tbuckley/cabot-search huggingface dataset:
A human mannose-binding protein is an acute-phase reactant that shares sequence homology with other vertebrate lectins.
Authors: R A Ezekowitz, L E Day, G A Herman
Journal: The Journal of Experimental Medicine (1988)

Mannose-binding proteins have been isolated from the liver of rats and humans and subsequently been found in the serum of rats, rabbits, and humans. We report the isolation of cDNA clones isolated from a human liver cDNA library that encodes a human mannose-binding protein. The primary structure has three domains: (a) an NH2-terminal cysteine-rich segment of 19 amino acids which appears to be involved in the formation of interchain disulfide bonds that would stabilize multimeric forms of the protein; (b) a collagen-like region consisting of 19 repeats of the sequence Gly-x-y; and (c) a COOH-terminal putative carbohydrate-binding domain consisting of 148 residues. This human mannose-binding protein bears 51% overall homology (allowing three gaps) with a rat mannose-binding protein C and 48% homology (allowing seven gaps) with a rat mannose-binding protein A. Like these homologous rat proteins, the human mannose-binding protein COOH-terminal sequences are homologous to the carbohydrate recognition portion of several other lectin-like proteins including mammalian hepatic receptors, an insect-soluble hemolymph, and a sea urchin lectin found in coelomic fluid. The apoproteins of dog and human surfactant and the human lymphocyte IgE Ec receptor have not been shown to have lectin-like properties, yet by homology are members of this family of lectin-like proteins. The human mannose-binding protein is preceded by a typical hydrophobic signal sequence and its hepatic secretion is induced as part of the acute-phase response consistent with its probable role in host defense.
Nanobodies Targeting Mouse/Human VCAM1 for the Nuclear Imaging of Atherosclerotic Lesions
Authors: Alexis Broisat, Sophie Hernot, Jakub Toczek, Jens De Vos, Laurent M. Riou, Sandrine Martin, Mitra Ahmadi, Nicole Thielens, Ulrich Wernery, Vicky Caveliers, Serge Muyldermans, Tony Lahoutte, Daniel Fagret, Catherine Ghezzi, Nick Devoogdt
Journal: Circulation Research (2012)

A noninvasive tool allowing the detection of vulnerable atherosclerotic plaques is highly needed. By combining nanomolar affinities and fast blood clearance, nanobodies represent potential radiotracers for cardiovascular molecular imaging. Vascular cell adhesion molecule-1 (VCAM1) constitutes a relevant target for molecular imaging of atherosclerotic lesions.We aimed to generate, radiolabel, and evaluate anti-VCAM1 nanobodies for noninvasive detection of atherosclerotic lesions.Ten anti-VCAM1 nanobodies were generated, radiolabeled with technetium-99m, and screened in vitro on mouse and human recombinant VCAM1 proteins and endothelial cells and in vivo in apolipoprotein E-deficient (ApoE(-/-)) mice. A nontargeting control nanobody was used in all experiments to demonstrate specificity. All nanobodies displayed nanomolar affinities for murine VCAM1. Flow cytometry analyses using human human umbilical vein endothelial cells indicated murine and human VCAM1 cross-reactivity for 6 of 10 nanobodies. The lead compound cAbVCAM1-5 was cross-reactive for human VCAM1 and exhibited high lesion-to-control (4.95±0.85), lesion-to-heart (8.30±1.11), and lesion-to-blood ratios (4.32±0.48) (P<0.05 versus control C57Bl/6J mice). Aortic arch atherosclerotic lesions of ApoE(-/-) mice were successfully identified by single-photon emission computed tomography imaging. (99m)Tc-cAbVCAM1-5 binding specificity was demonstrated by in vivo competition experiments. Autoradiography and immunohistochemistry further confirmed cAbVCAM1-5 uptake in VCAM1-positive lesions.The (99m)Tc-labeled, anti-VCAM1 nanobody cAbVCAM1-5 allowed noninvasive detection of VCAM1 expression and displayed mouse and human cross-reactivity. Therefore, this study demonstrates the potential of nanobodies as a new class of radiotracers for cardiovascular applications. The nanobody technology might evolve into an important research tool for targeted imaging of atherosclerotic lesions and has the potential for fast clinical translation.
A Comparison of High-Dose and Standard-Dose Epinephrine in Children with Cardiac Arrest
Authors: Maria Beatriz M. Perondi, Amelia G. Reis, Edison F. Paiva, Vinay M. Nadkarni, Robert A. Berg
Journal: New England Journal of Medicine (2004)

When efforts to resuscitate a child after cardiac arrest are unsuccessful despite the administration of an initial dose of epinephrine, it is unclear whether the next dose of epinephrine (i.e., the rescue dose) should be the same (standard) dose or a higher dose.We performed a prospective, randomized, double-blind trial to compare high-dose epinephrine (0.1 mg per kilogram of body weight) with standard-dose epinephrine (0.01 mg per kilogram) as rescue therapy for in-hospital cardiac arrest in children after failure of an initial, standard dose of epinephrine. The trial included 68 children, and Utstein-style reporting guidelines were used. The primary outcome measure was survival 24 hours after the arrest.The rate of survival at 24 hours was lower in the group assigned to a high dose of epinephrine as rescue therapy than in the group assigned to a standard dose: 1 of the 34 patients in the high-dose group survived for 24 hours, as compared with 7 of the 34 patients in the standard-dose group (unadjusted odds ratio for death with the high dose, 8.6; 97.5 percent confidence interval, 1.0 to 397.0; P=0.05). After adjustment by multiple logistic-regression analysis for differences in the groups at the time of arrest, the high-dose group tended to have a lower 24-hour survival rate (odds ratio for death, 7.9; 97.5 percent confidence interval, 0.9 to 72.5; P=0.08). The two treatment groups did not differ significantly in terms of the rate of return of spontaneous circulation (which occurred in 20 patients in the high-dose group and 21 of those in the standard-dose group; odds ratio, 1.1; 97.5 percent confidence interval, 0.4 to 3.0). None of the patients in the high-dose group, as compared with four of those in the standard-dose group, survived to hospital discharge. Among the 30 patients whose cardiac arrest was precipitated by asphyxia, none of the 12 who were assigned to high-dose epinephrine were alive at 24 hours, as compared with 7 of the 18 who were assigned to a standard dose (P=0.02).We did not find any benefit of high-dose epinephrine rescue therapy for in-hospital cardiac arrest in children after failure of an initial standard dose of epinephrine. The data suggest that high-dose therapy may be worse than standard-dose therapy.
Transcranial Doppler to detect on admission patients at risk for neurological deterioration following mild and moderate brain trauma
Authors: Paul Jaffres, Julien Brun, Philippe Declety, Jean-Luc Bosson, Bertrand Fauvage, Almuth Schleiermacher, Affif Kaddour, Daniel Anglade, Claude Jacquot, Jean-Francois Payen
Journal: Intensive Care Medicine (2005)
Sexual dimorphism in the osteoarthritis of STR/ort mice may be linked to articular cytokines
Authors: S Mahr
Journal: Annals of the Rheumatic Diseases (2003)

STR/ort mice spontaneously develop degenerative changes of the knee joints resembling human osteoarthritis (OA), with the males being more severely affected than the females.To analyse the early changes leading to OA by examining the articular cytokine expression and degenerative changes in STR/ort mice.122 STR/ort mice of both sexes aged between 2 and 15.5 months were included. Thin sections of the knees were analysed for osteoarthritic changes by haematoxylin/eosin staining. The articular cytokine expression was investigated by immunohistochemical staining using monoclonal antibodies specific for interleukin (IL)6, tumour necrosis factor alpha, transforming growth factor beta1 (TGFbeta1), IL1beta, IL4, and IL10, respectively.Both cartilage degeneration and articular cytokine expression differ between the sexes. The protection from cartilage degeneration in the female mice correlates with an increased expression of TGFbeta1 and IL4 at 2 months of age.The increased expression of TGFbeta1 and IL4 in young STR/ort female mice suggests that the sexual dimorphism is mediated through the articular expression of cytokines involved in cartilage metabolism.
Tregs in T cell vaccination: exploring the regulation of regulation
Authors: Irun R. Cohen, Francisco J. Quintana, Avishai Mimran
Journal: Journal of Clinical Investigation (2004)

T cell vaccination (TCV) activates Tregs of 2 kinds: anti-idiotypic (anti-id) and anti-ergotypic (anti-erg). These regulators furnish a useful view of the physiology of T cell regulation of the immune response. Anti-id Tregs recognize specific effector clones by their unique TCR CDR3 peptides; anti-id networks of CD4+ and CD8+ Tregs have been described in detail. Here we shall focus on anti-erg T regulators. Anti-erg T cells, unlike anti-id T cells, do not recognize the clonal identity of effector T cells; rather, anti-erg T cells recognize the state of activation of target effector T cells, irrespective of their TCR specificity. We consider several features of anti-erg T cells: their ontogeny, subset markers, and target ergotope molecules; mechanisms by which they regulate other T cells; mechanisms by which they get regulated; and therapeutic prospects for anti-erg upregulation and downregulation.
Inactivation of factor XII active fragment in normal plasma. Predominant role of C-1-inhibitor.
Authors: A de Agostini, H R Lijnen, R A Pixley, R W Colman, M Schapira
Journal: Journal of Clinical Investigation (1984)

To define the factors responsible for the inactivation of the active fragment derived from Factor XII (Factor XIIf ) in plasma, we studied the inactivation kinetics of Factor XIIf in various purified and plasma mixtures. We also analyzed the formation of 125I-Factor XIIf -inhibitor complexes by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE). In purified systems, the bimolecular rate constants for the reactions of Factor XIIf with C-1-inhibitor, alpha 2-antiplasmin, and antithrombin III were 18.5, 0.91, and 0.32 X 10(4) M-1 min-1, respectively. Furthermore, SDS-PAGE analysis revealed that 1:1 stoichiometric complexes were formed between 125I-Factor XIIf and each of these three inhibitors. In contrast, kinetic and SDS-PAGE studies indicated that Factor XIIf did not react with alpha 1-antitrypsin or alpha 2-macroglobulin. The inactivation rate constant of Factor XIIf by prekallikrein-deficient plasma was 14.4 X 10(-2) min-1, a value that was essentially identical to the value predicted from the studies in purified systems (15.5 X 10(-2) min-1). This constant was reduced to 1.8 X 10(-2) min-1 when Factor XIIf was inactivated by prekallikrein-deficient plasma that had been immunodepleted (less than 5%) of C-1-inhibitor. In addition, after inactivation in normal plasma, 74% of the active 125I-Factor XIIf was found to form a complex with C-1-inhibitor, whereas 26% of the enzyme formed complexes with alpha 2-antiplasmin and antithrombin III. Furthermore, 42% of the labeled enzyme was still complexed with C-1-inhibitor when 125I-Factor XII was inactivated in hereditary angioedema plasma that contained 32% of functional C-1-inhibitor. This study quantitatively demonstrates the dominant role of C-1-inhibitor in the inactivation of Factor XIIf in the plasma milieu.
Cardiospecificity of ( -receptor blockade: A comparison of the relative potencies on cardiac and peripheral vascular ( -adrenoceptors of propranolol, of practolol and its ortho-substituted isomer, and of oxprenolol and its para-substituted isomer
Authors: E. M. V. WILLIAMS, E. E. BAGWELL, B. N. SINGH
Journal: Cardiovascular Research (1973)

An attempt has been made to compare quantitatively the relative potencies of various compounds in blocking the effects of isoprenaline on peripheral blood flow and on heart rate. In anaesthetized dogs a cuff flow probe was placed around the descending aorta, and the inferior mesenteric artery was cannulated in a retrograde direction. Two to three-fold increases in peripheral blood flow conductance were produced by intra-arterial injections of isoprenaline so small that they had little effect on heart rate. Effects of larger intravenous doses of isoprenaline on heart rate were then measured, so that dose response curves for the peripheral and cardiac effects of isoprenaline were obtained in the same dog. Practolol blocked peripheral β-receptors to some extent, but was eight times more potent on the heart. Transference of the acetamide substituent from the para to the ortho position on the ring led to a loss of cardiospecificity. Conversely, the para-substituted isomer of oxprenolol was totally cardiospecific. It had the same potency as oxprenolol on the heart, but did not block the effects of isoprenaline on blood flow at all. Oxprenolol itself, and propranolol, were more potent in blocking peripheral than cardiac β-receptors.
Infection Risk with Bolus versus Maintenance Iron Supplementation in Hemodialysis Patients
Authors: M. Alan Brookhart, Janet K. Freburger, Alan R. Ellis, Lily Wang, Wolfgang C. Winkelmayer, Abhijit V. Kshirsagar
Journal: Journal of the American Society of Nephrology (2013)

Intravenous iron may promote bacterial growth and impair host defense, but the risk of infection associated with iron supplementation is not well defined. We conducted a retrospective cohort study of hemodialysis patients to compare the safety of bolus dosing, which provides a large amount of iron over a short period of time on an as-needed basis, with maintenance dosing, which provides smaller amounts of iron on a regular schedule to maintain iron repletion. Using clinical data from 117,050 patients of a large US dialysis provider merged with data from Medicare's ESRD program, we estimated the effects of iron dosing patterns during repeated 1-month exposure periods on risks of mortality and infection-related hospitalizations during the subsequent 3 months. Of 776,203 exposure/follow-up pairs, 13% involved bolus dosing, 49% involved maintenance dosing, and 38% did not include exposure to iron. Multivariable additive risk models found that patients receiving bolus versus maintenance iron were at increased risk of infection-related hospitalization (risk difference [RD], 25 additional events/1000 patient-years; 95% confidence interval [CI], 16 to 33) during follow-up. Risks were largest among patients with a catheter (RD, 73 events/1000 patient-years; 95% CI, 48 to 99) and a recent infection (RD, 57 events/1000 patient-years; 95% CI, 19 to 99). We also observed an association between bolus dosing and infection-related mortality. Compared with no iron, maintenance dosing did not associate with increased risks for adverse outcomes. These results suggest that maintenance iron supplementation may result in fewer infections than bolus dosing, particularly among patients with a catheter.
Plasma gaba, gaba-like activity and the brain gaba-benzodiazepine receptor complex in rats with chronic hepatic encephalopathy
Authors: Jill E. Maddison, Peter R. Dodd, Murray Morrison, Graham A. R. Johnston, Geoffrey C. Farrell
Journal: Hepatology (1987)

Plasma γ-aminobutyric acid (GABA)-like activity, plasma GABA and the brain GABA-benzodiazepine receptor complex were studied in rats with chronic hepatic encephalopathy. Portal vein ligation (after prior subcutaneous transposition of the spleen) results in complete portal bypass of splanchnic blood. In addition, significant hepatocellular damage was superimposed on this model of portosystemic shunting by ligation of the common bile duct. Plasma GABA-like activity (determined by radioreceptor assay) and true plasma GABA concentrations (determined by high-performance liquid chromatography) were found to be significantly increased in both portal vein-ligated and portal vein and bile duct-ligated rats, compared with controls. However, plasma GABA-like activity was consistently greater than the concentration of true GABA in the plasma of all rats. This suggested the presence of a GABA-like factor in plasma that can inhibit [ 3 H]GABA binding, but is not GABA itself. The concentration of this GABA-like factor was significantly increased in the plasma of rats with chronic hepatic encephalopathy Despite the significant increase in plasma GABA-like activity and plasma GABA concentrations, there was no alteration in the affinity or density of the physiologically relevant, low-affinity brain GABA binding site in the rats with portal vein ligation, with or without bile duct ligation. There was also no significant alteration in brain benzodiazepine binding in these rats. GABA enhancement of benzodiazepine binding was unchanged in the portal vein-ligated rats. However, the maximal enhancement of benzodiazepine binding was decreased in the rats with portal vein and bile duct ligation. There appears to be no substantial evidence that brain GABAergic neurotransmission is increased in these models of chronic hepatic encephalopathy.
Mutations in a human homologue of Drosophila crumbs cause retinitis pigmentosa (RP12)
Authors: Anneke I. den Hollander, Jacoline B. ten Brink, Yvette J.M. de Kok, Simone van Soest, L. Ingeborgh van den Born, Marc A. van Driel, Dorien J.R. van de Pol, Annette M. Payne, Shomi S. Bhattacharya, Ulrich Kellner, Carel B. Hoyng, Andries Westerveld, Han G. Brunner, Elisabeth M. Bleeker-Wagemakers, August F. Deutman, John R. Heckenlively, Frans P.M. Cremers, Arthur A.B. Bergen
Journal: Nature Genetics (1999)
Classic reaction kinetics can explain complex patterns of antibiotic action
Authors: Pia Abel zur Wiesch, Sören Abel, Spyridon Gkotzis, Paolo Ocampo, Jan Engelstädter, Trevor Hinkley, Carsten Magnus, Matthew K. Waldor, Klas Udekwu, Ted Cohen
Journal: Science Translational Medicine (2015)

Chemical reaction kinetics explain three different effects of drug-mediated bacterial killing.
The Paneth cell: a source of intestinal lysozyme.
Authors: T Peeters, G Vantrappen
Journal: Gut (1975)

An antiserum prepared against lysozyme isolated from mucosal scrapings of mouse small intestine was used to stain sections of mouse small intestine with the indirect fluorescent antibody technique. Mucosal fluorescence was confined to the base of the crypts of Lieberkuhn, where Paneth cells are located. After the intravenous administration of 4 mg of pilocarpine fluorescence was no longer found in the Paneth cell but in the crypt lumen. Perfusion studies confirmed these findings. The basal lysozyme output of 0-1 to 0-4 mug/ml was raised to peak rates of 1-8 to 6-5 mug/ml after the intravenous administration of 1 mg of pilocarpine. Our results demonstrate that the lysozyme of the succus entericus is, at least in part, derived from the Paneth cell, and is probably present in the Paneth cell granules. Its secretion is stimulated by pilocarpine. Our model could be very useful for studying the function of the Paneth cell, which probably forms part of an intestinal defence system.
AN INFECTIOUS GRANULAR VAGINITIS OF COWS
Authors: F. S. Jones, Ralph B. Little
Journal: The Journal of Experimental Medicine (1927)

A disease of cows characterized by swelling of the vulva, acute inflammation of the vaginal mucosa, accompanied by a more or less profuse mucopurulent exudate is described. After the acute inflammation subsides the mucosa becomes studded with tiny, round, raised, red nodules which persist 2 or 3 months or longer. The acute lesion consists in necrosis of the epithelium and accumulations of leucocytes and round cells in the edematous submucosa. The nodules in the later stages are made up of densely packed masses of lymphocytes in the submucosa which force the epithelial layer outward. A Gram-negative bacillus with tiny polar granules was found in the exudate. It measures I to 2micro in length and stains with difficulty. The organism was obtained in pure culture by inoculating the exudate into tubes of slanted agar to which defibrinated horse blood had been added. Growth occurs only in sealed tubes. The organism possesses slight pathogenicity for guinea pigs. When freshly isolated cultures were introduced into the vagina of heifers or young calves, acute inflammation resulted which terminated in the characteristic granular stage of the disease.
The presence, role and clinical use of spermatozoal RNAs
Authors: Meritxell Jodar, Sellappan Selvaraju, Edward Sendler, Michael P. Diamond, Stephen A. Krawetz
Journal: Human Reproduction Update (2013)

BACKGROUND Spermatozoa are highly differentiated, transcriptionally inert cells characterized by a compact nucleus with minimal cytoplasm. Nevertheless they contain a suite of unique RNAs that are delivered to oocyte upon fertilization. They are likely integrated as part of many different processes including genome recognition, consolidation-confrontation, early embryonic development and epigenetic transgenerational inherence. Spermatozoal RNAs also provide a window into the developmental history of each sperm thereby providing biomarkers of fertility and pregnancy outcome which are being intensely studied. METHODS Literature searches were performed to review the majority of spermatozoal RNA studies that described potential functions and clinical applications with emphasis on Next-Generation Sequencing. Human, mouse, bovine and stallion were compared as their distribution and composition of spermatozoal RNAs, using these techniques, have been described. RESULTS Comparisons highlighted the complexity of the population of spermatozoal RNAs that comprises rRNA, mRNA and both large and small non-coding RNAs. RNA-seq analysis has revealed that only a fraction of the larger RNAs retain their structure. While rRNAs are the most abundant and are highly fragmented, ensuring a translationally quiescent state, other RNAs including some mRNAs retain their functional potential, thereby increasing the opportunity for regulatory interactions. Abundant small non-coding RNAs retained in spermatozoa include miRNAs and piRNAs. Some, like miR-34c are essential to the early embryo development required for the first cellular division. Others like the piRNAs are likely part of the genomic dance of confrontation and consolidation. Other non-coding spermatozoal RNAs include transposable elements, annotated lnc-RNAs, intronic retained elements, exonic elements, chromatin-associated RNAs, small-nuclear ILF3/NF30 associated RNAs, quiescent RNAs, mse-tRNAs and YRNAs. Some non-coding RNAs are known to act as epigenetic modifiers, inducing histone modifications and DNA methylation, perhaps playing a role in transgenerational epigenetic inherence. Transcript profiling holds considerable potential for the discovery of fertility biomarkers for both agriculture and human medicine. Comparing the differential RNA profiles of infertile and fertile individuals as well as assessing species similarities, should resolve the regulatory pathways contributing to male factor infertility. CONCLUSIONS Dad delivers a complex population of RNAs to the oocyte at fertilization that likely influences fertilization, embryo development, the phenotype of the offspring and possibly future generations. Development is continuing on the use of spermatozoal RNA profiles as phenotypic markers of male factor status for use as clinical diagnostics of the father's contribution to the birth of a healthy child.