tbuckley/cabot-search huggingface dataset:
Fine idiotype analysis of B cell precursors in the T-dependent and T-independent responses to alpha 1-3 dextran in BALB/c mice.
Authors: R Stohrer, J F Kearney
Journal: The Journal of Experimental Medicine (1983)

In this study BALB/c B cell precursors responsive to the T-independent (TI) type 2 (TI-2) antigen, dextran B1355S (DEX), and the T-dependent (TD) derivative, dextran-Limulus hemocyanin (DEX-Hy) were examined for isotype and idiotope expression using the splenic focus assay. The predominant isotype detected in the TI assay was IgM, while IgA was the predominant isotype expressed in the TD assay. There was also a fourfold increase in the number of foci secreting more than one isotype in the TD assay vs. the TI assay without an overall change in anti-DEX precursor frequency, suggesting that carrier-primed T cells enhance the expression of non-IgM isotypes possibly by increasing the frequency of isotype switching by individual B cell precursors. A panel of distinct monoclonal antiidiotype antibodies (MAIDs) was then used to examine idiotope expression by antibodies secreted in splenic foci responding to DEX and DEX-Hy. This analysis revealed considerable diversity in the idiotope profiles expressed by all isotypes tested. There appeared to be no differences in idiotope diversity among the various isotypes. A similar diversity of idiotope profiles was obtained from both TI and TD splenic foci, indicating that a comparable degree of diversity was associated with the antibodies generated by TI and TD precursors. Idiotype analysis of IgM-IgA-secreting foci with a panel of monoclonal antiidiotope antibodies revealed slight idiotypic differences between the two isotypes secreted in the same focus in about half the cases. These results suggest that somatic variation occurs during the antigen-driven maturation of B cell precursors, within the 15-d time frame of the splenic focus assay, and may be associated with isotype switching.
Sociality Is Linked to Rates of Protein Evolution in a Highly Social Insect
Authors: B. G. Hunt, S. Wyder, N. Elango, J. H. Werren, E. M. Zdobnov, S. V. Yi, M. A.D. Goodisman
Journal: Molecular Biology and Evolution (2010)

Eusocial insects exhibit unparalleled levels of cooperation and dominate terrestrial ecosystems. The success of eusocial insects stems from the presence of specialized castes that undertake distinct tasks. We investigated whether the evolutionary transition to societies with discrete castes was associated with changes in protein evolution. We predicted that proteins with caste-biased gene expression would evolve rapidly due to reduced antagonistic pleiotropy. We found that queen-biased proteins of the honeybee Apis mellifera did indeed evolve rapidly, as predicted. However, worker-biased proteins exhibited slower evolutionary rates than queen-biased or nonbiased proteins. We suggest that distinct selective pressures operating on caste-biased genes, rather than a general reduction in pleiotropy, explain the observed differences in evolutionary rates. Our study highlights, for the first time, the interaction between highly social behavior and dynamics of protein evolution.
Intestinal smooth muscle dysfunction after intraperitoneal injection of zymosan in the rat: are oxygen radicals involved?
Authors: A van der Vliet, K I van der Poel, A Bast
Journal: Gut (1992)

Zymosan is frequently used as an activator of granulocytes to study inflammatory responses. We used zymosan as a model to understand the mechanisms involved in intestinal inflammatory diseases, and our special interest was focused on the smooth muscle function. Moreover, we investigated the role of oxidative stress in intestinal pathology after inflammatory processes. Intraperitoneal injection of zymosan induces a peritoneal inflammation, characterised by exudate in the peritoneum and peritoneal fibrosis. Three days after injection of zymosan (25-40 mg/100 g) we measured a decreased beta adrenergic smooth muscle response, while the muscarinic receptor-mediated contraction was not significantly affected. Efforts were made to correlate these observations with the development of oxidative stress; however, the intestinal glutathione balance remained undisturbed and no increase in lipid peroxidation products in the intestine was observed. Our conclusion is the peritoneal inflammation will lead to a release of various mediators, which may destroy receptor systems, among which are beta adrenoceptors. There was no evidence of an important role for reactive oxygen metabolites in this effect.
Vitamin D and lung disease
Authors: Paul E Pfeffer, Catherine M Hawrylowicz
Journal: Thorax (2012)

The classic role of vitamin D in the regulation of calcium and phosphate metabolism, and its effects on bone health, are well established. More recently a critical role in immunity and respiratory health has been proposed. This arises from evidence for the capacity to generate the active metabolite, 1α,25-dihydroxyvitamin D3 (1,25(OH)D3), locally in many tissues beyond the kidney; expression of the vitamin D receptor (VDR) in immune and structural cells not involved in calcium-phosphate homeostasis; and control by 1,25(OH)D3 of the transcription of genes associated with numerous different biological processes through its nuclear VDR. Abnormalities in the vitamin D axis, including a high prevalence of vitamin D insufficiency worldwide, now appear important in a wide range of pulmonary diseases including viral and bacterial respiratory infection, asthma, chronic obstructive pulmonary disease, and cancer. Actions of vitamin D on innate immune responses, for example, production of antimicrobial peptides and autophagy, and on adaptive immune responses, for example, promoting regulatory lymphocytes, are believed to underpin these associations.
PHYLOGENY OF IMMUNOGLOBULIN STRUCTURE AND FUNCTION
Authors: L. W. Clem, P. A. Small
Journal: The Journal of Experimental Medicine (1967)

Lemon sharks immunized with bovine serum albumin produced two molecular forms of antibodies detectable by passive hemagglutination of antigen-coated, tanned sheep erythrocytes. Throughout the course of immunization 2-ME-sensitive antibody was associated with a 19S immunoglobulin fraction (4-5 mg/ml serum) while late in the course of immunization antibody was found also associated with a 7S immunoglobulin fraction (7-8 mg/ml serum). No evidence for any anamnestic response was found in these animals. Naturally occurring hemagglutinins for sheep erythrocytes were found to be 2-ME-sensitive and present in the 19S immunoglobulin fraction. These immunoglobulin fractions were readily purified by DEAE-cellulose chromatography and Sephadex G-200 gel filtration. Both immunoglobulin molecules yielded equimolar amounts of H and L polypeptide chains when subjected to extensive reduction and alkylation followed by gel filtration in 5 M guanidine-HCl. Antigenically reactive H and L chains were obtained by partial reduction and alkylation followed by gel filtration in 1 M propionic acid. The 7S and 19S immunoglobulin H chains were indistinguishable by fingerprints of tryptic digests, disc electrophoretic patterns, antigenic properties, and mass (molecular weight approximately 70,000), thus suggesting these two molecules to belong to the same immunoglobulin class. The shark 19S and 7S immunoglobulin L chains were indistinguishable from each other by similar criteria and were different from the H chains. These L chains exhibited the electrophoretic heterogeneity of their mammalian counterparts. The 7S (shark immunoglobulin) molecule was shown to have a molecular weight of approximately 160,000 and to consist of 2H and 2L polypeptide chains (total mass congruent with180,000). The 19S molecule was shown to have a molecular weight of 800,000-900,000; therefore, there were probably five 7S subunits per 19S molecule, comparable to mammalian gammaM. Other reasons for considering the 7S and the 19S lemon shark molecules to belong to a class of immunoglobulins comparable to the gammaM class of mammals are that they both have high carbohydrate contents, and H chains of mass similar to micro chains. The lemon shark serum proteins with electrophoretic mobilities comparable to gamma G of mammals were not related to the immunoglobulins of this species. These proteins had no antibody activity and had no antigenic or chemical similarity to either the H chains, the L chains, or the intact immunoglobulin molecules from the lemon shark.
Persistent HPV Infection and Cervical Cancer Risk: Is the Scientific Rationale for Changing the Screening Paradigm Enough?
Authors: E. L. Franco
Journal: JNCI Journal of the National Cancer Institute (2010)

JNCI | Editorials 1451 Few cancer prevention discoveries have been as unequivocal as the finding that human papillomavirus (HPV) infection is a necessary cause of cervical cancer (1). The fact that HPV nucleic acid is found in nearly every exfoliated cervical cell specimen from women with high-grade cervical intraepithelial neoplasia (CIN) or cervical cancer is the justification for designing molecular-based assays to be used in screening. Yet, the paradigm for secondary prevention of this disease has thus far been difficult to challenge. Pap cytology testing has been the technological mainstay of cervical cancer screening programs for more than 50 years. North American and DOI: 10.1093/jnci/djq357 © The Author 2010. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oxfordjournals.org.
Choice of nasal nitric oxide technique as first-line test for primary ciliary dyskinesia
Authors: J. K. Marthin, K. G. Nielsen
Journal: European Respiratory Journal (2010)

Nasal nitric oxide (nNO) has a well-known potential as an indirect discriminative marker between patients with primary ciliary dyskinesia (PCD) and healthy subjects, but real-life experience and usefulness in young children is sparsely reported. Three nNO sampling methods were examined and compared as first-line tests for PCD. Healthy subjects, confirmed PCDs, consecutive referrals with PCD-like symptoms and patients with cystic fibrosis (CF) had nNO sampled during breath hold (BH-nNO), oral exhalation against resistance (OE-R-nNO) and tidal breathing (TB-nNO) aiming to expand age range into infancy. 282 subjects, 117 consecutive referrals, 59 PCDs, 49 CF patients and 57 healthy subjects, were included. All methods separated significantly between PCD and non-PCD, including CF with reliability, in ranking order BH-nNO>OE-R-nNO>TB-nNO. Acceptability in children ranked in reverse order. A problematic high fraction (39%) of false positive TB-nNO was found in young children. An unexpected large fraction (6.8%) of PCDs had nNO values above cut-off. nNO is a helpful first-line tool in real-life PCD work-up in all age groups if the sampling method is chosen according to age. nNO can be misleading in a few patients with true PCD. Further studies are strongly needed in young children.
AVE0118, Blocker of the Transient Outward Current ( <i>I</i> <sub>to</sub> ) and Ultrarapid Delayed Rectifier Current ( <i>I</i> <sub>Kur</sub> ), Fully Restores Atrial Contractility After Cardioversion of Atrial Fibrillation in the Goat
Authors: Sunniva de Haan, Maura Greiser, Erik Harks, Yuri Blaauw, Arne van Hunnik, Sander Verheule, Maurits Allessie, Ulrich Schotten
Journal: Circulation (2006)

The loss of atrial contractile function after cardioversion of atrial fibrillation (AF) contributes to the thromboembolic risk associated with AF. The newly developed blocker of the transient outward current (I(to)) and ultrarapid delayed rectifier current (I(Kur)) AVE0118 prolongs atrial action potential duration and might therefore enhance atrial contractility. We compared the ability of AVE0118 to restore atrial contraction after cardioversion of AF with the efficacy of conventional positive inotropic compounds in the goat model of AF.Eighteen goats were chronically instrumented with epicardial electrodes, a pressure transducer in the right atrium, and piezoelectric crystals to measure right atrial diameter. Atrial contractility and refractoriness and QT duration were measured before and after 1 week (3 to 8 days) of AF induced by repetitive burst pacing. The measurements were repeated after administration of digoxin (0.02 mg/kg), dobutamine (5 microg x kg(-1) x min(-1)), the Ca2+ sensitizer EMD57033 (1 mg x kg(-1) x min(-1)), the L-type Ca2+ channel agonist BayY5959 (0.1 mg x kg(-1) x min(-1)), and AVE0118 (0.01 to 0.2 mg x kg(-1) x min(-1)). The effect of AVE0118 on the configuration of atrial monophasic action potentials was determined for comparison. After 1 week of AF, atrial contractility during sinus rhythm or slow atrial pacing was reduced to <10%. Digoxin and dobutamine failed to increase atrial contractility. EMD57033 restored 41% and BayY5959 restored 48% of atrial contractility at baseline. BayY5959 significantly prolonged QT duration by 24.7%. AVE0118 enhanced atrial contraction to 156% of the baseline value. The positive inotropic effect was accompanied by a pronounced prolongation of atrial action potential duration and refractoriness, whereas QT duration remained unchanged.Conventional positive inotropic drugs showed limited effect on atrial contractility after cardioversion of AF or produced QT prolongation. In contrast, the I(to)/I(Kur) blocker AVE0118 fully restored atrial contraction without proarrhythmic effects on the ventricle.
CD133+ Cancer Stem-like Cells in Small Cell Lung Cancer Are Highly Tumorigenic and Chemoresistant but Sensitive to a Novel Neuropeptide Antagonist
Authors: Sana Sarvi, Alison C. Mackinnon, Nicolaos Avlonitis, Mark Bradley, Robert C. Rintoul, Doris M. Rassl, Wei Wang, Stuart J. Forbes, Christopher D. Gregory, Tariq Sethi
Journal: Cancer Research (2014)

Abstract Small cell lung cancer (SCLC) is a highly aggressive malignancy with poor survival rates, with initial responses nearly invariably followed by rapid recurrence of therapy-resistant disease. Drug resistance in SCLC may be attributable to the persistence of a subpopulation of cancer stem-like cells (CSC) that exhibit multiple drug resistance. In this study, we characterized the expression of CD133, one important marker of CSC in other cancers, in SCLC cancer cells. CD133 expression correlated with chemoresistance and increased tumorigenicity in vitro and in vivo accompanied by increased expression of Akt/PKB and Bcl-2. CD133 expression was increased in mouse and human SCLC after chemotherapy, an observation confirmed in clinical specimens isolated longitudinally from a patient receiving chemotherapy. We discovered in CD133+ SCLC cells, an increased expression of the mitogenic neuropeptide receptors for gastrin-releasing peptide and arginine vasopressin. Notably, these cells exhibited increased sensitivity to the growth inhibitory and proapoptotic effects of a novel broad spectrum neuropeptide antagonist (related to SP-G), which has completed a phase I clinical trial for SCLC. Our results offer evidence that this agent can preferentially target chemoresistant CD133+ cells with CSC character in SCLC, emphasizing its potential utility for improving therapy in this setting. Cancer Res; 74(5); 1554–65. ©2014 AACR.
Adhesive mechanisms governing interferon-producing cell recruitment into lymph nodes
Authors: Thomas G. Diacovo, Amanda L. Blasius, Tak W. Mak, Marina Cella, Marco Colonna
Journal: The Journal of Experimental Medicine (2005)

Natural interferon-producing cells (IPCs) are found in peripheral lymph nodes (PLNs), where they support NK cell, T cell, and B cell responses to pathogens. However, their route of entry and the adhesive mechanisms used to gain access to PLNs remain poorly defined. We report that IPCs can enter PLNs via a hematogenous route, which involves a multistep adhesive process, and that transmigration is enhanced by inflammation. Results indicate that L-selectin on IPCs is required for efficient attachment and rolling on high endothelial venules in vivo in both nonstimulated and inflamed PLNs. IPCs, however, also possess functional ligands for E-selectin that contribute to this process only in the latter case. In conjunction with selectin-mediated adhesion, both beta(1)- and beta(2)-integrins participate in IPC attachment to the inflamed vessel wall, whereas chemotaxis relies in part on the chemokine receptor CCR5. Identification of the adhesive machinery required for IPC trafficking into PLNs may provide opportunities to regulate immune responses reliant on the activity of these cells.
Robert Bransby Zachary Thomas Anderson Harold Kennedy ("Dag") Beardwood Helen Cochrane Joan Cooper Harold Handel Kenneth John Hinton Mallett Frank William Nash Henry Gordon Smylie James Trower Sweetnam Gerald Hedley Ellis Woodbine
Authors: L. Spitz, P. Daymond, P. McWilliam, A Lacey, J. Horton, A. Adams, G. Keen, C G Woodruff, G. Hatcher, K. Lovel, I. D Levack, T H. Pennington, C. Sweetnam, J. Temple, R D Lee
Journal: BMJ (1999)
Recurrent erythema multiforme: tissue typing in a large series of patients
Authors: J.K. SCHOFIELD, F.M. TATNALL, J. BROWN, D. MCCLOSKEY, C. NAVARRETE, I.M. LEIGH
Journal: British Journal of Dermatology (2006)

Previous reports have shown an increased frequency of certain HLA antigens in association with erythema multiforme, including HLA-B15(B62), HLA-B35, HLA-A33, HLA-DR53 and, more recently, HLA-DQB1*0301. A strong association with HLA-DQ3 has been documented in patients with recurrent erythema multiforme. We have performed HLA typing in 39 patients with recurrent erythema multiforme, of whom 33 were associated with herpes simplex virus infection. The results were compared with 309 controls. In the recurrent erythema multiforme patients there was a statistically significant increase in HLA-B62 and HLA-B35. An increase in HLA-DR53 was also found, although this did not reach statistical significance. There was no increase in HLA-A33. The presence of HLA-DQ3 in the study population approached that in the controls. Finally, the study population demonstrated a trend towards a reduction in the HLA antigens A1, B8 and DR3. The study confirms the previously reported associations with HLA-B62 (B15), HLA-B35 and HLA-DR53. We have been unable to confirm an association of HLA-A33 or HLA-DQ3 with erythema multiforme. The HLA antigens A1, B8, and DR3 are associated with autoimmune disease, reflecting an increased host response to tissue self antigens. Their absence in patients with recurrent erythema multiforme (REM) may be an indicator of a poor host response to an antigen, which in the case of REM is the herpes simplex virus.
A STUDY OF FIXATION FOR ELECTRON MICROSCOPY
Authors: G. E. Palade
Journal: The Journal of Experimental Medicine (1952)

Osmium tetroxide fixation of tissue blocks, as usually effected, is preceded by an acidification of the tissue. This acidification is probably responsible for morphological alterations which are notably disturbing in electron microscopy. The acidification and the resulting morphological alterations cannot be prevented by homogenizing the tissue directly in OsO(4) solutions or by adding enzyme inhibitors (fluoride, iodoscetamide) to the fixative. Fixation experiments with buffered OsO(4) solutions have shown that the appearance of the fixed cells is conditioned by the pH of the fixative. The quality of fixation can be materially improved by buffering the OsO(4) solutions at pH 7.3-7.5, The acetate-veronal buffer appeared to be the most favorable of the buffers tested, Because of these findings, 1 per cent OsO(4) buffered at pH 7.3-7.5 with acetate-veronal buffer is recommended as an appropriate fixative for electron microscopy.
Morbidity and mortality in the surgery arm of EORTC 08941 trial
Authors: P. Van Schil, J. Van Meerbeeck, G. Kramer, T. Splinter, C. Legrand, G. Giaccone, C. Manegold, N. van Zandwijk
Journal: European Respiratory Journal (2005)

Controversial results of surgical treatment after induction chemotherapy, especially in relation to the extent of resection, have previously been reported. Mortality and morbidity were studied in the surgical arm of the European Organisation for Research and Treatment of Cancer (EORTC) 08941 trial. EORTC 08941 is a multicentre, prospective, randomised, phase-III trial of surgical resection versus radiotherapy in patients with proven stage IIIA-N2 nonsmall cell lung cancer after an objective response to platinum-based induction chemotherapy. Operative results in the 167 patients randomised in the surgical arm are presented within this study. Among these patients, one switched to the radiotherapy arm and 17 patients did not get any protocol treatment or information is not yet available. Radical resection with negative surgical margins was obtained in 74 patients (49.7%). In 61 patients (40.9%), a pathological down-staging to N0 or N1 was present. Operative 30-day mortality was 4.0%. Post-operative complications were mainly pneumonia, respiratory insufficiency, arrhythmias, air leak, cardiac decompensation, empyema and bronchopleural fistula. In total, 12 (8.1%) patients underwent re-operation due to positive margins, haemothorax, empyema and bronchopleural fistula. In conclusion, surgical resection after induction chemotherapy in the multicentre European Organisation for Research and Treatment of Cancer trial has yielded acceptable rates of morbidity and mortality.
Influence of an Endotracheal Tube with Polyurethane Cuff and Subglottic Secretion Drainage on Pneumonia
Authors: Leonardo Lorente, María Lecuona, Alejandro Jiménez, María L Mora, Antonio Sierra
Journal: American Journal of Respiratory and Critical Care Medicine (2007)

Rationale: Subglottic secretion drainage (SSD) appears to be effective in preventing ventilator-associated pneumonia (VAP), primarily by reducing early-onset pneumonia; but it may not prevent late-onset pneumonia. We tested the hypothesis using an endotracheal tube incorporating an ultrathin polyurethane cuff (which reduces channel formation and fluid leakage from the subglottic area), in addition to an SSD lumen, which would reduce the incidence of late-onset VAP.Objectives: To compare the incidence of VAP, using an endotracheal tube with polyurethane cuff and subglottic secretion drainage (ETT-PUC-SSD) versus a conventional endotracheal tube (ETT-C) with polyvinyl cuff, without subglottic secretion drainage.Methods: Clinical randomized trial in a 24-bed medical–surgical intensive care unit. Patients expected to require mechanical ventilation for more than 24 hours were randomly assigned to one of two groups: one was ventilated with ETT-PUC-SSD and the other with ETT-C.Measurements and Main Results: Tracheal aspirate samples were obtained during endotracheal intubation, then twice per week and finally on extubation. VAP was found in 31 of 140 (22.1%) patients in the ETT-C group and in 11 of 140 (7.9%) in the ETT-PUC-SSD group (P = 0.001). Cox regression analysis showed ETT-C as a risk factor for global VAP (hazard ratio [HR], 3.3; 95% confidence interval [CI], 1.66–6.67; P = 0.001), early-onset VAP (HR, 3.3; 95% CI, 1.19–9.09; P = 0.02), and late-onset VAP (HR, 3.5; 95% CI, 1.34–9.01; P = 0.01).Conclusions: The use of an endotracheal tube with polyurethane cuff and subglottic secretion drainage helps prevent early- and late-onset VAP.Clinical trial registered with www.clinicaltrials.gov (NCT 00475579).