tbuckley/cabot-search huggingface dataset:
PWE-232 ADAMDEC1: a novel molecule in inflammation and bowel disease
Authors: N R O'shea, T S Chew, G Sewell, S Bloom, A Smith, A Segal
Journal: Gut (2012)

<h3>Introduction</h3> Innate immunity is attenuated in patients with Crohn9s disease (CD) with impaired neutrophil recruitment to skin and bowel, delayed clearance of <i>Escherichia coli</i> from the skin, and impaired secretion of pro-inflammatory cytokines from macrophages (Marks <i>et al</i>, 2006; Smith <i>et al</i>, 2009). The primary defect of acute inflammation results in failure to eradicate bacterial flora entering the bowel wall leading to the chronic granulomatous inflammation characteristic of CD. Microarray analysis of peripheral blood monocyte derived macrophage mRNA expression, confirmed by qPCR, revealed that ADAMDEC1 (ADAM like Decysin1) was under-expressed in 10% (6/60) of CD patients. ADAMDEC1, a Metalloprotease and Decysin, is part of a family of proteins involved in wound healing and tissue repair, and is almost exclusively expressed in macrophages, dendritic cells and the gastrointestinal tract. To determine the role of this protein we examined <i>E coli</i> induced inflammation and Dextran Sodium Sulphate (DSS) colitis in the Adamdec1 knockout (KO) mouse. <h3>Methods</h3> In an acute colitis model, Adamdec1 KO mice were exposed to 2% DSS for 7 days. Controls, wild type (WT) litter mates, were age, weight and sex matched (n=11 per group). Clinical colitis scores (weight loss, PR blood, loose stool) were recorded daily. Histology was obtained from small and large bowels. For bacterial inflammation, 5×10<sup>8</sup> heat killed <i>E coli</i> (HkEc) were injected subcutaneously (SC) into two sites on the backs of KO and WT mice (n=8 per group). Mice were weighed, injection sites inspected for ulceration and subcutaneous inflammatory nodules measured, daily. Injection sites were excised at different time points for histology and identification of infiltrating cells by FACS. <h3>Results</h3> Adamdec1 KO mice were more susceptible to DSS colitis. They demonstrated higher clinical colitis scores with an earlier and more dramatic weight loss (p&lt;0.001). A more florid inflammatory response was seen on histology. In response to a subcutaneous injection of <i>E coli</i>, Adamdec1 KO mice had significantly smaller inflammatory nodules and less ulceration at the injection sites after 48–72 h, compared with WT mice (p&lt;0.001). <h3>Conclusion</h3> Mice lacking Adamdec1 develop a phenotype that closely mirrors that observed in patients with CD, an attenuated and delayed <i>E coli</i> induced acute inflammatory and an increased susceptibility to bowel inflammation. These results suggest ADAMDEC1 plays an important role in the acute inflammatory response to bacteria and has a protective role within the intestine, reduced levels may have a pivotal role in the development and persistence of CD. <h3>Competing interests</h3> None declared.
The Toll-like receptor 4 ligands Mrp8 and Mrp14 are crucial in the development of autoreactive CD8+ T cells
Authors: Karin Loser, Thomas Vogl, Maik Voskort, Aloys Lueken, Verena Kupas, Wolfgang Nacken, Lars Klenner, Annegret Kuhn, Dirk Foell, Lydia Sorokin, Thomas A Luger, Johannes Roth, Stefan Beissert
Journal: Nature Medicine (2010)
Liver fibrosis induced by hepatic overexpression of PDGF-B in transgenic mice
Authors: Piotr Czochra, Borut Klopcic, Erik Meyer, Johannes Herkel, Jose Francisco Garcia-Lazaro, Florian Thieringer, Peter Schirmacher, Stefan Biesterfeld, Peter R. Galle, Ansgar W. Lohse, Stephan Kanzler
Journal: Journal of Hepatology (2006)
Reduced-Function CYP2C19 Genotype and Risk of Adverse Clinical Outcomes Among Patients Treated With Clopidogrel Predominantly for PCI
Authors: Jessica L. Mega, Tabassome Simon, Jean-Philippe Collet, Jeffrey L. Anderson, Elliott M. Antman, Kevin Bliden, Christopher P. Cannon, Nicolas Danchin, Betti Giusti, Paul Gurbel, Benjamin D. Horne, Jean-Sebastian Hulot, Adnan Kastrati, Gilles Montalescot, Franz-Josef Neumann, Lei Shen, Dirk Sibbing, P. Gabriel Steg, Dietmar Trenk, Stephen D. Wiviott, Marc S. Sabatine
Journal: JAMA (2010)

<h3>Content</h3>Clopidogrel, one of the most commonly prescribed medications, is a prodrug requiring CYP450 biotransformation. Data suggest its pharmacologic effect varies based on CYP2C19 genotype, but there is uncertainty regarding the clinical risk imparted by specific genotypes.<h3>Objective</h3>To define the risk of major adverse cardiovascular outcomes among carriers of 1 (≈ 26% prevalence in whites) and carriers of 2 (≈ 2% prevalence in whites) reduced-function CYP2C19 genetic variants in patients treated with clopidogrel.<h3>Data Sources and Study Selection</h3>A literature search was conducted (January 2000-August 2010) in MEDLINE, Cochrane Database of Systematic Reviews, and EMBASE. Genetic studies were included in which clopidogrel was initiated in predominantly invasively managed patients in a manner consistent with the current guideline recommendations and in which clinical outcomes were ascertained.<h3>Data Extraction</h3>Investigators from 9 studies evaluating CYP2C19 genotype and clinical outcomes in patients treated with clopidogrel contributed the relevant hazard ratios (HRs) and 95% confidence intervals (CIs) for specific cardiovascular outcomes by genotype.<h3>Results</h3>Among 9685 patients (91.3% who underwent percutaneous coronary intervention and 54.5% who had an acute coronary syndrome), 863 experienced the composite end point of cardiovascular death, myocardial infarction, or stroke; and 84 patients had stent thrombosis among the 5894 evaluated for such. Overall, 71.5% were noncarriers, 26.3% had 1 reduced-function CYP2C19 allele, and 2.2% had 2 reduced-function CYP2C19 alleles. A significantly increased risk of the composite end point was evident in both carriers of 1 (HR, 1.55; 95% CI, 1.11-2.17; P = .01) and 2 (HR, 1.76; 95% CI, 1.24-2.50; P = .002) reduced-function CYP2C19 alleles, as compared with noncarriers. Similarly, there was a significantly increased risk of stent thrombosis in both carriers of 1 (HR, 2.67; 95% CI, 1.69-4.22; P &lt; .0001) and 2 (HR, 3.97; 95% CI, 1.75-9.02; P = .001) CYP2C19 reduced-function alleles, as compared with noncarriers.<h3>Conclusion</h3>Among patients treated with clopidogrel for percutaneous coronary intervention, carriage of even 1 reduced-function CYP2C19 allele appears to be associated with a significantly increased risk of major adverse cardiovascular events, particularly stent thrombosis.
Lung proliferative and clearance responses to inhaled para-aramid RFP in exposed hamsters and rats: comparisons with chrysotile asbestos fibers.
Authors: D B Warheit, S I Snajdr, M A Hartsky, S R Frame
Journal: Environmental Health Perspectives (1997)

This study compared pulmonary effects of para-aramid respirable-sized, fiber-shaped particles (RFP) (p-aramid fibrils) and chrysotile asbestos fiber exposures in rats. Additional p-aramid inhalation studies were conducted in hamsters to compare species responses. The hamster results are preliminary. The parameters studied were clearance/biopersistence of inhaled p-aramid RFP or size-separated asbestos fibers as well as pulmonary cell proliferation and inflammation indices after 2-week inhalation exposures. Rats were exposed nose only to chrysotile asbestos fibers at concentrations of 459 and 782 fibers/ml or to p-aramid RFP at 419 or 772 fibrils/ml. Hamsters were exposed whole body to p-aramid RFP at concentrations of 358 and 659 fibrils/ml. Subsequently, animals were assessed immediately (time 0) as well as 5 days (10 days for hamsters), 1, 3, 6, and 12 months postexposure. Lung burdens for the p-aramid-exposed rats were 4.8 x 10(7) and 7.6 x 10(7) fibrils/lung, with similar numbers of chrysotile fibers > 5 microns recovered from the lungs of asbestos-exposed rats. In comparison, 1.4 x 10(6) fibrils/lung were recovered in the high-dose hamster group. Biopersistence studies in p-aramid-exposed rats and hamsters demonstrated an initial increase (relative to time 0) in retained p-aramid fibrils during the first month postexposure, which indicated breakage or shortening of inhaled fibrils. This result was associated with a progressive reduction, and increased residence time in the lung, in the mean lengths of the fibrils, which signified biodegradability of inhaled p-aramid fibrils in both species. In contrast, clearance of short chrysotile asbestos fibers was rapid, but clearance of the long chrysotile fibers was slow or insignificant, as evidenced by a progressive increase over time in the mean lengths of fibers recovered from the lungs of exposed rats. Two-week, high-dose exposures to p-aramid in both rats and hamsters produced transient increases in pulmonary inflammatory and cell proliferative responses. In contrast, inhalation of size-separated chrysotile asbestos fibers in rats produced persistent increases in cell labeling indices of airway, alveolar, and subpleural cells measured through a period of 1 to 3 months postexposure. These results suggest that inhaled p-aramid RFP are biodegradable in the lungs of exposed rats and hamsters. In contrast, exposures to chrysotile asbestos fibers in rats resulted in a selective pulmonary retention of long chrysotile fibers.
THE PATHOLOGY OF POLIOMYELITIS
Authors: ERNEST W. GOODPASTURE
Journal: JAMA (1941)

Because of the nature of the disease, the early lesions of acute poliomyelitis or infantile paralysis in man are accessible for study only at necropsy, and it is from such material that the cytopathologic picture has been built. Although the chordal and bulbar lesions afford the chief sources for clinical expressions of the disease in the form of palsies, the damaging effects of the infection in the central nervous system are more widespread. Focal areas of injury are present in most if not all cases in the pons, brain stem, motor cortex and meninges, so that a more descriptive terminology would appropriately designate the pathologic-anatomic aspects of the nervous involvement as meningoencephalomyelitis. Evidences of injury have been found likewise in the dorsal root ganglion, and a more complete search would probably disclose lesions rather constantly in these structures and perhaps likewise in peripheral ganglions. Some investigators have attached perhaps too
Necrotic cutaneous arachnidism in the U.K.
Authors: S.A. Sakka, J.P. Howse
Journal: British Journal of Dermatology (1994)

Journal Article Necrotic cutaneous arachnidism in the U.K. Get access S.A. Sakka, S.A. Sakka Department of Orthopaedic Surgery. Bedford Hospital Kempston Road. Bedford. U.K. Search for other works by this author on: Oxford Academic Google Scholar J.P. Howse J.P. Howse Department of Orthopaedic Surgery. Bedford Hospital Kempston Road. Bedford. U.K. Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 130, Issue 4, 1 April 1994, Pages 542–543, https://doi.org/10.1111/j.1365-2133.1994.tb03398.x Published: 01 April 1994
Compassionate Pain Relief: Is Heroin the Answer?
Authors: Edward N. Brandt
Journal: New England Journal of Medicine (1984)

There has been much political interest in the approval of heroin for the arrest of chronic pain, especially in patients with terminal illness. Indeed, legislation H.R. 5290, the proposed Compassionate Pain Relief Act, has been introduced to obtain such approval. This paper is a summary of the situation.H.R. 5290 would require the secretary of Health and Human Services to provide for the manufacture of heroin, which would be dispensed to patients through hospital and hospice pharmacies, on a prescription basis, for the relief of pain from cancer. The statutory requirements for the approval of new drugs by the Food . . .
Right Ventricular Diastolic Function 15 to 35 Years After Repair of Tetralogy of Fallot
Authors: Michael A. Gatzoulis, Andrew L. Clark, Seamus Cullen, Claus G. H. Newman, Andrew N. Redington
Journal: Circulation (1995)

We have shown previously that transient right ventricular restriction after tetralogy of Fallot repair prolongs postoperative course. This is a prospective study of right ventricular diastolic performance in late follow-up patients.We studied biventricular function, using Doppler echocardiographic examination. Pulmonary arterial, tricuspid, and mitral valves and superior vena cava Doppler spectrals were obtained in 41 patients (mean age, 28.8 years), 15 to 35 years (mean, 23.6) after complete repair of tetralogy of Fallot. Patients were considered to have evidence of right ventricular restriction if antegrade diastolic flow was detected in the main pulmonary artery, coinciding with atrial systole (A wave), throughout the respiratory cycle. Exercise function was measured by graded treadmill testing with respiratory mass spectrometry. Three patients were excluded because of pulmonary outflow obstruction (Doppler gradient > 40 mm Hg) or residual intracardiac shunts. Of the 38 patients, 37 were in sinus rhythm. Twenty (52.6%) had definite evidence of restriction with an A wave in the pulmonary artery, augmented during inspiration. In all 20 cases, there was superior vena caval flow reversal with atrial systole. Both inspiratory and expiratory transtricuspid E-wave deceleration time was significantly shorter in the restrictive group (P < .003 and P < .03, respectively). All patients had Doppler evidence of pulmonary regurgitation, but its duration was shorter in the restrictive group (P < .01) during inspiration. Cardiothoracic ratio was significantly lower in the restrictive group (P < .01), suggesting less severe pulmonary regurgitation. Both restrictive and nonrestrictive groups had reduced exercise MVO2 compared with healthy age- and sex-matched control subjects, but those with restrictive physiology had significantly better maximum oxygen uptake than the nonrestrictive group (P < .001).Isolated right ventricular restriction late after tetralogy of Fallot repair is common. Although it reflects abnormal hemodynamics, the A wave contributes to forward pulmonary arterial flow and shortens the duration of pulmonary regurgitation. Consequently, there is less cardiomegaly and improved exercise performance in those patients.
Evaluation of a triple-lumen central venous heparin-coated catheter versus a catheter coated with chlorhexidine and silver sulfadiazine in critically ill patients
Authors: M. N. Carrasco, A. Bueno, C. de las Cuevas, S. Jimenez, I. Salinas, A. Sartorius, T. Recio, M. Generelo, F. Ruiz-Ocaña
Journal: Intensive Care Medicine (2004)
A 4-year-old girl with manifestations of multiple chemical sensitivities.
Authors: A Woolf
Journal: Environmental Health Perspectives (2000)

Multiple chemical sensitivities (MCS) syndrome, also known as idiopathic environmental intolerance, is a controversial diagnosis that encompasses a wide range of waxing and waning, subjective symptoms referable to more than one body system and provoked by exposure to low levels of chemicals, foods, or other agents in the environment. Although MCS has been studied extensively, a unifying mechanism explaining the illness remains obscure, and clinicians are divided as to whether such a medical entity exists separately from psychosomatic syndromes. MCS is an adult diagnosis; there is little reference to pediatric cases in the scientific literature. In this case from the Pediatric Environmental Health Subspecialty Unit at Boston's Children's Hospital, I present the case of a preschool child who had suffered from milk allergy and poor weight gain as an infant, and then later developed asthma, allergic symptoms, sinusitis, headaches, fatigue, and rashes precipitated by an expanding variety of chemicals, foods, and allergens. I review definitions, mechanisms, diagnostic strategies, and management, and discuss some uniquely pediatric features of MCS as illustrated by this case.
Kallikrein-Related Peptidase 7 Promotes Multicellular Aggregation via the α5β1 Integrin Pathway and Paclitaxel Chemoresistance in Serous Epithelial Ovarian Carcinoma
Authors: Ying Dong, Olivia L. Tan, Daniela Loessner, Carson Stephens, Carina Walpole, Glen M. Boyle, Peter G. Parsons, Judith A. Clements
Journal: Cancer Research (2010)

Kallikrein-related peptidase 7 (KLK7) is upregulated in epithelial ovarian carcinoma (EOC) with high levels correlated with poor prognosis. However, the mechanisms underlying this relationship and the role of KLK7 in EOC progression are unknown. We report that two different KLK7 transcripts, KLK7-253 and KLK7-181, are simultaneously expressed in high-grade serous EOC. Multicellular aggregates (MCA), which promote cell survival and chemoresistance, were observed in SKOV-3 cells stably overexpressing KLK7-253 in particular. Importantly, these MCAs invade into a monolayer of mesothelial cells and form cancer cell foci. Blocking MCA using antibodies against KLK7 and alpha(5)beta(1) and beta(1) integrins confirmed the involvement of KLK7 and integrin-regulated cell adhesion. Increased levels of alpha(5)/beta(1) integrins and enhanced attachment to fibronectin and vitronectin, which was blocked with an anti-beta(1) integrin antibody, were also observed. Finally, Western blot and immunohistochemistry showed higher KLK7 and alpha(5)/beta(1) integrin levels in serous EOC cells from ascites and tumor samples from chemotherapy nonresponders with short postsurvival times. Additionally, both KLK7-253 and KLK7-181 clones were more resistant to paclitaxel treatment in vitro. These findings suggest a mechanism for the association of high KLK7 levels with chemoresistance and poor prognosis for serous EOC patients by promotion of peritoneal dissemination and reinvasion via increased MCA and alpha(5)beta(1) integrin-dependent cell adhesion.
Adding Triamcinolone to Endoscopic Ultrasound–Guided Celiac Plexus Blockade Does Not Reduce Pain in Patients With Chronic Pancreatitis
Authors: Tyler Stevens, Adele Costanzo, Rocio Lopez, Leonardo Kapural, Mansour A. Parsi, John J. Vargo
Journal: Clinical Gastroenterology and Hepatology (2011)
Effect of Prednisolone on Anaemia Associated with Macroglobulinaemia
Authors: W. R. Pitney, W. J. O'Sullivan, J. A. Owen
Journal: BMJ (1958)

=BR.f any stress or strain which he is undergoing, informing him of the importance of the annual vacation, of leaving his work and worries in the office, of hobbies and outside interests, and, finally, of relaxation. ConclusionThe employee is one of the most valuable assets in any company, and of the employees the management group or executives are particularly valuable because of their training, motivation, and high degree of technical and administrative skill.A health maintenance scheme for the executive is an essential part of any industrial medical programme.Its main object is the detection of disease in its incipiency in order that corrective action may be taken so as to maintain him in good health and increase his longevity and efficiency.
REQUESTS FOR REPRINTS
Authors: Stanley H. Macht
Journal: JAMA (1942)

<h3>To the Editor:—</h3> InThe Journal, July 4, appears a short scathing discourse by Richard Kovacs, M.D., concerning penny postcard requests for reprints. Dr. Kovacs condemns this procedure and titles it as a "reprint racket." According to his notations I suppose I should classify myself as one of the "penny postcard reprint racketeers"! Before doing this I wish to broach a few points in the defense of us "racketeers." Use of the penny postcard affords a tremendous saving in paper, secretarial time and physician's time. All three are vital in these days, when a physician's time is more crowded than ever because of the shortage created by the war. The physicians who request reprints are usually the ones who write scientific articles. They in turn spend funds for purchase of reprints and postage to supply requests for reprints. Therefore the outlay averages up in the long run. The few dollars spent in
CORONARY ARTERY CALCIUM SCORE PREDICTS THE LONG-TERM MORTALITY AMONG PATIENTS WITH NO OR MINIMAL CORONARY ARTERY RISK FACTOR DURING 20 YEARS OBSERVATION
Authors: Rine Nakanishi, Michael Blaha, Suguru Matsumoto, Anas Alani, Panteha Rezaeian, Christopher Dailing, Matthew Budoff
Journal: Journal of the American College of Cardiology (2014)
Abstract 4791: The role of microRNA-15a/16 in early B1 cell development in a mouse model of chronic lymphocytic leukemia
Authors: Chingiz Underbayev, Siddha Kasar, Heba Degheidy, Gerald Marti, Marilyn Lightfoote, Elizabeth Raveche
Journal: Cancer Research (2014)

Abstract New Zealand Black (NZB) mouse is a de-novo model of chronic lymphocytic leukemia (CLL) that has been studied as a model of B-cell lymphoproliferative disorder. In most human CLL and NZB there is decreased expression of the microRNA miR15a/16. In NZB (and some CLL patients) this is due a point mutation six bases downstream from pre-miR-16 region. In both NZB mouse model and human CLL, the disease is characterized by the presence of a malignant clone of B-1 cells expressing dull levels of CD5 (T cell marker), CD11b (myeloid marker) and B220 (B cell marker). In this report we investigated the molecular pathways that result in increased B-1 lineage development in the mouse model of CLL. Initially we observed that in NZB, the B-1 lineage cells had reduced expression of Pu.1 when compared to NZB B-2 cells. PU.1 is a transcription factor required for B lineage differentiation and PU.1 knockout mice were previously found by others to have only B-1 lineage cell differentiation. To study early B1/B2 divergent cell development pathways in the context of CLL and shed light on the potential malignant cell origin of this disease, we generated induced pluripotent stem cells (iPS) from NZB spleen stromal fibroblasts. Our in vivo and in vitro studies on NZB iPS and hematopoietic progenitors (LSK) differentiation towards B-cell lineage cells followed by multicolor flow based cell sorting revealed a substantial block in the maturation of NZB iPS cells compared to wild type counterparts. Preliminary data using congenic NZB mice with corrected mir-15a/16-1 locus demonstrated that normal levels of miR-15a/16 regulate B-cell differentiation towards a higher expression of PU.1 and B220 (CD45R) and lower levels of CD11b suggestive of an enhanced B2 cell maturation pathway. Our results support the hypothesis that decreased miR-15a plays a role in B1 lymphocyte development bias in the course of B cell maturation by regulating the expression of a number of genes such as B220, PU.1 and CD11b. This work will help further uncover early molecular events which determine the increased B1 versus B2 lineage commitment associated with low levels of miR-15a/16 as an initial lesion in the development of CLL. Citation Format: Chingiz Underbayev, Siddha Kasar, Heba Degheidy, Gerald Marti, Marilyn Lightfoote, Elizabeth Raveche. The role of microRNA-15a/16 in early B1 cell development in a mouse model of chronic lymphocytic leukemia. [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 4791. doi:10.1158/1538-7445.AM2014-4791