tbuckley/cabot-search huggingface dataset:
Regulation of lipopolysaccharide-mediated interleukin-1β release by N-acetylcysteine in THP-1 cells
Authors: M. Parmentier, N. Hirani, I. Rahman, K. Donaldson, W. MacNee, F. Antonicelli
Journal: European Respiratory Journal (2000)

Increased levels of inflammatory cytokines such as interleukin (IL)-1 and IL-8 occur in the bronchoalveolar lavage fluid in various lung diseases. Cytokine gene expression is controlled by transcription factors such as nuclear factor-kappaB (NF-kappaB) which can be activated by a number of stimuli including the oxidants prevent. It was hypothesized that lipopolysaccharide (LPS)-induced IL-1beta secretion may be modulated by the intracellular thiol redox status of the cells. The effect of the antioxidant compound, N-acetyl-L-cysteine (NAC), on IL-1beta release and regulation of NF-kappaB in a human myelo-monocytic cell line (THP-1) differentiated into macrophages was studied. LPS (10 microg x mL(-1)) increased IL-1beta release at 24 h compared to control levels (p&lt;0.001). NAC (5 mM) also enhanced LPS-induced IL-1beta release from THP-1 cells (p&lt;0.001). In addition, treatment of cells with cycloheximide, an inhibitor of protein synthesis, inhibited the NAC-mediated IL-1beta release. Under the same conditions, NF-kappaB binding was activated by LPS and NAC increased this LPS-mediated effect. Western blot analysis revealed that NAC treatment leads to an increase in p50 and p65 protein synthesis. These data indicate that N-acetyl-L-cysteine modulates interleukin-1kappa release by increasing levels of the homo- and heterodimeric forms of nuclear factor-kappaB.
Dysfunctional Mechanical Coupling of Upper Airway Tissues in Sleep Apnea Syndrome
Authors: FRÉDÉRIC SÉRIÈS, CLAUDE CÔTÉ, SYLVAIN ST. PIERRE
Journal: American Journal of Respiratory and Critical Care Medicine (1999)

The mechanical effect of musculus uvulae (MU) contraction on in vitro uvular shortening and/or displacement was measured in 15 patients with a sleep apnea hypopnea syndrome (SAHS) and in 8 snorers. Using freshly resected uvular tissues, passive and active uvular tissue-specific elastance and shortening were determined during stimulation of MU. No difference was found in maximum tetanic tension measured on uvular tissue between the two groups (47.2 +/- 14.8 g in SAHS and 39.1 +/- 16.5 g in snorers). Passive uvular-specific elastance was significantly less in snorers (0.36 +/- 0.27 g/% Lo) compared with patients with SAHS (0.84 +/- 0.39 g/% Lo) (p = 0.006). There was a negative correlation between uvular shortening and passive uvular specific elastance (r = 0.69, p = 0. 05). Maximal tetanic tension developed by isolated MU was higher in SAHS than in snorers (45.8 +/- 23.1 and 30.0 +/- 8.3 g, respectively, p = 0.04). A strong positive relationship was found between the apnea index and specific uvular elastance (r = 0.55, p = 0.007). We conclude that there is a significant difference between the uvular tissue elastance of SAHS and snorers, and that this difference influences the mechanical efficiency of MU contraction.
Quality of life in patients with locally advanced prostate cancer given endocrine treatment with or without radiotherapy: 4-year follow-up of SPCG-7/SFUO-3, an open-label, randomised, phase III trial
Authors: Per Fransson, Jo-Åsmund Lund, Jan-Erik Damber, Olbjörn Klepp, Fredrik Wiklund, Sophie Fosså, Anders Widmark
Journal: The Lancet Oncology (2009)
Open label, multi-centre phase II study of raltitrexed (‘Tomudex’) in patients with inoperable squamous-cell carcinoma of head and neck
Authors: S.J. Clarke, J. Zalcberg, I. Olver, P.L.R. Mitchell, D. Rischin, D. Dalley, M. Green, Y. Egan Davidson
Journal: Annals of Oncology (2000)
Pulmonary deposition of nebulised amiloride in cystic fibrosis: comparison of two nebulisers.
Authors: S H Thomas, M J O'Doherty, A Graham, C J Page, P Blower, D M Geddes, T O Nunan
Journal: Thorax (1991)

BACKGROUND Preliminary evidence suggests that regular inhalation of nebulised amiloride reduces sputum viscoelasticity, increases the clearance of sputum by mucociliary mechanisms and by coughing and reduces the rate of deterioration in lung function in patients with cystic fibrosis. These effects depend on adequate delivery of amiloride to the airways. This study was performed to quantify and compare pulmonary deposition of amiloride produced by two different nebuliser systems. METHODS The pulmonary deposition of nebulised amiloride (1 mg in 3 ml saline) was measured in eight patients with cystic fibrosis when given via a jet (System 22 with CR 60 compressor) and an ultrasonic (Fisoneb) nebuliser. Human serum albumin labelled with technectium-99m was used as an indirect marker for amiloride and its deposition in the lung was detected with a gamma camera. RESULTS Amiloride inhalation caused no side effects or changes in spirometric indices. The mean (SD) total pulmonary amiloride deposition was 57 (24) micrograms with the System 22 and 103 (53) micrograms with the Fisoneb nebuliser. Pulmonary deposition was completed more rapidly with the Fisoneb (4-5 minutes) than with the System 22 nebuliser (7-8 minutes) and the Fisoneb was preferred by the patients. CONCLUSIONS Both nebulisers appeared to deliver adequate amounts of amiloride to the lungs, but treatment with the Fisoneb nebuliser was quicker, more efficient, and more acceptable to the patients. Of the two nebulisers assessed, the Fisoneb would be preferred for clinical trials.
Randomised trial of efficacy of SPf66 vaccine against Plasmodium falciparum malaria in children in southern Tanzania
Authors: P.L Alonso, T Smith, J.R.M Armstrong Schellenberg, H Masanja, S Mwankusye, H Urassa, I Bastos de Azevedo, J Chongela, S Kobero, C Menendez, N Hurt, M.C Thomas, E Lyimo, N A Weiss, R Hayes, A Y Kitua, M C Lopez, W L Kilama, T Teuscher, M Tanner
Journal: The Lancet (1994)
Short-course adjuvant chemotherapy in high-risk stage I nonseminomatous germ cell tumors of the testis: a Medical Research Council report.
Authors: M H Cullen, S P Stenning, M C Parkinson, S D Fossa, S B Kaye, A H Horwich, S J Harland, M V Williams, R Jakes
Journal: Journal of Clinical Oncology (1996)

PURPOSE This United Kingdom Medical Research Council (UK-MRC) study prospectively evaluated efficacy and long-term toxicity of adjuvant chemotherapy in high-risk stage I nonseminomatous germ cell tumors of the testis (NSGCTT). PATIENTS AND METHODS Eligible patients were those identified by the local histopathologist as having features confirmed in MRC surveillance studies to indicate an approximate 50% risk of relapse. Central histopathology review was undertaken. Chemotherapy consisted of two courses of cisplatin 100 mg/m2, bleomycin 30 mg weekly x 3, and etoposide 120 mg/m2 x 3, every 21 days (BEP). RESULTS One hundred fourteen eligible cases were enrolled. Median time of follow-up was 4 years, with 93 patients followed-up for at least 2 years. There have been two relapses, including one patient who did not have a germ cell tumor (GCT), according to the reference histopathologist. This patient is alive with active disease, the other has died. There was one death after a cerebrovascular accident during treatment. Assessment of fertility, lung function, and audiometry pretreatment and more than 9 months posttreatment indicated no clinically significant changes. A mean decrease in transfer factor coefficient (KCO) of 15% of the predicted value was noted, but no patient had symptomatic respiratory dysfunction. CONCLUSION There have been only two relapses among 114 cases of high-risk stage I NSGCTT treated with two courses of adjuvant BEP chemotherapy. The 95% confidence interval (CI) excludes a true relapse rate of more than 5%. Of 104 patients confirmed on histopathology review to have GCT, there has been only one relapse. Adjuvant chemotherapy is free from significant long-term toxicity, offering an effective alternative to surveillance or retroperitoneal lymph node dissection (RPLND) followed by surveillance, and may be preferred by some patients.
Effect of androgen therapy and anemia on serum erythropoietin levels in patients with aplastic anemia and myelodysplastic syndromes
Authors: Josefa Piedras, Guadalupe Hernández, Xavier López-Karpovitch
Journal: American Journal of Hematology (1998)

Immunoreactive serum erythropoietin (EPO) was measured in anemic and non-anemic patients with acquired non-severe aplastic anemia (AA; n = 22) and myelodysplastic syndromes (MDS; n = 31) receiving or not androgens to examine the effect of androgen therapy and anemia on EPO levels in these disorders. Soluble transferrin receptor (TfR) and absolute reticulocyte count (ARC) were also assayed in order to evaluate erythropoietic activity. AA and MDS patients were stratified for anemia and androgen treatment as follows: 12 untreated anemic patients; 17 anemic patients during androgen therapy; 14 non-anemic patients without any treatment (> 1 year); and 10 non-anemic patients on androgen therapy. Although EPO levels in non-anemic patients were significantly higher than in healthy controls (n = 29) no statistically significant differences in Hb and EPO values were found between non-anemic patients receiving or not androgen therapy. In the linear regression analysis between Hb and log EPO concentration, no statistically significant differences in the slopes between untreated and androgen-treated anemic groups nor between both groups and patients with iron deficiency anemia (n = 23) were observed. However, the y intercept (log EPO) of regression line was significantly higher in androgen-treated anemic patients than in the androgen therapy-free anemic group. Serum TfR levels were higher in treated than in untreated anemic patients, whereas ARC was not different between both groups. These data seemingly indicate that (1) androgens at pharmacological doses do not increase serum EPO levels in non-anemic AA and MDS patients, and (2) in patients with AA and MDS, androgen-driven EPO stimulation is appreciably enhanced by anemia.
Necrotising pneumonia and empyema caused by Clostridium bifermentnas.
Authors: D P Misra, D J Hurst
Journal: Thorax (1980)

Macrophages play an important role during the development and progression of atherosclerotic plaques. α<sub>v</sub>β<sub>3</sub> integrins are highly expressed by macrophages; thus, targeting α<sub>v</sub>β<sub>3</sub> may allow targeting of culprit macrophage-loaded atherosclerotic lesions <i>in vivo</i>. <b>Methods:</b> An α<sub>v</sub>β<sub>3</sub>-targeted Arg-Gly-Asp (RGD) peptide was labeled with the cyanine 5.5 (Cy 5.5) dye and applied to image atherosclerotic plaques in apolipoprotein E–deficient mice. <b>Results:</b> The peptide–dye conjugate binds to α<sub>v</sub>β<sub>3</sub> integrin–positive RAW264.7 macrophages with high affinity. Competition experiments confirmed binding specificity of the probe. A significant fluorochrome accumulation in atherosclerotic plaques was demonstrated 24 h after injection by fluorescence reflectance imaging, which was blocked with high efficiency by competition with the unlabeled peptide. Conversely, the nonconjugated dye revealed only a minor fluorescence signal in the plaques. Fluorescence microscopy revealed colocalization of the probe with macrophages in the plaque of a mouse model for accelerated atherosclerosis, which was corroborated in human carotid artery specimens. In addition to macrophage-associated signals, binding of the probe to the neointima or elastica of the arteries was observed. <b>Conclusion:</b> RGD-Cy 5.5, combined with near-infrared optical imaging methods, allows the specific imaging of α<sub>v</sub>β<sub>3</sub>-integrin expression on macrophages recruited to vascular lesions and may serve to estimate macrophage-bound inflammatory activity of atherosclerotic lesions.
Dihydroartemisinin-piperaquine failure associated with a triple mutant including kelch13 C580Y in Cambodia: an observational cohort study
Authors: Michele D Spring, Jessica T Lin, Jessica E Manning, Pattaraporn Vanachayangkul, Sok Somethy, Rathvicheth Bun, Youry Se, Soklyda Chann, Mali Ittiverakul, Piyaporn Sia-ngam, Worachet Kuntawunginn, Montri Arsanok, Nillawan Buathong, Suwanna Chaorattanakawee, Panita Gosi, Winita Ta-aksorn, Nitima Chanarat, Siratchana Sundrakes, Nareth Kong, Thay Kheang Heng, Samon Nou, Paktiya Teja-isavadharm, Sathit Pichyangkul, Sut Thang Phann, Sujata Balasubramanian, Jonathan J Juliano, Steven R Meshnick, Char Meng Chour, Satharath Prom, Charlotte A Lanteri, Chanthap Lon, David L Saunders
Journal: The Lancet Infectious Diseases (2015)
Identification of a novel inducible cell-surface ligand of CD5 on activated lymphocytes.
Authors: L Biancone, M A Bowen, A Lim, A Aruffo, G Andres, I Stamenkovic
Journal: The Journal of Experimental Medicine (1996)

CD5 is a 67-kD glycoprotein that is expressed on most T lymphocytes and on a subset of mature B cells. Although its physiologic function is unknown, several lines of evidence suggest that CD5 may play a role in the regulation of T cell activation and in T cell-antigen presenting cell interactions. Using a CD5-immunoglobulin fusion protein (CD5Rg, for receptorglobulin) we have uncovered a new CD5 ligand (CD5L) expressed on the surface of activated splenocytes. Stimulation of murine splenocytes with anti-CD3 and anti-CD28 antibodies induce transient expression of CD5L on B lymphocytes that lasts for approximately 72 h. Binding of CD5Rg to activated splenocytes is trypsin resistant and independent of divalent cations. However, it is pronase sensitive and dependent on N-linked glycosylation of CD5, since treatment of CD5Rg with PNGaseF on N-glycanase completely abrogates its ability to bind activated splenocytes. It addition to splenocytes, CD5L is expressed on activated murine T cell clones. Immunoprecipitation, antibody, and recombinant protein blocking studies indicate that CD5L is distinct from CD72, which has been proposed to be a CD5 ligand. To determine whether CD5-CD5L interaction might play a role in vivo, we tested the effect of CD5Rg in a murine model of antibody-mediated membranous glomerulonephritis. Injection of CD5Rg was found to abrogate development of the disease. Taken together, our results help identify a novel ligand of CD5 and propose a role for CD5 in the regulation of immune responses.
Treating hypertension after stroke
Authors: R J Davenport
Journal: BMJ (1994)

intake of hindmilk and hence of vitamin K.4 If the baby needs extra vitamin K it can be given as a separate supplement.Slattery makes some cogent points about the ethics of routine treatment of babies with vitamin K in the absence of controlled trials looking at possible side effects.'I Interpreting statistics on haemorrhagic disease of the newborn in relation to feeding and prophylactic treatment is extremely difficult.In the, leaflets we have collected the incidence of haemorrhagic disease quoted to parents varies from 1 in 50 to 10 in 1-7 million babies.We welcome the developing debate on the size of the problem and the benefits and risks of the alternative preventive strategies.In particular, we value discussion about the appropriateness of a randomised controlled trial.Despite the practical difficulties and the long wait for results2 we believe that a trial is appro- priate, given that the whole population of newborn babies is currently targeted.Careful attention should be paid to producing clear information based on research for all parents considering treatment for their child.
Variability of Serum Cholesterol Values in Baboons
Authors: JACK P. STRONG, PAUL B. RADELAT, MARION A. GUIDRY, C. A. MCMAHAN
Journal: Circulation Research (1964)

Variability of serum cholesterol in baboons was studied in order to obtain estimates of biological and technical variation for use in planning a long term dietary experiment. Variability due to animals, to laboratories, to the day on which blood was drawn, and to laboratory work day was estimated. Implications for the design of experiments involving serum cholesterol in baboons are discussed.
Acute myeloid leukemia of donor origin after allogeneic stem cell transplantation from a sibling who harbors germline XPD and XRCC3 homozygous polymorphisms
Authors: Hilda Rachel Diamond, Maria Helena Ornellas, Alberto Orfao, Bernadete E Gomes, Mércia M Campos, Teresa S Fernandez, Roberto I da Silva, Gilda Alves, Claudia Lage, Dayse A da Silva, Arthur Moellmann-Coelho, Geydson S da Cruz, Luis Fernando Bouzas, Eliana Abdelhay
Journal: Journal of Hematology & Oncology (2011)

A 54-year-old woman was diagnosed with infiltrative ductal breast carcinoma. Two years after treatment, the patient developed an acute myeloid leukemia (AML) which harbored del(11q23) in 8% of the blast cells. The patient was submitted for allogeneic stem cell transplantation (aSCT) from her HLA-compatible sister. Ten months after transplantation, she relapsed with an AML with basophilic maturation characterized by CD45low CD33high, CD117+, CD13-/+, HLA Drhigh, CD123high, and CD203c+ blast cells lacking expression of CD7, CD10, CD34, CD15, CD14, CD56, CD36, CD64, and cytoplasmic tryptase. Karyotype analysis showed the emergence of a new clone with t(2;14) and FISH analysis indicated the presence of MLL gene rearrangement consistent with del(11q23). Interestingly, AML blast cell DNA tested with microsatellite markers showed the same pattern as the donor's, suggesting that this AML emerged from donor cells. Additionally, polymorphisms of the XPA, XPD, XRCC1, XRCC3 and RAD51 DNA repair genes revealed three unfavorable alleles with low DNA repair capacity. In summary, we report the first case of AML involving XPD and XRCC3 polymorphisms from donor origin following allogeneic stem cell transplantation and highlight the potential need for careful analysis of DNA repair gene polymorphisms in selecting candidate donors prior to allogeneic stem cell transplantation.
PPARγ/mTOR signalling: striking the right balance in cartilage homeostasis
Authors: Francesco Dell'Accio, Joanna Sherwood
Journal: Annals of the Rheumatic Diseases (2015)

Osteoarthritis (OA) is still a highly prevalent and disabling disease for which we do not have a cure. In the last decade, however, the unravelling of molecular mechanisms controlling joint homeostasis, the advances in targeting technologies, and the improvement of animal models allowing the use of mouse genetics has led to the identification of molecular targets that, in animal models,1–4 and possibly also in humans5 can arrest disease or even revert its course. Such strategies include blockade of extracellular matrix-degrading enzymes,6 hypoxia-inducible factor 2α blockade3 ,4 to prevent chondrocyte hypertrophy, the support of parathyroid hormone/parathyroid hormone related protein signalling—an injury-induced homeostatic mechanism affecting both cartilage homeostasis and bone remodelling,2 improving bone turnover using strontium ranelate,5 and blockade of the filamin-core binding factor interaction thereby supporting chondrocytic differentiation using kartogenin.7 Although only strontium ranelate has been tested in the clinic, there is little doubt that the availability of multiple targets will stimulate and instruct the experimentation needed to bridge the gap to the clinic.

In this issue of the journal, Vasheghani et al 8 have demonstrated that PPARγ-driven mTOR (mammalian target of rapamycin) inhibition protects cartilage from experimental OA, at least in part by supporting autophagy,8 a process that, by suppressing protein synthesis and enabling the use of cellular components to generate energy, allows cells to escape death in conditions of stress or lack of nutrients.9

The authors previously reported that cartilage-specific disruption of the gene encoding for the transcription factor PPARγ results in spontaneous OA in mice.10 To ensure that this phenotype was not driven by skeletal dysplasia determined by the absence of PPARγ during development, they generated a new mutant in which PPARγ could be deleted postnatally in chondrocytes upon administration of doxycycline. The mice did not develop …
Human single chain antibodies against heparin: selection, characterization, and effect on coagulation
Authors: Els M. A. van de Westerlo, Toon F. C. M. Smetsers, Michel A. B. A. Dennissen, Robert J. Linhardt, Jacques H. Veerkamp, Goos N. P. van Muijen, Toin H. van Kuppevelt
Journal: Blood (2002)
Death Receptor Regulation and Celecoxib-Induced Apoptosis in Human Lung Cancer Cells
Authors: X. Liu, P. Yue, Z. Zhou, F. R. Khuri, S.-Y. Sun
Journal: JNCI Journal of the National Cancer Institute (2004)

Background: Celecoxib, a cyclooxygenase 2 inhibitor, has chemopreventive and therapeutic activities toward lung cancer and other epithelial malignancies. Celecoxib can induce apoptosis in various cancer cell lines through a mechanism that is independent of its cyclooxygenase 2 inhibitory activity but is otherwise largely uncharacterized. We investigated the mechanism of celecoxib-induced apoptosis further. Methods: All experiments were conducted in human non-small-cell lung carcinoma (NSCLC) cell lines; results in celecoxib-treated and untreated cells were compared. Cell survival was assessed with a sulforhodamine B assay. Apoptosis was assessed by DNA fragmentation with an enzyme-linked immunosorbent assay, by terminal deoxynucleotidyltransferase-mediated dUTP nick-end-labeling (TUNEL) assay, and by western blot analysis of caspase activation. Death receptor gene and protein expression was detected by northern and western blot analysis, respectively. Gene silencing was achieved with small interfering RNA (siRNA) technology. Results: Celecoxib treatment decreased cell survival, activated caspase cascades, and increased DNA fragmentation, all of which were abrogated when caspase 8 expression was silenced with caspase 8 siRNA. Celecoxib treatment induced the expression of death receptors, particularly that of DR5. Overexpression of a dominant negative Fas-associated death domain mutant, but not of BCL2, reduced the level of celecoxib-induced apoptosis, and silencing of DR5 expression by DR5 siRNA suppressed celecoxib-induced caspase 8 activation and apoptosis. Combination treatment with celecoxib and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) induced additional apoptosis. For example, survival of A549 cells was decreased with 50 μM celecoxib alone by 38.7% (95% confidence interval [CI] = 35.2% to 42.2%), with TRAIL alone by 29.3% (95% CI = 25.1% to 33.6%), but with their combination by 77.5% (95% CI = 74.5% to 79.5%), a greater than additive effect. Conclusion: Celecoxib appears to induce apoptosis in human NSCLC through the extrinsic death receptor pathway.