tbuckley/cabot-search huggingface dataset:
Exacerbated inflammatory arthritis in response to hyperactive gp130 signalling is independent of IL-17A
Authors: G W Jones, C J Greenhill, J O Williams, M A Nowell, A S Williams, B J Jenkins, S A Jones
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Objective</h3> Interleukin (IL)-17A producing CD4 T-cells (T<sub>H</sub>-17 cells) are implicated in rheumatoid arthritis (RA). IL-6/STAT3 signalling drives T<sub>H</sub>-17 cell differentiation, and hyperactive gp130/STAT3 signalling in the <i>gp130</i><sup>F/F</sup> mouse promotes exacerbated pathology. Conversely, STAT1-activating cytokines (eg, IL-27, IFN-γ) inhibit T<sub>H</sub>-17 commitment. Here, we evaluate the impact of STAT1 ablation on T<sub>H</sub>-17 cells during experimental arthritis and relate this to IL-17A-associated pathology. <h3>Methods</h3> Antigen-induced arthritis (AIA) was established in wild type (WT), <i>gp130</i><sup>F/F</sup> mice displaying hyperactive gp130-mediated STAT signalling and the compound mutants <i>gp130<sup>F/F</sup>:Stat1<sup>−/−</sup></i> and <i>gp130<sup>F/F</sup>:Il17a<sup>−/−</sup></i> mice. Joint pathology and associated peripheral T<sub>H</sub>-17 responses were compared. <h3>Results</h3> Augmented gp130/STAT3 signalling enhanced T<sub>H</sub>-17 commitment in vitro and exacerbated joint pathology. Ablation of STAT1 in <i>gp130</i><sup>F/F</sup> mice (<i>gp130<sup>F/F</sup>:Stat1<sup>−/−</sup></i>) promoted the hyperexpansion of T<sub>H</sub>-17 cells in vitro and in vivo during AIA. Despite this heightened peripheral T<sub>H</sub>-17 cell response, disease severity and the number of joint-infiltrating T-cells were comparable with that of WT mice. Thus, gp130-mediated STAT1 activity within the inflamed synovium controls T-cell trafficking and retention. To determine the contribution of IL-17A, we generated <i>gp130<sup>F/F</sup></i>:IL-17a<sup>−/−</sup> mice. Here, loss of IL-17A had no impact on arthritis severity. <h3>Conclusions</h3> Exacerbated gp130/STAT-driven disease in AIA is associated with an increase in joint infiltrating T-cells but synovial pathology is IL-17A independent.
Antibodies Associated With Epstein-Barr Virus in Burkitt's Lymphoma During Injections of BCG or Irradiated Autochthonous Tumor Cells2
Authors: Peter Gunvén, George Klein, Julius Onyango, Gertrude Henle, Werner Henle, Peter Clifford, Surjit Singh, Aberra Demissie, Arne Svedmyr
Journal: JNCI Journal of the National Cancer Institute (1973)

Journal Article Antibodies Associated With Epstein-Barr Virus in Burkitt's Lymphoma During Injections of BCG or Irradiated Autochthonous Tumor Cells Get access Peter Gunvén, Peter Gunvén 3Department of Tumor Biology, Karolinska Institute, 10401 Stockholm, Sweden Search for other works by this author on: Oxford Academic PubMed Google Scholar George Klein, George Klein 3Department of Tumor Biology, Karolinska Institute, 10401 Stockholm, Sweden Search for other works by this author on: Oxford Academic PubMed Google Scholar Julius Onyango, Julius Onyango 3Department of Tumor Biology, Karolinska Institute, 10401 Stockholm, Sweden Search for other works by this author on: Oxford Academic PubMed Google Scholar Gertrude Henle, Gertrude Henle 5Virus Laboratories, the Children's Hospital of Philadelphia and the School of Medicine, University of Pennsylvania, Philadelphia, Pa Search for other works by this author on: Oxford Academic PubMed Google Scholar Werner Henle, Werner Henle 5Virus Laboratories, the Children's Hospital of Philadelphia and the School of Medicine, University of Pennsylvania, Philadelphia, Pa Search for other works by this author on: Oxford Academic PubMed Google Scholar Peter Clifford, Peter Clifford 7Department of Head and Neck Surgery, Kenyatta National Hospital, Nairobi Search for other works by this author on: Oxford Academic PubMed Google Scholar Surjit Singh, Surjit Singh 7Department of Head and Neck Surgery, Kenyatta National Hospital, Nairobi Search for other works by this author on: Oxford Academic PubMed Google Scholar Aberra Demissie, Aberra Demissie 9Virus Department, Central Microbiological Laboratory of the Stockholm County, Stockholm Search for other works by this author on: Oxford Academic PubMed Google Scholar Arne Svedmyr Arne Svedmyr 9Virus Department, Central Microbiological Laboratory of the Stockholm County, Stockholm Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 51, Issue 1, July 1973, Pages 45–56, https://doi.org/10.1093/jnci/51.1.45 Published: 01 July 1973 Article history Received: 07 December 1972 Accepted: 27 February 1973 Published: 01 July 1973
Evidence for a possible role of the brain kallikrein-kinin system in the modulation of the cerebral circulation.
Authors: T Kamitani, M H Little, E F Ellis
Journal: Circulation Research (1985)

Experiments by others have shown that exogenous bradykinin dilates cerebral arterioles and that the brain contains kininogen and kallikrein, the latter being the enzyme which converts kininogen to bradykinin. The objective of these experiments was to determine if bradykinin produced from endogenous brain kininogen can affect the cerebral microcirculation. Rabbit pial arteriolar diameter was measured with a microscope using the closed cranial window technique. Topical application of bradykinin (10(-8)-10(-5) M) induced a dose-dependent vasodilation (8-46%) which was completely inhibited by the cyclooxygenase enzyme inhibitors indomethacin and meclofenamic acid. Topical application of 1 U of tissue kallikrein per milliliter of artificial cerebrospinal fluid induced 43% dilation, which could be prevented by local treatment with indomethacin or the proteinase inhibitor aprotinin. The action of aprotinin and indomethacin was specific, since aprotinin did not affect the dilation produced by bradykinin, and indomethacin did not affect dilation produced by adenosine. A second application of kallikrein had no effect on cerebral diameter, yet the arterioles still responded normally to exogenous bradykinin, indicating that the first application of kallikrein depleted brain kininogen. We suggest that activation of brain kallikrein and subsequent formation of kinin from brain kininogen may be important in modulation of cerebral blood flow or generation of cerebral edema.
EFFECTS OF SEDATIVE DRUGS ON THE ELECTROENCEPHALOGRAM
Authors: MARGARET LENNOX
Journal: American Journal of Psychiatry (1946)

A study is presented of the electroencephalographic effects of small oral doses of the usual sedative drugs (phenobarbital, sodium amytal, nembutal, seconal, paraldehyde, chloral) in 10 normal subjects with normal EEGs. Data on 45 psychiatric patients who had received oral sedation within 24 hours of the electroencephalographic recording are compared with a control group of 45 psychiatric patients who had received no sedation. Patients with a diagnosis of epilepsy or of organic central nervous system disease were excluded from this study. The results of the two methods of study are in essential agreement and lead to the following conclusions: 1. The commonly used barbiturates given orally in small doses may change a normal to an abnormal EEG. Paraldehyde and chloral do not cause prolonged alterations in the normal EEG under the conditions of this study. 2. The change occurs in an estimated 35 percent of individuals with normal electroencephalographic tracings. This change is of a nature and degree to require reevaluation of studies on patients receiving sedatives. 3. The change usually consists of an increase in fast activity, but it may consist of an increase in slow activity. In either case, the direction of the change is more constant for the individual than for the drug employed. 4. The factors which influence the appearance of an abnormal EEG after sedation are individual susceptibility, drug employed, time interval and dosage. The highest percentage of abnormal records occurs in the patients who received 0.3 gram or more of barbiturate 12 to 14 hours before the EEG. Miss Dorothy Nixon and Miss Olga Noto rendered valuable technical assistance.
Expression and mutational status of treatment-relevant targets and key oncogenes in 123 malignant salivary gland tumours
Authors: J. Cros, E. Sbidian, S. Hans, H. Roussel, F. Scotte, E. Tartour, D. Brasnu, P. Laurent-Puig, P. Bruneval, H. Blons, C. Badoual
Journal: Annals of Oncology (2013)

Malignant tumours of the salivary glands (MSGT) are rare and pleomorphic entities. Patients with advanced disease may benefit from targeted therapy; however, specific targets for optimising and personalising treatments are yet to be identified.Immunohistochemistry for C-KIT, EGFR, HER2, MUC1, phospho-mTOR, androgen/estrogens/progesterone receptors and Ki67 was carried out and evaluated in terms of progression-free and overall survival. High throughput molecular screening of key oncogenes was done in 107 patients using routine diagnostic methods and Sequenom technology.Several therapy leads were identified, including high levels of HER2 and androgen receptors in salivary duct carcinomas, C-KIT in myoepithelial carcinomas and EGFR in mucoepidermoid carcinomas. Recurrent mutations involving downstream elements of the EGFR pathway were found in HRAS, notably in tumours with a myoepithelial component, and in other key oncogenes (KRAS/NRAS/PI3KCA/BRAF/MAP2K). On the other hand, <1% of samples had EGFR or HER2 mutations.Several tumour subtypes overexpressed targets of directed therapies suggesting potential therapy leads. Genotyping results suggest activation downstream of EGFR in 18 of the 107 samples that could be associated with low efficacy of EGFR inhibitors. Other molecules, such as PI3K/MEK or mTOR inhibitors, may have anti-tumour activity in this subgroup. The high mutation rate in HRAS highlights a novel key oncogenic event in MSGT.
Effects of Abdominal Strapping on Forced Expiration in Tetraplegic Patients
Authors: MARC ESTENNE, ALAIN VAN MUYLEM, MASSIMO GORINI, WILLIAM KINNEAR, ANDRÉ HEILPORN, ANDRÉ DE TROYER
Journal: American Journal of Respiratory and Critical Care Medicine (1998)

Patients with traumatic transection of the lower segments of the cervical cord contract the clavicular portion of the pectoralis major during forced expiration and cough, and the rise in intrathoracic pressure resulting from this contraction produces dynamic airway compression in many patients. Because the abdominal muscles are paralyzed, however, there is paradoxical expansion of the abdomen, which may reduce the rise in intrathoracic pressure and the degree of airway collapse. To evaluate the magnitude of this effect, we measured expiratory flow rate (V˙exp) and esophageal pressure (Pes) during a series of forced expiratory vital capacity maneuvers and constructed isovolume-pressure flow (IVPF) curves before and after abdominal strapping in eight C 5-8 tetraplegic subjects. Strapping produced small and inconsistent changes in maximal V˙exp and Pes and resulted in the development of small flow plateaus in only four patients. In tetraplegic subjects, abdominal strapping thus has small effects on forced expiration and is unlikely, therefore, to improve the efficiency of cough.
Basal secretion and anaphylactic release of rat mast cell protease-II (RMCP-II) from ex vivo perfused rat jejunum: translocation of RMCP-II into the gut lumen and its relation to mucosal histology.
Authors: C L Scudamore, A M Pennington, E Thornton, L McMillan, G F Newlands, H R Miller
Journal: Gut (1995)

The kinetics of the release of rat mast cell protease-II (RMCP-II) from mucosal mast cells in the jejunum of Nippostrongylus brasiliensis primed (immune) rats was investigated using ex vivo perfusion of a segment of jejunum through the cranial mesenteric artery. The aim of the study was to assess the role of the protease in anaphylaxis and in particular to ascertain whether it is responsible for the histological changes, which include widespread epithelial shedding, seen in the mucosa in in vivo models of anaphylaxis. Perfusion of the jejunal vasculature with a Krebs-Ringer buffer showed that there was basal secretion of RMCP-II by jejunal mast cells in all rats studied. The baseline concentration of RMCP-II was significantly greater (p < 0.05) in immune rats (> 7 ng/ml) previously exposed to nippostrongylus infection than in control, naive animals (< 2 ng/ml). Challenge of immune rats with 100 or 400 worm equivalents of whole worm antigen resulted in an immediate (within 40 seconds) and significant (p < 0.02) increase in the concentration of RMCP-II (to > 3 micrograms/ml) in the vascular perfusate, which was not seen in naive rats or immune rats challenged with an irrelevant antigen. Greater amounts of RMCP-II were also recovered from the jejunal lumen of immune rats compared with naive rats after challenge of both groups with worm antigen. Despite the release of microgram quantities of RMCP-II into the gut lumen and vascular perfusate, however, there were no significant changes seen in the mucosal histology. These results suggest that RMCP-II alone is not responsible fore the loss of gut epithelium seen during anaphylaxis in the rat.
Circulating plasma cells detected by flow cytometry as a predictor of survival in 302 patients with newly diagnosed multiple myeloma
Authors: Grzegorz S. Nowakowski, Thomas E. Witzig, David Dingli, Michal J. Tracz, Morie A. Gertz, Martha Q. Lacy, John A. Lust, Angela Dispenzieri, Philip R. Greipp, Robert A. Kyle, S. Vincent Rajkumar
Journal: Blood (2005)
Effect of Distal Embolization on Myocardial Perfusion Reserve After Percutaneous Coronary Intervention
Authors: Joseph B. Selvanayagam, Adrian S.H. Cheng, Michael Jerosch-Herold, Kazem Rahimi, Italo Porto, William van Gaal, Keith M. Channon, Stefan Neubauer, Adrian P. Banning
Journal: Circulation (2007)

Background— Studies have shown that a subset of patients demonstrate persistent impairment in microcirculatory function after percutaneous coronary intervention (PCI). Distal embolization of plaque contents has been postulated as the main mechanism for this. We sought to investigate this further by evaluating PCI-induced changes in myocardial perfusion reserve index (MPRI) over time in segments with “distal-type” procedure-related myonecrosis using high-resolution quantitative cardiovascular magnetic resonance imaging. Methods and Results— Forty patients undergoing PCI were studied with pre-PCI and 24-hour post-PCI delayed-enhancement magnetic resonance imaging and first-pass perfusion magnetic resonance imaging at rest and stress. Twenty patients underwent a third magnetic resonance imaging scan at 6 months. For perfusion imaging, 3 short-axis images were acquired during every heartbeat with a T1-weighted turboFLASH sequence. MPRI was calculated as the ratio of hyperemic to resting myocardial blood flow and subdivided according to the presence and location of new delayed hyperenhancement. Twenty-one patients demonstrated new distal hyperenhancement after PCI. Mean MPRI in revascularized myocardial segments not demonstrating new HE was significantly increased after the procedure (2.06 [95% CI, 1.99 to 2.13] before PCI and 2.52 [95% CI, 2.42 to 2.62] after PCI; P &lt;0.001). In contrast, MPRI in segments with distal hyperenhancement was reduced after PCI (2.16 [95% CI, 1.95 to 2.37] before PCI; 2.00 [95% CI, 1.82 to 2.19] after PCI; mixed-model z =−4.82; P &lt;0.001). Changes in mean MPRI 24 hours after PCI in segments upstream to new injury were not significantly different compared with perfusion changes in remote myocardium ( z =−0.68; P =0.50). At 6 months after the procedure, mean MPRI in segments with new injury improved significantly compared with MPRI measured in these segments at 24 hours after PCI. Conclusions— MPRI is reduced in myocardial segments that demonstrate new distal irreversible injury at 24 hours after PCI. These reductions are confined to the segments with injury and do not affect the entire supply territory of the culprit vessel.
Surface expression of functional T cell receptor chains formed by interlocus recombination on human T lymphocytes.
Authors: F Davodeau, M A Peyrat, J Gaschet, M M Hallet, F Triebel, H Vié, D Kabelitz, M Bonneville
Journal: The Journal of Experimental Medicine (1994)

Structural diversity of lymphocyte antigen receptors (the immunoglobulin [Ig] of B cells and the alpha/beta or gamma/delta T cell receptor [TCR] of T cells) is generated through somatic rearrangements of V, D, and J gene segments. Classically, these recombination events involve gene segments from the same Ig or TCR locus. However, occurrence of "trans" rearrangements between distinct loci has also been described, although in no instances was the surface expression of the corresponding protein under normal physiological conditions demonstrated. Here we show that hybrid TCR genes generated by trans rearrangement between V gamma and (D) J beta elements are translated into functional antigen receptor chains, paired with TCR alpha chains. Like classical alpha/beta T cells, cells expressing these hybrid TCR chains express either CD4 or CD8 coreceptors and are frequently alloreactive. These results have several implications in terms of T cell repertoire selection and relationships between TCR structure and specificity. First, they suggest that TCR alloreactivity is determined by the repertoire selection processes operating during lymphocyte development rather than by structural features specific to V alpha V beta regions. Second, they suggest the existence of close structural relationships between gamma/delta and alpha/beta TCR and more particularly, between V gamma and V beta regions. Finally, since a significant fraction of PBL (at least 1/10(4)) expressed hybrid TCR chains on their surface, these observations indicate that trans rearrangements significantly contribute to the combinatorial diversification of the peripheral immune repertoire.
Involvement of endogenous tachykinins in LTD4-induced airway responses
Authors: J Ishikawa, M Ichinose, M Miura, N Kageyama, H Yamauchi, M Tomaki, Y Sasaki, K Shirato
Journal: European Respiratory Journal (1996)

Leukotriene D4-(LTD4) has been reported to cause tachykinin release from airway sensory nerves. However, the functional significance of endogenously released tachykinins in LTD4-mediated airway responses has not been fully clarified. The aim of this study was to investigate whether LTD4-induced airway responses are due, in part, to tachykinin release in guinea-pigs. Airway plasma exudation and bronchoconstriction were assessed by measuring extravasation of Evans blue dye and by mean pulmonary resistance (RL) in the presence of atropine (1 mg.kg-1 i.v.) and propranolol (1 mg.kg-1 i.v.), respectively. LTD4 (5 micrograms.mL-1 for 1 min) inhalation caused increase in plasma exudation and RL. Capsaicin pretreatment of animals to deplete sensory neuropeptides significantly inhibited LTD4-induced plasma exudation in the main bronchi, but not in the central (cIPA) and peripheral intrapulmonary airways (pIPA). Pretreatment with specific tachykinin neurokinin-1 (NK1)-receptor antagonists, FK 888 (10 mg.kg-1 i.v.) and CP 96345 (4 mg.kg-1 i.v.), also significantly reduced LTD4-induced plasma exudation in the main bronchi, and in the main bronchi and cIPA, respectively. However, these antagonists did not significantly affect the LTD4-induced increase in RL. In contrast, neurokinin-2 (NK2)-receptor antagonist, SR 48968 (0.3 mg.kg-1 i.v.), significantly inhibited the bronchoconstriction after LTD4-inhalation. These results suggest that leukotriene D4-induced bronchoconstriction and plasma exudation in guinea-pigs are, in part, due to tachykinin release from airway sensory nerves.
An integrative genomics approach to infer causal associations between gene expression and disease
Authors: Eric E Schadt, John Lamb, Xia Yang, Jun Zhu, Steve Edwards, Debraj GuhaThakurta, Solveig K Sieberts, Stephanie Monks, Marc Reitman, Chunsheng Zhang, Pek Yee Lum, Amy Leonardson, Rolf Thieringer, Joseph M Metzger, Liming Yang, John Castle, Haoyuan Zhu, Shera F Kash, Thomas A Drake, Alan Sachs, Aldons J Lusis
Journal: Nature Genetics (2005)
Implementation of a neuromuscular training programme in female adolescent football: 3-year follow-up study after a randomised controlled trial
Authors: Hanna Lindblom, Markus Waldén, Siw Carlfjord, Martin Hägglund
Journal: British Journal of Sports Medicine (2014)

Neuromuscular training (NMT) has been shown to reduce anterior cruciate ligament injury rates in highly structured clinical trials. However, there is a paucity of studies that evaluate implementation of NMT programmes in sports.To evaluate the implementation of an NMT programme in female adolescent football 3 years after a randomised controlled trial (RCT).Cross-sectional follow-up after an RCT using the Reach, Effectiveness, Adoption, Implementation, and Maintenance Sports Setting Matrix (RE-AIM SSM) framework. Questionnaires were sent to the Swedish Football Association (FA), to eight district FAs and coaches (n=303) that participated in the RCT in 2009, and coaches who did not participate in the RCT but were coaching female adolescent football teams during the 2012 season (n=496).Response rates were 100% among the FAs, 57% among trial coaches and 36% among currently active coaches. The reach of the intervention was high, 99% of trial coaches (control group) and 91% of current coaches were familiar with the programme. The adoption rate was 74% among current coaches, but programme modifications were common among coaches. No district FA had formal policies regarding implementation, and 87% of current coaches reported no club routines for programme use. Maintenance was fairly high; 82% of trial coaches from the intervention group and 68% from the control group still used the programme.Reach and adoption of the programme was high among coaches. However, this study identified low programme fidelity and lack of formal policies for its implementation and use in clubs and district FAs.
Robotic Transrectal Ultrasonography During Robot-Assisted Radical Prostatectomy
Authors: Andrew J. Hung, André Luís De Castro Abreu, Sunao Shoji, Alvin C. Goh, Andre K. Berger, Mihir M. Desai, Monish Aron, Inderbir S. Gill, Osamu Ukimura
Journal: European Urology (2012)
Bacterial motif DNA as an adjuvant for the breakdown of immune self-tolerance to pyruvate dehydrogenase complex
Authors: David E. J. Jones, Jeremy M. Palmer, Alastair D. Burt, Claire Walker, Amanda J. Robe, John A. Kirby
Journal: Hepatology (2002)

Bacterial DNA containing unmethylated CpG dinucleotide motifs is immunostimulatory to mammals, skewing CD4(+) T-cell responses toward the Th1 phenotype. Autoreactive T-cell responses seen in primary biliary cirrhosis (PBC) are typically of the Th1 phenotype, raising the possibility that bacterial DNA might play a role in the generation of pathologic autoimmunity. We therefore studied the effects of CpG motif-containing oligodeoxynucleotides (ODN) on responses to pyruvate dehydrogenase complex (PDC, the autoantigen in PBC) in a murine model. Sensitization of SJL/J mice with non-self-PDC has been shown to result in induction of autoreactive T-cell responses to PDC sharing characteristics with those seen in patients with PBC. Administration of CpG ODN to SJL/J mice at the time of sensitization with PDC resulted in a significant skewing of splenic T-cell response to self-PDC, with significant augmentation of the Th1 cytokine response (interleukin [IL] 2 and interferon [IFN] gamma) and reduction of the Th2 response (IL-4 and IL-10). In fact, CpG ODN seemed to be more effective at biasing the response phenotype and as effective at inducing liver histologic change as complete Freund's adjuvant (CFA), the standard adjuvant used for induction of Th1 responses in murine autoimmune and infectious immunity models. In conclusion, our findings raise the possibility that bacteria play a role in the development of autoimmunity (in PBC at least) through the potential of their DNA to shift the T-cell responses toward the phenotype associated with autoimmune damage. Moreover, this study suggests caution in the therapeutic use of CpG ODN as vaccine adjuvants.