tbuckley/cabot-search huggingface dataset:
Ciprofloxacin dry powder for inhalation in non-cystic fibrosis bronchiectasis: a phase II randomised study
Authors: Robert Wilson, Tobias Welte, Eva Polverino, Anthony De Soyza, Hugh Greville, Anne O'Donnell, Jeff Alder, Peter Reimnitz, Barbara Hampel
Journal: European Respiratory Journal (2012)

This phase II, randomised, double-blind, multicentre study (NCT00930982) investigated the safety and efficacy of ciprofloxacin dry powder for inhalation (DPI) in patients with non-cystic fibrosis bronchiectasis. Adults who were culture positive for pre-defined potential respiratory pathogens (including Pseudomonas aeruginosa and Haemophilus influenzae) were randomised to ciprofloxacin DPI 32.5 mg or placebo administered twice daily for 28 days (with 56 days of follow-up). Bacterial density in sputum (primary end-point), pulmonary function tests, health-related quality of life and safety were monitored throughout the study. 60 subjects received ciprofloxacin DPI 32.5 mg and 64 received placebo. Subjects on ciprofloxacin DPI had a significant reduction (p<0.001) in total sputum bacterial load at the end of treatment (-3.62 log10 CFU·g(-1) (range -9.78-5.02 log10 CFU·g(-1))) compared with placebo (-0.27 log10 CFU·g(-1) (range -7.96-5.25 log10 CFU·g(-1))); the counts increased thereafter. In the ciprofloxacin DPI group, 14 (35%) out of 40 subjects reported pathogen eradication at end of treatment versus four (8%) out of 49 in the placebo group (p=0.001). No abnormal safety results were reported and rates of bronchospasm were low. Ciprofloxacin DPI 32.5 mg twice daily for 28 days was well tolerated and achieved significant reductions in total bacterial load compared with placebo in subjects with non-cystic fibrosis bronchiectasis.
Long-term outcomes of endoscopic submucosal dissection for colorectal epithelial neoplasms
Authors: K. Niimi, M. Fujishiro, S. Kodashima, O. Goto, S. Ono, K. Hirano, C. Minatsuki, N. Yamamichi, K. Koike
Journal: Endoscopy (2010)

Background and aims: Endoscopic submucosal dissection (ESD) provides a high en bloc resection rate with less invasiveness than surgical resection for large or scarring gastrointestinal neoplasms. However, detailed outcomes in colorectal ESD are still lacking. The aim of our study was to elucidate short- and long-term outcomes of colorectal ESD.
Exercise-Induced Changes in Metabolic Intermediates, Hormones, and Inflammatory Markers Associated With Improvements in Insulin Sensitivity
Authors: Kim M. Huffman, Cris A. Slentz, Lori A. Bateman, Dana Thompson, Michael J. Muehlbauer, James R. Bain, Robert D. Stevens, Brett R. Wenner, Virginia Byers Kraus, Christopher B. Newgard, William E. Kraus
Journal: Diabetes Care (2010)

OBJECTIVE To understand relationships between exercise training-mediated improvements in insulin sensitivity (SI) and changes in circulating concentrations of metabolic intermediates, hormones, and inflammatory mediators. RESEARCH DESIGN AND METHODS Targeted mass spectrometry and enzyme-linked immunosorbent assays were used to quantify metabolic intermediates, hormones, and inflammatory markers at baseline, after 6 months of exercise training, and 2 weeks after exercise training cessation (n = 53). A principal components analysis (PCA) strategy was used to relate changes in these intermediates to changes in SI. RESULTS PCA reduced the number of intermediates from 90 to 24 factors composed of biologically related components. With exercise training, improvements in SI were associated with reductions in by-products of fatty acid oxidation and increases in glycine and proline (P &amp;lt; 0.05, R2 = 0.59); these relationships were retained 15 days after cessation of exercise training (P &amp;lt; 0.05, R2 = 0.34). CONCLUSIONS These observations support prior observations in animal models that exercise training promotes more efficient mitochondrial β-oxidation and challenges current hypotheses regarding exercise training and glycine metabolism.
Cryptogenic organising pneumonia
Authors: J-F. Cordier
Journal: European Respiratory Journal (2006)

Organising pneumonia is defined histopathologically by intra-alveolar buds of granulation tissue, consisting of intermixed myofibroblasts and connective tissue. Although nonspecific, this histopathological pattern, together with characteristic clinical and imaging features, defines cryptogenic organising pneumonia when no cause or peculiar underlying context is found. Rapid clinical and imaging improvement is obtained with corticosteroid treatment, but relapses are common after stopping treatment.
Should endometriomas be treated before IVF–ICSI cycles?
Authors: Edgardo Somigliana, Paolo Vercellini, Paola Viganó, Guido Ragni, Pier Giorgio Crosignani
Journal: Human Reproduction Update (2005)

The laparoscopic excision of ovarian endometriomas appears to increase the chances of spontaneous conception, but the value of this treatment in women selected for IVF–ICSI cycles is debated. Studies recruiting women with unilateral disease and comparing ovarian responsiveness in the affected and contralateral intact gonads indicate that excision of endometriomas is associated with a quantitative damage to ovarian reserve. There are no randomized trials comparing laparoscopic excision to expectant management before IVF–ICSI cycles. The idea that surgery increases IVF pregnancy rates is not supported by the available evidence. However, the chance of conception is not the only issue that has to be considered. Some potential drawbacks are associated with both therapeutical strategies. Specifically, costs and hazard of surgical complications support expectant management whereas oocyte retrieval risks, the possibility of missing occult malignancy and endometriosis progression due to ovarian stimulation would favour surgical treatment. Alternative therapeutical options include medical treatment and ultrasound-guided aspiration. Whereas prolonged GnRH agonist down-regulation may be beneficial, data on ultrasound aspiration are more controversial.
Hypocomplementaemic urticarial vasculitis associated with non-Hodgkin lymphoma and treatment with intravenous immunoglobulin
Authors: D. Shah, A.W. Rowbottom, C.L. Thomas, P. Cumber, M.M.U. Chowdhury
Journal: British Journal of Dermatology (2007)

Conflicts of interest: none declared. Sir, Urticarial vasculitis differs from urticaria in both clinical and pathological aspects. It can be associated with low complement levels in approximately 50% of patients. Hypocomplementaemic urticarial vasculitis usually has no cause found. However, in a minority of cases it has been associated with various infections, drugs, cold and sun exposure.1 There have also been various neoplastic conditions associated with hypocomplementaemic urticarial vasculitis.2 3–4 We report a 59‐year‐old woman who presented with urticarial vasculitis and hypocomplementaemia associated with a low‐grade non‐Hodgkin lymphoma (NHL). She presented in March 2003 with an 8‐year history of urticaria. Her rash consisted of intermittent weals with surrounding erythema (Fig. 1) on her limbs and trunk, with occasional angio‐oedema. New weals appeared approximately twice a month, each lasting for up to 3 days. There was no dermographism and no obvious triggers were identified. At presentation she had no other medical problems or allergies. There was no significant family history and she was a lifelong nonsmoker.
Nature of T-cell macrophage interaction in helper-cell induction in vitro. II. Two stages of T-helper-cell differentiation analyzed in irradiation and allophenic chimeras.
Authors: P Erb, B Meier, T Matsunaga, M Feldmann
Journal: The Journal of Experimental Medicine (1979)

The genetic restriction in the T-cell-macrophage-like cell interaction in helper cell induction was investigated with allophenic and irradiation chimeras of various types. Using T cells from P leads to F1 chimeras, there was a restriction of cooperation with the parental haplotype accessory cells, unless the chimeric mice were repopulated with macrophages of the opposite haplotype before priming. T cells from primed or unprimed F1 leads to P chimeras only cooperated with recipient type accessory cells. These observations led to the hypothesis that there are two stages in the genesis of immunocompetence of T helper cells, one dependent on the thymus, and the other on peripheral macrophage-like cells. Purified T cells from P1 + P2 leads to F1 irradiation chimeras behaved in an unexpected manner in the unprimed state, preferring to cooperate with their own haplotype macrophages. This self preference was lost after antigen priming in vivo and was not noted in allophenic chimeras. This loss of self preference was restricted to the haplotypes represented in the chimeras, and did not extend to third party haplotypes. While these in vitro induced helper cells from chimeric mice show clear genetic restrictions at the T-cell macrophage-like cell interaction, there was no evidence for a matching T-B genetic restriction.
Dual Suppression of the Cyclin-Dependent Kinase Inhibitors CDKN2C and CDKN1A in Human Melanoma
Authors: Ahmad Jalili, Christine Wagner, Mikhail Pashenkov, Gaurav Pathria, Kirsten D. Mertz, Hans R. Widlund, Mathieu Lupien, Jean- Philippe Brunet, Todd R. Golub, Georg Stingl, David E. Fisher, Sridhar Ramaswamy, Stephan N. Wagner
Journal: JNCI Journal of the National Cancer Institute (2012)

Resistance to BRAF V600E inhibitors is associated with reactivation of mitogen-activated protein kinase (MAPK) signaling at different levels in melanoma.To identify downstream effectors of MAPK signaling that could be used as potential additional therapeutic targets for BRAF V600E inhibitors, we used hTERT/CDK4R24C/p53DDimmortalized primary human melanocytes genetically modified to ectopically express BRAFV600E or NRASG12D and observed induction of the AP-1 transcription factor family member c-Jun.Using a dominant negative approach, in vitro cell proliferation assays, western blots, and flow cytometry showed that MAPK signaling via BRAF V600E promotes melanoma cell proliferation at G1 through AP-1-mediated negative regulation of the INK4 family member, cyclin-dependent kinase inhibitor 2C (CDKN2C), and the CIP/KIP family member, cyclin-dependent kinase inhibitor 1A (CDKN1A).These effects were antagonized by pharmacological inhibition of CDKN2C and CDKN1A targets CDK2 and CDK4 in vitro.In contrast to BRAFV600E or NRASG12D-expressing melanocytes, melanoma cells have an inherent resistance to suppression of AP-1 activity by BRAF V600E -or MEK-inhibitors.Here, CDK2/4 inhibition statistically significantly augmented the effects of BRAF V600E -or MEK-inhibitors on melanoma cell viability in vitro and growth in athymic nude Foxn1 nu mice (P = .03when mean tumor volume at day 13 was compared for BRAF V600E inhibitor vs BRAF V600E inhibitor plus CDK2/4 inhibition; P = .02when mean tumor volume was compared for MEK inhibitor vs MEK inhibitor plus CDK2/4 inhibition; P values were calculated by a two-sided Welch t test; n = 4-8 mice per group).
Human neutrophil-mediated fungistasis against Histoplasma capsulatum. Localization of fungistatic activity to the azurophil granules.
Authors: S L Newman, L Gootee, J E Gabay
Journal: Journal of Clinical Investigation (1993)

Human neutrophils (PMN) demonstrated potent fungistatic activity against Histoplasma capsulatum (Hc) yeasts in a sensitive microassay that quantifies the growth of yeasts by the incorporation of [3H]leucine. At a PMN:yeast ratio of 1:2, PMN inhibited the growth of yeasts by 37%. Maximum inhibition of 85% to 95% was achieved at a PMN/yeast ratio of 10:1 to 50:1. Opsonization of the yeasts in fresh or heat-inactivated serum was required for PMN-mediated fungistasis, but ingestion of the yeasts was not required. Recognition and phagocytosis of opsonized yeasts was via PMN complement receptor (CR) type 1 (CR1), CR3, and FcRIII (CD16). PMN fungistatic activity was evident by 2 h, was maximum at 24 h, and persisted up to 5 d. In contrast, yeasts multiplied within monocytes to a greater extent than in culture medium alone. PMN from three patients with chronic granulomatous disease (CGD) inhibited the growth of Hc yeasts by an average of 97%, compared with 86% in three normal controls. Furthermore, preincubation of PMN with the lysosomotropic agent NH4Cl inhibited fungistatic activity in a concentration-dependent manner. Finally, experiments with subcellular fractions of PMN demonstrated that the principal component of the fungistatic activity of PMN was localized in the azurophil granules. These data demonstrate that human PMN possess potent fungistatic activity against Hc yeasts and further show that fungistasis is mediated by antimicrobial agents contained in the azurophil granules.
Plasmacytoid Dendritic Cells Delineate Immunogenicity of Influenza Vaccine Subtypes
Authors: Shohei Koyama, Taiki Aoshi, Takeshi Tanimoto, Yutaro Kumagai, Kouji Kobiyama, Takahiro Tougan, Kazuo Sakurai, Cevayir Coban, Toshihiro Horii, Shizuo Akira, Ken J. Ishii
Journal: Science Translational Medicine (2010)

Rare, circulating dendritic cells differentially shape the immunogenicity mechanisms for protection against H1N1 influenza.
A new scalp formulation of calcipotriene plus betamethasone compared with its active ingredients and the vehicle in the treatment of scalp psoriasis: A randomized, double-blind, controlled trial
Authors: Gregor B.E. Jemec, Cecilia Ganslandt, Jean-Paul Ortonne, Yves Poulin, A. David Burden, Pablo de Unamuno, Berit Berne, Américo Figueiredo, Joar Austad
Journal: Journal of the American Academy of Dermatology (2008)
Phase I study of olaparib plus gemcitabine in patients with advanced solid tumours and comparison with gemcitabine alone in patients with locally advanced/metastatic pancreatic cancer
Authors: J. Bendell, E.M. O'Reilly, M.R. Middleton, I. Chau, H. Hochster, A. Fielding, W. Burke, H. Burris
Journal: Annals of Oncology (2015)
Regulation of the Aurora-A gene following topoisomerase I inhibition: implication of the Myc transcription Factor
Authors: Sandy Courapied, Julia Cherier, Arnaud Vigneron, Marie-Bérangère Troadec, Sandrine Giraud, Isabelle Valo, Claude Prigent, Erick Gamelin, Olivier Coqueret, Benjamin Barré
Journal: Molecular Cancer (2010)

Abstract During the G2 phase of the cell cycle, the Aurora-A kinase plays an important role in centrosome maturation and progression to mitosis. In this study, we show in colorectal cell lines that Aurora-A expression is downregulated in response to topoisomerase I inhibition. Using chromatin immunoprecipitation assays, we have observed that the Myc transcription factor and its Max binding partner are associated with the Aurora-A promoter during the G2 phase of the cell cycle. RNA interference experiments indicated that Myc is involved in the regulation of the Aurora-A gene. Following topoisomerase I inhibition, the expression of Myc decreased whereas Mad was upregulated, and the association of Myc and Max with the promoter of the kinase was inhibited. In parallel, an increased association of Mad and Miz-1 was detected on DNA, associated with an inhibition of the recruitment of transcriptional coactivators. Interestingly, a gain of H3K9 trimethylation and HP1γ recruitment was observed on the Aurora-A promoter following sn38 treatment, suggesting that this promoter is located within SAHF foci following genotoxic treatment. Since Aurora-A is involved in centrosome maturation, we observed as expected that topoisomerase I inhibition prevented centrosome separation but did not affect their duplication. As a consequence, this led to G2 arrest and senescence induction. These results suggest a model by which the Aurora-A gene is inactivated by the G2 checkpoint following topoisomerase I inhibition. We therefore propose the hypothesis that the coordinated overexpression of Myc and Aurora-A, together with a downregulation of Mad and Miz-1 should be tested as a prognosis signature of poor responses to topoisomerase I inhibitors.
Microdevices in Medicine
Authors: Dennis L. Polla, Arthur G. Erdman, William P. Robbins, David T. Markus, Jorge Diaz-Diaz, Raed Rizq, Yunwoo Nam, Hui Tao Brickner, Amy Wang, Peter Krulevitch
Journal: Annual Review of Biomedical Engineering (2000)

The application of microelectromechanical systems (MEMS) to medicine is described. Three types of biomedical devices are considered, including diagnostic microsystems, surgical microsystems, and therapeutic microsystems. The opportunities of MEMS miniaturization in these emerging disciplines are considered, with emphasis placed on the importance of the technology in providing a better outcome for the patient and a lower overall health care cost. Several case examples in each of these areas are described. Key aspects of MEMS technology as it is applied to these three areas are described, along with some of the fabrication challenges.
Efficacies of different external controls for excessive foot pronation: a meta-analysis
Authors: Roy T H Cheung, Raymond C K Chung, Gabriel Y F Ng
Journal: British Journal of Sports Medicine (2011)

Objectives This meta-analysis investigated the efficacies of foot orthoses, motion control footwear and therapeutic adhesive taping in controlling foot pronation as compared with no-intervention conditions. Data sources Electronic searches on four electronic databases were performed and the reference lists of the screened articles were also scrutinised. Review methods Two reviewers screened the quasi-randomised or clinical controlled trials that examined the efficacy of the selected interventions in controlling calcaneal eversion. Heterogeneity and publication bias were assessed by I 2 index and Egger's regression intercept, respectively. Trial quality was rated by the Physiotherapy Evidence Database scale. Results 29 studies were selected. The I 2 indices revealed large heterogeneity which supported the use of a random effect model of meta-analysis. The Egger's regression intercepts suggested that publication bias of the included studies was marginally present in the motion control footwear and the therapeutic adhesive taping groups (p=0.06–0.07). All three interventions were effective in reducing calcaneal eversion (p&lt;0.001) with therapeutic adhesive taping being most effective whereas Low-dye taping was less effective than the other taping techniques, such as high-dye and stirrups taping. Custom-made foot orthoses were more effective than prefabricated orthoses. Motion control footwear with heel flare or wedge design was less effective than those with dual midsole materials. Conclusions Foot orthoses, motion control footwear and therapeutic adhesive taping were able to control rearfoot eversion with therapeutic adhesive taping being the most effective. In the clinical practice, selection of an antipronation intervention should be based on patient characteristics, type of activity and personal preference.
Neurotransmitter Transporters in the Central Nervous System
Authors: J. Masson, C. Sagné, M. Hamon, S. El Mestikawy
Journal: Pharmacological Reviews (1999)

Intercellular communication in the central nervous system (CNS)2 requires the precise control of the duration and the intensity of neurotransmitter action at specific molecular targets. After they have been released at the synapse, neurotransmitters activate pre- and/or postsynaptic receptors (Fig.[
Emergency use of nebulised bronchodilator drugs in British hospitals.
Authors: B R O'Driscoll, G M Cochrane
Journal: Thorax (1987)

A telephone survey was conducted to determine the emergency use of nebulised bronchodilator drugs by the registrar or senior house officer on duty for medical admissions at 67 British hospitals. All used a nebulised beta agonist (usually 5 mg salbutamol) as first line treatment for severe acute asthma or reversible obstructive lung disease. Twenty three doctors used ipratropium bromide occasionally and 38 used it frequently, usually mixing ipratropium and a beta agonist in the nebuliser chamber. Only five doctors routinely specified whether the nebuliser should be driven by air or by oxygen. In the case of a hypercapnic patient with chronic bronchitis, 11 respondents would not specify which gas should be used and a further 14 would use oxygen, a potentially dangerous practice. In the case of a hypoxic asthmatic patient, 22 doctors would not prescribe oxygen as the driving gas. The driving gas flow rate was almost invariably determined by nursing staff. Intravenous aminophylline was used by all 67 respondents (52 of them frequent users) but only 24 used intravenous beta agonists (five of them frequent users). It is concluded that nebulised bronchodilator drugs are the most commonly used treatment for acute asthma and reversible obstructive lung disease in hospital, but further instruction in their use is required for the staff who use them most frequently.
Growth Rate of Experimental Tumor After the Use of Laser Energy
Authors: Hoye, Robert C., Weiss, George H., Ketcham, Alfred S.
Journal: JNCI Journal of the National Cancer Institute (1966)

Journal Article Growth Rate of Experimental Tumor After the Use of Laser Energy Get access Robert C. Hoye, Robert C. Hoye Surgery Branch, National Cancer Institute,4Bethesda, Maryland 20014 Search for other works by this author on: Oxford Academic PubMed Google Scholar George H. Weiss, George H. Weiss Surgery Branch, National Cancer Institute,4Bethesda, Maryland 20014 Search for other works by this author on: Oxford Academic PubMed Google Scholar Alfred S. Ketcham Alfred S. Ketcham Surgery Branch, National Cancer Institute,4Bethesda, Maryland 20014 Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 37, Issue 6, December 1966, Pages 819–823, https://doi.org/10.1093/jnci/37.6.819 Published: 01 December 1966 Article history Received: 03 June 1966 Published: 01 December 1966
Constitutively Activated Akt-1 Is Vital for the Survival of Human Monocyte-Differentiated Macrophages
Authors: Hongtao Liu, Harris Perlman, Lisa J. Pagliari, Richard M. Pope
Journal: The Journal of Experimental Medicine (2001)

Recent data from mice deficient for phosphatase and tensin homologue deleted from chromosome 10 or src homology 2 domain–containing 5′ inositol phosphatase, phosphatases that negatively regulate the phosphatidylinositol 3-kinase (PI3K) pathway, revealed an increased number of macrophages in these animals, suggesting an essential role for the PI3K pathway for macro-phage survival. Here, we focused on the role of the PI3K-regulated serine/threonine kinase Akt-1 in modulating macrophage survival. Akt-1 was constitutively activated in human macrophages and addition of the PI3K inhibitor, LY294002, suppressed the activation of Akt-1 and induced cell death. Furthermore, suppression of Akt-1 by inhibition of PI3K or a dominant negative (DN) Akt-1 resulted in loss of mitochondrial transmembrane potential, activation of caspases-9 and -3, and DNA fragmentation. The effects of PI3K inhibition were reversed by the ectopic expression of constitutively activated Akt-1 or Bcl-xL. Inhibition of PI3K/Akt-1 pathway either by LY294002 or DN Akt-1 had no effect on the constitutive or inducible activation of nuclear factor (NF)-κB in human macrophages. However, after inhibition of the PI3K/Akt-1 pathway, a marked decrease in the expression of the antiapoptotic molecule Mcl-1, but not other Bcl-2 family members was observed, and Mcl-1 rescued macrophages from LY294002-induced cell death. Further, inhibition of Mcl-1 by antisense oligonucleotides, also resulted in macrophage apoptosis. Thus, our findings demonstrate that the constitutive activation of Akt-1 regulates macrophage survival through Mcl-1, which is independent of caspases, NF-κB, or Bad.