tbuckley/cabot-search huggingface dataset:
Central Nervous System Effects of Human Immunodeficiency Virus Type 1
Authors: T P Bridge, L J Ingraham
Journal: Annual Review of Medicine (1990)

CD40 is a cell-surface member of the TNF (tumor necrosis factor) receptor superfamily. Upon activation, CD40 can license dendritic cells to promote antitumor T cell activation and re-educate macrophages to destroy tumor stroma. Numerous agonist CD40 ...Read More
Inhibition of nuclear factor- B activation by IRFI 042, protects against endotoxin-induced shock
Authors: D. Altavilla, G. Squadrito, L. Minutoli, B. Deodato, A. Bova, A. Sardella, P. Seminara, M. Passaniti, G. Urna, S. F Venuti, A. P Caputi, F. Squadrito
Journal: Cardiovascular Research (2002)

The aim of our study was to investigate the effect of IRFI 042, a novel dual vitamin E-like antioxidant, on nuclear factor-kappaB (NF-kappaB) activation, TNF-alpha gene priming and on the release of the mature protein during endotoxin shock.Endotoxin shock was produced in male rats by a single intravenous (i.v.) injection of 20 mg kg(-1) of Salmonella enteritidis lipopolysaccharide (LPS). Survival rate, mean arterial blood pressure, serum TNF-alpha and plasma malondialdehyde (MAL) levels were investigated. We then evaluated in the liver TNF-alpha mRNA levels, NF-kappaB binding activity and the inhibitory protein IkappaBalpha. Moreover we studied in LPS stimulated (50 microg ml(-1)) peritoneal macrophages (Mphi), NF-kappaB activation, cytoplasmic IkappaB-alpha degradation, the message for TNF-alpha, and TNF-alpha and MAL levels.LPS administration reduced survival rate (0%, 72 h after LPS administration), decreased mean arterial blood pressure, augmented serum TNF-alpha (60+/-11 ng ml(-1)) and enhanced plasma malondialdehyde (MAL) levels (55+/-7.1 nmol l(-1)). LPS shocked rats also had increased TNF-alpha mRNA levels, augmented liver NF-kappaB binding activity in the nucleus and decreased levels of the inhibitory protein IkappaBalpha. In addition, in vitro LPS stimulation (50 microg ml(-1)) significantly induced NF-kappaB activation and cytoplasmic IkappaBalpha degradation in Mphi, enhanced TNF-alpha mRNA levels and increased Mphi TNF-alpha and MAL. Treatment with IRFI 042 (20 mg kg(-1), i.v., 5 min after endotoxin challenge) protected against LPS-induced lethality (90% survival rate 24 h and 80% survival rate 72 h after LPS injection, respectively), reduced hypotension, blunted plasma MAL (9.0+/-0.9 nmol l(-1)) and decreased serum TNF-alpha (15+/-3 ng ml(-1)). The antioxidant also inhibited the loss of IkappaBalpha protein from the hepatic cytoplasm, blunted the increased NF-kappaB binding activity in the liver and decreased hepatic liver mRNA for TNF-alpha. Furthermore 'in vitro' IRFI 042 (50 microM) significantly inhibited activation of NF-kappaB through inhibition of IkappaBalpha degradation, reduced the amount of TNF-alpha mRNA, decreased LPS-induced TNF-alpha release and blunted lipid peroxidation (MAL) in LPS stimulated Mphi.These data suggest that IRFI 042 blocks the activation of NF-kappaB, reduces TNF-alpha mRNA levels, and finally reverses endotoxic shock.
Refining American Joint Committee on Cancer/Union for International Cancer Control TNM Stage and Prognostic Groups for Human Papillomavirus–Related Oropharyngeal Carcinomas
Authors: Shao Hui Huang, Wei Xu, John Waldron, Lillian Siu, Xiaowei Shen, Li Tong, Jolie Ringash, Andrew Bayley, John Kim, Andrew Hope, John Cho, Meredith Giuliani, Aaron Hansen, Jonathan Irish, Ralph Gilbert, Patrick Gullane, Bayardo Perez-Ordonez, Ilan Weinreb, Fei-Fei Liu, Brian O'Sullivan
Journal: Journal of Clinical Oncology (2015)

Purpose To refine stage and prognostic group for human papillomavirus (HPV) –related nonmetastatic (M0) oropharyngeal cancer (OPC). Methods All patients with nonmetastatic (M0) p16-confirmed OPC treated with radiotherapy with or without chemotherapy from 2000 to 2010 were included. Overall survival (OS) was compared among TNM stages for patients with HPV-related and HPV-unrelated OPC separately. For HPV-related OPC, recursive partitioning analysis (RPA) derived new RPA stages objectively. Cox regression was used to calculate adjusted hazard ratios (AHRs) to derive AHR stages. The performance of survival prediction of RPA stage and AHR stage was assessed against the current seventh edition TNM stages. Prognostic groups were derived by RPA, combining RPA stage and nonanatomic factors. Results The cohort comprised 573 patients with HPV-related OPC and 237 patients with HPV-unrelated OPC, with a median follow-up of 5.1 years. Lower 5-year OS with higher TNM stage was evident for patients with HPV-unrelated OPC (stage I, II, III, and IV 5-year OS: 70%, 58%, 50%, and 30%, respectively; P = .004) but not for patients with HPV-related OPC (stage I, II, III, and IV 5-year OS: 88%, 78%, 71%, and 74%, respectively; P = .56). RPA divided HPV-related OPC into RPA-I (T1-3N0-2b), RPA-II (T1-3N2c), and RPA-III (T4 or N3; 5-year OS: 82%, 76%, and 54%, respectively; P &lt; .001). AHR also yielded a valid classification, but RPA stage demonstrated better survival prediction. A further RPA (including RPA stage, age, and smoking pack-years [PYs]) derived the following four valid prognostic groups for survival: group I (T1-3N0-N2c_≤ 20 PY), group II (T1-3N0-N2c_&gt; 20 PY), group III (T4 or N3_age ≤ 70), and group IVA (T4 or N3_age &gt; 70; 5-year OS: 89%, 64%, 57%, and 40%, respectively; P &lt; .001). Conclusion An RPA-based TNM stage grouping (stage I/II/III: T1-3N0-N2b/T1-3N2c/T4 or N3, with M1 as stage IV) is proposed for HPV-related OPC as a result of significantly improved survival prediction compared with the seventh edition TNM, and prognostication is further improved by an RPA-based prognostic grouping within the American Joint Committee on Cancer/Union for International Cancer Control TNM framework for HPV-related OPC.
Quality of life after total laparoscopic hysterectomy versus total abdominal hysterectomy for stage I endometrial cancer (LACE): a randomised trial
Authors: Monika Janda, Val Gebski, Alison Brand, Russel Hogg, Thomas W Jobling, Russel Land, Tom Manolitsas, Anthony McCartney, Marcelo Nascimento, Deborah Neesham, James L Nicklin, Martin K Oehler, Geoff Otton, Lewis Perrin, Stuart Salfinger, Ian Hammond, Yee Leung, Tom Walsh, Peter Sykes, Hextan Ngan, Andrea Garrett, Michael Laney, Tong Yow Ng, Karfai Tam, Karen Chan, C David H Wrede, Selvan Pather, Bryony Simcock, Rhonda Farrell, Andreas Obermair
Journal: The Lancet Oncology (2010)
Cardiac Arrest and Cardiopulmonary Resuscitation Outcome Reports
Authors: Ian Jacobs, Vinay Nadkarni, Jan Bahr, Robert A. Berg, John E. Billi, Leo Bossaert, Pascal Cassan, Ashraf Coovadia, Kate D’Este, Judith Finn, Henry Halperin, Anthony Handley, Johan Herlitz, Robert Hickey, Ahamed Idris, Walter Kloeck, Gregory Luke Larkin, Mary Elizabeth Mancini, Pip Mason, Gregory Mears, Koenraad Monsieurs, William Montgomery, Peter Morley, Graham Nichol, Jerry Nolan, Kazuo Okada, Jeffrey Perlman, Michael Shuster, Petter Andreas Steen, Fritz Sterz, James Tibballs, Sergio Timerman, Tanya Truitt, David Zideman
Journal: Circulation (2004)

Outcome after cardiac arrest and cardiopulmonary resuscitation is dependent on critical interventions, particularly early defibrillation, effective chest compressions, and advanced life support. Utstein-style definitions and reporting templates have been used extensively in published studies of cardiac arrest, which has led to greater understanding of the elements of resuscitation practice and progress toward international consensus on science and resuscitation guidelines. Despite the development of Utstein templates to standardize research reports of cardiac arrest, international registries have yet to be developed. In April 2002, a task force of the International Liaison Committee on Resuscitation (ILCOR) met in Melbourne, Australia, to review worldwide experience with the Utstein definitions and reporting templates. The task force revised the core reporting template and definitions by consensus. Care was taken to build on previous definitions, changing data elements and operational definitions only on the basis of published data and experience derived from those registries that have used Utstein-style reporting. Attention was focused on decreasing the complexity of the existing templates and addressing logistical difficulties in collecting specific core and supplementary (ie, essential and desirable) data elements recommended by previous Utstein consensus conferences. Inconsistencies in terminology between in-hospital and out-of-hospital Utstein templates were also addressed. The task force produced a reporting tool for essential data that can be used for both quality improvement (registries) and research reports and that should be applicable to both adults and children. The revised and simplified template includes practical and succinct operational definitions. It is anticipated that the revised template will enable better and more accurate completion of all reports of cardiac arrest and resuscitation attempts. Problems with data definition, collection, linkage, confidentiality, management, and registry implementation are acknowledged and potential solutions offered. Uniform collection and tracking of registry data should enable better continuous quality improvement within every hospital, emergency medical services system, and community.
Heavy chain–only antibodies are spontaneously produced in light chain–deficient mice
Authors: Xiangang Zou, Michael J. Osborn, Daniel J. Bolland, Jennifer A. Smith, Daniel Corcos, Maureen Hamon, David Oxley, Amanda Hutchings, Geoff Morgan, Fatima Santos, Peter J. Kilshaw, Michael J. Taussig, Anne E. Corcoran, Marianne Brüggemann
Journal: The Journal of Experimental Medicine (2007)

In healthy mammals, maturation of B cells expressing heavy (H) chain immunoglobulin (Ig) without light (L) chain is prevented by chaperone association of the H chain in the endoplasmic reticulum. Camelids are an exception, expressing homodimeric IgGs, an antibody type that to date has not been found in mice or humans. In camelids, immunization with viral epitopes generates high affinity H chain–only antibodies, which, because of their smaller size, recognize clefts and protrusions not readily distinguished by typical antibodies. Developmental processes leading to H chain antibody expression are unknown. We show that L−/− (κ−/−λ−/−-deficient) mice, in which conventional B cell development is blocked at the immature B cell stage, produce diverse H chain–only antibodies in serum. The generation of H chain–only IgG is caused by the loss of constant (C) γ exon 1, which is accomplished by genomic alterations in CH1-circumventing chaperone association. These mutations can be attributed to errors in class switch recombination, which facilitate the generation of H chain–only Ig-secreting plasma cells. Surprisingly, transcripts with a similar deletion can be found in normal mice. Thus, naturally occurring H chain transcripts without CH1 (VHDJH-hinge-CH2-CH3) are selected for and lead to the formation of fully functional and diverse H chain–only antibodies in L−/− animals.
Double, double, toil and trouble – fire burn, and theory bubble!
Authors: Birgitta Dresp
Journal: Behavioral and Brain Sciences (2003)

Lehar's Gestalt Bubble model introduces a computational approach to holistic aspects of three-dimensional scene perception. The model as such has merit because it manages to translate certain Gestalt principles of perceptual organization into formal codes or algorithms. The mistake made in this target article is to present the model within the theoretical framework of the question of consciousness. As a scientific approach to the problem of consciousness, the Gestalt Bubble fails for several reasons. This commentary addresses three of these: (1) the terminology surrounding the concept of consciousness is not rigorously defined; (2) it is not made evident that three-dimensional scene perception requires consciousness at all; and (3) it is not clearly explained by which mechanism(s) the “picture-in-the-head,” supposedly represented in the brain, would be made available to different levels of awareness or consciousness.
Morphology and metabolism of an aortic intima-media preparation in which an intact endothelium is preserved.
Authors: A D Morrison, L Berwick, L Orci, A I Winegrad
Journal: Journal of Clinical Investigation (1976)

An in vitro preparation of rabbit aortic "intima-media" previously shown to exhibit stable rates of respiration and glucose metabolism and the high rate of aerobic glycolysis considered characteristic of the metabolism of this tissue was subjected to electron microscopic examination. In samples examined immediately after the aortae were dissected free of adipose tissue and adventitia, under conditions similar to those now in common use, marked and widespread alterations in endothelial cell structure were present, including loss of cell integrity. The vascular smooth muscle cells retained a normal electron microscopic (EM) appearance. During subsequent incubation with 5 mM glucose in Krebs-Ringer bicarbonate (KRB), pH 7.4, under the conditions usually employed in studies of this preparation, large zones of the luminal surface were rapidly denuded of endothelium, and the remaining endothelial cells exhibited a wide range of ultrastructural alterations. The smooth muscle cells, however, continued to maintain a normal EM appearance. A method was developed to prepare segments of rabbit aortic intima-media which retained an intact layer of endothelium resembling that observed in tissue fixed in situ. During a 1-h incubation with 5 mM glucose in KRB, pH 7.4, gas phase 5% CO2/95% O2, containing 6% bovine serum albumin, the intact aortic intima-media preparation retains an essentially unmodified EM appearance and exhibits linear rates of respiration. Under these conditions the intact aortic intima-media preparation exhibits significantly higher rates of O2 uptake and glucose uptake than those observed in our previous preparation or in other reported aortic intima-media preparations. The intact aortic intima-media does not exhibit the high rate of aerobic glycolysis during in vitro incubation that has been considered characteristic of the metabolism of rabbit, rat, and swine aortic intima-media. In addition, the magnitude of the Pasteur effect was far greater than that observed in other aortic intima-media preparations. The data suggest that component cells of the aortic intima-media may derive a major fraction of their energy requirements from respiration; they raise further questions concerning the significance of the high rate of aerobic glycolysis observed when aortic intima-media preparations are incubated in vitro, and they suggest that documentation of the EM appearance of the endothelium in such preparations is desirable.
Glutathione in induced sputum of healthy individuals and patients with asthma
Authors: N Dauletbaev
Journal: Thorax (2001)

Glutathione is central to the antioxidant defences of the lung. The aim of this study was to determine whether sputum induction can be used for the measurement of glutathione in the respiratory tract.Saliva and induced sputum (3% NaCl, 20 minutes) samples were collected from 10 healthy individuals and 10 patients with stable asthma receiving treatment with inhaled corticosteroids. Samples were chilled on ice and dispersed by dilution with ice cold phosphate buffered saline and pipetting. Cell-free supernatants were obtained by centrifugation of samples and filtration of supernatants and analysed for total glutathione, glutathione disulfide, and albumin content. The cells were treated with dithiothreitol and cell numbers, cell viability, and differential cell patterns were determined.As judged by cell viability and percentage of non-squamous cells, adequate sputum samples were obtained from nine healthy and nine asthmatic subjects. The salivary total glutathione content was low (median concentration 1.2 microM (range 0.8-1.5) in healthy subjects and 0.9 microM (0.7-1. 2) in asthmatic subjects). The sputum total glutathione content of both healthy and asthmatic subjects was within the same range (3.9 (1.0-12.3) microM and 6.4 (1.3-19.2) microM, respectively; p=0.35). Surprisingly, and in marked contrast to results obtained with bronchoalveolar lavage, sputum levels of glutathione disulfide represented more than 50% of the total glutathione in both groups (50.9% (range 24.6-83.1) and 72.3% (range 36.5-97.4), respectively; p=0.2).The results of this study indicate that sputum induction can be used to measure the glutathione content of bronchial secretions. Sputum glutathione levels of stable asthmatic patients did not differ significantly from healthy controls.
Antibiotic regimens in severe and acute purulent exacerbations of chronic bronchitis.
Authors: A. Pines, H. Raafat, K. Plucinski, J. S. Greenfield, M. Solari
Journal: BMJ (1968)

Purulent exacerbations of chronic bronchitis are usually treated with antibiotics.Tetracycline, penicillin with strepto- mycin, and ampicillin are those most often used.Though innumerable courses of these drugs have been given in this illness, no comparative trial of their efficacy has ever been made (Stuart-Harris, 1966).We report a randomized and " blindly " assessed comparison of these antibiotics in hospital inpatients, all of whom were moderately or severely ill.* Patients withdrawn because of deterioration oer side-effects.
Potential role of helix-loop-helix proteins in cardiac gene expression.
Authors: S M Evans, B A Walsh, C B Newton, J S Thorburn, P D Gardner, M van Bilsen
Journal: Circulation Research (1993)

Because helix-loop-helix (HLH) transcription factors appear to play an important role in mesodermal development, we have investigated the potential role of these factors in cardiac gene expression. HLH proteins interact with DNA at consensus "E-box" sites and may be tissue specific or more widely expressed. We have examined cardiac cells for expression and regulation of widely expressed factors Pan1/Pan2 and the inhibitor of differentiation (Id) by RNase protection analysis. The effect of MyoD, Id, and Pan1/Pan2 expression on skeletal and cardiac promoters in cardiac cells was examined by transient cotransfection studies. Our results indicate that neonatal ventricular cells are a functional HLH environment, because MyoD can activate a skeletal muscle-specific promoter in these cells. MyoD, however, has no effect on the expression of several genes that are expressed in cardiac cells. In addition, Id may be an early response gene for signal transduction in cardiac cells, because increases in Id mRNA occurred within 30 minutes of stimulation with serum or phenylephrine. Activities of three cardiac promoter elements in primary ventricular myocytes were not downregulated by Id. Surprisingly, expression of Pan1 and Pan2 exhibited a strong negative effect on cardiac expression of the myosin light chain-2 promoter.
Gastric damage and granulocyte infiltration induced by indomethacin in tumour necrosis factor receptor 1 (TNF-R1) or inducible nitric oxide synthase (iNOS) deficient mice
Authors: M H L P Souza
Journal: Gut (2004)

<b>Background:</b> Tumour necrosis factor α (TNF-α) is involved in non-steroidal anti-inflammatory drug induced gastropathy. Nitric oxide (NO) is a mediator of gastrointestinal mucosal defence but, paradoxically, it also contributes to mucosal damage. <b>Aims:</b> We optimised the C57BL/6 mouse model of indomethacin induced gastropathy to evaluate the role of TNF-α and inducible nitric oxide synthase (iNOS) generated NO in gastric damage and granulocyte infiltration using tumour necrosis factor receptor 1 (TNF-R1−/−) or iNOS (iNOS−/−) deficient mice. <b>Methods:</b> Different doses of indomethacin (2.5, 5, 10, 20 mg/kg) were administered and animals were assessed 6, 12, or 24 hours later. Gastric damage was measured by the sum of all erosions in the gastric mucosa, and gastric granulocyte infiltration was determined by myeloperoxidase (MPO) activity. Other groups of wild-type mice received thalidomide, dexamethasone, fucoidin, l-NAME, or 1400W, and then indomethacin was administered. Additionally, indomethacin was administered to TNF-R1−/− or iNOS−/−. Gastric damage and MPO activity were evaluated 12 hours later. <b>Results:</b> Indomethacin induced dose and time dependent gastric damage and increase in MPO activity in wild-type mice, with the greatest effect at a dose of 10 mg/kg and after 12 hours. Treatment with thalidomide, dexamethasone, or fucoidin reduced gastric damage and MPO activity induced by indomethacin. After indomethacin administration, TNF-R1−/− had less gastric damage and MPO activity than controls. Genetic (knockout mice) or pharmacological (1400W and l-NAME) inhibition of iNOS activity reduced indomethacin induced gastric damage, despite no reduction in MPO activity. <b>Conclusion:</b> TNF-α, acting via TNF-R1, is involved in indomethacin induced gastric damage and granulocyte infiltration. Furthermore, iNOS generated NO is involved in gastric damage induced by indomethacin.
ROS-responsive microspheres for on demand antioxidant therapy in a model of diabetic peripheral arterial disease
Authors: Kristin M. Poole, Christopher E. Nelson, Rucha V. Joshi, John R. Martin, Mukesh K. Gupta, Skylar C. Haws, Taylor E. Kavanaugh, Melissa C. Skala, Craig L. Duvall
Journal: Biomaterials (2014)
Acute Myocarditis Associated With Coxsackievirus B4 Mimicking Influenza Myocarditis
Authors: Takeshi Ikeda, Tsunenori Saito, Gen Takagi, Shigeru Sato, Hitoshi Takano, Yusuke Hosokawa, Meiso Hayashi, Kuniya Asai, Masahiro Yasutake, Kyoichi Mizuno
Journal: Circulation (2013)
Imaging Immune Response <i>In vivo</i>: Cytolytic Action of Genetically Altered T Cells Directed to Glioblastoma Multiforme
Authors: Jelena Lazovic, Michael C. Jensen, Evette Ferkassian, Brenda Aguilar, Andrew Raubitschek, Russell E. Jacobs
Journal: Clinical Cancer Research (2008)

Abstract Purpose: Clinical trials have commenced to evaluate the feasibility of targeting malignant gliomas with genetically engineered CTLs delivered directly to the tumor bed in the central nervous system. The objective of this study is to determine a suite of magnetic resonance imaging (MRI) measurements using an orthotopic xenograft murine model that can noninvasively monitor immunologically mediated tumor regression and reactive changes in the surrounding brain parenchyma. Experimental Design: Our preclinical therapeutic platform is based on CTL genetic modification to express a membrane tethered interleukin-13 (IL-13) cytokine chimeric T-cell antigen receptor. This enables selective binding and signal transduction on encountering the glioma-restricted IL-13 α2 receptor (IL-13Rα2). We used MRI to visualize immune responses following adoptive transfer of IL-13Rα2-specific CD8+ CTL clones. Results: Based on MRI measurements, several phases following IL-13Rα2-specific T-cell adoptive transfer could be distinguished, all of which correlated well with glioblastoma regression confirmed on histology. The first detectable changes, 24 hours post-treatment, were significantly increased T2 relaxation times and strongly enhanced signal on T1-weighted postcontrast images. In the next phase, the apparent diffusion coefficient was significantly increased at 2 and 3 days post-treatment. In the last phase, at day 3 after IL-13Rα2-specific T-cell injection, the volume of hyperintense signal on T1-weighted postcontrast image was significantly decreased, whereas apparent diffusion coefficient remained elevated. Conclusions: The present study indicates the feasibility of MRI to visualize different phases of immune response when IL-13Rα2-specific CTLs are administered directly to the glioma tumor bed. This will further the aim of better predicting clinical outcome following immunotherapy.