tbuckley/cabot-search huggingface dataset:
Activation of Insulin-like Growth Factor Signaling Induces Apoptotic Cell Death Under Prolonged Hypoxia by Enhancing Endoplasmic Reticulum Stress Response
Authors: Hiroko Endo, Kohei Murata, Mutsuko Mukai, Osamu Ishikawa, Masahiro Inoue
Journal: Cancer Research (2007)

Abstract Malignant cells in solid tumors survive under prolonged hypoxia and can be a source of resistance to current cancer therapies. Mammalian target of rapamycin (mTOR), one of the downstream molecules of the insulin-like growth factor (IGF) pathway, is a key regulator of translation, integrating multiple environmental and nutritional cues. The activity of mTOR is known to be suppressed under hypoxic conditions in cancer cells, whereas the contribution of this suppression to cell survival has not yet been clarified. We show that stimulating IGF signaling provoked caspase-dependent apoptosis under low oxygen tension in two cancer cell lines, COLO 320 and AsPC-1. In concurrence with increased levels of BAD phosphorylation, cell death was not accompanied by cytochrome c release from mitochondria. The cells were rescued from apoptosis when phosphatidylinositol 3-kinase (PI3K) or mTOR activity was inhibited, suggesting that these signals are critical in the observed cell death. IGFs and insulin enhanced the endoplasmic reticulum (ER) stress response as monitored by induction of the CCAAT/enhancer binding protein homologous protein (CHOP) proteins and the X box protein-1 splicing under hypoxic conditions, and this response was suppressed by inhibiting PI3K and mTOR activity. IGF-induced cell death under hypoxic conditions was prevented by treatment with cycloheximide, suggesting that de novo protein synthesis is required. Indeed, suppression of CHOP protein levels with small hairpin RNA reduced cell death. Taken together, the data suggest that stimulating IGF signaling under hypoxic conditions provokes apoptosis by enhancing the ER stress response. [Cancer Res 2007;67(17):8095–103]
Role of basophils in immunological memory responses to pneumococcal protein antigens and S. pneumoniae infections in mice
Authors: Andrea Bischof, Christina Brumshagen, Regina Maus, Matthias Mack, Susan Hollingshead, David Briles, Tobias Welte, Ulrich Maus
Journal: European Respiratory Journal (2012)

Basophils have been shown to play an important role in memory immune responses to vaccination with pneumococcal protein antigens. We here examined whether increased basophil counts would provide increased humoral immune responses and thus protection against  S. pneumoniae . Mice underwent primary and secondary immunization with pneumococcal surface protein A (PspA). Prior to secondary immunization, mice were treated with IL-3 or IL-3 complexed with α-IL-3 antibody (IL-3 complex) to increase basophil pool sizes. Subsequently, mice were challenged with invasive  S. pneumoniae  and developing bacteremia and survival were monitored over time. Treatment of mice with IL-3 and even more so IL-3 complex resulted in strongly expanded basophil pool sizes and significantly increased PspA-specific antibody titers that protected mice from pneumococcal sepsis but unexpectedly did not improve their survival. However, passive immunization of mice with antiserum of IL-3 complex-treated, PspA-immunized mice significantly improved their survival after challenge with invasive  S. pneumoniae . These data show that although IL-3 complex treatment of mice boosts their basophil counts and protects mice from pneumococcal sepsis, it still exerts severe side-effects in mice after intratracheal challenge with  S. pneumoniae , and as such does not offer as adjuvant-independent approach to improve lung protective immunity against lung-tropic pathogens.
Are early life factors considered when managing respiratory disease? A British Thoracic Society survey of current practice: Table 1
Authors: Charlotte E Bolton, Andrew Bush, John R Hurst, Sailesh Kotecha, Lorcan McGarvey, Janet Stocks, Martin J Walshaw
Journal: Thorax (2012)

We hypothesised that early life events are not routinely considered by most respiratory specialists.Respiratory Specialists were surveyed via the British Thoracic Society (BTS) on whether they asked patients about birth weight, preterm birth and prenatal and postnatal complications.Only a small minority (mostly hospital paediatricians) of the 123 who replied asked most respiratory patients about one of more early life factors. Patient recall of the information when asked was low.The survey results suggest little current consideration is given to early life factors in adult respiratory medicine, despite increasing evidence that early life factors do impact on later respiratory health. Improving training, increasing awareness and exploring new approaches to obtaining the information are required.
Rethinking NHS networking
Authors: J. Keen
Journal: BMJ (1998)

The government white paper The New NHS, published in December 1997, 1 reaffirmed the NHS Executive's commitment to an NHS-wide electronic network.The network was originally conceived in essentially administrative terms, but it is now to be used to support clinical work.Now is therefore a good time to consider the future direction of NHS networking.This article focuses on the economic and political issues of electronic networks in primary care and considers two questions.Firstly, can the benefits of networks outweigh the costs, or are they simply poor investments?Secondly, if a case can be made, then what problems will need to be addressed in the new networking strategy?
Randomized Study of High-Dose and Low-Dose Interleukin-2 in Patients With Metastatic Renal Cancer
Authors: James C. Yang, Richard M. Sherry, Seth M. Steinberg, Suzanne L. Topalian, Douglas J. Schwartzentruber, Patrick Hwu, Claudia A. Seipp, Linda Rogers-Freezer, Kathleen E. Morton, Donald E. White, David J. Liewehr, Maria J. Merino, Steven A. Rosenberg
Journal: Journal of Clinical Oncology (2003)

Purpose: This three-arm randomized study compares response rates and overall survival of patients with metastatic renal cell cancer (RCC) receiving high-dose or one of two low-dose interleukin-2 (IL-2) regimens. Patients and Methods: Patients with measurable metastatic RCC and a good performance status were randomized to receive either 720,000 U/kg (high-dose [HD]) or 72,000 U/kg (low-dose [LD]), both given by intravenous (IV) bolus every 8 hours. After randomly assigning 117 patients, a third arm of low-dose daily subcutaneous IL-2 was added, and an additional 283 patients were randomly assigned. Results: A total of 156 patients were randomly assigned to HD IV IL-2, and 150 patients to LD IV IL-2. Toxicities were less frequent with LD IV IL-2 (especially hypotension), but there were no IL-2-related deaths in any arm. There was a higher response proportion with HD IV IL-2 (21%) versus LD IV IL-2 (13%; P = .048) but no overall survival difference. The response rate of subcutaneous IL-2 (10%, partial response and complete response) was similar to that of LD IV IL-2, differing from HD IV (P = .033). Response durability and survival in completely responding patients was superior with HD IV compared with LD IV therapy (P = .04). Conclusion: Major tumor regressions, as well as complete responses, were seen with all regimens tested. IL-2 was more clinically active at maximal doses, although this did not produce an overall survival benefit. The immunological factors which constrain the curative potential of IL-2 to only a small percentage of patients need to be further elucidated.
Nutritional Systems Biology: Definitions and Approaches
Authors: Gianni Panagiotou, Jens Nielsen
Journal: Annual Review of Nutrition (2009)

Nutrigenetics and nutrigenomics are nascent areas that are evolving quickly and riding on the wave of "personalized medicine" that is providing opportunities in the discovery and development of nutraceutical compounds. The human genome sequence and sequences of model organisms provide the equivalent of comprehensive blueprints and parts lists that describe dynamic networks and the bases for understanding their responses to external and internal perturbations. Unfolding the interrelationships among genes, gene products, and dietary habits is fundamental for identifying individuals who will benefit most from, or be placed at risk by, intervention strategies. More accurate assessment of the inputs to human health and the consequences of those inputs measured as accurate transcriptomic, proteomic, and metabolomic analyses would bring personalized health/diet to practice far faster than would waiting for a predictive knowledge of genetic variation. It is widely recognized that systems and network biology has the potential to increase our understanding of how nutrition influences metabolic pathways and homeostasis, how this regulation is disturbed in a diet-related disease, and to what extent individual genotypes contribute to such diseases.
Childhood tuberculosis in a developed country
Authors: J Mortensen, P Lange, HK Storm, K Viskum
Journal: European Respiratory Journal (1989)

From 1975 to 1985, 25 Danish children (aged less than 15 yrs) and 40 children of immigrants were notified for tuberculosis in Copenhagen for the first time. A follow-up was undertaken in 1987. The annual rate of tuberculosis per 100,000 among the Danish children was 5 and among immigrant children 68-200 depending on the nationality. At the time of diagnosis, no significant differences were present between Danes and immigrants as regards age, sex, occurrence of symptoms or previous BCG immunization, whereas there were significantly more bacteriologically proven cases among the immigrants. All Danish children had respiratory tuberculosis only, whereas 13 immigrant children had extrapulmonary manifestations including one case of miliary and two cases of meningeal tuberculosis. At follow-up, all patients were cured for tuberculosis and had experienced a normal physical development.
Improving musculoskeletal clinical skills teaching. A regionwide audit and intervention study
Authors: L. Kay, D. Walker
Journal: Annals of the Rheumatic Diseases (1998)

To identify factors that influence medical students' perceptions of the quality of a clinical skills course; to apply these factors to the course at one hospital; to measure the effect of this change.Cross sectional questionnaire survey; application of identified factors; repeat questionnaire survey.Three teaching hospitals and five district general hospitals in north east England.Third year medical students attending locomotor clinical skills courses in two consecutive years.Score awarded by students in five categories; numbers of patients seen by each student; comparisons with other clinical skills weeks.Response rates were 71 of 150 and 89 of 161. Factors associated with a high awarded score were: organisation of the course by a rheumatologist (p < 0.01); teaching from a rheumatologist (p < 0.01); higher number of patients seen (r = 0.76). Mean number of patients seen varied widely, from 7 per student at one hospital to 20.4 at another. Teaching hospitals scored poorly. In the second year, after making changes at one teaching hospital the mean total score improved (p < 0.01), and students saw more patients (p < 0.01). The ranking of this hospital rose from 6 to 1. The additional cost of the modified course was 640 pounds per student.The standard of teaching of locomotor clinical skills varies widely and can be improved by application of factors identified in this survey, although additional costs are incurred.
Histamine reactivity during the refractory period after exercise induced asthma.
Authors: A G Hahn, S G Nogrady, D M Tumilty, S R Lawrence, A R Morton
Journal: Thorax (1984)

An episode of exercise induced asthma will usually be followed by a period during which further exercise will not induce asthma. Postulated mechanisms include persistence of catecholamines released during exercise, development of tolerance to released mediators, and mediator depletion. To investigate the underlying mechanism further eight asthmatic men underwent three experimental protocols as follows: two treadmill runs of eight minutes; two incremental challenges with histamine inhalation; and a treadmill run of eight minutes followed by an incremental challenge with histamine inhalation. In each case the two challenges began 40 minutes apart. Patients performed the paired exercise trial first. Refractoriness to bronchoconstriction was shown in the repeated exercise studies but did not occur with repeated histamine challenge. The geometric mean histamine concentrations required to produce a 20% fall in forced expiratory volume in one second (FEV1) were 1.53 mg/ml and 0.93 mg/ml for the first and second challenges respectively (NS) and 1.4 mg/ml (NS) for the histamine challenge after exercise. It is concluded that refractoriness to exercise induced asthma is not explained by the development of smooth muscle tolerance to repeated histamine exposure or by the persistence of catecholamines released during exercise. The data are consistent with the theory of mediator depletion as the cause of refractoriness.
Mortality and morbidity from malaria in Gambian children after introduction of an impregnated bednet programme
Authors: U. D'Alessandro, B. Olaleye, P. Langerock, M.K. Aikins, M.C. Thomson, M.K. Cham, B.M. Greenwood, W. McGuire, S. Bennett, M.K. Cham, B.A. Cham
Journal: The Lancet (1995)
Epidermal MHC class II antigen expression in systemic sclerosis
Authors: M.H.A. Rustin, Rosemary Bains, Pauline M. Dowd
Journal: British Journal of Dermatology (1989)

Journal Article Epidermal MHC class II antigen expression in systemic sclerosis Get access M.H.A. Rustin, M.H.A. Rustin Department of Dermatology, University College and Middlesex School of Medicine, The Middlesex Hospital, Mortimer Street, London WIN 8AA, U.K. Search for other works by this author on: Oxford Academic Google Scholar Rosemary Bains, Rosemary Bains Department of Histopathology, University College and Middlesex School of Medicine, The Middlesex Hospital, Mortimer Street, London WIN 8AA, U.K. Search for other works by this author on: Oxford Academic Google Scholar Pauline M. Dowd Pauline M. Dowd Department of Dermatology, University College and Middlesex School of Medicine, The Middlesex Hospital, Mortimer Street, London WIN 8AA, U.K. Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 121, Issue 2, 1 August 1989, Pages 275–276, https://doi.org/10.1111/j.1365-2133.1989.tb01811.x Published: 01 August 1989
Identification and Characterization of a Novel Gene, <b> <i>C13orf25</i> </b>, as a Target for 13q31-q32 Amplification in Malignant Lymphoma
Authors: Akinobu Ota, Hiroyuki Tagawa, Sivasundaram Karnan, Shinobu Tsuzuki, Abraham Karpas, Shigeki Kira, Yasuko Yoshida, Masao Seto
Journal: Cancer Research (2004)

Abstract The amplification at 13q31-q32 has been reported in not only hematopoietic malignancies but also in other solid tumors. We identified previously frequent amplification of chromosomal band 13q31-q32 in 70 cases of diffuse large B-cell lymphoma patients by conventional comparative genomic hybridization analysis. In an attempt to identify a candidate gene within this region, we used array comparative genomic hybridization and fluorescent in situ hybridization to map the 13q31-q32 amplicon. We then screened the 65 expressed sequence tags and Glypican 5 (GPC5) by reverse transcription-PCR and Northern blotting. As a result, we identified a novel gene, designated Chromosome 13 open reading frame 25 (C13orf25), which was overexpressed in B-cell lymphoma cell lines and diffuse large B-cell lymphoma patients with 13q31-q32 amplifications. However, GPC5, which has been reported to be a target gene for 13q31-q32 amplification, was truncated in one cell line, Rec1, possessing the amplification, and its expression in various cell lines with amplification at 13q31-q32 was not significantly different from that in other cell lines without amplification, suggesting that GPC5 is not likely to be the candidate gene. Additional analysis identified two major transcripts in the C13orf25 gene. The two transcripts A and B predicted open reading frames of 32 and 70-amino acid polypeptides, respectively. The former has been reported as bA121J7.2, which is conserved among species. Transcript-B also contained seven mature microRNAs in its untranslated region. These results suggest that the C13orf25 gene is the most likely candidate gene for the 13q31-q32 amplicon found in hematopoietic malignancies.
“The ABC of GOLD A-B-C-D”
Authors: Frits M.E. Franssen, MeiLan K. Han
Journal: European Respiratory Journal (2013)

Chronic obstructive pulmonary disease (COPD) is the cause of considerable morbidity and mortality with the global burden of disease projected to increase even further in forthcoming years [1]. Although significant advances have been made in our understanding, assessment and management of COPD in the past decade, the heterogeneity of clinical features and variability in disease course continue to be only partially explained by currently available metrics. Hence, COPD subtype determination remains challenging.

Until the late 1990s, COPD was defined by abnormal expiratory airflow [2, 3]. Although there was no consensus about a universal staging system, forced expiratory volume in 1 s (FEV1) alone was generally used to define disease severity [3]. FEV1 does capture many facets of disease severity and hence algorithms were proposed for the management of COPD, based on the reduction in FEV1 [3]. However, this approach is problematic in that not all aspects of the disease are adequately captured by FEV1. Furthermore, such algorithms were not globally implemented [2] and attention from the healthcare community, scientific societies and government officials for COPD was generally low.

In 1997 the Global Initiative for Chronic Obstructive Lung Disease (GOLD) was launched in order to raise worldwide awareness of COPD and improve prevention and treatment of the disease. In the first GOLD workshop summary report [4], COPD was defined as “a disease state characterized by airflow limitation that is not fully reversible and is associated with an abnormal inflammatory response of the lungs to noxious particles or gases”. Furthermore, it stated that “symptoms, functional abnormalities and complications of COPD can all be explained on the basis of this underlying inflammation and the resulting pathology” [4]. A unidimensional classification of disease severity …
Analysis of apoptotic and antiapoptotic signalling pathways induced by Helicobacter pylori
Authors: S Maeda
Journal: Gut (2002)

<b>Background and aims:</b> Although it is reported that <i>Helicobacter pylori</i> induces apoptosis on gastric epithelial cells, the mechanism remains unknown. Antiapoptotic effects generated by <i>H pylori</i> have not yet been evaluated. <b>Methods:</b> (1) <i>H pylori</i> strains (type 1 wild, TN2-Δ<i>cagE,</i> TN2-Δ<i>vacA</i>) were cocultured with MKN45, TMK1, and HeLa cells, and cell viability and apoptosis were assessed by trypan blue exclusion and DNA laddering, respectively. (2) Activation of caspases-3, 7, and 8, cytochrome c release from the mitochondria, and Fas, Fas associated death domain protein (FADD), Bax, Bak, and Bcl-X expression were evaluated by immunoblot analysis. (3) To investigate whether nuclear factor kappa B (NFκB) activation induced by <i>cag</i> pathogenicity island (PAI) positive <i>H pylori</i> affects antiapoptosis, MKN45 cells stably expressing super-repressor Iκβα were cocultured with <i>H pylori</i>, and cell viability and caspase activation were evaluated. NFκB regulated gene expression was also evaluated by ribonuclease protection assay. <b>Results:</b> (1) Wild-type and Δ<i>vacA</i> mutant <i>H pylori</i> induced apoptosis more potently than the Δ<i>cagE</i> mutant. Inhibition of cell contact between <i>H pylori</i> and cancer cells and heat killing <i>H pylori</i> diminished cell death. (2) Caspases-3, 7, and 8 were activated time dependently by <i>H pylori</i> as well as by the agonist anti-Fas. Cytochrome c release from mitochondria was observed and was not inhibited by caspase-8 inhibitor. Although protein expression of Fas, FADD, Bax, Bak, and Bcl-X in the whole cell lysates was not changed by <i>H pylori</i>, Bax was decreased from mitochondria free cytosol suggesting that Bax was translocated into mitochondria. (3) Cell death and the activities of caspases-3 and 8 were promoted in MKN45 cells stably expressing super-repressor Iκβα that inhibits NFκB activation. Antiapoptotic proteins c-IAP1 and c-IAP2 were upregulated by the wild-type strains. <b>Conclusion:</b><i>cag</i> PAI positive <i>H pylori</i> is capable of inducing apoptotic effects mainly through the mitochondrial pathway. Antiapoptotic effects mediated by NFκB activation were also observed.
Postsplenectomy Blood Salvage in Anemic Patients
Authors: P. De Rai, R. Biffi, P. Rebulla
Journal: JAMA (1987)

<h3>To the Editor.—</h3> Intraoperative auto-transfusion, namely, the technique of blood aspiration from the surgical field and intravenous reinfusion of washed red blood cells, is employed in elective and emergency surgery with increasing frequency.<sup>1</sup>We used this technique to recover red blood cells trapped in the spleen of three patients (Table) in whom splenectomy had to be performed because of severe anemia associated with considerable splenomegaly. Patients 1and 2, suffering from thalassemia, had potent irregular red blood cell alloantibodies in the serum, which made transfusion of compatible blood extremely difficult; patient 3 had myelofibrosis. <h3>Methods.—</h3> The procedure was performed as follows. Splenectomy was carried out with careful dissection of the vascular structures. The spleen was then placed on a sterile table, weighed, and perfused through the arterial stump with heparinized saline (30 × 10<sup>3</sup>U/L). Perfusion was performed at a constant pressure of 150 mm Hg by means of
FAILURE OF SOMATOSTATIN TO CORRECT MANIFEST DIABETIC KETOACIDOSIS
Authors: K. Lundbaek, AaP. Hansen, H. Ørskov, S.E. Christensen, J. Iversen, K. Seyer-Hansen, K.G.M.M. Alberti, R. Whitefoot, K.G.M.M. Alberti, R. Whitefoot
Journal: The Lancet (1976)
The effect of montelukast on lung function and exhaled nitric oxide in infants with early childhood asthma
Authors: D. A. Straub, A. Moeller, S. Minocchieri, J. Hamacher, F. H. Sennhauser, G. L. Hall, J. H. Wildhaber
Journal: European Respiratory Journal (2005)

Effective treatment of respiratory symptoms, airway inflammation and impairment of lung function is the goal of any asthma therapy. Although montelukast has been shown to be a possible add-on therapy for anti-inflammatory treatment in older children, its efficacy in infants and young children is not well known. The aim of this study was to investigate its effect in infants and young children with early childhood asthma. In a prospective randomised double-blind placebo-controlled study, 24 young children (10-26 months) with wheeze, allergy and a positive family history of asthma consistent with the diagnosis of early childhood asthma were randomised to receive montelukast 4 mg or placebo. The forced expiratory volume in 0.5 seconds (FEV0.5) was measured using the raised volume rapid thoracic compression technique, and fractional exhaled nitric oxide (FeNO) and symptom scores were determined. No change was noted in FEV0.5, FeNO or symptom score in the placebo group following the treatment period. In contrast, significant improvements in mean+/-SD FEV0.5 (189.0+/-37.8 and 214.4+/-44.9 mL before and after treatment, respectively), FeNO (29.8+/-10.0 and 19.0+/-8.5 ppb) and median symptom score (5.5 and 1.5) were noted following treatment with montelukast. In conclusion, montelukast has a positive effect on lung function, airway inflammation and symptom scores in very young children with early childhood asthma.