tbuckley/cabot-search huggingface dataset:
The Nonpsychotic Organic Brain Syndrome
Authors: BENJAMIN FELDSHUH, JANET SILLEN, BARBARA PARKER, WILLIAM FROSCH
Journal: American Journal of Psychiatry (1973)

The New York State mental hospital system has recently limited the admission of the "simply senile," those with organic brain syndrome who are neither psychotic nor severely depressed. The authors studied 53 such people and concluded that these patients are usually severely ill and often need psychiatric hospitalization before their placement in the community.
Ethnic variation in the frequency of IBD related polymorphisms in IRGM, ATG16L1 and IL23R
Authors: D. G. Walker, A. S. Bancil, P. S. Rai, H. R. Williams, J. Chambers, J. S. Kooner, T. R. Orchard
Journal: Gut (2011)

<h3>Introduction</h3> Recent genome wide association studies have identified a number of key single nucleotide polymorphisms (SNPs) that contribute to the susceptibility of inflammatory bowel disease (IBD). SNPs in the autophagy-related 16-like 1 gene (<i>ATG16L1</i>; <i>rs2241880</i>) and immunity-related GTPase family M gene (<i>IRGM</i>; <i>rs13361189</i> and <i>rs4958847</i>) have been shown to confer susceptibility to Crohn9s Disease (CD) in European/North American populations. In addition, a SNP in the interleukin 23 Receptor (<i>IL23R</i>, <i>rs11209026</i>) has been shown to confer protection against both CD and ulcerative colitis (UC) in Caucasian patients. These findings are in contrast to studies from East Asia that have shown no association of these SNPs with inflammatory bowel disease (IBD). The aim was to investigate the prevalence of IBD related SNPs in <i>ATG16L1, IRGM</i> and <i>IL23R</i> in a cohort of South Asian IBD patients and controls. The results were compared with a cohort of white Northern European IBD patients to determine if there is interethnic variation in the minor allele frequency for the disease cohorts. <h3>Methods</h3> IBD patients were recruited from the IBD clinics of five hospitals in North West London. Indian Asian patients with all four grandparents originating from South Asia and a confirmed diagnosis of IBD were included in the study. Patients and controls were genotyped using pyrosequencing and the results compared using the χ<sup>2</sup> test. <h3>Results</h3> 216 Indian Asian IBD patients (60 CD: 156 UC), 203 healthy Indian Asian controls and 146 white Northern European IBD patients (98 CD: 48UC) were recruited. All SNPs were in Hardy Weinberg equilibrium. There was no significant difference in the minor allele frequency (MAF) between Indian Asian IBD patients and ethnically matched controls for any of the 4 SNPs. However, the MAF for SNPs in <i>IRGM</i> and <i>IL23R</i> was significantly different between Indian Asian and European CD cohorts (<i>IRGM rs13361189</i>: 0.23 vs 0.11, p=0.004; <i>IRGM rs4958847,</i> 0.28 vs 0.15<i></i> p=0.005; <i>IL23R</i> 0.8 vs 6.1, p=0.02). <h3>Conclusion</h3> The polymorphisms of <i>ATG16L1</i>, <i>IRGM</i> and <i>IL23R</i> that are associated with IBD in Western populations show no association with IBD in Indian Asians. These findings are similar to a Japanese study that showed these SNPs were not associated with CD in this ethnic group; however, one cannot exclude the possibility that an analysis of a larger sample size in the Indian Asian population might unveil such an association. The SNP frequencies in the South Asian IBD cohorts were significantly different to the European disease controls for SNPs in <i>IRGM</i> and <i>IL23R</i> showing that there are clear interethnic variations in risk allele frequencies.
Shirley Avril Nicol (née Mackintosh)
Authors: John Nicol
Journal: BMJ (2004)

Former clinical medical officer in family planning Newcastle and Ashington (b Hull 1932; q Edinburgh 1956), died from lung cancer on 20 October 2004.​2004.




Figure 1




Avril met her husband, Bill, an orthopaedic surgeon, while training in anaesthetics near Dundee. For five years they combined work in Transkei, South Africa, with bringing up their five children. On settling in Halifax she gave anaesthetics at the local hospitals and also worked in family planning. When Bill's new career as a church minister took them to north east England, she continued to work in family planning in and around Newcastle and Ashington. She leaves Bill, five children, and six grandchildren.
A conversation with Marc Feldmann
Authors: Ushma S. Neill
Journal: Journal of Clinical Investigation (2014)

Sir Marc Feldmann’s research over the last 30 years has focused on the understanding of autoimmune disease, specifically the treatment of rheumatoid arthritis (RA). Feldmann (Figure ​(Figure1),1), now at the Kennedy Institute of Rheumatology at Oxford University, championed the importance of antigen presentation and cytokines in autoimmunity, a concept that led to TNF-α blockade. This idea was considered heretical in the 1980s until he and Sir Ravinder Maini led clinical trials showing that blocking TNF-α effectively treated rheumatoid arthritis refractory to previous therapy. TNF-α antibodies Remicade, Humira, and Enbrel are now the cornerstone of a $25 billion industry. Many more stories about getting pharma to speed delivery to patients and the power of persistence can be seen on the JCI website, http://www.jci.org/kiosk/cgm.
A Flow Cytometry Method to Quantitate Internalized Immunotoxins Shows that Taxol Synergistically Increases Cellular Immunotoxins Uptake
Authors: Yujian Zhang, Johanna K. Hansen, Laiman Xiang, Seiji Kawa, Masanori Onda, Mitchell Ho, Raffit Hassan, Ira Pastan
Journal: Cancer Research (2010)

Tumor microenvironments present significant barriers to penetration by antibodies, immunoconjugates, and other immunotoxins. In this report, we illustrate a novel strategy to increase tumor cell uptake of immunotoxin by combination with Taxol. SS1P is an immunotoxin composed of the Fv portion of a mesothelin-specific antibody fused to a bacterial toxin that is presently undergoing phase II testing in mesothelioma. Using novel flow cytometry and gel filtration methods, we quantified SS1P uptake in individual tumor cells along with levels of shed mesothelin (sMSLN), a barrier of SS1P therapy. The validity of our flow cytometric method was confirmed by the ability to similarly quantitate tumor cell uptake of Herceptin and an immunotoxin targeting HER2/neu. SS1P uptake peaked several hours after SS1P was cleared from the blood, reflecting an intratumor distribution process of SS1P that is independent of blood supply. Using the methods developed, we demonstrated that Taxol could improve SS1P penetration into tumors in parallel with an associated reduction of sMSLN in tumor extracellular fluid. Our findings offer a mechanistic rationale to combine SS1P with Taxol or another cytotoxic drug as a strategy to increase immunotoxin uptake by tumor cells. Further, we suggest one basis to understand why chemotherapy and antibody-based therapies cooperate when combined in cancer treatment.
Down Syndrome and Acute Myeloid Leukemia: The Paradox of Increased Risk for Leukemia and Heightened Sensitivity to Chemotherapy
Authors: Yaddanapudi Ravindranath
Journal: Journal of Clinical Oncology (2003)

Article Tools EDITORIALS Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.2003.05.086 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 12885833 Down Syndrome and Acute Myeloid Leukemia: The Paradox of Increased Risk for Leukemia and Heightened Sensitivity to Chemotherapy Yaddanapudi RavindranathxYaddanapudi RavindranathSearch for articles by this author Show More Georgia Ginopolis Chair for Pediatric Cancer and Hematology, Wayne State University School of Medicine, Children’s Hospital of Michigan, Detroit, MI https://doi.org/10.1200/JCO.2003.05.086 First Page Full Text PDF Figures and Tables © 2003 by American Society of Clinical Oncology
Validation and Reliability Testing of the EORTC QLQ-NMIBC24 Questionnaire Module to Assess Patient-reported Outcomes in Non–Muscle-invasive Bladder Cancer
Authors: Jane M. Blazeby, Emma Hall, Neil K. Aaronson, Lisa Lloyd, Rachel Waters, John D. Kelly, Peter Fayers
Journal: European Urology (2014)

Well-developed and well-tested patient-reported outcome measures for non-muscle-invasive bladder cancer (NMIBC) are required.
Injury and illness surveillance during the 24th Men's Handball World Championship 2015 in Qatar
Authors: Tone Bere, Juan-Manuel Alonso, Arnlaug Wangensteen, Arnhild Bakken, Cristiano Eirale, H Paul Dijkstra, Hosny Ahmed, Roald Bahr, Nebojsa Popovic
Journal: British Journal of Sports Medicine (2015)

Background The IOC encourages international federations to establish systematic athlete injury and illness surveillance programmes. Objective To describe pattern of injuries and illnesses during the 24th Men's Handball World Championship 2015 by implementing the IOC injury and illness surveillance protocol. Methods The medical staff of participating teams (n=24) were requested to report all new injuries and illnesses during matches and/or training on a daily basis throughout the event (15 January to 1 February, 2015). Exposure (number of player-hours) during all matches was calculated for all players (n=384) and for each of the 4 player positions (wing, back, line and goalkeeper). Results Medical staff of all teams submitted 96.7% (n=325) of the daily report forms. In total, 27.1% of the players were injured, and of the 132 injuries reported, 40% were time-loss injuries. The total incidence of injuries was 104.5 per 1000 player-hours. The highest risk of injury was found among line players, and more injuries occurred during the first half of the matches. The most frequent injury location was the ankle, followed by the thigh, knee and head/face. The majority of injuries were contusion, sprain or strain. In total, 10.9% of the players were affected by an illness during the event. Of the 42 cases recorded, 31 (73.8%) were reported as respiratory tract infection. Conclusions The risk of injury in handball is high among Olympic sports. Preventive measures should focus on contusions, ankle sprains, and thigh muscle strains, as well as measures aimed to reduce upper respiratory tract infections.
Enhanced <i>In Vivo</i> Human Immunodeficiency Virus-1 Replication in the Lungs of Human Immunodeficiency Virus–Infected Persons with <i>Pneumocystis carinii</i> Pneumonia
Authors: HENRY KOZIEL, SUE KIM, CHRISTINE REARDON, XIUHONG LI, ROBERT GARLAND, PAULA PINKSTON, HARDY KORNFELD
Journal: American Journal of Respiratory and Critical Care Medicine (1999)

The relationship of serum human immunodeficiency virus-1 (HIV-1) RNA levels to HIV-1 RNA levels in other compartments, such as the lungs, is not well characterized. The purpose of this study was to determine the viral burden of HIV-1 in the lungs by comparing HIV-1 RNA in cell-free bronchoalveolar lavage fluid (BALF) with that in serum. Specimens were examined from 77 HIV-seropositive adults (CD4+ cell counts: 0 to 700 cells/mm3; 48% receiving prescribed antiretroviral agents), comprising 43 asymptomatic individuals who were compared with 34 persons with active lung disease caused by Pneumocystis carinii (n = 26), bacteria (n = 3), Mycobacterium avium complex (n = 2), Nocardia sp. (n = 1), Aspergillus sp. (n = 1), or pulmonary Kaposi's sarcoma (n = 1). For serum HIV-1 RNA, the proportion of subjects with detectable levels and the mean values were similar for asymptomatic individuals and persons with active lung disease (85% versus 86%, respectively) (6.64 × 104 versus 1.81 × 105 HIV-1 RNA copies/ml; p = 0.13). In contrast, HIV-1 RNA in BALF was more often detected (16% versus 62%; p = 0.001), and mean values were higher (1.04 × 105 versus 3.31 × 106 HIV-1 RNA copies/ml; p = 0.032), in subjects with active lung disease than in asymptomatic subjects, independent of early or advanced clinical stages of HIV-related disease. For both study groups, HIV-1 RNA levels in BALF exceeded those in serum in 56% of cases by up to 66-fold, and did not correlate with local levels of tumor necrosis factor- α , granulocyte–macrophage colony-stimulating factor, or interleukin-16. HIV-1 proviral DNA in cells from BALF was detected in up to 86% of subjects, more frequently in persons with advanced HIV disease (p = 0.0496), and often involved > 10% of BALF cells, but did not correlate with HIV-1 RNA detected in BALF. These data provide evidence for active HIV-1 replication in the lungs. HIV-1 replication is compartmentalized relative to serum, may be restricted, is independent of HIV-1 proviral DNA and clinical stage of HIV, and may be influenced by pulmonary disease such as P. carinii pneumonia or by other local or lung-specific factors. The lungs represent a large reservoir for HIV-1, and may present a source of persistent HIV-1 replication even during periods of apparent clinical latency of HIV-1 infection. Koziel H, Kim S, Reardon C, Li X, Garland R, Pinkston P, Kornfeld H. Enhanced in vivo human immunodeficiency virus-1 replication in the lungs of human immunodeficiency virus–infected persons with Pneumocystis carinii pneumonia.
Hepatitis B Virus Envelope Variation After Transplantation With and Without Hepatitis B Immune Globulin Prophylaxis
Authors: W F Carman, C Trautwein, J van Deursen, K Colman, E Dornan, G McIntyre, J Waters, V Kliem, R Müller, H C Thomas, M P Manns
Journal: Hepatology (1996)

Hepatitis B virus (HBV) replicates via an intermediate RNA step. High frequency of polymerase errors with additional selection pressure leads to mutations in the HBV genome. We investigated the number, type, and antigenic effects of mutations in the coding region of the HBV surface antigen in eight patients who underwent orthotopic liver transplantation (OLT) for HBV-related end-stage liver disease and were experiencing infection of the graft and who received hepatitis B surface antigen antibody (anti-HBs) prophylaxis (hepatitis B immune globulin [HBIG]) after OLT. Controls were chronic HBV patients who underwent kidney transplantation and received the same immunosuppressive regime but no HBIG. The S-gene was amplified from serum before and after transplantation, sequenced, and changes in the genome were analyzed. In the five patients who experienced reinfection while receiving anti-HBs, clear mutations occurred in the S-gene. In the patient who did not receive HBIG and those who experienced reinfection only after termination of HBIG, no mutations were found in the S-gene. In the kidney recipients, mutations in the S-gene occurred in only one of eight patients. Because the a determinant contains neutralizing epitopes, this region was chosen for antibody binding to quantify antigenic effects of the mutations. The two patients who selected mutations in the a determinant and became reinfected while receiving HBIG had reduced antibody binding after OLT. Our results suggest that HBIG after OLT imposes a selection pressure on the S-gene, and that mutations are one mechanism for reinfection while receiving HBIG.
A New Euphoriant for Depressive Mental States
Authors: G. T. Stockings
Journal: BMJ (1947)

<h3>Abstract</h3> Extrachromosomal circular DNA of chromosomal origin (eccDNA) can rapidly shape the evolution and adaptation of mitotically dividing cells such as tumor cells. However, whether eccDNA has a permanent impact on genome evolution through the germline is largely unexplored. Here, we propose that a large fraction of the syntenic changes that are found between mammalian species are caused by germline transposition of eccDNA. We have previously shown the existence of eccDNA in mammalian meiotic cells. By reanalysis of available synteny maps, we now find that up to 6% of mammalian genomes might have rearranged via a circular DNA intermediate. Hence, eccDNA in the germline is expected to have large effects on evolution of gene order. <h3>Highlights</h3> Extrachromosomal circular DNA (eccDNA) is present in mammalian germline cells showing that eccDNAs are not excluded, repressed or eliminated during meiosis Large eccDNA reinsertions into the genome can change gene synteny in a recognizable pattern based on its circular junction and integration breakpoint. By reanalyzing synteny maps form 8 mammalian species, we show that 6% of genome of the ungulates cow and sheep can be explained by eccDNA insertions. We propose that reinsertion of large eccDNA that are fixed in germline cells may have contributed to speciation barriers and evolution of new species
THE I<scp>G</scp>A SYSTEM
Authors: Mary Ann South, Max D. Cooper, Frank A. Wollheim, Richard Hong, Robert A. Good
Journal: The Journal of Experimental Medicine (1966)

1. Five patients with congenital or acquired agammaglobulinemia, lacking detectable IgA in serum or saliva, were transfused with 1 to 2 liters of normal plasma. In 2 of these patients IgA was demonstrated in parotid saliva collected after transfusion, but in none of the 5 was salivary IgG or IgM found. This observation indicates the selective transport of IgA into saliva. 2. The observation by others of an immunochemical difference between serum and sahvary IgA globulin was confirmed. In contrast to serum IgA, salivary IgA is attached to a protein having antigenicity which migrates as a gamma(1) globulin. We have termed this protein component "transport piece". 3. The transport piece has been found in an unbound form in the saliva of persons completely lacking IgA: agammaglobulinemic patients, ataxia-telangiectasia patients, a healthy person lacking IgA, and a newborn infant. Free transport piece still occurs in the normal child's saliva after IgA production begins. By adulthood there is usually no free transport piece in the saliva. 4. Heat-aggregated salivary IgA, like heat-aggregated serum IgA, does not fix complement. 5. Our findings offer support for the view that there is a distinct local antibody system for the protection of the mucous surfaces.
Antiasthmatic Effects of Mediator Blockade versus Topical Corticosteroids in Allergic Rhinitis and Asthma
Authors: ANDREW M. WILSON, LINDA C. ORR, ERIKA J. SIMS, OWEN J. DEMPSEY, BRIAN J. LIPWORTH
Journal: American Journal of Respiratory and Critical Care Medicine (2000)

To compare the antiasthmatic efficacy of inflammatory mediator blockade versus topical corticosteroid therapy in patients with seasonal allergic rhinitis (SAR) and asthma, 14 patients were enrolled into a single-blind, double-dummy, placebo-controlled crossover study comparing 2 wk therapy of (1) 400 μ g orally inhaled budesonide plus 200 μ g intranasal budesonide (BUD) or (2) 10 mg oral montelukast plus 10 mg oral cetirizine (ML + CZ). Before each treatment period, patients received 7 to 10 d placebo washout. All treatments were given once daily in the morning. Throughout the study, patients recorded the following domiciliary measures: peak expiratory flow (PEF), rescue inhaler requirement, asthma symptoms, and daily activity score. Laboratory measurements were made at trough of adenosine monophosphate (AMP) bronchial challenge and exhaled nitric oxide (NO). Compared with pooled placebo (PL), there were significant (p < 0.05) improvements in all domiciliary measures with both treatments (mean PEF [L/min] PL: 463; BUD: 478; ML + CZ: 483). For geometric mean AMP PC20 (mg/ml), there was an improvement (p < 0.05), compared with PL (47), for ML + CZ (133) but not for BUD (51); whereas for NO (ppb) there was significant suppression with BUD (7.6) but not ML + CZ (11.5) compared with PL (13.6). In conclusion, both combined mediator blockade and combined topical corticosteroids are equally effective antiasthma therapy in patients with asthma and SAR.
Antisecretory factor suppresses intestinal inflammation and hypersecretion
Authors: E Johansson, E Jennische, S Lange, I Lönnroth
Journal: Gut (1997)

Antisecretory factor (AF) is a recently identified regulatory protein which inhibits the intestinal fluid secretion induced by cholera toxin.To test the effect of AF on: (a) inflammation and hypersecretion induced by toxin A from Clostridium difficile; and (b) morphological changes and hypersecretion induced by okadaic acid (the blue mussel toxin) in rat intestinal mucosa.Morphological changes and fluid accumulation were observed in intestinal loops challenged with 1 microgram of toxin A or 3 micrograms of okadaic acid administered before or after injection of 0.1 microgram of recombinant AF (rAF).The cytotoxic and inflammatory reaction caused by toxin A was abolished after treatment with rAF given either intraveneously or intraluminally prior to the toxin or one hour after the toxin. The intestinal fluid response induced by toxin A and okadaic acid was reduced 55-80% by rAF. However, the characteristic increase in goblet cells at the tips of villi in the okadaic acid treated mucosa was not inhibited by rAF.Results suggest that AF might be involved in protection against inflammation and in counteracting dehydration caused by enterotoxins. Both effects are probably mediated via the enteric nervous system.
Intensive Treatment of Diabetes Is Associated With a Reduced Rate of Peripheral Arterial Calcification in The Diabetes Control and Complications Trial
Authors: Rickey E. Carter, Daniel T. Lackland, Patricia A. Cleary, Eunsil Yim, Maria F. Lopes-Virella, Gregory E. Gilbert, Trevor J. Orchard
Journal: Diabetes Care (2007)

Peripheral arterial disease (PAD) is a significant contributor to the morbidity and mortality of >2 million Americans (1). In addition to its own specific disease risks, PAD has been shown to be a predictor of cardiovascular mortality and coronary artery disease, as well as a general marker for the atherosclerotic disease process (2,3). PAD complications, especially in the lower limb, are significantly greater in individuals with diabetes compared with those without diabetes, and the risk imparted by diabetes is similar or greater in magnitude to that seen for ischemic heart disease and stroke (4,5).

The aortofemoral arteries are prime sites for PAD; hence, determination of claudication and measurement of blood flow in the lower extremities are the most common assessments (6). A relatively low ankle systolic blood pressure (ankle-to-brachial ratio index [ABI]) has been found to be an indicator of atherosclerosis/occlusion in this region (5). Conversely, in diabetes, a high-pressure ABI due to medial wall arterial calcification and noncompressible vessels may also be associated with adverse outcomes, including diabetic kidney disease (7). Sex differences have been reported in ABI measurements in type 1 diabetes, with women having a greater frequency of low ABI and men having a higher frequency of high ABI (7). Here, we extend these analyses by examining the effect of previous intensive diabetes management on the development of abnormally high and low ABIs in the Diabetes Control and Complications Trial (DCCT)/Epidemiology of Diabetes Interventions and Complications (EDIC) cohort with the hypothesis that …