tbuckley/cabot-search huggingface dataset:
Histone deacetylase inhibitor panobinostat reduces hypoxia-related cisplatin resistance in NSCLC cells by HDAC-mediated Hifα destabilization
Authors: Carina Fischer, Katharina Leithner, Christoph Wohlkoenig, Elvira Stacher, Andrea Olschewski, Horst Olschewski, Andelko Hrzenjak
Journal: European Respiratory Journal (2013)

Background:  Lung cancer is one of the most frequent cancer types and a leading cause of cancer death worldwide. Cisplatin is an important chemotherapeutic for lung cancer; although, its positive effects are diminished under hypoxia.  Aims and objectives:  Hypoxia-based cisplatin resistance can be overcome by combining cisplatin with panobinostat, a potent histone deacetylase inhibitor.  Methods:  After co-treatment of NSCLC cells with cisplatin and low concentration panobinostat, cell viability and activation of apoptosis were analyzed.  Results:  Expression of most class 1 and 2 HDACs was increased in NSCLC cells and tumor samples. Cell proliferation was significantly inhibited by panobinostat in concentration- and time-dependent manner, both under normoxia and hypoxia. Compared to cisplatin treatment alone, co-treatment with 16 nM panobinostat markedly decreased cell viability. Those effects were more prominent in malignant NSCLC cells than in non-malignant bronchial epithelial cells. Co-treatment markedly induced apoptosis by causing chromatin fragmentation, activation of caspase 3 and 7 and activation of PARP. Apoptosis induction was of higher significance under hypoxic conditions, where cisplatin alone revealed only mild toxicity. In hypoxia co-treatment led to destabilization of Hif1α and Hif2α and to down-regulation of HDAC4, responsible for acetylation and thereby associated destabilization of Hifα.  Conclusion:  Co-treatment with panobinostat and cisplatin was able to reduce hypoxia-based cisplatin resistance in NSCLC cells, via HDAC4-mediated destabilization of Hifα. This may provide a new therapeutic strategy for NSCLC.
Alternative approaches in IVF
Authors: B. C. J. M. Fauser
Journal: Human Reproduction Update (2002)

Various new developments in clinical and basic science which may impact on IVF in the near or distant future will be discussed in this review. These key areas include the regulation of early follicle development and the extended in-vitro culture of oocytes and embryos. Moreover, alternative compounds and ovarian stimulation protocols will be discussed, along with highlights in the development of the cryopreservation of excess oocytes or embryos. Finally, the health economics of IVF is addressed.
Lung Cancer Risk Among Beauticians and Other Female Workers: Brief Communication2
Authors: H. R. Menck, M. C. Pike, B. E. Henderson, J. S. Jing
Journal: JNCI Journal of the National Cancer Institute (1977)

Lung cancer risk among occupational groups of women was reviewed. A previous suggestion of a sixfold risk of developing lung cancer among beauticians was not confirmed; however, an approximately twofold risk was found.
The mechanism of coronary collateral vasoconstriction in response to cyclooxygenase blockade.
Authors: J D Altman, R J Bache
Journal: Circulation Research (1994)

The present study was performed to examine the mechanism by which cyclooxygenase blockade produces vasoconstriction in well-developed coronary collateral vessels. Eight dogs were studied 4 to 6 months after occlusion of the left anterior descending coronary artery (LAD) had been performed to stimulate collateral vessel growth. At the time of study, the LAD was cannulated at the site of occlusion for measurement of retrograde blood flow as an index of collateral blood flow. Levels of 6-ketoprostaglandin F1 alpha were 32 +/- 13% higher in blood diverted from the collateral-dependent LAD than in aortic blood (P < .05); the increase in this stable product of prostacyclin metabolism indicated production of prostacyclin across the coronary collateral system. Administration of arachidonic acid into the left main coronary artery to reach collateral vessels entering the LAD resulted in a 21 +/- 6% increase in retrograde flow (P < .01), demonstrating cyclooxygenase activity with production of vasodilator prostaglandins in the collateral system. Ibuprofen (10 mg/kg IV) caused a 55 +/- 7% decrease in retrograde flow (P < .03), suggesting that cyclooxygenase blockade inhibited tonic production of vasodilator prostaglandins in the collateral system. In contrast, neither thromboxane synthase inhibition with dazmegrel nor thromboxane receptor blockade with SQ 30741 caused a significant change in collateral flow, thus failing to support thromboxane-induced collateral constriction. After cyclooxygenase blockade, prostacyclin infused into the left main coronary artery was able to restore retrograde flow to the preibuprofen level.(ABSTRACT TRUNCATED AT 250 WORDS)
Effect of transmural pressure on preloads and collapse of immature bronchi
Authors: PK McFawn, HW Mitchell
Journal: European Respiratory Journal (1997)

Immature airways are highly compliant compared to the adult, suggesting that trachea and bronchi from immature animals may be easily compressed. Although tracheal compression has been extensively studied, the effect of transmural pressure on occlusion of immature bronchi has been neglected. The transmural pressure at which the lumen closed was determined from the transmittance of pressure along the lumen of isolated bronchi from late-term foetal, 1 and 4 week old pigs. Bronchi from eight cases of sudden infant death syndrome (SIDS) were also studied. In several experiments, smooth muscle tone was produced either by electrical field stimulation or carbachol challenge, and the relationship between active muscle tone and resting transmural pressure was studied. Bronchi from foetal, 1 and 4 week old pigs were occluded by intraluminal pressures of -4, -5 and -24 cmH2O. SIDS bronchi closed at -11 cmH2O. Histological and endoscopic investigations showed that closure of the bronchi occurred along a plane and was not uniform along the bronchus. Carbachol precontraction increased the transmural pressure required to close bronchi by approximately 5 cmH2O. The relationship between muscle tone and resting pressure was the same in all age groups, except when transmural pressure was at or below closing pressure. Bronchi from immature animals and human infants are vulnerable to collapse by small changes in transmural pressure. Bronchial closure is partly dependent on smooth muscle tone, particularly in younger animals.
Perceptions and factors affecting poor adherence to inhaled steroids among bronchial asthma patients in Kuwait
Authors: Radhakrishna Panicker, Nermina Arifhodzic, Mona Al-Ahmed, Shahariar Huda
Journal: European Respiratory Journal (2012)

Background - Poor adherence to regular inhaled steroids is a cause of poor asthma control.  Aim –To assess adherence to treatment, factors of poor adherence, perception on inhaled steroids among asthmatics in Kuwait  Design -  Observational study  Subjects-150 asthmatics (95 m,55f) 15-60 years, were recruited and followed up for 12 consecutive months from January 2009 to December and asked to fill in a questionnaire of adherence, beliefs about asthma,treatment and reasons for non adherence.  Results –First 3 months, 66 (44%) were adherent to twice daily dosage,but at 12 months only 25%. More males were adherent at 3 months (63.6% vs. 36.4% p  Logistic regression analysis of the beliefs for non adherence showed 52 % did not consider asthma as a serious disease. 82% stopped medicine because of fear of side effects (p  Conclusion:- Adherence to inhaled steroids was poor. Factors were, females, fear of side effects, influence of friends and relatives with wrong information on steroids and poor understanding about asthma.  Since the employed and educated patients showed good adherence, asthma education is important in asthma management.In non-adherence, the clinician should find methods to overcome the barriers of non adherence.
THE TYPE OF CASE THE BONESETTER GETS
Authors: F. W. Stuart
Journal: BMJ (1925)

r~~~~~~~~~~~~~~~~(1;m~I MEDICAL JOUMEAS The effect was remarkable.I was called away, but returned in three hours to find the clhild's appearance woniderfully improved.A feed had been taken, anid the depressioni of the fonitanelle, which had been very marked, had vanished, and the patient's appearance was nio loniger that of a dyinjg clhild.A second transfusion was performed a few lhours later in the hiope of intensifying this evidenitly beneficial effect; 25 c.cm. of citrated blood were easily introduced, usinig the samne syrinige and needle all the time, and necessitating three introductions of tlle ieedle inlto the mothier's veini and three inito the child's vein.Unfortunately twenty-four hours later the chlild went into con- vulsionis and died, but I do niot associate this with the transfusion in any way, for there were maniy pus cells in the urine, and there was probably a general blood infection.There was no difficulty
ORAL TOLERANCE FOR THE TREATMENT OF AUTOIMMUNE DISEASES
Authors: Howard L. Weiner, MD
Journal: Annual Review of Medicine (1997)

Orally administered autoantigens suppress autoimmunity in animal models, including experimental allergic encephalomyelitis, collagen and adjuvant-induced arthritis, uveitis, and diabetes in the non-obese diabetic mouse. Low doses of oral antigen induce antigen-specific regulatory T-cells in the gut, which act by releasing inhibitory cytokines such as transforming growth factor-beta, interleukin-4, and interleukin-10 at the target organ. Thus, one can suppress inflammation at a target organ by orally administering an antigen derived from the site of inflammation, even if it is not the target of the autoimmune response. Initial human trials of orally administered antigen have shown positive findings in patients with multiple sclerosis and rheumatoid arthritis. A double-blind, placebo-controlled, phase III multi-center trial of oral myelin in 515 relapsing-remitting multiple sclerosis patients is in progress, as are phase II clinical trials investigating the oral administration of type II collagen in rheumatoid arthritis, S-antigen in uveitis, and insulin in type I diabetes.
Efficacy and safety of indacaterol acetate on ICS background therapy in asthma
Authors: Jutta Beier, Motoi Hosoe, Ana Maria Tanase, Yota Takahashi, Naoko Kataoka, Bettina Hederer
Journal: European Respiratory Journal (2014)

Introduction 

QMF149 is an investigational inhaled fixed-dose combination of indacaterol acetate (IND, long acting β2-agonist) and mometasone furoate (MF, inhaled corticosteroid) delivered via the Breezhaler® device for once daily maintenance treatment of asthma and COPD. In this study we assessed the effects of indacaterol acetate 150 µg (IND150) and 75 µg (IND75) compared with placebo (PBO).

Methods 

In this double-blind, placebo-controlled study, 335 asthma patients aged 18 to 75 years were randomised to one of the three treatment groups (IND150, IND75, PBO) once daily for 12 weeks. All patients received MF 200 µg once daily as a background therapy throughout the study. Primary endpoint was trough FEV1 (tFEV1) at Week 12.

Results 

At Week 12, a statistically significant improvement in tFEV1 was achieved for IND150 (106 mL; p<0.002) and IND75 (80 mL; p<0.019) compared with PBO. On Day 2, IND150 was statistically superior to IND75 (67 mL; p=0.018) in tFEV1, and IND150 was consistently numerically better than IND75 at all other timepoints over 12 weeks. IND150 and IND75 demonstrated an improvement in Asthma Control Questionnaire (ACQ)-5 with reduction of ≥0.5 at all timepoints compared with baseline (clinically meaningful). There was a positive trend for IND150 and IND75 in rescue use and peak expiratory flow rate vs PBO with a numerical benefit of IND150 over IND75. Study treatments were well tolerated with low incidence of adverse events in all groups (IND150: 28%, IND75: 36%, PBO: 39%).

Conclusion 

IND150 and IND75 resulted in statistically significant improvements vs PBO in tFEV1 at Week 12 (Primary endpoint). Furthermore IND150 demonstrated greater effects than IND75 on lung function and rescue use.
Increased echodensity of myocardial wall in the diabetic heart: An ultrasound tissue characterization study
Authors: Vitantonio Di Bello, Luigi Talarico, Eugenio Picano, Carmine Di Muro, Luigi Landini, Marco Paterni, Elena Matteucci, Costantino Giusti, Ottavio Giampietro
Journal: Journal of the American College of Cardiology (1995)
A potassium ionophore (Nigericin) inhibits stimulation of human lymphocytes by mitogens.
Authors: R P Daniele, S K Holian, P C Nowell
Journal: The Journal of Experimental Medicine (1978)

Nigericin, an ionophore that exchanges K+ for H+ across most biologic membranes, reversibly inhibited the proliferative response of human lymphocytes to phytohemagglutinin (PHA). Inhibition occurred at nigericin concentrations of 10(-8) M or greater, and only during the early event of mitogenesis. There was no effect if nigericin was added 24 h or later after the initiation of PHA-stimulated cultures. The effect was not the result of toxicity or impaired mitochondrial respiration. At similar concentrations, nigericin also inhibited lymphocyte responses in mixed lymphocyte cultures and to other mitogens including concanavalin A, pokeweed mitogen, and the calcium ionophore A23187. The findings support the view that one or more transmembranous events, mediated by changes in cation flux and/or membrane potential, are critical in the initial stages of lymphocyte mitogenesis.
Dynamic regulation of PU.1 expression in multipotent hematopoietic progenitors
Authors: Stephen L. Nutt, Donald Metcalf, Angela D'Amico, Matthew Polli, Li Wu
Journal: The Journal of Experimental Medicine (2005)

PU.1 is an Ets family transcription factor that is essential for fetal liver hematopoiesis. We have generated a PU.1gfp reporter strain that allowed us to examine the expression of PU.1 in all hematopoietic cell lineages and their early progenitors. Within the bone marrow progenitor compartment, PU.1 is highly expressed in the hematopoietic stem cell, the common lymphoid progenitor, and a proportion of common myeloid progenitors (CMPs). Based on Flt3 and PU.1 expression, the CMP could be divided into three subpopulations, Flt3+ PU.1hi, Flt3− PU.1hi, and Flt3− PU.1lo CMPs. Colony-forming assays and in vivo lineage reconstitution demonstrated that the Flt3+ PU.1hi and Flt3− PU.1hi CMPs were efficient precursors for granulocyte/macrophage progenitors (GMPs), whereas the Flt3− PU.1lo CMPs were highly enriched for committed megakaryocyte/erythrocyte progenitors (MEPs). CMPs have been shown to rapidly differentiate into GMPs and MEPs in vitro. Interestingly, short-term culture revealed that the Flt3+ PU.1hi and Flt3− PU.1hi CMPs rapidly became CD16/32high (reminiscent of GMPs) in culture, whereas the Flt3− PU.1lo CMPs were the immediate precursors of the MEP. Thus, down-regulation of PU.1 expression in the CMP is the first molecularly identified event associated with the restriction of differentiation to erythroid and megakaryocyte lineages.
Immunopathogenicity and Oncogenicity of Murine Leukemia Virus. III. Quantitation of Spontaneous Virus Expression23
Authors: B. P. Croker, P. J. McConahey, E. D. Murphy, F. J. Dixon
Journal: JNCI Journal of the National Cancer Institute (1977)

Journal Article Immunopathogenicity and Oncogenicity of Murine Leukemia Virus. III. Quantitation of Spontaneous Virus Expression Get access B. P. Croker, B. P. Croker Search for other works by this author on: Oxford Academic PubMed Google Scholar P. J. McConahey, P. J. McConahey Search for other works by this author on: Oxford Academic PubMed Google Scholar E. D. Murphy, E. D. Murphy Search for other works by this author on: Oxford Academic PubMed Google Scholar F. J. Dixon F. J. Dixon Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 59, Issue 1, July 1977, Pages 199–205, https://doi.org/10.1093/jnci/59.1.199 Published: 01 July 1977 Article history Received: 03 November 1976 Accepted: 19 January 1977 Published: 01 July 1977
Activation-induced Cell Death Drives Profound Lung CD4<sup>+</sup>T-Cell Depletion in HIV-associated Chronic Obstructive Pulmonary Disease
Authors: Iulia Popescu, M. Bradley Drummond, Lucio Gama, Tiffany Coon, Christian A. Merlo, Robert A. Wise, Janice E. Clements, Gregory D. Kirk, John F. McDyer
Journal: American Journal of Respiratory and Critical Care Medicine (2014)

Rationale: As overall survival improves, individuals with HIV infection become susceptible to other chronic diseases, including accelerated chronic obstructive pulmonary disease (COPD).Objectives: To determine whether individuals with HIV-associated COPD exhibit dysregulated lung mucosal T-cell immunity compared with control subjects.Methods: Using flow cytometry, we evaluated peripheral blood and lung mucosal T-cell immunity in 14 HIV+COPD+, 13 HIV+COPD−, and 7 HIV−COPD+ individuals.Measurements and Main Results: HIV+COPD+ individuals demonstrated profound CD4+ T-cell depletion with reduced CD4/CD8 T-cell ratios in bronchoalveolar lavage–derived lung mononuclear cells, not observed in peripheral blood mononuclear cells, and diminished CD4+ T cell absolute numbers, compared with control subjects. Furthermore, HIV+COPD+ individuals demonstrated decreased pulmonary HIV-specific and staphylococcal enterotoxin B–reactive CD4+ memory responses, including loss of multifunctionality, compared with HIV+COPD− control subjects. In contrast, lung mucosal HIV-specific CD8+ T-cell responses were preserved. Lung CD4+ T cells from HIV+COPD+ individuals expressed increased surface Fas death receptor (CD95) and programmed death-1, but similar bronchoalveolar lavage viral loads as control subjects. However, programmed death-1 expression inversely correlated with HIV-specific lung CD4+IFN-γ+ T-cell responses, suggesting functional exhaustion. Moreover, lung CD4+ T cells from HIV+COPD+ patients demonstrated increased basal and HIV antigen-induced expression of the early apoptosis marker annexin V compared with control subjects, which was significantly attenuated with anti-Fas blockade. Lastly, lung mucosal, but not blood, CD4+/CD8+ ratios from HIV+ patients significantly correlated with the FEV1, but not in HIV−COPD+ patients.Conclusions: Together, our results provide evidence for profound lung mucosal CD4+ T-cell depletion via a Fas-dependent activation-induced cell death mechanism, along with impaired HIV-specific CD4+ immunity as immunologic features of HIV-associated COPD.
Hydrogen peroxide in exhaled air is increased in stable asthmatic children
Authors: Q Jobsis, HC Raatgeep, PW Hermans, JC de Jongste
Journal: European Respiratory Journal (1997)

Exhaled air condensate provides a noninvasive means of obtaining samples from the lower respiratory tract. Hydrogen peroxide (H2O2) in exhaled air has been proposed as a marker of airway inflammation. We hypothesized that in stable asthmatic children the H2O2 concentration in exhaled air condensate may be elevated as a result of airway inflammation. In a cross-sectional study, 66 allergic asthmatic children (of whom, 41 were treated with inhaled steroids) and 21 healthy controls exhaled through a cold trap. The resulting condensate was examined fluorimetrically for the presence of H2O2. All subjects were clinically stable, nonsmokers, without infection. The median H2O2 level in the exhaled air condensate of the asthmatic patients was significantly higher than in healthy controls (0.60 and 0.15 micromol, respectively; p<0.05), largely because of high values in the stable asthmatic children who did not use anti-inflammatory treatment (0.8 micromol; p<0.01 compared to controls). We conclude that hydrogen peroxide is elevated in exhaled air condensate of children with stable asthma, and may reflect airway inflammation.
Emissions from incomplete wood combustion cause an immune response in endobronchial biopsies
Authors: Greg Rankin, Maria Sehlstedt, Jamshid Pourazar, Ala Muala, Robin Nyström, Christopher Boman, Anders Blomberg, Thomas Sandström
Journal: European Respiratory Journal (2013)

Smoke from combustion of solid biomass is a major contributor to respiratory disease and is an important, understudied source of particulate matter (PM). Epidemiological studies have indicated adverse effects on obstructive airway diseases, acute lower respiratory tract infections and tuberculosis.  The mechanisms by which wood smoke exhibits its effects on human health are not well understood. We hypothesised that wood smoke generated from incomplete combustion would cause airway inflammation.  14 healthy subjects underwent controlled chamber exposure on two occasions to filtered air and to sooty wood smoke (PM∼314µg/m3), generated by a common Swedish wood stove firing birch logs. The study was performed in a double-blind randomized cross-over fashion and the subjects alternated between exercise (VE=20 L/min/m2) and rest at 15-minute intervals for 3 hours. Endobronchial biopsies were taken 24 hours after exposure and processed for GMA immunohistochemistry. Sections were stained for inflammatory cells and adhesion molecules.  A significant increase in T cells occurred in the airway submucosa and epithelium after wood smoke exposure along with an increase in mast cell number in the submucosa (p  Emissions from incomplete combustion of birch logs causes a modest immune response in the proximal airways of healthy subjects as seen by an influx of T cells and mast cells. Further research is needed to determine the mechanisms behind the present findings and the role of T cells and their subpopulations will be further investigated.
Upconversion Nanophosphors Naluf<sub>4</sub>:Yb,Tm for Lymphatic Imaging <i>In Vivo</i> by Real-Time Upconversion Luminescence Imaging under Ambient Light and High-Resolution X-ray CT
Authors: Yun Sun, Juanjuan Peng, Wei Feng, Fuyou Li
Journal: Theranostics (2013)

Lanthanide upconversion nanophosphor (UCNP) has attracted increasing attention for potential applications in bioimaging due to its excellence in deep and high contrast imaging.To date, most upconversion imaging applications were demonstrated in dark surroundings without ambient light for higher signal-to-noise ratio, which hindered the application of optical imaging guided surgery.Herein, the new established NaLuF 4 -based UCNP (NaLuF 4 :Yb,Tm, ∼17 nm) with bright upconversion emission around 800 nm as imaging signal was used to realize imaging under ambient light to provide more convenient for clinician.Moreover, due to the existance of heavy element lutetium (Lu) in the host lattice, the NaLuF 4 :Yb,Tm nanoparticles can also be used as an X-ray CT imaging agent to enhance the imaging depth and in vivo imaging resolution.
Beta haemolytic streptococci and reactive arthritis in adults.
Authors: C Deighton
Journal: Annals of the Rheumatic Diseases (1993)

There is an increasing occurrence of reactive group A beta haemolytic streptococci (BHS) phenomena. This review makes a case for considering BHS in the differential diagnosis of adult reactive arthritis. This is based on (a) published reports over the past 45 years describing first attacks of rheumatic fever in adults; (b) the longstanding observation that polyarthritis is the most commonly expressed Jones major criterion in adults; (c) the broad spectrum of clinical expression of disease following streptococcal infection, with the re-emergence of the term 9poststreptococcal reactive arthritis9. The arthritis in adult rheumatic fever is characterised by sequential involvement of large weightbearing joints. Recurrent, severe, prolonged arthritis has been a prominent feature of adult poststreptococcal reactive arthritis. Carditis has been reported in 33% of adult patients with rheumatic fever. Consequently long term antibiotic prophylaxis for adults with reactive BHS phenomena should be strongly considered, and guidelines are suggested for this in individual patients. Further areas for research are discussed, particularly the interrelations between bacteria and host in disease expression, and the possibility that BHS might play a part in chronic arthritides and vasculitides.