tbuckley/cabot-search huggingface dataset:
Atopy in cough sensitivity to capsaicin and bronchial responsiveness in young females
Authors: M Fujimura, K Kasahara, M Yasui, S Myou, Y Ishiura, Y Kamio, T Hashimoto, T Matsuda
Journal: European Respiratory Journal (1998)

We have shown previously that female sex is a determinant of cough sensitivity to inhaled capsaicin, but the relationship between atopy and the cough sensitivity has not been examined. The capsaicin cough threshold, defined as the lowest concentration of capsaicin causing five or more coughs, nonspecific bronchial responsiveness, defined as the provocative concentration of methacholine causing a 20% fall in the forced expiratory volume in one second (PC20), total immunoglobulin E (IgE) and specific IgEs to eight common aeroallergens (house dust 1, 2 and 6, Dermatophagoides pteronyssinus and D. farinae, Japanese cedar, ragweed and orchard grass) in the serum were measured in 71 nonsmoking, healthy young women aged 20.6+/-0.1 yrs (mean+/-EM). A structured interviewer-led questionnaire on allergic diseases revealed that one and six subjects had mild current and past asthma, respectively. These seven subjects were excluded from the data analysis. PC20 was significantly lower in 42 subjects showing a positive specific IgE than in 22 subjects showing a negative specific IgE to any of the eight allergens (p&lt;0.05), while the capsaicin cough threshold was not significantly different between the subgroups. PC20 was significantly lower in subjects with positive specific IgE to Dermatophagoides and house dust, but not to the three kinds of pollen examined. It was confirmed that atopy indicated by specific immunoglobulin E to mite-related antigens, but not to pollen antigens, is associated with nonspecific bronchial responsiveness, and it is suggested that atopy is not a determinant of airway cough sensitivity in healthy, nonasthmatic subjects.
Molecular changes induced by the curcumin analogue D6 in human melanoma cells
Authors: Carla Rozzo, Manuela Fanciulli, Cristina Fraumene, Antonio Corrias, Tiziana Cubeddu, Ilaria Sassu, Sara Cossu, Valentina Nieddu, Grazia Galleri, Emanuela Azara, Maria Antonietta Dettori, Davide Fabbri, Giuseppe Palmieri, Marina Pisano
Journal: Molecular Cancer (2013)

In a previous report, we described the in vitro and in vivo antiproliferative and proapoptotic activity of a hydroxylated biphenyl (D6), a structural analogue of curcumin, on malignant melanoma and neuroblastoma tumours. In this paper, we investigated the molecular changes induced by such a compound, underlying cell growth arrest and apoptosis in melanoma cells. To shed light on the mechanisms of action of D6, we firstly demonstrated its quick cellular uptake and subsequent block of cell cycle in G2/M phase transition. A gene expression profile analysis of D6-treated melanoma cells and fibroblasts was then carried out on high density microarrays, to assess gene expression changes induced by this compound. The expression profile study evidenced both an induction of stress response pathways and a modulation of cell growth regulation mechanisms. In particular, our data suggest that the antiproliferative and proapoptotic activities of D6 in melanoma could be partially driven by up-regulation of the p53 signalling pathways as well as by down-regulation of the PI3K/Akt and NF-kB pathways. Modulation of gene expression due to D6 treatment was verified by western blot analysis for single proteins of interest, confirming the results from the gene expression profile analysis. Our findings contribute to the understanding of the mechanisms of action of D6, through a comprehensive description of the molecular changes induced by this compound at the gene expression level, in agreement with the previously reported anti-tumour effects on melanoma cells.
A STUDY OF PASSIVE IMMUNITY TO MENINGOCOCCUS INFECTION IN THE CHICK EMBRYO
Authors: G. John Buddingh, Alice D. Polk
Journal: The Journal of Experimental Medicine (1939)

1. 14 day old chick embryos are protected against subsequent meningococcus infection through the amniotic route by the intravenous administration of an homologous antiserum produced in hens, by a commercial concentrated polyvalent meningococcus antiserum and by a commercial meningococcus antitoxin. 2. Titrations of the different antisera indicate that the homologous and commercial polyvalent sera have approximately the same protective value and are much more effective than the commercial antitoxin. The titrations also show that the chick embryo is a sensitive indicator of the amount of antibodies present in a given amount of serum. 3. The mechanism of the protective action of the antisera is not apparent from these experiments except that in the treated embryos there is a relative inhibition of the growth and presumably a neutralization of the injurious products of the meningococci.
Cell-mediated lympholysis of N-(3-nitro-4-hydroxy-5-iodophenylacetyl)-beta-anaylglycylglycyl-modified autologous lymphocytes. Effector cell specificity to modified cell surface components controlled by the H-2K and H-2D serological regions of the murine major histocompatibility complex.
Authors: T G Rehn, G M Shearer, H S Koren, J K Inman
Journal: The Journal of Experimental Medicine (1976)

Splenic lymphocytes from four C57BL/10 congenic mouse strains were sensitized in vitro to N(-3-nitro-4-hydroxy-5-iodophenylacetyl)-beta-alanylglycylglycyl-(N) modified autologous lymphocytes. The effector cells generated after 5 days of culture were assayed on a series of either N-modified phytohemagglutinin-stimulated spleen cells or N-modified tumor cells. The results indicated in all cases that both N modification of the targets and H-2 homology between the modified stimulating and target cells are required for lysis to occur. In each case the effector cells were found to lyse N-modified target cells only when there was homology at either or both ends of the major histocompatibility complex (MHC) between the stimulator and target cells. B10.BR lysed targets sharing alleles at K (or K plus I-A) and/or at D. B10.A effector cell specificity was mapped to K (or K plus I-A) and/or the D half of the MHC (D or D plus I-C and/or S). The two regions of specificity determined for B10.D2 effector cells were D (or D plus S plus I-C) and a region not including D of the MHC. C57BL/10 effector cells lysed N-modified targets only if there was target cell H-2 homology at K, I-A, and I-B or at the D serological region. As in the trinitrophenyl (TNP) system (6) B10.BR and B10.A effector cells lysed targets sharing K end H-2 serological regions greater than target cells sharing D-end serological regions. The C57BL/10 effector cells were shown to react to the K end greater than the D end, which differed from the equal reactivity seen in the TNP system for this strain. The data are consistent with the hypothesis that the antigen recognized by the effector cell includes an altered H-2 serological cell surface product. That the reaction is not "hapten specific" and the H-2 homology is required only for effector:target cell interaction was excluded by the use of two F1 combinations in which lysis of only N-modified target cells sharing the H-2 haplotype with the stimulating parental strain was obtained. Finally, it was demonstrated that N and TNP modification create distinct new antigenic determinants, since an effector cell sensitized to one modifying agent will lyse only H-2 matched target modified with that same modifying agent.
Diversity and evolution of phycobilisomes in marine Synechococcus spp.: a comparative genomics study
Authors: Christophe Six, Jean-Claude Thomas, Laurence Garczarek, Martin Ostrowski, Alexis Dufresne, Nicolas Blot, David J Scanlan, Frédéric Partensky
Journal: Genome biology (2007)

Marine Synechococcus owe their specific vivid color (ranging from blue-green to orange) to their large extrinsic antenna complexes called phycobilisomes, comprising a central allophycocyanin core and rods of variable phycobiliprotein composition. Three major pigment types can be defined depending on the major phycobiliprotein found in the rods (phycocyanin, phycoerythrin I or phycoerythrin II). Among strains containing both phycoerythrins I and II, four subtypes can be distinguished based on the ratio of the two chromophores bound to these phycobiliproteins. Genomes of eleven marine Synechococcus strains recently became available with one to four strains per pigment type or subtype, allowing an unprecedented comparative genomics study of genes involved in phycobilisome metabolism.By carefully comparing the Synechococcus genomes, we have retrieved candidate genes potentially required for the synthesis of phycobiliproteins in each pigment type. This includes linker polypeptides, phycobilin lyases and a number of novel genes of uncharacterized function. Interestingly, strains belonging to a given pigment type have similar phycobilisome gene complements and organization, independent of the core genome phylogeny (as assessed using concatenated ribosomal proteins). While phylogenetic trees based on concatenated allophycocyanin protein sequences are congruent with the latter, those based on phycocyanin and phycoerythrin notably differ and match the Synechococcus pigment types.We conclude that the phycobilisome core has likely evolved together with the core genome, while rods must have evolved independently, possibly by lateral transfer of phycobilisome rod genes or gene clusters between Synechococcus strains, either via viruses or by natural transformation, allowing rapid adaptation to a variety of light niches.
Exendin-4, a glucagon-like peptide 1 receptor agonist, protects cholangiocytes from apoptosis
Authors: M Marzioni, G Alpini, S Saccomanno, C Candelaresi, J Venter, C Rychlicki, G Fava, H Francis, L Trozzi, A Benedetti
Journal: Gut (2008)

<h3>Background and aims:</h3> Progression of chronic cholestatic disorders towards ductopenia results from the dysregulation of cholangiocyte survival, with cell death by apoptosis prevailing over compensatory proliferation. Currently, no therapy is available to sustain cholangiocyte survival in the course of those disorders. It was recently shown that cholangiocytes express the glucagon-like peptide-1 receptor (GLP-1R); its activation results in enhanced proliferative reaction to cholestasis. The GLP-1R selective agonist exendin-4 sustains pancreatic β cell proliferation and prevents cell death by apoptosis. Exendin-4 is now employed in humans as a novel therapy for diabetes. The aim of the present study was to verify whether exendin-4 is effective in preventing cholangiocyte apoptosis. <h3>Methods:</h3> In vitro, tests were carried out to determine if exendin-4 is able to prevent apoptosis of cholangiocytes isolated from normal rats induced by glycochenodeoxycholic acid (GCDCA); in vivo, animals subjected to 1 week of bile duct ligation and to a single intraperitoneal injection of CCl<sub>4</sub> were treated with exendin-4 for 3 days. <h3>Results:</h3> Exendin-4 prevented GCDCA-induced Bax mitochondrial translocation, cytochrome c release and an increase in caspase 3 activity. Phosphatidylinositol 3-kinase, but not cAMP/protein kinase A or Ca<sup>2+</sup>/calmodulin-dependent protein kinase inhibitors, neutralised the effects of exendin-4. In vivo, exendin-4 administration prevented the increase in TUNEL (terminal deoxynucleotidyl transferase-mediated triphosphate end-labelling)-positive cholangiocytes and the loss of bile ducts observed in bile duct-ligated rats treated with CCl<sub>4</sub>. <h3>Conclusion:</h3> Exendin-4 prevents cholangiocyte apoptosis both in vitro and in vivo; such an effect is due to the ability of exendin-4 to counteract the activation of the mitochondrial pathway of apoptosis. These findings support the hypothesis that exendin-4 may be effective in slowing down the progression of cholangiopathies to ductopenia.
Fitness cost of antibiotic susceptibility during bacterial infection
Authors: Damien Roux, Olga Danilchanka, Thomas Guillard, Vincent Cattoir, Hugues Aschard, Yang Fu, Francois Angoulvant, Jonathan Messika, Jean-Damien Ricard, John J. Mekalanos, Stephen Lory, Gerald B. Pier, David Skurnik
Journal: Science Translational Medicine (2015)

The quest to stem antibiotic resistance might be exacerbated by enhanced fitness and virulence displayed by the drug-resistant microbes.
Synergistic Antitumor Effect of the Activated PPARγ and Retinoid Receptors on Human Osteosarcoma
Authors: Bai-Cheng He, Liang Chen, Guo-Wei Zuo, Wenli Zhang, Yang Bi, Jiayi Huang, Yi Wang, Wei Jiang, Qing Luo, Qiong Shi, Bing-Qiang Zhang, Bo Liu, Xia Lei, Jinyong Luo, Xiaoji Luo, Eric R. Wagner, Stephanie H. Kim, Connie J. He, Yawen Hu, Jikun Shen, Qixin Zhou, Farbod Rastegar, Zhong-Liang Deng, Hue H. Luu, Tong-Chuan He, Rex C. Haydon
Journal: Clinical Cancer Research (2010)

Osteosarcoma is the most common primary malignancy of bone. The long-term survival of osteosarcoma patients hinges on our ability to prevent and/or treat recurrent and metastatic lesions. Here, we investigated the activation of peroxisome proliferator-activated receptor gamma (PPARgamma) and retinoid receptors as a means of differentiation therapy for human osteosarcoma.We examined the endogenous expression of PPARgamma and retinoid receptors in a panel of osteosarcoma cells. Ligands or adenovirus-mediated overexpression of these receptors were tested to inhibit proliferation and induce apoptosis of osteosarcoma cells. Osteosarcoma cells overexpressing the receptors were introduced into an orthotopic tumor model. The effect of these ligands on osteoblastic differentiation was further investigated.Endogenous expression of PPARgamma and isotypes of retinoic acid receptor (RAR) and retinoid X receptor (RXR) is detected in most osteosarcoma cells. Troglitazone, 9-cis retinoic acid (RA), and all-trans RA, as well as overexpression of PPARgamma, RARalpha, and RXRalpha, inhibit osteosarcoma cell proliferation and induce apoptosis. A synergistic inhibitory effect on osteosarcoma cell proliferation is observed between troglitazone and retinoids, as well as with the overexpression pairs of PPARgamma/RARalpha, or PPARgamma/RXRalpha. Overexpression of PPARgamma, RARalpha, RXRalpha, or in combinations inhibits osteosarcoma tumor growth and cell proliferation in vivo. Retinoids (and to a lesser extent, troglitazone) are shown to promote osteogenic differentiation of osteosarcoma cells and mesenchymal stem cells.Activation of PPARgamma, RARalpha, and RXRalpha may act synergistically on inhibiting osteosarcoma cell proliferation and tumor growth, which is at least partially mediated by promoting osteoblastic differentiation of osteosarcoma cells.
Metal-catalyzed asymmetric oxidations
Authors: Carsten Bolm
Journal: Medicinal Research Reviews (1999)

Recent advances in enantioselective metal-catalyzed oxidations are presented. Two transformations are discussed in detail: (a) asymmetric Baeyer-Villiger reactions of racemic and prochiral cyclic ketones giving optically active lactones, and (b) sulfide oxidations affording enantiomerically enriched sulfoxides. For both reactions, new metal/ligand combinations have been introduced which allow catalysis of these reactions with high enantioselectivities. For some substrates, the ee-values are above 90%. As previously demonstrated, sulfoxides can be iminated to give the corresponding sulfoximines. Under appropriate reaction conditions, this transformation is stereospecific and enantiopure sulfoximines are obtained. These highly oxidized sulfur reagents have now been modified to give beta-amino acid analogues which may be incorporated into peptides. Two variants have been realized: either the sulfoximine-containing pseudo-amino acids are connected with standard alpha-amino acids to give mixed pseudopeptides, or the sulfoxime units are mutually attached to give homooligomers, which can be regarded as beta-peptide analogues.
Feedback Circuit among INK4 Tumor Suppressors Constrains Human Glioblastoma Development
Authors: Ruprecht Wiedemeyer, Cameron Brennan, Timothy P. Heffernan, Yonghong Xiao, John Mahoney, Alexei Protopopov, Hongwu Zheng, Graham Bignell, Frank Furnari, Webster K. Cavenee, William C. Hahn, Koichi Ichimura, V. Peter Collins, Gerald C. Chu, Michael R. Stratton, Keith L. Ligon, P. Andrew Futreal, Lynda Chin
Journal: Cancer Cell (2008)

We have developed a nonheuristic genome topography scan (GTS) algorithm to characterize the patterns of genomic alterations in human glioblastoma (GBM), identifying frequent p18INK4C and p16INK4A codeletion. Functional reconstitution of p18INK4C in GBM cells null for both p16INK4A and p18INK4C resulted in impaired cell-cycle progression and tumorigenic potential. Conversely, RNAi-mediated depletion of p18INK4C in p16INK4A-deficient primary astrocytes or established GBM cells enhanced tumorigenicity in vitro and in vivo. Furthermore, acute suppression of p16INK4A in primary astrocytes induced a concomitant increase in p18INK4C. Together, these findings uncover a feedback regulatory circuit in the astrocytic lineage and demonstrate a bona fide tumor suppressor role for p18INK4C in human GBM wherein it functions cooperatively with other INK4 family members to constrain inappropriate proliferation.
Polyethylene Glycol–Derivatized Cysteine-Substitution Variants of Recombinant Staphylokinase for Single-Bolus Treatment of Acute Myocardial Infarction
Authors: Désiré Collen, Peter Sinnaeve, Eddy Demarsin, Huberte Moreau, Marc De Maeyer, Laurent Jespers, Yves Laroche, Frans Van de Werf
Journal: Circulation (2000)

Background —Thrombolytic therapy of acute myocardial infarction (AMI) is evolving toward bolus administration. Derivatization of proteins with polyethylene glycol (PEG) may reduce their clearance. Methods and Results —A staphylokinase (SakSTAR) variant with 12 amino acid substitutions to reduce its antigenicity, SakSTAR (K35A, E65Q, K74R, E80A, D82A, T90A, E99D, T101S, E108A, K109A, K130T, K135R), and with Ser in position 3 mutated into Cys (code SY161), was derivatized with maleimide-PEG with M r of 5000 (P5), 10 000 (P10), or 20 000 (P20). The PEGylated variants recognized only one third of the antibodies elicited with wild-type SakSTAR in AMI patients. In experimental animals, plasma clearances were reduced 2.5- to 5-fold with P5, 5- to 20-fold with P10, and 20-fold with P20, and bolus injection induced pulmonary plasma clot lysis at doses inversely related to their clearance. Intravenous bolus injection of 5 mg of the P5, P10, or P20 variants in AMI patients was associated with plasma half-lives (t 1/2α ) of 13, 30, and 120 minutes and clearances of 75, 43, and 8 mL/min, respectively, compared with 3 minutes and 360 mL/min for SakSTAR. Injection of 5 mg P5 variant restored TIMI-3 flow within 60 minutes in 14 of 18 AMI patients (78%, 95% CI 55% to 91%) and of 2.5 mg in 7 of 11 patients (63%, 95% CI 35% to 85%), both in the absence of fibrinogen degradation. The immunogenicity of the variants was significantly ( P &lt;0.002) reduced. Conclusions —The staphylokinase variant SY161-P5, derivatized with one linear polyethylene glycol molecule of M r 5000, is a promising fibrin-selective agent for single-bolus coronary thrombolysis.
The effect of eccentric and concentric loading speed on the normal achilles tendon: an in vivo biomechanical study
Authors: E Sweeney, S Chaudhury, H Screen, R Woledge, D Bader, N Maffulli, D Morrissey
Journal: British Journal of Sports Medicine (2011)

Background Tendinopathy is a common and disabling condition that can end an athlete's career. Eccentric loading has proven to be an effective treatment measure for tendinopathy. However, current evidence is unclear regarding the optimum speed for eccentric loading. Objectives To compare the effects of two different speeds of eccentric and concentric loading on Achilles tendon force and muscle activation in healthy volunteers. Methods Nine healthy volunteers (4 male, 5 female, age range 19–24) performed eccentric and concentric heel raises/drops at two speeds, in a random order. Motion analysis, force plate and electromyography (EMG) data were collected in order to measure Achilles tendon force and muscle activation. Results The effect of speed on Achilles tendon force was not significant (p=0.74) but the effect of contraction type was significant (p&lt;0.05). There was a significant difference between eccentric and concentric loading on EMG output for gastrocnemius medialis, lateralis and soleus (p&lt;0.001 for all) but there was no significant effect of speed (p=0.05, 0.32, 0.06 respectively). For tibialis anterior and fibularis longus there was a significant effect of speed on EMG (p&lt;0.001 for both) but not of contraction type (p=0.10, 0.30 respectively). Conclusion There is no effect of speed on Achilles tendon force and the effect of speed on EMG activity is only significant for tibialis anterior and fibularis longus, therefore mechanical challenges to the tendon that are speed dependent are not likely to be due to force magnitude. The differential effects on muscle training may be significant. Further studies in patients are warranted.
Introduction of Solutions of Lead into the Bladder, for the Decomposition of Phosphatic Calculi
Authors: S. E. Hoskins
Journal: BMJ (1851)

IN a paper which the Royal Society did me the honour of publishing,2 some account was given of the decomposition of Phosphatic Calculi, by solutions of certain salts of lead, so dilute as to admit of their reten.tion by the living bladder, without irritation or inconvenience.The adaptation of the principle of double decomposition to the dis- integration of vesical calculus, is in strict accordance with chemical usage: it supplies a class of agents, more energetic as regards the concretion, and less injurious to the organ in which it is contained, than any of the uncombined solvents hitherto employed.The solvent, no matter how dilute, can only be tolerated for a minute or two at I Des Tumeurs Synoviales de la Partie Tnferieure de l'Avant-Bras, de Li Face Palmpire din Poignet et de la Mdain.These presentke an coneouy poxu ue