tbuckley/cabot-search huggingface dataset:
CELLS INVOLVED IN THE IMMUNE RESPONSE
Authors: Nabih I. Abdou, Maxwell Richter
Journal: The Journal of Experimental Medicine (1969)

The antigen-reactive cells in normal rabbit bone marrow could be isolated from a suspension of marrow cells by passage of the cells through an antigen-sensitized glass bead column. The cells which passed through the column were deficient in antigen-reactive cells directed to the antigen used to sensitize the glass beads, whereas the cells eluted from the column could transfer antibody-forming capacity to irradiated recipients only with respect to the specific sensitizing antigen. Separation of the bone marrow antigen-reactive cells could not be achieved by passage of the cells through nonsensitized glass bead columns or in the presence of excess free antigen in the column. Cells which were retained by, and later eluted from, the antigen-sensitized glass bead columns were mostly small mononuclear cells, whereas cells which passed through the columns were morphologically similar to the original unfractionated bone marrow cell suspension. The data indicate the presence of an antibody or antibody-like structure, with defined immunological specificity, on the surface of the normal bone marrow antigen-reactive cell.
Il Buono, Il Brutto, Il Cattivo
Authors: Rajeev Saggar, Dinesh Khanna, Paul R Forfia, Rajan Saggar
Journal: Thorax (2014)

We appreciate the constructive commentary by Dr Paul Corris and colleagues1 that highlights the merits and limitations of our manuscript. A recent editorial from Dr Vincent Cottin requested that clinical trials, in the setting of pulmonary fibrosis (PF)-associated pulmonary hypertension (PH), ‘should first be conducted in subjects with disproportionate elevation of pulmonary vascular resistance as compared to the severity of pulmonary fibrosis…in whom PH likely contributes the most to exercise limitation and morbidity’.2 

In this spirit, the purpose of our study is to emphasise the inclusion of a specific, although less common PF-PH phenotype (excluding sarcoidosis and scleroderma) with advanced pulmonary haemodynamics …
Muscle metabolism changes with age and maturation: How do they relate to youth sport performance?
Authors: Neil Armstrong, Alan R Barker, Alison M McManus
Journal: British Journal of Sports Medicine (2015)

To provide an evidence-based review of muscle metabolism changes with sex-, age- and maturation with reference to the development of youth sport performance.A narrative review of data from both invasive and non-invasive studies, from 1970 to 2015, founded on personal databases supported with computer searches of PubMed and Google Scholar.Youth sport performance is underpinned by sex-, age- and maturation-related changes in muscle metabolism. Investigations of muscle size, structure and metabolism; substrate utilisation; pulmonary oxygen uptake kinetics; muscle phosphocreatine kinetics; peak anaerobic and aerobic performance; and fatigue resistance; determined using a range of conventional and emerging techniques present a consistent picture. Age-related changes have been consistently documented but specific and independent maturation-related effects on muscle metabolism during exercise have proved elusive to establish. Children are better equipped for exercise supported primarily by oxidative metabolism than by anaerobic metabolism. Sexual dimorphism is apparent in several physiological variables underpinning youth sport performance. As young people mature there is a progressive but asynchronous transition into an adult metabolic profile.The application of recent developments in technology to the laboratory study of the exercising child and adolescent has both supplemented existing knowledge and provided novel insights into developmental exercise physiology. A sound foundation of laboratory-based knowledge has been established but the lack of rigorously designed child-specific and sport-specific testing environments has clouded the interpretation of the data in real life situations. The primary challenge remains the translation of laboratory research into the optimisation of youth sports participation and performance.
H-2D Ligand Expression by Ly49A<b>+</b> Natural Killer (NK) Cells Precludes Ligand Uptake from Environmental Cells
Authors: Jacques Zimmer, Vassilios Ioannidis, Werner Held
Journal: The Journal of Experimental Medicine (2001)

To study the adaptation of natural killer (NK) cells to their major histocompatibility complex (MHC) class I environment we have established a novel mouse model with mosaic expression of H-2Dd using a Cre/loxP system. In these mice, we noticed that NK cells expressing the inhibitory receptor for Dd, Ly49A, were specifically underrepresented among cells with low Dd levels. That was due to the acquisition of Dd molecules by the Ly49A+ NK cells that have lost their Dd transgene. The uptake of H-2D molecules via the Ly49A receptor was restricted to strong ligands of Ly49A. Surprisingly, when Ly49A+ NK cells were Dd+, uptake of the alternative ligand Dk was not detectable. Similarly, one anti-Ly49A mAb (A1) bound inefficiently when Ly49A was expressed on Dd+ NK cells. Concomitantly, functional assays demonstrated a reduced capacity of Ly49A to inhibit H-2bDd as compared with H-2b NK cells, rendering Ly49A+ NK cells in Dd+ mice particularly reactive. Minor reductions of Dd levels and/or increases of activating ligands on environmental cells may thus suffice to abrogate Ly49A-mediated NK cell inhibition. The mechanistic explanation for all these phenomena is likely the partial masking of Ly49A by Dd on the same cell via a lateral binding site in the H-2Dd molecule.
Validation of Serum Amyloid α as an Independent Biomarker for Progression-Free and Overall Survival in Metastatic Renal Cell Cancer Patients
Authors: Joost S Vermaat, Frank L Gerritse, Astrid A van der Veldt, Wijnand M Roessingh, Tatjana M Niers, Sjoukje F Oosting, Stefan Sleijfer, Jeanine M Roodhart, Jos H Beijnen, Jan H Schellens, Jourik A Gietema, Epie Boven, Dick J Richel, John B Haanen, Emile E Voest
Journal: European Urology (2012)
Neuralized1 causes apoptosis and downregulates Notch target genes in medulloblastoma
Authors: Natalia Teider, Deborah K. Scott, Adrianne Neiss, S. Dilhan Weeraratne, Vladimir M. Amani, Yifei Wang, Victor E. Marquez, Yoon-Jae Cho, Scott L. Pomeroy
Journal: Neuro-Oncology (2010)

Neuralized (Neurl) is a highly conserved E3 ubiquitin ligase, which in Drosophila acts upon Notch ligands to regulate Notch pathway signaling. Human Neuralized1 (NEURL1) was investigated as a potential tumor suppressor in medulloblastoma (MB). The gene is located at 10q25.1, a region demonstrating frequent loss of heterozygosity in tumors. In addition, prior publications have shown that the Notch pathway is functional in a proportion of MB tumors and that Neurl1 is only expressed in differentiated cells in the developing cerebellum. In this study, NEURL1 expression was downregulated in MB compared with normal cerebellar tissue, with the lowest levels of expression in hedgehog-activated tumors. Control of gene expression by histone modification was implicated mechanistically; loss of 10q, sequence mutation, and promoter hypermethylation did not play major roles. NEURL1-transfected MB cell lines demonstrated decreased population growth, colony-forming ability, tumor sphere formation, and xenograft growth compared with controls, and a significant increase in apoptosis was seen on cell cycle and cell death analysis. Notch pathway inhibition occurred on the exogenous expression of NEURL1, as shown by decreased expression of the Notch ligand, Jagged1, and the target genes, HES1 and HEY1. From these studies, we conclude that NEURL1 is a candidate tumor suppressor in MB, at least in part through its effects on the Notch pathway.
How fast do test-leaders learn to perform spirometries? Quality control in routine spirometry testing
Authors: Martin Anderson, Mikaela Qvarfordt, Magnus Svartengren
Journal: European Respiratory Journal (2013)

Once performed only in highly specialized laboratories, spirometries are now days often used in screening both in clinical practice and occupational medical supervision. This often means large number of tests, little time for measurements and often brief training of test leaders. In this study we assess the quality development over time in the LifeGene study spirometries.  15 test leaders with limited previous experience of spirometry were employed. The spirometer software only showed FEV1, FVC, FEV1/FVC as well as the Quality Grade (QG) on screen. Test-leaders were encouraged to continue testing until the highest QG was achieved.  5128 persons 18 to 45 yrs were tested at one center during 6 months. Both flow volume curves and slow vital capacity was measured in 10 min and 20 s (average). ERS/ATS Quality grade A was achieved in >90% of the subjects within the first two weeks. Quality did not improve over time.  In this screening inexperienced test leaders achieved high quality tests within 2 weeks after one day of introduction and training. This is in concordance with Enright et al (Am Rev Respir Dis 1991; 143:1215-1223). Our conclusion is that high quality can be achieved within a few weeks with little training providing that; 1) QG and feedback are provided on-screen during testing, 2) that the testing is led by this information, and 3) that the number of tests performed per test leader and day is high.
Income and child mortality in developing countries: a systematic review and meta-analysis
Authors: Bernadette O'Hare, Innocent Makuta, Levison Chiwaula, Naor Bar-Zeev
Journal: Journal of the Royal Society of Medicine (2013)

Objective We aimed to quantify the relationship between national income and infant and under-five mortality in developing countries. Design We conducted a systematic literature search of studies that examined the relationship between income and child mortality (infant and/or under-five mortality) and meta-analysed their results. Setting Developing countries. Main outcome measures Child mortality (infant and /or under-five mortality). Results The systematic literature search identified 24 studies, which produced 38 estimates that examined the impact of income on the mortality rates. Using meta-analysis, we produced pooled estimates of the relationship between income and mortality. The pooled estimate of the relationship between income and infant mortality before adjusting for covariates is −0.95 (95% CI −1.34 to −0.57) and that for under-five mortality is −0.45 (95% CI −0.79 to −0.11). After adjusting for covariates, pooled estimate of the relationship between income and infant mortality is −0.33 (−0.39 to −0.26) while the estimate for under-five mortality is −0.28 (−0.37 to −0.19). If a country has an infant mortality of 50 per 1000 live births and the gross domestic product per capita purchasing power parity increases by 10%, the infant mortality will decrease to 45 per 1000 live births. Conclusion Income is an important determinant of child survival and this work provides a pooled estimate for the relationship.
Brain Mast Cells Act as an Immune Gate to the Hypothalamic-Pituitary-Adrenal Axis in Dogs
Authors: Itsuro Matsumoto, Yasuhisa Inoue, Toshio Shimada, Tadaomi Aikawa
Journal: The Journal of Experimental Medicine (2001)

Mast cells perform a significant role in the host defense against parasitic and some bacterial infections. Here we show that in the dog, degranulation of brain mast cells evokes hypothalamic-pituitary-adrenal responses via histamine release. A large number of mast cells were found in a circumscribed ventral region of the hypothalamus, including the pars tuberalis and median eminence. When these intracranial mast cells were passively sensitized with immunoglobulin E via either the intracerebroventricular or intravenous route, there was a marked increase in the adrenal cortisol secretion elicited by a subsequent antigenic challenge (whether this was delivered via the central or peripheral route). Comp.48/80, a mast cell secretagogue, also increased cortisol secretion when administered intracerebroventricularly. Pretreatment (intracerebroventricularly) with anti-corticotropin--releasing factor antibodies or a histamine H(1) blocker, but not an H(2) blocker, attenuated the evoked increases in cortisol. These data show that in the dog, degranulation of brain mast cells evokes hypothalamic-pituitary-adrenal responses via centrally released histamine and corticotrophin-releasing factor. On the basis of these data, we suggest that intracranial mast cells may act as an allergen sensor, and that the activated adrenocortical response may represent a life-saving host defense reaction to a type I allergy.
Identification and quantification of mite allergens
Authors: C. M. Luczynska
Journal: Allergy (1998)

Allergens from the house dust mite are ubiquitous in house dust. Exposure to these allergens can cause acute symptoms in patients who are sensitized to house‐dust mite and have asthma or other allergic diseases, such as rhinitis or atopic dermatitis. It is not clear how much mite‐allergen exposure is a risk factor for the development of sensitization or for triggering acute symptoms. Therefore, it is important to be able to quantify accurately the amount of mite allergen present in the indoor environment in order to carry out studies to identify risk factors for exposure, to investigate exposure‐response effects, and to monitor the progress of allergen‐reducing regimens.
A Key Regulatory Role of the Transcription Factor NFATc2 in Bronchial Adenocarcinoma via CD8+ T Lymphocytes
Authors: Joachim H. Maxeiner, Roman Karwot, Kerstin Sauer, Petra Scholtes, Ildiko Boross, Michael Koslowski, Özlem Türeci, Rainer Wiewrodt, Markus F. Neurath, Hans A. Lehr, Susetta Finotto
Journal: Cancer Research (2009)

The Ca(2+)-regulated calcineurin/nuclear factor of activated T cells (NFAT) cascade controls alternative pathways of T-cell activation and peripheral tolerance. Here, we describe reduction of NFATc2 mRNA expression in the lungs of patients with bronchial adenocarcinoma. In a murine model of bronchoalveolar adenocarcinoma, mice lacking NFATc2 developed more and larger solid tumors than wild-type littermates. The extent of central tumor necrosis was decreased in the tumors in NFATc2((-/-)) mice, and this finding was associated with reduced tumor necrosis factor-alpha and interleukin-2 (IL-2) production by CD8(+) T cells. Adoptive transfer of CD8(+) T cells of NFATc2((-/-)) mice induced transforming growth factor-beta(1) in the airways of recipient mice, thus supporting CD4(+)CD25(+)Foxp-3(+)glucocorticoid-induced tumor necrosis factor receptor (GITR)(+) regulatory T (T(reg)) cell survival. Finally, engagement of GITR in NFATc2((-/-)) mice induced IFN-gamma levels in the airways, reversed the suppression by T(reg) cells, and costimulated effector CD4(+)CD25(+) (IL-2Ralpha) and memory CD4(+)CD127(+) (IL-7Ralpha) T cells, resulting in abrogation of carcinoma progression. Agonistic signaling through GITR, in the absence of NFATc2, thus emerges as a novel possible strategy for the treatment of human bronchial adenocarcinoma in the absence of NFATc2 by enhancing IL-2Ralpha(+) effector and IL-7Ralpha(+) memory-expressing T cells.
Assessing ESCROs: Yesterday and Tomorrow
Authors: Henry T. Greely
Journal: The American Journal of Bioethics (2013)

Click to increase image sizeClick to decrease image size Acknowledgments 1. My discussion is limited entirely to the United States. This is a result not of my lack of interest, but of the limitations of my knowledge. I hope that this article can stimulate (perhaps in the peer commentaries) some discussion of how other countries, with their own ethical, scientific, and regulatory cultures, have chosen to regulate (or not) stem cell research. 2. I have found only one publication that assesses the value of ESCROs and it does so in the limited context of their role in reviewing the provenance of hESC lines (Patel and Lomax 2011). 3. The organization of the National Academies is not obvious. Congress chartered the National Academy of Sciences (NAS) in 1863, in a bill signed (much to the Academy's pride) by President Abraham Lincoln. The National Academy of Engineering (NAE) followed in 1964, under the charter of the NAS. In 1970 the NAS added the Institute of Medicine (IOM) as a body parallel to the NAS and the NAE. The NAS created the NRC in 1916, in the prelude to American entry into the First World War, to advise the federal government. The NRC is, in language repeated at the beginning of all NRC reports, “The principal operating agency of both the National Academy of Sciences and the National Academy of Engineering in providing services to the government, the public, and the scientific and engineering communities.” However, the IOM also issues its own reports, not through the NRC. So NAS or NAE reports come from the NRC, IOM reports come from the IOM, and some reports (like this one) come from both the NRC and the IOM. The overall complex calls itself “The National Academies.” Although this committee was technically the product of a joint effort by the NRC and the IOM, and was not appointed by “the NAS,” its report has been widely referred to as the “NAS Guidelines,” produced by the “NAS Committee.” To avoid confusion, I will so refer to them in this article.
Treatments no longer in development for rheumatoid arthritis
Authors: E Keystone
Journal: Annals of the Rheumatic Diseases (2002)

Much of our experience with biological agents in autoimmune disease has been derived from studies of T cell directed therapy in rheumatoid arthritis (RA) (box 1). Data from these studies have provided substantial insight into study design, product development, and T cell biology. Initial studies entailed targeting of CD4 T cells with murine monoclonal antibodies (mAb) of differing isotypes directed at a variety of epitopes on the CD4 molecule. Between 1989–1994, eight short-term open label trials yielded promising results with clinical responses in 60%–75% of patients (reviewed in Strand and Keystone1). In 1996, seven years after the initial studies were published, the first randomised placebo controlled trial (RCT) of murine anti-CD4 mAb showing no clinical benefit was reported.2 A similar discrepancy in clinical outcome between early uncontrolled trials and placebo RCTs was also observed with a murine anti-CD5 immunotoxin conjugate,3 as well as the chimeric anti-CD4 mAb, cM412.4,5 This difference probably reflects both expectation bias on the part of the investigator and patient with “new and innovative therapy” as well as a placebo effect. In studies of anti-CD5 immunotoxin conjugate, for example a placebo rate as high 50% was observed. A review of the problem by Epstein suggested that the results reflect more of an expectation bias than a placebo effect.6 His conclusion is based on an analysis of several trials involving chimeric anti-CD4 mAb in which the clinical benefit observed in the experimental group of the RCT was significantly lower than that observed in the open label groups. A placebo effect would be expected to yield comparable clinical responses between the two groups. The discrepancy between open label and RCT responses emphasises the magnitude of experimental bias in open label studies and as well as the need for vigorous blinding in RCTs. The …
Onchocerca Volvulus in a Paratyphoid Abscess
Authors: H. de Glanville
Journal: BMJ (1954)

MEDICAUL JOURNAL~~~~~~~~~~~~~~ẽxtended down the right side of the trunk from 2 in.(5 cm.) behind the posterior axillary line forward to the midline and down to about 1 in.below the right inguinal ligament.There was a bilateral rounded swelling of the
Oxaliplatin plus vinorelbine in advanced non-small-cell lung cancer: final results of a multicenter phase II study
Authors: I. Monnet, H. de Cremoux, P. Soulié, S. Saltiel-Voisin, M. Bekradda, J.-C. Saltiel, E. Brain, O. Rixe, Y. Yataghene, J.-L. Misset, E. Cvitkovic
Journal: Annals of Oncology (2002)

BackgroundOxaliplatin and vinorelbine are both active agents against non-small-cell lung cancer (NSCLC). In a previous phase I trial, we showed that oxaliplatin (130 mg/m2, day 1) and vinorelbine (26 mg/m2/day, days 1 and 8) can be safely combined when given every 21 days. We completed the evaluation of this new platinum-based doublet in advanced NSCLC patients in a multicenter phase II study.Patients and methodsTwenty-eight chemotherapy-naïve patients (22 men and six women; median age 58 years, range 33–70), including 20 with stage IV disease, received this out-patient combination, with 5-hydroxytryptamine-3-receptor agonists as the only prophylactic measure.ResultsA total of 117 cycles were given, for a median of three per patient (range 1–8). Of 26 eligible patients, nine achieved a partial response (WHO criteria), giving an objective response rate of 35% [95% confidence interval (CI) 17% to 56%]. The median progression free survival was 5.0 months (95% CI 3.1 to 6.9), median overall survival was 9.8 months (95% CI 2.2 to 17.5) and the 1-year survival rate was 37%. Neutropenia was the principal toxicity, grade 4 occurring in 11 patients (39%) and 25cycles (22%). Four patients (14%) experienced one episode of febrile neutropenia each. Acute oxaliplatin-related neurosensory toxicity was prevalent, but was mild to moderate in the majority of patients (82%) and reversible. Grade 1/2 vomiting (65% of patients) and diarrhea (32% of patients) were easily managed.ConclusionsThe oxaliplatin–vinorelbine doublet is a safe and active out-patient combination. It may represent an interesting alternative in the management of patients with NSCLC, and serve as a new doublet to which other active agents could be added.
Acute Exacerbations of Idiopathic Pulmonary Fibrosis
Authors: Harold R. Collard, Bethany B. Moore, Kevin R. Flaherty, Kevin K. Brown, Robert J. Kaner, Talmadge E. King, Joseph A. Lasky, James E. Loyd, Imre Noth, Mitchell A. Olman, Ganesh Raghu, Jesse Roman, Jay H. Ryu, David A. Zisman, Gary W. Hunninghake, Thomas V. Colby, Jim J. Egan, David M. Hansell, Takeshi Johkoh, Naftali Kaminski, Dong Soon Kim, Yasuhiro Kondoh, David A. Lynch, Joachim Müller-Quernheim, Jeffrey L. Myers, Andrew G. Nicholson, Moisés Selman, Galen B. Toews, Athol U. Wells, Fernando J. Martinez
Journal: American Journal of Respiratory and Critical Care Medicine (2007)

Section:ChooseTop of pageAbstract <<SIGNIFICANCE OF ACUTE EXA...CURRENT DIAGNOSIS AND MAN...RECOGNIZED COMPONENTS OF ...PROPOSED DEFINITION AND D...POTENTIAL ETIOLOGY AND BI...FUTURE DIRECTIONSReferencesCITING ARTICLES
Cellular electrophysiology in cardiac hypertrophy and failure
Authors: G. Hart
Journal: Cardiovascular Research (1994)

Journal Article Cellular electrophysiology in cardiac hypertrophy and failure Get access George Hart George Hart Department of Cardiovascular Medicine, University of Oxford, John Radcliffe Hospital, Oxford OX3 9DU, United Kingdom: Dr G Hart. I am grateful to Dr Kathryn Ryder for her comments on an earlier version of this review, and to Prof A Mugelli for allowing me to refer to a paper which was under review. I acknowledge the British Heart Foundation for support. Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, Volume 28, Issue 7, July 1994, Pages 933–946, https://doi.org/10.1093/cvr/28.7.933 Published: 01 July 1994 Article history Received: 16 November 1993 Accepted: 10 February 1994 Published: 01 July 1994