tbuckley/cabot-search huggingface dataset:
THE PHENOMENON OF LOCAL SKIN REACTIVITY TO BACTERIAL FILTRATES: ELICITATION OF LOCAL REACTIVITY BY WAY OF THE VASCULAR SYSTEM
Authors: Gregory Shwartzman
Journal: The Journal of Experimental Medicine (1935)

The skin of the rabbit's ear is considerably more resistant than the abdominal skin to the phenomenon of local skin reactivity to bacterial filtrates. Ten times the provocative dose is required if it is given into the vein of the prepared ear and thirty times the provocative dose if it is given into the vein of the non-prepared ear. The state of reactivity cannot be elicited by a preparatory intravenous injection of bacterial filtrates alone into clamped and non-clamped ears. The state also fails to appear in combination with cold, xylol, ethyl urethane, pilocarpine hydrochloride, atropine, calcium gluconate, guinea pig liver extract, histamine dihydrochloride, adrenalin chloride, and pituitrin. Preparatory intravenous injections of toxins are capable of eliciting the state of reactivity in the rabbit's ear when they are accompanied by thermal hyperemia (i.e., exposure to 45 degrees , 50 degrees , and 55 degrees C.). It is also possible to induce the state of reactivity when a mixture of the preparatory factors with testicular extract is given into the veins of clamped ears. The incubation period required may be less than 2 hours. In the light of the above experiments, there are discussed various observations concerning the elicitation of the phenomena of organ reactivity by means of live bacterial cultures and the filtrates thereof.
Increased peripheral platelet destruction and caspase-3–independent programmed cell death of bone marrow megakaryocytes in myelodysplastic patients
Authors: Ewout J. Houwerzijl, Nel R. Blom, Johannes J. L. van der Want, Henk Louwes, Mariet T. Esselink, Jan W. Smit, Edo Vellenga, Joost Th. M. de Wolf
Journal: Blood (2004)
M1 Concordance to asthma medications in patients receiving long-term Omalizumab treatment
Authors: MS Elsherbiny, V Mitchell, AH Mansur, L Afridi, B Ahitan
Journal: Thorax (2013)

<h3>Introduction</h3> It is estimated that 5% of adult asthma patients have uncontrolled asthma despite high dose corticosteroid therapy. Omalizumab is a monoclonal anti-IgE antibody that has been shown to improve asthma control.<sup>1 </sup>As asthma control improves, concordance to other prescribed asthma medication may decline which may undermine omalizumab effectiveness. The extent of such non-concordance is explored in this study. <h3>Methods</h3> The records of40 patients receiving long-term omalizumab treatment have been reviewed for concordance. Medication history was retrieved for all patients, which included all prescriptions issued by their General Practitioner over most recent twelve months, detailing the doses and the number of tablets and/or inhalers patients received. Patients were classified as non-concordant if their medication history showed less than 75% adherence. Concordant and non-concordant groups were compared in relation to asthma control questionnaire (ACQ), Fractional exhaled nitric oxide (FeNO), forced expiratory volume in one second (FEV1), and number of asthma related admissions and frequency of severe steroid requiring asthma exacerbations at baseline line of omalizumab treatment. <h3>Results</h3> Sufficient information was only available for 25 patients (20 female) receiving long-term omalizumab treatment with a mean age of 44 years (range 19 to 68 years) and mean weight of 78kg (SD = 20.78). The prevalence of non-concordance was 64% (n = 16). All non-concordant patients had 50% or less prescription filling history. Overall non-concordant patients had a higher FEV1 before starting omalizumab treatment (mean FEV1 = 1.865, 95% predicted) compared to concordant patients (mean FEV1 = 1.401, 95% predicted), better ACQ scores (mean = 2.26), less number of patients on oral steroids (56.25% n = 9) compared to (66.7% n = 6). <h3>Conclusion</h3> The prevalence of non-concordance in patients receiving long-term omalizumab treatment is high and may undermine treatment effectiveness. The non-concordant patients had overall less severe asthma than concordant patients. Further research is needed to determine the effect of such non-concordance on the effectiveness of omalizumab in the long term. <h3>Reference</h3> Efficacy and safety of a recombinant anti-immunoglobulin E antibody (omalizumab) in severe allergic asthma. Holgate ST, Omalizumab 011 International Study Group.
Peptic ulcer in India and its aetiology
Authors: S. L. Malhotra
Journal: Gut (1964)

SYNOPSIS A study of the incidence of peptic ulcer amongst railway workers in various parts of India has shown that ulcer is more common in wet and humid areas than in the dry and arid regions.This observation is also supported by the ulcer incidence reported in other studies from India, Africa, and the West.Saliva appears to have an important role in the prevention of ulcer, because of its rich content of blood group antigens.There may be unrecognized factors in the saliva which may be ulcerogenic and others which prevent ulcer.Parasympathetic overaction also appears to contribute to ulcer formation due to its effect on salivation, sexual activity, and stress and strain.The prevalence of peptic ulcer in India shows striking variations, the disease being common in some parts of the country and rare in others (Somervell and Orr, 1936;Dogra, 1940).The ulcer is uncommon in the Punjab but the disease as so far reported from the Punjab is rare in the arid plains though by no means uncommon in the humid hill districts of Kangra, being 12 times more common than in the plains (Wig, 1959; Chuttani and Saigal, 1958).Hadley (1959) had noted similar variations in the incidence of the disease in various parts of the country: Ludhiana (Punjab) 0-2y%, Srinagar (Kash- mir) 2-5y%, and Vellore (south India) 1-6y%. METHODS AND MATERIALCLINICAL DATA The clinical data are derived from the hospital admissions to the various railway hospitals in the country during 1960 (Table I).Out- patients have not been included in this study as out-patient records have the serious disadvantage of being less precise.Figures for peptic ulcer perforations have also been collected for the year 1960.Perforation is a particularly painful and serious disease and expedites the hospital admission of almost all in whom it develops and, therefore, such data are a useful index of the prevalence of peptic ulcer in a given area.
Phylogeny of the "Forgotten" Cellular Slime Mold, Fonticula alba, Reveals a Key Evolutionary Branch within Opisthokonta
Authors: M. W. Brown, F. W. Spiegel, J. D. Silberman
Journal: Molecular Biology and Evolution (2009)

The shared ancestry between Fungi and animals has been unequivocally demonstrated by abundant molecular and morphological data for well over a decade. Along with the animals and Fungi, multiple protists have been placed in the supergroup Opisthokonta making it exceptionally diverse. In an effort to place the cellular slime mold Fonticula alba, an amoeboid protist with aggregative, multicellular fruiting, we sequenced five nuclear encoded genes; small subunit ribosomal RNA, actin, beta-tubulin, elongation factor 1-alpha, and the cytosolic isoform of heat shock protein 70 for phylogenetic analyses. Molecular trees demonstrate that Fonticula is an opisthokont that branches sister to filose amoebae in the genus Nuclearia. Fonticula plus Nuclearia are sister to Fungi. We propose a new name for this well-supported clade, Nucletmycea, incorporating Nuclearia, Fonticula, and Fungi. Fonticula represents the first example of a cellular slime mold morphology within Opisthokonta. Thus, there are four types of multicellularity in the supergroup—animal, fungal, colonial, and now aggregative. Our data indicate that multicellularity in Fonticula evolved independent of that found in the fungal and animal radiations. With the rapidly expanding sequence and genomic data becoming available from many opisthokont lineages, Fonticula may be fundamental to understanding opisthokont evolution as well as any possible commonalities involved with the evolution of multicellularity.
Aprikalim a potassium adenosine triphosphate channel opener reduces neurologic injury in a rabbit model of spinal cord ischemia
Authors: Vasileios A Lozos, Ioannis K Toumpoulis, Georgios Agrogiannis, Evangelos J Giamarellos-Bourboulis, Themistocles P Chamogeorgakis, Ioannis K Rizos, Efstratios S Patsouris, Constantine E Anagnostopoulos, Chris K Rokkas
Journal: International Journal of Surgery (2013)
Genomics of elite sporting performance: what little we know and necessary advances
Authors: Yannis Pitsiladis, Guan Wang, Bernd Wolfarth, Robert Scott, Noriyuki Fuku, Eri Mikami, Zihong He, Carmen Fiuza-Luces, Nir Eynon, Alejandro Lucia
Journal: British Journal of Sports Medicine (2013)

Numerous reports of genetic associations with performance-related phenotypes have been published over the past three decades but there has been limited progress in discovering and characterising the genetic contribution to elite/world-class performance, mainly owing to few coordinated research efforts involving major funding initiatives/consortia and the use primarily of the candidate gene analysis approach. It is timely that exercise genomics research has moved into a new era utilising well-phenotyped, large cohorts and genome-wide technologies--approaches that have begun to elucidate the genetic basis of other complex traits/diseases. This review summarises the most recent and significant findings from sports genetics and explores future trends and possibilities.
Effect of no treatment, cimetidine 1 g/day, cimetidine 2 g/day and cimetidine combined with atropine on nocturnal gastric secretion in cimetidine non-responders.
Authors: T Gledhill, M Buck, R H Hunt
Journal: Gut (1984)

We have studied nocturnal acid secretion in patients with duodenal ulcer who met predetermined criteria of poor clinical response to cimetidine. Different groups of patients were investigated receiving either no treatment, cimetidine 1 g/day, cimetidine 2 g/day or cimetidine 1 g/day combined with atropine 4.8 mg/day. The results were compared with those obtained from other patients with duodenal ulcer who were studied in our department but who were not classified as according to their clinical response to cimetidine. The results show that despite adequate absorption, cimetidine has a decreased effect at controlling acid secretion in the poor responders and that increasing the dose of drug does not improve response. Control of acid output was, however, dramatically improved when cimetidine was combined with atropine which suggests that patients who do not respond to H2-receptor blockade should be treated by a combination of cimetidine with an anticholinergic agent.
Studies on the mechanism of phagocytosis. II. The interaction of macrophages with anti-immunoglobulin IgG-coated bone marrow-derived lymphocytes.
Authors: F M Griffin, J A Griffin, S C Silverstein
Journal: The Journal of Experimental Medicine (1976)

We have examined the effect of the distribution of anti-immunoglobulin IgG molecules on the surface of bone marrow-derived lymphocytes upon the interaction of these cells with macrophages. Lymphocytes which were diffusely coated with antibodies to surface immunoglogulin were ingested by macrophages. Lymphocytes which had the same number of anti-immunoglobulin IgG molecules redistributed to one pole of the surface bound to the macrophages' Fc receptors but were not ingested. These results confirm our previous hypothesis that ingestion of an immunologically coated particle requires the sequential, circumferential binding of specific receptors on the plasma membrane of a phagocytic cell to immunologic ligands distributed over the entire particle surface. Macrophages which had bound capped lymphocytes by the macrophages' Fc receptors removed the immune complex caps from the lymphocyte surface without destroying the lymphocytes. These lymphocytes remained attached to the macrophage surface. The finding that macrophages can phagocytize immune complexes from the surface of a cell without destroying the cell to which these complexes are attached may be important in understanding the effects of antigens and antibodies on cells participating in a humoral immune response, in identifying the mechanisms by which chronic viral infections are established, and in defining the roles of blocking antibodies in tumor immunity.
New Roles of HDL in Inflammation and Hematopoiesis
Authors: Xuewei Zhu, John S. Parks
Journal: Annual Review of Nutrition (2012)

High-density lipoprotein (HDL) levels are inversely associated with coronary heart disease due to HDL's ability to transport excess cholesterol in arterial macrophages to the liver for excretion [i.e., reverse cholesterol transport (RCT)]. However, recent advances highlight additional atheroprotective roles for HDL beyond bulk cholesterol removal from cells through RCT. By promoting cellular free cholesterol (FC) efflux, HDL and its apolipoproteins (apoA-I and apoE) decrease plasma membrane FC and lipid raft content in immune and hematopoietic stem cells, decreasing inflammatory and cell proliferation signaling pathways. HDL and apoA-I also dampen inflammatory signaling pathways independent of cellular FC efflux. In addition, HDL lipid and protein cargo provide protection against parasitic and bacterial infection, endothelial damage, and oxidant toxicity. Here, current knowledge is reviewed regarding the role of HDL and its apolipoproteins in regulating cellular cholesterol homeostasis, highlighting recent advances on novel functions and mechanisms by which HDLs regulate inflammation and hematopoiesis.
Thrombogenic Effects of Antiphospholipid Antibodies Are Mediated by Intercellular Cell Adhesion Molecule-1, Vascular Cell Adhesion Molecule-1, and P-Selectin
Authors: Silvia S. Pierangeli, Ricardo G. Espinola, Xiaowei Liu, E. Nigel Harris
Journal: Circulation Research (2001)

Abstract —Recent studies have shown that antiphospholipid (aPL) enhances expression of intercellular cell adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and E-selectin on endothelial cells (ECs) and that these effects are correlated with increased adhesion of leukocytes to endothelium in cremaster muscle in vivo and with thrombosis in a mouse model. Activation of ECs by aPL may create a hypercoagulable state that precedes and contributes to thrombosis in patients with aPL syndrome (APS). This study proposed to examine whether this in vivo activation of ECs and enhanced thrombosis by aPL are mediated by ICAM-1, P-selectin, or VCAM-1. The dynamics of thrombus formation and the number of adhering leukocytes were studied in ICAM-1–deficient (ICAM-1 −/− ) mice or ICAM-1–/P-selectin–deficient (ICAM-1 −/− /P-selectin −/− ) mice treated with affinity-purified aPL antibodies (ap IgG-APS) or with control IgG and compared with wild-type mice treated in a similar fashion. In another set of experiments, the adhesion of leukocytes to cremaster muscle and the dynamics of thrombus formation were studied in CD1 mice treated with aPL or control IgG before and 30 minutes after intravenous infusion with 100 μg monoclonal antibody anti–VCAM-1. The results indicate that the enhanced adhesion of leukocytes to endothelium in wild-type mice was significantly reduced in ICAM-1 −/− and completely abrogated in ICAM-1 −/− /P-selectin −/− mice treated with ap IgG-APS compared with wild-type mice treated with ap IgG-APS (6.9±2.3, 0.4±0.4 versus 35±12, respectively). More importantly, this correlated with a significant reduction in thrombus size compared with wild-type mice treated with ap IgG-APS (895±259 μm 2 , 859±243 μm 2 versus 3816±672 μm 2 , respectively). Infusion of the mice with anti–VCAM-1 antibodies significantly reversed the enhanced adhesion of leukocytes (14.9±3 to 11.3±2.1) and thrombus size 3830±1008 μm 2 versus 876±548 μm 2 ) in mice treated with ap IgG-APS. The data indicate that ICAM-1, P-selectin, and VCAM-1 expression are important in thrombotic complications by aPL antibodies and may provide novel targets for therapy in patients with APS.
Collagen v expression in skin, tendons and capsules of athletic population after shoulder dislocation and acl injuries
Authors: M A Akhtar, T G Ingman, C M Robinson, J F Keating, A Y Muir, H Simpson, D Salter
Journal: British Journal of Sports Medicine (2011)

Introduction Cruciate ligament ruptures and shoulder dislocations are often caused by trauma, but predisposing intrinsic factors might also influence the risk. Collagen type V is widely distributed in tissues and helps regulate the diameters of fibrils of the abundant collagen type I. Mutations in its genes have been identified which can result in connective tissue fragility, particularly in skin and joints. The aim of this study was to localise collagen V in skin, hamstring tendons and shoulder capsules of patients following sports injuries. Patients and methods Localisation of collagen V was studied by immunohistochemical staining of paraffin embedded sections of skin, tendons and capsules of patients attending for shoulder stabilisation for recurrent instability or primary anterior cruciate ligament (ACL) reconstruction between November 2008 and July 2009. Results 40 patients were studied, 25 undergoing primary ACL reconstruction and 15 undergoing shoulder stabilisation. The mean age of patients was 26 years. 34 patients (85%) were male and 6 female (15%). Most common sport played was football in 13 patients (32%) followed by rugby in 10 (25%) and skiing in 5 (12%). Skin epidermis stained negative but dermal papilla, papillary and reticular dermis, blood vessels, sweat glands, sebaceous glands and arrector pilli stained positive to varying degrees for collagen V. Synovial surface of the capsule, blood vessels and extracellular matrix stained positive to varying degrees. Tendon sheath, collagen fibres, blood vessels and interfascicular connective tissue stained positive to varying degrees, but skeletal muscle was negative for collagen V. Discussion We looked at the expression and distribution of collagen V in skin, tendons and capsules of patients undergoing shoulder stabilisation or ACL reconstruction following sports injuries. There may be a link in the distribution of collagen V and strength of tissues, which can predispose individuals to injuries while playing sports and can also affect healing process. Further studies are needed to study this link.
High prevalence of asymptomatic cervical spine subluxation in patients with rheumatoid arthritis waiting for orthopaedic surgery
Authors: M H Neva
Journal: Annals of the Rheumatic Diseases (2005)

<b>Objective:</b> To study the prevalence of cervical spine subluxation in patients with rheumatoid arthritis waiting for orthopaedic surgery, and symptoms that might be associated with the disorders. <b>Methods:</b> 194 patients with rheumatoid arthritis were referred for orthopaedic surgery at Jyväskylä Central Hospital, 154 (79%) of whom volunteered for the present study including clinical examination, laboratory tests, radiographs of the cervical spine, hands, and feet, and self report questionnaires. Definition of anterior atlantoaxial subluxation (aAAS) was &gt;3 mm and of subaxial subluxation (SAS) ⩾3 mm. Atlantoaxial impaction (AAI) was analysed following to the Sakaguchi-Kauppi method. <b>Results:</b> 67 patients (44%) had cervical spine subluxation or previous surgical fusion. The prevalence of aAAS, AAI, SAS, or previous fusion was 27 (18%), 24 (16%), 29 (19%), and 8 (5%), respectively; 69% of patients with cervical spine subluxations (those with fusions excluded) reported neck pain, compared with 65% of patients without subluxations (p = 0.71). The prevalence of occipital, temporal, retro-orbital, and radicular pain in upper extremities was similar in patients with or without cervical spine subluxations (54% <i>v</i> 43%; 17% <i>v</i> 31%; 25% <i>v</i> 24%; 47% <i>v</i> 48%, respectively). However, patients with subluxations were older, had longer disease duration, more active disease, poorer function according to the Health Assessment Questionnaire, and had more often erosive disease. <b>Conclusions:</b> Asymptomatic cervical spine subluxation is common in patients with rheumatoid arthritis waiting for orthopaedic surgery. Regardless of symptoms, the possibility of cervical spine subluxation in patients with severe rheumatoid arthritis should be considered in preoperative evaluation.
Phenotypes of childhood wheeze: Early symptom pattern vs. long term disease course
Authors: Ben Spycher, Raquel Granell, Jonathan Sterne, John Henderson
Journal: European Respiratory Journal (2011)

Aim:  Wheezing in childhood is phenotypically heterogeneous. We investigated how phenotypes defined by early symptom pattern are related to phenotypes based on later retrospective time course.   Method:  We analysed data on wheeze-related symptoms (frequency and duration of episodes, shortness of breath (SOB), fever and triggers (chest infection, smoke, cold weather, “other”)) in children from a population based birth cohort (ALSPAC) at ages 6m (n=2261), 18m (2400) and 30m (1786). We used latent class analysis to identify phenotypes, which were compared to previously published phenotypes based on 7 measurements of current wheeze in the first 7yrs of life (Thorax 2008;63:974–980).   Results:  We identified 5 phenotypes at age 6m and 6 at ages 18m and 30m. At each age, 2 groups of severe wheezers (frequent episodes, long duration, SOB) were identified, one with episodes triggered mainly by infections and cold weather and one with “other” triggers predominating. Other phenotypes were characterised by moderate or mild symptoms and differed in patterns of triggers. Phenotypes were similar at different ages. Among children with mild wheeze, >60% were classified longitudinally as “transient early” or “prolonged early wheezers” while >34%, >46% and >63% of children in the severe groups at ages 6m, 18m, and 30m respectively were classified as “persistent wheezers”.   Conclusion:  In children   Funding: European Respiratory Society/Marie Curie Joint Research Fellowship - Number MC 1614-2010.
Peptidylarginine deiminase 2, 3 and 4 have distinct specificities against cellular substrates: novel insights into autoantigen selection in rheumatoid arthritis
Authors: Erika Darrah, Antony Rosen, Jon T Giles, Felipe Andrade
Journal: Annals of the Rheumatic Diseases (2011)

Objective To define the relationship between autoantigen citrullination and different peptidylarginine deiminase (PAD) enzymes in rheumatoid arthritis (RA). Methods Citrullinated autoantigens were identified by immunoblotting control and ionomycin-activated human primary neutrophil lysate with RA sera. Autoantigen identity and citrullination sites were defined by mass spectrometry. PAD isoenzyme expression in human neutrophils was determined by immunoblotting. PAD substrate specificity was addressed in HL-60 cell lysates co-incubated with human recombinant PAD2, PAD3 and PAD4. Results Although prominent protein citrullination is observed in ionomycin-activated neutrophils, RA sera only recognised a limited number of these citrullinated molecules. Among these, the authors identified that β and γ-actins are citrullinated on at least 10 arginine residues, generating a novel 47 kDa species that is frequently recognised by RA autoantibodies. Interestingly, the authors showed that the PAD enzymes expressed in human neutrophils (ie, PAD2, PAD3 and PAD4) have unique substrate specificities, independent of their subcellular distribution. Thus, only PAD2 was able to citrullinate native β/γ-actin, while histone H3 was only citrullinated by PAD4. Conclusion These studies identified β and γ-actins as novel citrullinated autoantigens in RA, allowing enzyme specificity against intracellular substrates to be addressed. The studies provide evidence that PAD enzymes have the intrinsic capacity to select unique protein targets. The authors propose that unique PAD specificity may play a role in autoantigen selection in RA.