tbuckley/cabot-search huggingface dataset:
An alloresponse in humans is dominated by cytotoxic T lymphocytes (CTL) cross-reactive with a single Epstein-Barr virus CTL epitope: implications for graft-versus-host disease.
Authors: S R Burrows, R Khanna, J M Burrows, D J Moss
Journal: The Journal of Experimental Medicine (1994)

The phenomenon of T cell allorecognition is difficult to accommodate within the framework of a T cell repertoire positively selected in the thymus, unless allorecognition results from the cross-reactions of self-major histocompatibility complex restricted T cells. Herein, we demonstrate the dual specificity of cytotoxic T lymphocyte (CTL) clones for the immunodominant Epstein-Barr virus (EBV) epitope FLRGRAYGL, presented on HLA-B8, and the alloantigen HLA-B*4402. CTL which recognized peptide FLRGRAYGL in association with HLA-B8 could be reactivated in vitro from healthy individuals who had been exposed previously to EBV, using stimulator cells expressing the cross-reacting alloantigen HLA-B*4402. Limiting dilution analysis of the alloresponse to HLA-B*4402 in eight healthy individuals revealed that HLA-B8+, EBV-sero+ donors had higher CTL precursor frequencies for alloantigen HLA-B*4402 than EBV-sero- control donors. It is surprising that the majority (65-100%) of anti-HLA-B*4402 CTL, generated in limiting dilution mixed lymphocyte reactions between responder cells from HLA-B8+, EBV-sero+ individuals and HLA-B*4402+ stimulators, also recognized the EBV CTL epitope FLRGRAYGL/HLA-B8. In contrast to previous studies showing extensive diversity in the T cell repertoire against individual alloantigens, these data demonstrate that the response to an alloantigen can be dominated by CTL cross-reactive with a single viral epitope, thus illustrating a possible mechanism for the frequent clinical association between herpesvirus exposure and graft-versus-host disease after bone marrow transplants.
Effect of theophylline on airway responses to inhaled platelet-activating factor in man
Authors: KF Chung, JW Lammers, M McCusker, NM Roberts, GM Nichol, PJ Barnes
Journal: European Respiratory Journal (1989)

It has been suggested that theophylline may possess anti-inflammatory actions which underlie its antiasthma properties. We examined whether theophylline could inhibit the bronchoconstriction and the bronchial hyperresponsiveness induced by inhaled platelet-activating factor (PAF) in eight nonasthmatic subjects in a double-blind, cross-over study. After oral theophylline (6 mg.kg-1), plasma theophylline at 1 h was 10.4 +/- 1.8 mg.ml-1 (mean +/- SEM) compared to 0.39 +/- 0.19 mg.ml-1 on the placebo day (p less than 0.005). PAF, inhaled in five successive doses every 15 min, caused a 56 +/- 11% fall in Vp30 (flow at 30% of vital capacity from a partial expiratory manoeuvre) after the first dose at 5 min, and diminishing responses with successive doses. Theophylline had no significant effect on PAF-induced bronchoconstriction. PAF caused a significant decrease in PC40 (the concentration of methacholine needed to cause 40% fall in baseline Vp30) from a baseline of 12.8 mg.ml-1 (geometric standard error of mean (GSEM) 1.98) to 7.9 (1.79) mg.ml-1 on day 3 and 6.9 (1.74) on day 7 (p less than 0.02). There was no significant difference when mean PC40 values on corresponding days after PAF were compared between placebo and theophylline treatment periods. Our results suggest that theophylline has negligible influence on the airway effects of PAF.
Adoptive Cell Therapy for Lymphoma with CD4 T Cells Depleted of CD137-Expressing Regulatory T Cells
Authors: Matthew J. Goldstein, Holbrook E. Kohrt, Roch Houot, Bindu Varghese, Jack T. Lin, Erica Swanson, Ronald Levy
Journal: Cancer Research (2012)

Abstract Adoptive immunotherapy with antitumor T cells is a promising novel approach for the treatment of cancer. However, T-cell therapy may be limited by the cotransfer of regulatory T cells (Treg). Here, we explored this hypothesis by using 2 cell surface markers, CD44 and CD137, to isolate antitumor CD4 T cells while excluding Tregs. In a murine model of B-cell lymphoma, only CD137negCD44hi CD4 T cells infiltrated tumor sites and provided protection. Conversely, the population of CD137posCD44hi CD4 T cells consisted primarily of activated Tregs. Notably, this CD137pos Treg population persisted following adoptive transfer and maintained expression of FoxP3 as well as CD137. Moreover, in vitro these CD137pos cells suppressed the proliferation of effector cells in a contact-dependent manner, and in vivo adding the CD137posCD44hi CD4 cells to CD137negCD44hi CD4 cells suppressed the antitumor immune response. Thus, CD137 expression on CD4 T cells defined a population of activated Tregs that greatly limited antitumor immune responses. Consistent with observations in the murine model, human lymphoma biopsies also contained a population of CD137pos CD4 T cells that were predominantly CD25posFoxP3pos Tregs. In conclusion, our findings identify 2 surface markers that can be used to facilitate the enrichment of antitumor CD4 T cells while depleting an inhibitory Treg population. Cancer Res; 72(5); 1239–47. ©2012 AACR.
Gene expression profiling of chronic myeloid leukemia with variant t(9;22) reveals a different signature from cases with classic translocation
Authors: Francesco Albano, Antonella Zagaria, Luisa Anelli, Nicoletta Coccaro, Luciana Impera, Crescenzio Francesco Minervini, Angela Minervini, Antonella Russo Rossi, Giuseppina Tota, Paola Casieri, Giorgina Specchia
Journal: Molecular Cancer (2013)

The t(9;22)(q34;q11) generating the BCR/ABL1 fusion gene represents the cytogenetic hallmark of chronic myeloid leukemia (CML). About 5-10% of CML cases show variant translocations with the involvement of other chromosomes in addition to chromosomes 9 and 22. The molecular bases of biological differences between CML patients with classic and variant t(9;22) have never been clarified.In this study, we performed gene expression microarray analysis to compare CML patients bearing variant rearrangements and those with classic t(9;22)(q34;q11). We identified 59 differentially expressed genes significantly associated with the two analyzed groups. The role of specific candidate genes such as TRIB1 (tribbles homolog 1), PTK2B (protein tyrosine kinase 2 beta), and C5AR1 (complement component 5a receptor 1) is discussed.Our results reveal that in CML cases with variant t(9;22) there is an enhancement of the MAPK pathway deregulation and show that kinases are a common target of molecular alterations in hematological disorders.
Studies with pain rating scales.
Authors: W W Downie, P A Leatham, V M Rhind, V Wright, J A Branco, J A Anderson
Journal: Annals of the Rheumatic Diseases (1978)

Good correlation has been shown between pain scores derived from 4 different rating scales. The correlation was maintained when presentation of the scales was separated by a series of questions and by physical examination. There is good evidence that the 4 scales are measuring the same underlying pain variable as they calibrate well. There is also evidence that an 11-point (0-10) numerical rating scale performs better than both a 4-point simple descriptive scale or a continuous (visual analogue) scale.
Mobilisation with movement and exercise, corticosteroid injection, or wait and see for tennis elbow: randomised trial
Authors: Leanne Bisset, Elaine Beller, Gwendolen Jull, Peter Brooks, Ross Darnell, Bill Vicenzino
Journal: BMJ (2006)

To investigate the efficacy of physiotherapy compared with a wait and see approach or corticosteroid injections over 52 weeks in tennis elbow.Single blind randomised controlled trial.Community setting, Brisbane, Australia.198 participants aged 18 to 65 years with a clinical diagnosis of tennis elbow of a minimum six weeks' duration, who had not received any other active treatment by a health practitioner in the previous six months.Eight sessions of physiotherapy; corticosteroid injections; or wait and see.Global improvement, grip force, and assessor's rating of severity measured at baseline, six weeks, and 52 weeks.Corticosteroid injection showed significantly better effects at six weeks but with high recurrence rates thereafter (47/65 of successes subsequently regressed) and significantly poorer outcomes in the long term compared with physiotherapy. Physiotherapy was superior to wait and see in the short term; no difference was seen at 52 weeks, when most participants in both groups reported a successful outcome. Participants who had physiotherapy sought less additional treatment, such as non-steroidal anti-inflammatory drugs, than did participants who had wait and see or injections.Physiotherapy combining elbow manipulation and exercise has a superior benefit to wait and see in the first six weeks and to corticosteroid injections after six weeks, providing a reasonable alternative to injections in the mid to long term. The significant short term benefits of corticosteroid injection are paradoxically reversed after six weeks, with high recurrence rates, implying that this treatment should be used with caution in the management of tennis elbow.
Pulmonary Mycobacterium malmoense and aspergillus infection: a fatal combination?
Authors: F G Bollert, P J Sime, W MacNee, G K Crompton
Journal: Thorax (1994)

Three patients with chronic obstructive pulmonary disease developed coexisting Mycobacterium malmoense and aspergillus infection. All suffered progressive lung destruction leading to early death despite prolonged antimycobacterial chemotherapy.
Atrioventricular nodal reentry. Clinical, electrophysiological, and therapeutic considerations.
Authors: M Akhtar, M R Jazayeri, J Sra, Z Blanck, S Deshpande, A Dhala
Journal: Circulation (1993)

BACKGROUND Atrioventricular (AV) nodal reentry is a relatively common cause of regular, narrow QRS tachycardia. The underlying basis for this arrhythmia is functional (and anatomic) duality of pathways in the region of the AV node, although the exact boundaries of the reentrant circuit have not been convincingly defined. During the more common type of AV nodal reentry (seen in approximately 90% of cases), a slow conducting pathway is used in the anterograde direction, and a fast pathway is operative in the retrograde direction. In the uncommon form, the direction of impulse propagation within the reentrant circuit is reversed. In this article, the clinical, ECG, and electrophysiological features of AV nodal reentry as well as approaches to therapy are discussed. METHODS AND RESULTS Clinical diagnosis may be made from the surface ECG. In the common type of AV nodal reentry, the P wave is obscured by the QRS or may be present in its terminal portion. The P wave in the uncommon form occurs late (i.e., in or after the T wave), producing a pattern of long RP and short PR. Both forms of AV nodal reentry are controllable with various therapeutic modalities. For acute termination, adenosine is probably the ideal agent. Prevention of recurrences can be achieved with several pharmacological agents, including beta-blockers, calcium channel blockers, and class Ia, Ic, and III antiarrhythmic agents. Curative therapy is now available with a variety of nonpharmacological methods. However, the most promising therapy at the present time is catheter modification of the AV node by ablation of either the fast or slow pathway, using radiofrequency energy. Ablation of the fast pathway carries a higher risk of second- or third-degree AV block. Slow pathway ablation, by providing a high rate of success and minimal risk of AV block, seems to be a more acceptable initial approach. CONCLUSIONS AV nodal reentry is a common cause of paroxysmal supraventricular tachycardia, and a precise diagnosis can be made with intracardiac electrophysiological evaluation. Although the arrhythmia responds to a variety of antiarrhythmic agents, curative therapy can now be offered with catheter modification of the AV node using radiofrequency energy. At the time of this writing, it seems that catheter modification of the AV node is rapidly becoming the therapy of initial choice in patients with symptomatic AV nodal reentrant tachycardia requiring treatment.
Cataloguing the Effects of Genetic Variants in 5' Upstream Regions of Eicosanoid Related Genes
Authors: James R. Perkins, Jose A. Cornejo-Garcia, Inmaculada Doña, Natalia Blanca-López, Maria del Carmen Plaza-Serón, Juan A. Ranea, Veronique Godineau, Cristobalina Mayorga, Maria J. Torres, Gabriela Canto, Miguel Blanca
Journal: Journal of Allergy and Clinical Immunology (2015)
HOST-PARASITE RELATIONSHIPS IN EXPERIMENTAL PNEUMONIA DUE TO PNEUMOCOCCUS TYPE III
Authors: W. Barry Wood, Mary Ruth Smith
Journal: The Journal of Experimental Medicine (1950)

Experimental pneumonia was produced with a highly virulent strain of type III pneumococcus which synthesizes, during rapid growth, large amounts of capsular polysaccharide. The type III pneumonia differed from that caused by pneumococcus I in that (a) death occurred more promptly in the type III infection, (b) the local pulmonary lesion became more heavily infected, and (c) frank suppuration was common even after otherwise effective chemotherapy. The greater pathogenicity of the type III organism was shown by special histologic techniques to be due primarily to its capsular slime layer which interferes with surface phagocytosis. Capsular polysaccharide shed from the organism during growth was also demonstrated in high concentration in certain parts of the pneumonic lesion. Removal of the excess polysaccharide from the alveoli resulted from (a) lymphatic drainage to regional lymph nodes and (b) phagocytosis, particularly by macrophages. The possible relationship of the free carbohydrate to the malignancy and the characteristically viscous exudate of type III pneumonia was discussed. The lung abscesses which resulted from type III infection were observed to occur in those areas in which the maximum number of organisms had accumulated. Evidence was obtained that suppuration was due, not to necrotoxic products peculiar to the type III pneumococcus, but rather to the survival of large numbers of bacteria in the tissues, brought about primarily by the antiphagocytic effect of the slime layer. When pneumonia was produced with an intermediate type III mutant lacking the protective slime layer, back mutation to the mucoid parent occurred during the course of the infection, and the mucoid form eventually predominated in the lung as a result of selective phagocytosis of the intermediate organisms. Similar mutation to the maximally virulent type III form was noted with a transformed intermediate type III strain grown from single cell preparations.
* Cetuximab combined with multi-targeted sirna against HSP90, UBCH5, and SRC circumvented oncogene addiction, transactivation, and acquired resistance as a result of EGFR ubiquitination, and mutations/deletions in the kinase domain of EGFR in colorectal CA
Authors: J. Giannios
Journal: Gut (2011)

<h3>Introduction</h3> Colorectal carcinoma (CRC) cells develop resistance to cetuximab through insertion mutations at exon 20, ubiquitination and c-Src which activates EGFR in the absence of ligand despite treatment with cetuximab. We aim to circumvent this acquired resistance. <h3>Methods</h3> CRC cells were obtained from metastatic patients resistant to cetuximab due to insertion mutations at exon 20, ubiquitination and overexpressed c-Src. Orthotopic mouse CRC models generated from our patients9 tumour cells were injected with multitargeted siRNA against HSP90, UbcH5 and c-Src. <h3>Results</h3> Multi-targeted siRNA inhibited expression of the E2 enzyme UbcH5, blocking the covalent attachment of ubiquitin to target protein EGFR, and neutralizing the multi-enzyme cascade. E1 deactivated ubiquitin, blocking transfer to the cysteine residue of E2 ubiquitin conjugating enzyme (UbcH5). This inhibited the E2 ligation of ubiquitin via its carboxy terminus to lysine residues of the protein substrate EGFR. Multi-targeted siRNA inhibited expression of HSP90 resulting in degradation of EGFR with kinase domain deletion type mutations in exon 19, substitutions in exon 21, and resistant insertion mutations at exon 20. Inhibition of c-Src circumvented transactivation and inhibited EGFR signalling, inhibiting tumour proliferation, and metastasis to the liver, and peritoneum. Addiction to EGFR was circumvented. Inhibition of EGFR blocked the activation of downstream mediators including STAT3, AKT, Erk/MAPK and PI3K, while IRF-1 was upregulated. There was enhanced cell to cell adhesion and membrane localisation of b-catenin, while MMP-9 invasive activity was blocked. HIF-1a/Met pathway was blocked downregulating CAIX. VEGFR-2 and VEGFR-3 were blocked inhibiting vascularisation and lymphangiogenesis, respectively. We observed type I, II and III PCD in tumour cells. <h3>Conclusion</h3> These results indicate that systemic treatment of multitargeted siRNA against UbcH5, c-Src and HSP90 circumvented resistance to cetuximab suppressing tumour growth and metastasis in orthotopic mouse mCRC model.
Long term increases in coronary arterial conductance during five day infusion of low dose nicorandil
Authors: E Bassenge, B Fink, O Sommer, C Huckstorf
Journal: Cardiovascular Research (1994)

Journal Article Long term increases in coronary arterial conductance during five day infusion of low dose nicorandil Get access E Bassenge, E Bassenge University of Freiburg, Department of Applied Physiology, Hermann-Herder-Strasse 7, D-79104 Freiburg, Germany: E Bassenge, B Fink, O Sommer, C Huckstorf. Correspondence to Professor Bassenge. Search for other works by this author on: Oxford Academic PubMed Google Scholar B Fink, B Fink University of Freiburg, Department of Applied Physiology, Hermann-Herder-Strasse 7, D-79104 Freiburg, Germany: E Bassenge, B Fink, O Sommer, C Huckstorf. Search for other works by this author on: Oxford Academic PubMed Google Scholar O Sommer, O Sommer University of Freiburg, Department of Applied Physiology, Hermann-Herder-Strasse 7, D-79104 Freiburg, Germany: E Bassenge, B Fink, O Sommer, C Huckstorf. Search for other works by this author on: Oxford Academic PubMed Google Scholar C Huckstorf C Huckstorf University of Freiburg, Department of Applied Physiology, Hermann-Herder-Strasse 7, D-79104 Freiburg, Germany: E Bassenge, B Fink, O Sommer, C Huckstorf. Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, Volume 28, Issue 6, June 1994, Pages 912–916, https://doi.org/10.1093/cvr/28.6.912 Published: 01 June 1994 Article history Received: 06 January 1994 Accepted: 21 March 1994 Published: 01 June 1994
Two different dosages of cefotaxime in the treatment of spontaneous bacterial peritonitis in cirrhosis: Results of a prospective, randomized, multicenter study
Authors: Antoni Rimola, Joan M. Salmerón, Gerardo Clemente, Luis Rodrigo, Antoni Obrador, M. Luisa Miranda, Carlos Guarner, Ramon Planas, Ricard Solá, Victor Vargas, Fernando Casafont, Francesc Marco, Miquel Navasa, Rafael Bañares, Vicente Arroyo, Joan Rodés
Journal: Hepatology (1995)

Cefotaxime (CTX) is considered one of the first-choice antibiotics in the therapy of spontaneous bacterial peritonitis (SBP) in cirrhosis. Because CTX is largely metabolized in the liver, this drug may also be effective in SBP by administering lower doses than those habitually used. To investigate this possibility, a prospective, randomized, multicenter study was performed to compare the therapeutic efficacy of two different dosages of CTX in 143 patients with SBP: 71 (group I) were allocated to receive a high dose (2 g every 6 hours, which is one of the most frequently recommended doses in this infection), and 72 (group II) were allocated to receive a low dose (2 g every 12 hours). At inclusion, both groups were similar in relation to clinical and laboratory data, with the exception of a higher incidence of positive ascitic fluid culture in group I than in group II (59% vs. 40%; P = .029). The rate of infection resolution was similar for both groups (77% vs. 79%). Hospital survival was also similar in both groups (69% vs. 79%). No difference was observed between patients with positive or negative ascitic fluid cultures with regard to infection resolution and patient survival. The duration of antibiotic therapy was similar in both groups (9.0 +/- 3.3 days in group I vs. 8.8 +/- 3.1 days in group II). In a subset of 13 patients from group I and 11 patients from group II CTX levels were determined in serum (peak and trough) and ascitic fluid (concomitantly with trough serum). Peak serum levels were similar in patients from both groups.(ABSTRACT TRUNCATED AT 250 WORDS)
Store-refilling involves both L-type calcium channels and reverse-mode sodium calcium exchange in airway smooth muscle
Authors: S. Hirota, L. J. Janssen
Journal: European Respiratory Journal (2007)

The aim of the present study was to examine the relative contributions to store-refilling of the two following voltage-regulated calcium ion influx pathways: 1) L-type-Ca 2+ channels; and 2) the reverse-mode of the sodium–calcium exchanger (NCX). Successive acetylcholine-induced contractions, triggered in bovine tracheal smooth muscle strips, were measured to determine the effect of intervention on contractions as an indication of the extent of store-refilling. Pre-treating the tissues with cromakalim significantly reduced the magnitude of successive contractions. Zero-Ca 2+ bathing media abolished the contractions, an effect that was completely reversed upon reintroduction of Ca 2+ . Inhibition of L-type Ca 2+ channels, with nifedipine, significantly reduced the magnitude of the contractions. Similarly, inhibition of the reverse-mode of the NCX, with KB-R7943, significantly reduced the magnitude of the contractions. However, neither nifedipine nor KB-R7943 alone reduced contractions to the same extent as observed under zero-Ca 2+ conditions. Concurrent treatment with nifedipine and KB-R7943 almost abolished successive contractions. Furthermore, concurrent treatment with nifedipine and zero-Na + bathing media displayed a significantly greater effect than nifedipine alone. Probing the expression of NCX1 isoforms by Western blotting revealed the presence of three bands of 160, 120 and 110 kDa. The 120- and 110-kDa bands were identified as variably spliced NCX isoforms, NCX1.1 and NCX1.3, respectively. Taken together, these data suggest that influx of calcium ions through both L-type calcium channels and the reverse-mode of the sodium–calcium exchanger is necessary for complete store-refilling in airway smooth muscle.