple diffusion. Transferrin and ferritin-specific immunoabsorption and also gel filtration established that no other soluble iron binding proteins were involved in absorption.
Loratadine in the treatment of mosquito‐bite‐sensitive children
Authors: A. Karppinen, H. Kautiainen, T. Reunala, L. Petman, T. Reunala, H. Brummer‐Korvenkontio
Journal: Allergy (2000)

Children frequently experience harmful whealing and delayed papules from mosquito bites. Whealing is mediated by antisaliva IgE antibodies and histamine, but the effect of antihistamines on mosquito-bite symptoms has not been evaluated in children.The effect of loratadine (0.3 mg/kg) was examined in 28 mosquito-bite-sensitive children (aged 2-11 years). The double-blind, placebo-controlled, crossover study was performed with exposure to Aedes aegypti laboratory mosquitoes. The size of the bite lesion and the intensity of pruritus (visual analog scale) were measured at 15 min and at 2, 6, and 24 h.Loratadine decreased the size of the wheals by 45% (P < 0.001, 25 children) and accompanying pruritus by 78% (P = 0.011, 12 children) at 15 min compared to placebo. The size of the 24-h delayed bite lesion also decreased significantly (P = 0.004), but there was no change at 2 or 6 h. Loratadine was well tolerated and no marked side-effects were recorded.This study in children shows that prophylactically given loratadine decreases significantly the whealing and pruritus caused by mosquito bites and also reduces the size of the 24-h bite lesions. Therefore, the therapeutic profile of loratadine extends from immediate to delayed allergic symptoms in mosquito-bite-sensitive children.
Infection in Solid-Organ Transplant Recipients
Authors: Timothy J.S. Cross, Phillip A. Berry, Andrew K. Burroughs
Journal: New England Journal of Medicine (2008)

To the Editor: In his review of infections in recipients of solid-organ transplants, Fishman (Dec. 20 issue)1 discusses Clostridium difficile diarrhea in the immediate post-transplantation period. Although this infection has been reported previously in liver-transplant recipients,2 there is mounting evidence that gastric acid suppression may be implicated in this infection both in the community and in hospitalized patients,3,4 including patients with cirrhosis.5 In many institutions that perform transplantation, it is standard practice to prescribe proton-pump inhibitors in the immediate post-transplantation period in order to provide protection against stress ulceration and bleeding in the intensive care setting and subsequently as . . .
Use of bisphosphonates among women and risk of atrial fibrillation and flutter: population based case-control study
Authors: Henrik Toft Sørensen, Steffen Christensen, Frank Mehnert, Lars Pedersen, Roland D Chapurlat, Steven R Cummings, John A Baron
Journal: BMJ (2008)

<b>Objective</b> To assess the association between atrial fibrillation and flutter and use of bisphosphonates for osteoporosis among women. <b>Design</b> Population based case-control study, using medical databases from Denmark. <b>Setting</b> Northern Denmark. <b>Participants</b> 13 586 patients with atrial fibrillation and flutter and 68 054 population controls, all with complete hospital and prescription history. <b>Main outcome measure</b> Adjusted relative risk of atrial fibrillation and flutter. <b>Results</b> 435 cases (3.2%) and 1958 population controls (2.9%) were current users of bisphosphonates for osteoporosis. Etidronate and alendronate were used with almost the same frequency among cases and controls. The adjusted relative risk of current use of bisphosphonates compared with non-use was 0.95 (95% confidence interval 0.84 to 1.07). New users had a relative risk of 0.75 (95% confidence interval 0.49 to 1.16), broadly similar to the estimate for continuing users (relative risk 0.96, 95% confidence interval 0.85 to 1.09). The relative risk estimates were independent of number of prescriptions and the position of the atrial fibrillation and flutter diagnosis in the discharge record, and were similar for inpatients and outpatients. <b>Conclusion</b> No evidence was found that use of bisphosphonates increases the risk of atrial fibrillation and flutter.
Public clonotype usage identifies protective Gag-specific CD8+ T cell responses in SIV infection
Authors: David A. Price, Tedi E. Asher, Nancy A. Wilson, Martha C. Nason, Jason M. Brenchley, Ian S. Metzler, Vanessa Venturi, Emma Gostick, Pratip K. Chattopadhyay, Mario Roederer, Miles P. Davenport, David I. Watkins, Daniel C. Douek
Journal: The Journal of Experimental Medicine (2009)

Despite the pressing need for an AIDS vaccine, the determinants of protective immunity to HIV remain concealed within the complexity of adaptive immune responses. We dissected immunodominant virus-specific CD8+ T cell populations in Mamu-A*01+ rhesus macaques with primary SIV infection to elucidate the hallmarks of effective immunity at the level of individual constituent clonotypes, which were identified according to the expression of distinct T cell receptors (TCRs). The number of public clonotypes, defined as those that expressed identical TCR β-chain amino acid sequences and recurred in multiple individuals, contained within the acute phase CD8+ T cell population specific for the biologically constrained Gag CM9 (CTPYDINQM; residues 181–189) epitope correlated negatively with the virus load set point. This independent molecular signature of protection was confirmed in a prospective vaccine trial, in which clonotype engagement was governed by the nature of the antigen rather than the context of exposure and public clonotype usage was associated with enhanced recognition of epitope variants. Thus, the pattern of antigen-specific clonotype recruitment within a protective CD8+ T cell population is a prognostic indicator of vaccine efficacy and biological outcome in an AIDS virus infection.
Effectiveness of five different approaches in management of urinary tract infection: randomised controlled trial
Authors: P Little, M V Moore, S Turner, K Rumsby, G Warner, J A Lowes, H Smith, C Hawke, G Leydon, A Arscott, D Turner, M Mullee
Journal: BMJ (2010)

<h3>Abstract</h3> Probabilistic models have provided the underpinnings for state-of-the-art performance in many single-cell omics data analysis tasks, including dimensionality reduction, clustering, differential expression, annotation, removal of unwanted variation, and integration across modalities. Many of the models being deployed are amenable to scalable stochastic inference techniques, and accordingly they are able to process single-cell datasets of realistic and growing sizes. However, the community-wide adoption of probabilistic approaches is hindered by a fractured software ecosystem resulting in an array of packages with distinct, and often complex interfaces. To address this issue, we developed scvi-tools (https://scvi-tools.org), a Python package that implements a variety of leading probabilistic methods. These methods, which cover many fundamental analysis tasks, are accessible through a standardized, easy-to-use interface with direct links to Scanpy, Seurat, and Bioconductor workflows. By standardizing the implementations, we were able to develop and reuse novel functionalities across different models, such as support for complex study designs through nonlinear removal of unwanted variation due to multiple covariates and reference-query integration via scArches. The extensible software building blocks that underlie scvi-tools also enable a developer environment in which new probabilistic models for single cell omics can be efficiently developed, benchmarked, and deployed. We demonstrate this through a code-efficient reimplementation of Stereoscope for deconvolution of spatial transcriptomics profiles. By catering to both the end user and developer audiences, we expect scvi-tools to become an essential software dependency and serve to formulate a community standard for probabilistic modeling of single cell omics.
WARFARIN VERSUS ASPIRIN FOR PREVENTION OF STROKE IN HEART FAILURE: A META-ANALYSIS
Authors: Kathan Mehta, Peeyush Grover, Nileshkumar J. Patel, Neeraj Shah, Vikas Singh, Abhishek Deshmukh, George R. Marzouka, Ankit Rathod, Ghanshyam Savani, Ankit Chothani, Apurva O. Badheka, Mauricio G. Cohen
Journal: Journal of the American College of Cardiology (2013)
A Randomized, Double-Blind, Placebo-Controlled Trial on Restenosis Prevention by the Receptor Tyrosine Kinase Inhibitor Imatinib
Authors: Dietlind Zohlnhöfer, Jörg Hausleiter, Adnan Kastrati, Julinda Mehilli, Christoph Goos, Helmut Schühlen, Jürgen Pache, Gisela Pogatsa-Murray, Uwe Heemann, Josef Dirschinger, Albert Schömig
Journal: Journal of the American College of Cardiology (2005)
Tumour necrosis factor and endotoxin synergistically activate intestinal phospholipase A2 in mice. Role of endogenous platelet activating factor and effect of exogenous platelet activating factor.
Authors: X Sun, M S Caplan, W Hsueh
Journal: Gut (1994)

Previous studies have shown that: (a) platelet activating factor induces shock and intestinal injury, (b) exogenous platelet activating factor stimulates synthesis of endogenous platelet activating factor, and (c) tumour necrosis factor alpha and endotoxin synergise to induce shock and bowel injury in animals. These last two effects are largely mediated by platelet activating factor forming phospholipase A2 A2, a key enzyme for platelet activating factor synthesis, was examined in mouse intestine. It was found that tumour necrosis factor alpha and endotoxin synergise to stimulate platelet activating factor forming phospholipase A2 activity in the intestine, as well as platelet activating factor production, and these effects were blocked by pretreatment with platelet activating factor antagonists, SRI-63-441 and WEB 2086. In addition, exogenous platelet activating factor stimulates intestinal phospholipase A2 activity. These results show that tumour necrosis factor alpha and lipopolysaccharide synergistically activate the phospholipase A2 that participates in platelet activating factor formation, and this activation is largely mediated by endogenous platelet activating factor. Furthermore, platelet activating factor itself increases phospholipase A2 activity, suggesting that platelet activating factor induces its own synthesis, probably by phospholipase A2 activation.
Neurobehavioral Functioning of Adults with Pituitary Disease
Authors: Christina Meyers
Journal: Psychotherapy and Psychosomatics (1998)

Neurobehavioral disorders are not infrequent in adults with pituitary disease. The disorders can be due to compression of brain structures important for cognitive and emotional function, effects of hormonal imbalance on sensitive structures, post-surgical disruption of connecting pathways, adverse reactions to medical therapy, and adverse delayed effects of radiation therapy. A multidisciplinary team approach to the treatment of pituitary tumors will allow for the early diagnosis of neurobehavioral disorders and the institution of pharmacologic and behavioral interventions.
SERIAL MEASUREMENT OF GALECTIN-3 PREDICTS CHRONIC HEART FAILURE OUTCOMES AND VENTRICULAR REMODELING: RESULTS FROM THE PROBNP OUTPATIENT TAILORED CHRONIC HEART FAILURE THERAPY (PROTECT) STUDY
Authors: Shweta Motiwala, Jackie Szymonifka, Arianna Belcher, Rory Weiner, Aaron Baggish, Patrick Sluss, Hanna Gaggin, Anju Bhardwaj, James Januzzi
Journal: Journal of the American College of Cardiology (2013)
Functional Effects of Endothelin and Regulation of Endothelin Receptors in Isolated Human Nonfailing and Failing Myocardium
Authors: Burkert Pieske, Beate Beyermann, Volker Breu, Bernd M. Löffler, Klaus Schlotthauer, Lars S. Maier, Stephan Schmidt-Schweda, Hanjörg Just, Gerd Hasenfuss
Journal: Circulation (1999)

An activated endothelin (ET) system may be of pathophysiological relevance in human heart failure. We characterized the functional effects of ET-1, ET receptors, and ET-1 peptide concentration in left ventricular myocardium from 10 nonfailing hearts (NF) and 27 hearts in end-stage failure due to idiopathic dilative cardiomyopathy (DCM).Inotropic effects were characterized in isolated muscle strips (1 Hz; 37 degrees C). ET-1 0.0001 to 0.3 micromol/L significantly (P<0.05) increased twitch force by maximally 59+/-10% in NF and by 36+/-11% in DCM (P<0.05 versus NF). Preincubation with propranolol 1 micromol/L and prazosin 0.1 micromol/L did not affect the response to ET-1, but the mixed ET receptor antagonist bosentan and the ETA receptor antagonist BQ-123 shifted the concentration-response curves for ET-1 rightward. The ETB receptor agonist sarafotoxin S6c 0.001 to 0.3 micromol/L had no functional effects. The inotropic response to ET-1 was not associated with increased intracellular Ca2+ transients, as assessed in aequorin-loaded muscle strips. ET receptor density (Bmax; radioligand binding) was 62.5+/-12.5 fmol/mg protein in NF and 122. 4+/-24.3 fmol/mg protein in DCM (P<0.05 versus NF). The increase in Bmax in DCM resulted from an increase in ETA receptors without change in ETB receptors. ET-1 peptide concentration (radioimmunoassay) was higher in DCM than in NF (14 447+/-2232 versus 4541+/-1340 pg/mg protein, P<0.05).ET-1 exerts inotropic effects in human myocardium through ETA receptor-mediated increases in myofibrillar Ca2+ responsiveness. In DCM, functional effects of ET-1 are attenuated, but ETA receptor density and ET-1 peptide concentration are increased, indicating an activated local cardiac ET system and possibly a reduced postreceptor signaling efficiency.
Dogma destroyed: colonic crypts absorb.
Authors: D W Powell
Journal: Journal of Clinical Investigation (1995)

Gastroenterologists and gastrointestinal physiologists have be- come wary of dogma.Once the dogma of acid's primacy as the cause of peptic ulcer disease was destroyed by a spiral-shaped bacillus called Helicobacter pylon, the gastrointestinal investi- gator is now more open and willing to accept new ideas and to seek new evidence to support them.If "acid equals ulcer" was perhaps the most infallible of gastroenterologic dogma, i.e., our
A Case-Control Study of Spermicides and Gonorrhea
Authors: Harland Austin
Journal: JAMA (1984)

A case-control study was done to evaluate the effectiveness of vaginal spermicides as a prophylaxis against gonorrhea. The subjects included 735 women with gonorrhea and 958 controls seen in a sexually transmitted disease clinic. The relative risk (RR) of gonorrhea for spermicide users compared with nonusers was 0.67 with 90% confidence limits, 0.44 to 1.0. This RR was 0.47 (90% confidence limits, 0.25 to 0.87) after the exclusion of women using oral contraceptives, an intrauterine device, or with a tubal ligation. The protective effect of spermicides was confined largely to women who had also used diaphragms or whose partners had used condoms. The RR of gonorrhea for spermicide and condom users relative to nonusers of spermicides, condoms, and diaphragms was 0.41 (90% confidence limits, 0.21 to 0.79), while for spermicide and diaphragm users, this RR was 0.45 (90% confidence limits, 0.15 to 1.3). These results suggest that a woman can appreciably decrease her risk of contracting gonorrhea if she uses spermicides in conjunction with either the diaphragm or the condom. (<i>JAMA</i>1984;251:2822-2824)
Abstract 1231: <i>In vitro</i> anticancer activity of imidazo-acridinone (HKH40A) in panels of human patient-derived tumor xenografts (PDXs) and human leukemia and lymphoma cell lines
Authors: Heinz H. Fiebig, Armin Maier, Gerhard Kelter, Vincent Vuaroqueaux, Humcha K. Hariprakasha, Christopher Michejda
Journal: Cancer Research (2014)

Abstract HKH40A is a synthetic, DNA-intercalating (Kosakowska-Cholody et al., 2009) anticancer agent consisting of an imidazo-acridinone linked to a 1,8-naphthalimide moiety via a 1,4-dipropylpiperazine linker. It displayed strong inhibitory activity in the NCI-60 tumor cell line panel in vitro with an IC50 of about 1 nM in selected tumor cell lines (Hariprakasha et al. 2007). In addition, anticancer activity was observed in hepatoma models both in vitro and in vivo. We have investigated the in vitro anticancer activity of HKH40A in 3D cultures, using panels of 206 PDXs and 11 human leukemia and lymphoma cell lines. The 3D clonogenic assay was performed in a 96 well format using a metabolic readout as an equivalent for colony formation. PDXs and hematologic cell lines were propagated in immunedeficient mice. HKH40A proved to be very potent with a mean IC50 of 6 nM and a mean IC70 of 12 nM. Overall, the hematological cell lines were more sensitive than the solid tumor models. Selective activity (definition: IC50 &amp;lt; 1/3 of mean IC50) was seen in 4 out of 6 acute myeloid leukaemias (AMLs), in 1 out of 1 chronic lymphocytic leukemia (CLL) and in 1 out of 3 non-Hodgkin lymphomas (NHLs). Among the solid tumors, pleural mesotheliomas were most sensitive followed by soft tissue sarcomas and anal cancer. Selective activity was observed in a subset of 8 out of 30 colon cancer models, which presented IC50 values &amp;lt; 1/3 of the mean IC50 of all tumors. The drug sensitivity data will be correlated to mutational and transcriptomic (Whole Exome Sequencing and Affymetrix HG-U133 plus 2.0 array profiles) characteristics of the PDXs to identify predictive biomarkers of drug response and resistance. Overall, HKH40A is a novel imidazo-acridinone with high in vitro activity mainly in AMLs and NHLs as well as in pleural mesotheliomas, soft tissue sarcomas and in a subset of colon cancer models. The identification of predictive biomarkers is ongoing. *Deceased during an NCI retreat Citation Format: Heinz H. Fiebig, Armin Maier, Gerhard Kelter, Vincent Vuaroqueaux, Humcha K. Hariprakasha, Christopher Michejda. In vitro anticancer activity of imidazo-acridinone (HKH40A) in panels of human patient-derived tumor xenografts (PDXs) and human leukemia and lymphoma cell lines. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1231. doi:10.1158/1538-7445.AM2014-1231
The Clinical Relevance of the miR-197/CKS1B/STAT3-mediated PD-L1 Network in Chemoresistant Non-small-cell Lung Cancer
Authors: Yu Fujita, Shigehiro Yagishita, Keitaro Hagiwara, Yusuke Yoshioka, Nobuyoshi Kosaka, Fumitaka Takeshita, Tomohiro Fujiwara, Koji Tsuta, Hiroshi Nokihara, Tomohide Tamura, Hisao Asamura, Makoto Kawaishi, Kazuyoshi Kuwano, Takahiro Ochiya
Journal: Molecular Therapy (2015)

Programmed cell death ligand-1 (PD-L1) has recently gained considerable attention for its role in tumor immune escape. Here, we identify a miR-197/CKS1B/STAT3-mediated PD-L1 network in chemoresistant non-small-cell lung cancer (NSCLC), independent of immunoinhibitory signals. miR-197 is downregulated in platinum-resistant NSCLC specimens, resulting in the promotion of chemoresistance, tumorigenicity, and pulmonary metastasis in vitro and in vivo. Mechanistic investigations reveal that a miR-197-mediated CKS1B/STAT3 axis exerts tumor progression regulated by various oncogenic genes (Bcl-2, c-Myc, and cyclin D1), and PD-L1 is a putative biomarker of this axis. Furthermore, we demonstrate that a miR-197 mimic sensitizes PD-L1(high) drug-resistant cells to chemotherapy. These results indicate that the biological interaction between PD-L1 and chemoresistance occurs through the microRNA regulatory cascade. More importantly, expression levels of miR-197 are inversely correlated with PD-L1 expression (n = 177; P = 0.026) and are associated with worse overall survival (P = 0.015). Our discoveries suggest that the miR-197/CKS1B/STAT3-mediated network can drive tumor PD-L1 expression as a biomarker of this cascade, and miR-197 replacement therapy may be a potential treatment strategy for chemoresistant NSCLC.
The Expression of Genetic Information
Authors: John W. Littlefield
Journal: New England Journal of Medicine (1963)

IT has become widely accepted that within a cell genetic information is coded in the sequence of bases in deoxyribonucleic acid (DNA), that DNA can direct the synthesis both of itself and of ribonucleic acid (RNA) with an analogous base sequence and that the base sequence in RNA can be translated into the sequence of amino acids in a protein. The amino acid sequence in a protein molecule determines its function; the kinds and amounts of proteins in a cell determine what kind of cell it is. Since each cell contains many different proteins there are many different RNA templates, . . .