RSSEffects of peptides lys-glu-asp-gly and ala-glu-asp-gly on hormonal activity and structure of the thyroid gland in hypophysectomized young chickens and old hens.
Source
Chita State Medical Academy, Russia. bi_kuznik@mail.ru.
Abstract
Hypophysectomy in 5-days chickens and old hens was followed by hormonal disturbances and structural changes in the thyroid gland. Administration of peptides Lys-Glu-Asp-Gly and Ala-Glu-Asp-Gly synthesized on the basis the amino acid composition of extracts from the anterior and posterior lobes of the pituitary gland, respectively, to hypophysectomized birds for 40 days significantly reduced the degree of these changes. The normalizing effect of synthetic peptides on the concentration of thyrotrophic hormone and thyroid hormones in old hens was less pronounced than in chickens.
- PMID:
- 22268052
- [PubMed - in process]
Changes in feeding behavior after peripheral loperamide administration in rats.
Source
Laboratory of Physiology of Reinforcement, P. K. Anokhin Institute of Normal Physiology, Russian Academy of Medical Sciences, Moscow, Russia. s-sudakov@mail.ru.
Abstract
Changes in the parameters of operant feeding behavior and body weight were studied in rats after intragastric administration of μ-opioid receptor agonist loperamide. Loperamide administration significantly suppressed foraging behavior in rats and reduced their body weight. Our findings suggest that peripheral loperamide administration, according to the hypothesis of reciprocal interactions between the central and peripheral parts of the endogenous opioid system, suppresses activity of central opioid mechanisms of feeding behavior organization. Changes in feeding behavior can appear due to disturbances in the mechanisms of assessment of food reward. We hypothesized that natural activation of μ-opioid receptors of the stomach with food-derived peptides can be associated with "sensory satiation" mechanism limiting excessive food intake.
- PMID:
- 22268026
- [PubMed - in process]
Tyrosines in the Carboxy-terminus of Syk once Phosphorylated Interact with Signaling Proteins including TULA-2, a Negative Regulator of Mast Cell Degranulation.
Source
NIDCR, United States.
Abstract
Activation of the high affinity IgE receptor (FcεRI) results in the tyrosine phosphorylation of two conserved tyrosines located close to the carboxy terminus of the protein tyrosine kinase Syk. Synthetic peptides representing the last ten amino acids of the tail of Syk with these two tyrosines either nonphosphorylated or phosphorylated were used to precipitate proteins from mast cell lysates. Proteins specifically precipitated by the phosphorylated peptide were identified by mass spectrometry. These included the adaptor proteins SLP-76, Nck-1, Grb2 and GADS and the proteins phosphatases SHIP-1 and UBASH3B (also known as TULA-2). The presence of these in the precipitates was further confirmed by immunoblotting. Using the peptides as probes in far westerns showed direct binding of the phosphorylated peptide to Nck-1 and SHIP-1. Immunoprecipitations suggested that there were complexes of these proteins associated with Syk especially after receptor activation; in these complexes are Nck, SHIP-1, SLP-76, Grb2 and TULA-2 (UBASH3B or STS-1). The decreased expression of TULA-2 by treatment of mast cells with siRNA increased the FcεRI-induced tyrosine phosphorylation of the activation loop tyrosines of Syk and the phosphorylation of phospholipase C-2γ. There was parallel enhancement of the receptor-induced degranulation and NFAT or NFκB activation indicating that TULA-2 like SHIP-1 functions as a negative regulator of FcεRI signaling in mast cells. Therefore the terminal tyrosines of Syk once phosphorylated bind complexes of proteins that are positive and negative regulators of signaling in mast cells.
Phosphorylation of the amyloid-β peptide at serine 8 attenuates its clearance via insulin degrading and angiotensin converting enzymes.
Source
University of Bonn, Germany;
Abstract
Accumulation of amyloid β-peptides (Aβ) in the brain is a common pathological feature of Alzheimer's disease (AD). Aggregates of Aβ are neurotoxic and appear to be critically involved in the neurodegeneration during AD pathogenesis. Accumulation of Aβ could be caused by increased production as indicated by several mutations in the amyloid precursor protein or the γ-secretase components presenilin-1 or -2 that cause familial early onset AD. However, recent data also indicate a decreased clearance rate of Aβ in AD brains. We recently demonstrated that Aβ undergoes phosphorylation by extracellular or cell surface localized protein kinase A, leading to increased aggregation. Here we provide evidence that phosphorylation of monomeric Aβ at serine residue 8 also decreases its clearance by microglial cells. By using mass spectrometry, we demonstrate that phosphorylation at serine 8 inhibits the proteolytic degradation of monomeric Aβ by the insulin degrading enzyme (IDE), a major Aβ degrading enzyme released from microglial cells. Phosphorylation also decreased the degradation of Aβ by the angiotensin converting enzyme (ACE). In contrast, Aβ degradation by plasmin was largely unaffected by phosphorylation. Thus, phosphorylation of Aβ could play a dual role in Aβ metabolism. It decreases its proteolytic clearance and also promotes its aggregation. The inhibition of extracellular Aβ phosphorylation, stimulation of cell-surface protease expression and/or increasing their activity could be explored to promote Aβ degradation in AD therapy or prevention.
Pyroglutamate A(beta) aggravates behavioral deficits in 5XFAD mice.
Source
University of Goettingen, Germany;
Abstract
Pyroglutamate-modified Abeta peptides at amino acid position three (AβpE3-42) are gaining considerable attention as potential key players in the pathogenesis of Alzheimer disease (AD). AβpE3-42 is abundant in AD brain and has a high aggregation propensity, stability and cellular toxicity. The aim of the present work was to study the direct effect of elevated AβpE3-42 levels on ongoing AD pathology using transgenic mouse models. To this end, we generated a novel mouse model (TBA42) that produces AβpE3-42. TBA42 mice showed age-dependent behavioral deficits and AβpE3-42- accumulation. The Aβ profile of an established AD mouse model, 5XFAD, was characterized using immunoprecipitation followed by mass spectrometry. Brains from 5XFAD mice demonstrated a heterogeneous mixture of full-length, N-truncated and modified Aβ peptides: Aβ1-42, Aβ1-40, AβpE3-40, AβpE3-42, Aβ3-42, Aβ4-42 and Aβ5-42. 5XFAD and TBA42 mice were then crossed to generate bigenic FAD42 mice. At six months of age, FAD42 mice showed an aggravated behavioral phenotype compared to single transgenic 5XFAD or TBA42 mice. ELISA and plaque load measurements revealed that AβpE3 levels were elevated in FAD42 mice. No change in Aβx-42 or other Aβ isoforms was discovered by ELISA and mass spectrometry. These observations argue for a seeding effect of AβpE-42 in FAD42 mice.
Novel myeloma-associated antigens revealed in the context of syngeneic hematopoietic stem cell transplantation.
Source
Cancer Vaccine Center, Dana-Farber Cancer Institute, Boston, MA, United States;
Abstract
Targets of curative donor-derived graft-versus-myeloma (GvM) responses following allogeneic hematopoietic stem cell transplantation (HSCT) remain poorly defined, partly because immunity against minor histocompatibility antigens (mHAgs) complicates the elucidation of multiple myeloma (MM)-specific targets. We hypothesized that syngeneic HSCT would facilitate the identification of GvM-associated antigens since donor immune responses in this setting should exclusively target unique tumor antigens in the absence of donor-host genetic disparities. We therefore studied the development of tumor immunity in an HLA-A0201+ MM patient who achieved durable remission after myeloablative syngeneic HSCT. Using high-density protein microarrays to screen post-HSCT plasma, we identified six antigens that elicited high-titer (1:5,000-1:10,000) antibodies that correlated with clinical tumor regression. Two antigens (DAPK2, PIM1) had enriched expression in primary MM tissues. Both elicited antibody responses in other MM patients following chemotherapy or HSCT (11 and 6 of 32 patients for DAPK2 and PIM1, respectively). The index patient also developed specific CD8+ T cell responses to HLA-A2 restricted peptides derived from DAPK2 and PIM1. Peptide-specific T cells recognized HLA-A2+ MM-derived cell lines and primary MM tumor cells. Coordinated T and B cell immunity develops against MM-associated antigens following syngeneic HSCT. DAPK1 and PIM1 are promising target antigens for MM-directed immunotherapy.
Bacillus subtilis RapA phosphatase domain interaction with its substrate Spo0F~P and inhibitor PhrA peptide.
Source
The Scripps Research Institute, Department of Molecular and Experimental Medicine, 10550 North Torrey Pines Road, MEM-116, La Jolla, CA 92037.
Abstract
Rap proteins in Bacillus subtilis regulate the phosphorylation level or the DNA-binding activity of response regulators such as Spo0F, involved in sporulation initiation, or ComA, regulating competence development. Rap proteins can be inhibited by specific peptides generated by the export-import processing pathway of the Phr proteins. Rap proteins have a modular organization comprising an amino terminal alpha-helical domain connected to a domain formed by six tetratricopeptide (TPR) repeats. In this study, the molecular basis for the specificity of the RapA phosphatase for its substrate Spo0F∼P and its inhibitor pentapeptide PhrA was analyzed in part by generating chimeric proteins with RapC that targets the DNA-binding domain of ComA, rather than Spo0F∼P, and is inhibited by the PhrC pentapeptide. In vivo analysis of sporulation efficiency or competence-induced gene expression as well as in vitro biochemical assays allowed the identification of the amino terminal sixty amino acids as sufficient to determine Rap specificity for its substrate and the central TPR3-5 repeats as providing binding specificity toward the Phr peptide inhibitor. The results allowed the prediction and testing of key residues in RapA that are essential for PhrA binding and specificity, thus demonstrating how the widespread structural fold of the TPR repeat is highly versatile to use a common interaction mechanism for a variety of functions in eukaryotic and prokaryotic organisms.
Perturbing the oxidizing environment of the periplasm stimulates the PhoQ/PhoP system in E. coli.
Source
Department of Biology, University of Pennsylvania, 433 S. University Ave Philadelphia, PA 19104-6018.
Abstract
The PhoQ/PhoP two-component system is repressed by divalent cations such as Mg(2+) and Ca(2+) in the growth medium and stimulated by low pH, and certain cationic antimicrobial peptides. In E. coli, it has recently been shown that the histidine kinase PhoQ is also modulated by at least two additional factors, the small membrane proteins SafA and MgrB. This raises the possibility that the PhoQ/PhoP circuit has additional regulatory components and integrates additional input signals. We screened E. coli transposon insertion mutants to look for proteins that modulate the activity of the PhoQ/PhoP system and uncovered a role for DsbA, a periplasmic oxidant that facilitates the formation of disulfide bonds. Deletion of dsbA or dsbB, which maintains a pool of oxidized DsbA, leads to increased transcription of at least two PhoP-regulated genes. Addition of the reducing agent DTT to wild-type cells has a similar effect and treatment of a dsbA null strain with the oxidant Cu(2+)rescues the reporter gene expression phenotype. We also demonstrate that expression of an MgrB mutant that lacks cysteines blocks the effect of a dsbA null mutation on PhoQ/PhoP activity, suggesting that MgrB acts downstream of DsbA in this pathway. Taken together, these results demonstrate that a decrease in the oxidizing activity of the periplasm stimulates PhoQ/PhoP and may reveal a new input stimulus for this important two-component system.
Chemical Biology Approaches Reveal Conserved Features of a C-Terminal Processing PDZ Protease.
Source
Centre for Medical Biotechnology, Faculty of Biology, University Duisburg-Essen, Universitätsstrasse 2, 45117 Essen (Germany).
Abstract
Several proteases like the high temperature requirement A (HtrA) protein family containing internal or C-terminal PDZ domains play key roles in protein quality control in the cell envelope of Gram-negative bacteria. While several HtrA proteases have been extensively characterized, many features of C-terminal processing proteases such as tail-specific protease (Tsp) are still unknown. To fully understand these cellular control systems, individual domains need to be targeted by specific peptides acting as activators or inhibitors. Here, we describe the identification and design of potent inhibitors and activators of Tsp. Suitable synthetic substrates of Tsp were identified and served as a basis for the generation of boronic acid-based peptide inhibitors. In addition, a proteomic screen of E. coli cell envelope proteins using a synthetic peptide library was performed to identify peptides capable of amplifying Tsp's proteolytic activity. The implications of these findings for the regulation of PDZ proteases and for future mechanistic studies are discussed.
Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Vasoactive Peptides with Angiogenesis-Regulating Activity Predict Cancer Risk in Males.
Source
Authors' Affiliations: 1Department of Clinical Sciences, Lund University, Section of Oncology, Lund; 2Department of Clinical Sciences, Lund University, Malmö; Department of 3Oncology, 4Surgery, and 5Center of Emergency Medicine, Skåne University Hospital, Lund and Malmö, Sweden; 6BRAHMS Biomarkers, Thermo Fisher Scientific, Hennigsdorf; 7Waltraut Bergmann Foundation, Hohen Neuendorf, Germany; 8Cardiology Division, Cardiovascular Research Center, Massachusetts General Hospital, Harvard Medical School, Boston; 9Broad Institute of Harvard and MIT, Cambridge; and 10Framingham Heart Study, Framingham, Massachusetts.
Abstract
BACKGROUND:
Tumor development requires angiogenesis, and antiangiogenesis has been introduced in the treatment of cancer patients; however, how the cardiovascular phenotype correlates with cancer risk remains ill-defined. Here, we hypothesized that vasoactive peptides previously implicated in angiogenesis regulation predict long-term cancer risk.
METHODS:
We measured midregional proatrial natriuretic peptide (MR-proANP), proadrenomedullin (MR-proADM), and C-terminal preprovasopressin (copeptin) in fasting plasma from participants of the Malmö Diet and Cancer Study that were free from cancer prior to the baseline exam in 1991 to 1994 (1,768 males and 2,293 females). We used Cox proportional hazards models to determine the time to first cancer event in relation to baseline levels of vasoactivepeptides during a median follow-up of 15 years.
RESULTS:
First cancer events occurred in 366 males and in 368 females. In males, one SD increase of MR-proANP, copeptin, and MR-proADM was independently related to incident cancer [HR (95% CI)] by 0.85 (0.74-0.96), P = 0.012; 1.17 (1.04-1.32), P = 0.009; and 1.12 (0.99-1.26), P = 0.065, respectively, and a summed biomarker score identified an almost 2-fold difference in cancer risk between the top and bottom quartile (P < 0.001). In younger males, the biomarker score identified a more than 3-fold increase in risk between the top and bottom quartile (P < 0.001). Among females, we found no relationship between biomarkers and cancer incidence.
CONCLUSIONS:
Our data suggest that vasoactive peptide biomarkers predict cancer risk in males, particularly in younger males.Impact: Our findings may have implications for cancer risk prediction and present novel, potentially drug modifiable, mechanisms underlying cancer development. Cancer Epidemiol Biomarkers Prev; 1-10. ©2012 AACR.
Cu(II) Coordination Chemistry of Patellamide Derivatives: Possible Biological Functions of Cyclic Pseudopeptides.
Source
Universität Heidelberg, Anorganisch-Chemisches Institut, Im Neuenheimer Feld 270, 69120 Heidelberg (Germany). peter.comba@aci.uni-heidelberg.de.
Abstract
Two synthetic derivatives of the naturally occurring cyclic pseudooctapeptides patellamide A-F and ascidiacyclamide, that is, H(4) pat(2) , H(4) pat(3) , as well as their Cu(II) complexes are described. These cyclic peptide derivatives differ from the naturally occurring macrocycles by the variation of the incorporated heterocyclic donor groups and the configuration of the amino acids connecting the heterocycles. The exchange of the oxazoline and thiazole groups by dimethylimidazoles or methyloxazoles leads to more rigid macrocycles, and the changes in the configuration of the side chains leads to significant differences in the folding of the cyclic peptides. These variations allow a detailed study of the various possible structural changes on the chemistry of the Cu(II) complexes formed. The coordination of Cu(II) with these macrocyclic species was monitored by high-resolution electrospray mass spectrometry (ESI-MS), spectrophotometric (UV/Vis) and circular dichroic (CD) titrations, and electron paramagnetic resonance (EPR) spectroscopy. Density functional theory (DFT) calculations and molecular mechanics (MM) simulations have been used to model the structures of the Cu(II) complexes and provide a detailed understanding of their geometric preferences and conformational flexibility. This is related to the Cu(II) coordination chemistry and the reactivity of the dinuclear Cu(II) complexes towards CO(2) fixation. The variation observed between the natural and various synthetic peptide systems enables conclusions about structure-reactivity correlations, and our results also provide information on why nature might have chosen oxazolines and thiazoles as incorporated heterocycles.
Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Nanochemoprevention by encapsulation of (-)-epigallocatechin-3-gallate with bioactive peptides/chitosan nanoparticles for enhancement of its bioavailability.
Source
College of Food Science and Technology, Nanjing Agricultural University, Nanjing 210095, People's Republic of China. zengxx@njau.edu.cn.
Abstract
Nanochemoprevention by oral consumption was developed by the encapsulation of (-)-epigallocatechin-3-gallate (EGCG) with nanoparticles that were electrostatically assembled from bioactive caseinophosphopeptides and chitosan, which was highly biocompatible and able to enhance the bioavailability of EGCG.
Conformational stability of collagen triple helices functionalized in the Yaa position by click chemistry.
Source
Department of Chemistry, University of Basel, St. Johanns-Ring 19, 4056 Basel, Switzerland.
Abstract
Click chemistry was used to introduce moieties as sterically demanding as monosaccharides into the Yaa position of collagen model peptides. The effect of different triazolyl derivatives as well as the configuration of the functionalized proline residue on the thermal stability of the collagen triple helices was examined.
GPCRs and cancer.
Source
Department of Pharmaco-Biology, University of Calabria, Rende (CS), Italy.
Abstract
G-protein-coupled receptors (GPCRs), which represent the largest gene family in the human genome, play a crucial role in multiple physiological functions as well as in tumor growth and metastasis. For instance, various molecules like hormones, lipids, peptides and neurotransmitters exert their biological effects by binding to these seven-transmembrane receptors coupled to heterotrimeric G-proteins, which are highly specialized transducers able to modulate diverse signaling pathways. Furthermore, numerous responses mediated by GPCRs are not dependent on a single biochemical route, but result from the integration of an intricate network of transduction cascades involved in many physiological activities and tumor development. This review highlights the emerging information on the various responses mediated by a selected choice of GPCRs and the molecular mechanisms by which these receptors exert a primary action in cancer progression. These findings provide a broad overview on the biological activity elicited by GPCRs in tumor cells and contribute to the identification of novel pharmacological approaches for cancer patients.
Glycosylation Assists Binding of HIV Protein gp120 to Human CD4 Receptor.
Source
Organic Chemistry, University of Hamburg, Martin-Luther-King-Platz 6, 20146 Hamburg (Germany), Homepage: www.chemie.uni-hamburg.de/oc/meyer; Present address: Alberta Glycomics Centre, Department of Chemistry, University of Alberta, Edmonton, T6G 2G2 Alberta (Canada).
Abstract
The role of glycosylation of proteins on its binding affinity is not well understood. Even a monosaccharide (magenta) placed at a glycosylation site can significantly enhance binding of peptides to their receptor. If glycosylated, an HIV protein binds stronger and faster to its primary receptors on human cells.
Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Molecular Changes Induced in Rat Liver by Hemorrhage and Effects of Melanocortin Treatment.
Source
* Postdoctoral Fellow, Center for Surgical Research, ** Director, Center for Preclinical Investigation, Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico, Milano, Italy. † Assistant Professor of Pharmacology, ‡Postgraduate Student, # Postdoctoral Fellow, †† Full Professor of Pharmacology, Department of Biomedical Sciences, Section of Pharmacology, University of Modena and Reggio Emilia, Modena, Italy. § Research Assistant, Department of Internal Medicine, University of Milano, Milano, Italy. ‖ Associate Professor of Pharmaceutical Chemistry, Department of Pharmaceutical Chemistry and Toxicology, University of Napoli "Federico II," Napoli, Italy.
Abstract
BACKGROUND:
Melanocortin peptides improve hemodynamic parameters and prevent death during severe hemorrhagic shock. In the present research we determined influences of a synthetic melanocortin 1/4 receptor agonist on the molecular changes that occur in rat liver during hemorrhage.
METHODS:
Controlled-volume hemorrhage was performed in adult rats under general anesthesia by a stepwise blood withdrawal until mean arterial pressure fell to 40 mmHg. Then rats received either saline or the synthetic melanocortin 1/4 receptor agonist Butir-His-D-Phe-Arg-Trp-Sar-NH2 (Ro27-3225; n = 6-8 per group). Hemogasanalysis was performed throughout a 60-min period. Gene expression in liver samples was determined at 1 or 3 h using quantitative real-time polymerase chain reaction.
RESULTS:
At 1 h, in saline-treated shocked rats, there were significant increases in activating transcription factor 3 (Atf3), early growth response 1 (Egr1), heme oxygenase (decycling) 1 (Hmox1), FBJ murine osteosarcoma viral oncogene homolog (Fos), and jun oncogene (Jun). These changes were prevented by Ro27-3225 (mean ± SEM: Atf3 152.83 ± 58.62 vs. 579.00 ± 124.13, P = 0.002; Egr1 13.21 ± 1.28 vs. 26.63 ± 1.02, P = 0.001; Hmox1 3.28 ± 0.31 vs. 166.54 ± 35.03, P = 0.002; Fos 4.36 ± 1.03 vs. 14.90 ± 3.44, P < 0.001; Jun 6.62 ± 1.93 vs. 15.07 ± 2.09, P = 0.005; respectively). Increases in alpha-2-macroglobulin (A2m), heat shock 70kD protein 1A (Hspa1a), erythropoietin (Epo), and interleukin-6 (Il6) occurred at 3 h in shocked rats and were prevented by Ro27-3225 treatment (A2m 6.90 ± 0.82 vs. 36.73 ± 4.00, P < 0.001; Hspa1a 10.34 ± 3.28 vs. 25.72 ± 3.64, P = 0.001; Epo 0.49 ± 0.13 vs. 2.37 ± 0.73, P = 0.002; Il6 1.05 ± 0.15 vs. 1.88 ± 0.23, P < 0.001; respectively). Further, at 3 h in shocked rats treated with Ro27-3225 there were significant increases in tight junction protein 1 (Tjp1; 27.30 ± 2.43 vs. 5.03 ± 1.68, P < 0.001) and nuclear receptor subfamily 4, group A, member 1 (Nr4a1; 91.03 ± 16.20 vs. 30.43 ± 11.0, P = 0.01) relative to sham animals. Treatment with Ro27-3225 rapidly restored blood pressure, hemogasanalysis parameters, and lactate blood levels.
CONCLUSIONS:
Melanocortin treatment significantly prevents most of the systemic and hepatic detrimental changes induced by hemorrhage.
Accuracy of Diagnostic Antibody Tests for Coeliac Disease in Children: Summary of an Evidence Report.
Source
*Centre for Social Policy Research, University of Bremen, Bremen †Medical Review Board of the Statutory Health Insurance Funds (MDS), Essen, Germany ‡Epidemiology and Biostatistics Unit, Institute for Maternal and Child Health IRCCS Burlo Garofolo, Trieste, Italy §Dr von Haunersches Kinderspital, Ludwig Maximilians Universität München, München, Germany ||Hans Christian Andersen Children's Hospital, Odense University Hospital, Odense C, Denmark ¶Department of Paediatrics, Medical and Health Science Centre, University of Debrecen, Debrecen, Hungary #Heim Pal Children's Hospital, Budapest, Hungary.
Abstract
OBJECTIVE:
The aim of this study was to summarise the evidence from 2004 to September 2009 on the performance of laboratory-based serological and point of care (POC) tests for diagnosing coeliac disease (CD) in children using histology as reference standard.
PATIENTS AND METHODS:
We searched MEDLINE and EMBASE for studies reporting on children for tests based on IgA and IgG anti-gliadin (AGA), endomysial (EmA), anti-transglutaminase-2 (TG2), and anti-deamidated gliadin peptides(DGP) antibodies or POC tests. For inclusion, histological analysis of duodenal biopsies and sensitivity and specificity for index tests had to be reported. Data were pooled and summary measures calculated for sensitivity, specificity, positive and negative likelihood ratios ("LR+", "LR-"), and diagnostic odds ratios (DOR). In case of elevated statistical heterogeneity, studies reaching 90% sensitivity or specificity were reported.
RESULTS:
A total of 2510 articles were reviewed; 16 entered meta-analysis, reporting on 3110 patients (1876 with CD, 1234 without CD). For IgA-EmA, sensitivity was ≥90% in 7/11 studies and pooled specificity 98.2%. For IgA-anti-TG2, 11/15 studies yielded sensitivities ≥90% and 13/15 specificities ≥90%. For IgA-DGP, sensitivity ranged between 80.7% and 95.1% (specificity 86.3%-93.1%); for IgG-DGP between 80.1% and 98.6% (specificity 86.0-96.9%). IgA-EmA had the highest pooled DOR (554) and LR+ (31.8) for a laboratory test, followed by IgA-anti-TG2, IgG-DGP, IgA-DGP and IgA-AGA. POC tests showed a pooled sensitivity of 96.4% for IgA-TG2 (specificity 97.7%).
CONCLUSIONS:
IgA-EmA and IgA-anti-TG2 tests appear highly accurate to diagnose CD. IgG-anti-DGP tests may help in excluding CD. IgA-AGA and IgA-DGP tests show inferior accuracy. POC tests may achieve high accuracy in the hands of experienced readers, but IgA-anti-TG2/EmA were superior.
Comparative proteomic analysis of the venom of the snake taipan, Oxyuranus scutellatus, from Papua New Guinea and Australia: Role of neurotoxic and procoagulant effects in venom toxicity.
Source
Instituto Clodomiro Picado, Facultad de Microbiología, Universidad de Costa Rica, San José, Costa Rica.
Abstract
The venom proteomes of populations of the highly venomous taipan snake, Oxyuranus scutellatus, from Australia and Papua New Guinea (PNG), were characterized by reverse-phase HPLC fractionation, followed by analysis of chromatographic fractions by SDS-PAGE, N-terminal sequencing, MALDI-TOF mass fingerprinting, and collision-induced dissociation tandem mass spectrometry of tryptic peptides. Proteins belonging to the following eight protein families were identified in the two venoms: phospholipase A(2) (PLA(2)), Kunitz-type inhibitor, metalloproteinase (SVMP), three-finger toxin (3FTx), serine proteinase, cysteine-rich secretory proteins (CRISP), and coagulation factor V-like protein. In addition, C-type lectin/lectin-like protein and venom natriuretic peptide were identified in the venom of specimens from PNG. PLA(2)s comprised more than 65% of the venoms of these two populations. Antivenoms generated against the venoms of these populations showed a pattern of cross-neutralization, corroborating the immunological kinship of these venoms. Toxicity experiments performed in mice suggest that, at low venom doses, neurotoxicity leading to respiratory paralysis represents the predominant mechanism of prey immobilization and death. However, at high doses, such as those injected in natural bites, intravascular thrombosis due to the action of the prothrombin activator may constitute a potent and very rapid mechanism for killing prey.
Copyright © 2011. Published by Elsevier B.V.
Highly sensitive cardiac troponin T in heart failure: Comparison with echocardiographic parameters and natriuretic peptides.
Source
Department of Cardiovascular, Respiratory and Metabolic Medicine, Graduate School of Medicine, Kagoshima University, Kagoshima, Japan.
Abstract
BACKGROUND:
Circulating cardiac troponin T is a marker of cardiomyocyte injury, and predicts adverse outcomes in patients with chronic heart failure. However, the significance of highly sensitive cardiac troponin T (hs-TnT) in cardiac dysfunction remains uncertain. The purpose of this study is to evaluate the correlation between hs-TnT and echocardiographic parameters or natriuretic peptides in patients with heart failure.
METHODS AND RESULTS:
We analyzed 283 consecutive out- or in-patients who had B-type natriuretic peptide (BNP) ≥20pg/mL and were examined by echocardiography (mean age 66.5±13.9 years old; 159 males). Hs-TnT, BNP, N-terminal pro-BNP (NT-proBNP), and creatinine levels were measured simultaneously. LVEDD (left ventricular end-diastolic dimension), LVEF (left ventricular ejection fraction), E', E/E', left ventricular (LV) Tei index, and right ventricular (RV) Tei index were determined with echocardiography. The linear regression analyses demonstrated that loghs-TnT correlated with LVEDD (R=0.242, p<0.0001), LVEF (R=-0.369, p<0.0001), E' (R=-0.447, p<0.0001), E/E' (R=0.364, p<0.0001), LV Tei index (R=0.303, p<0.0001), RV Tei index (R=0.443, p<0.0001), and estimated glomerular filtration rate (eGFR) (R=-0.489, p<0.0001). Using multiple variable regression analysis, loghs-TnT independently correlated with LVEF, E/E', RV Tei index, and eGFR. Furthermore, loghs-TnT significantly correlated with logBNP (R=0.567, p<0.0001) or logNT-proBNP (R=0.647, p<0.0001). Multiple variable regression analysis demonstrated that loghs-TnT independently correlated with logBNP, age, and eGFR, or with logNT-proBNP, age, sex, and eGFR.
CONCLUSIONS:
The hs-TnT correlated with cardiac dysfunction evaluated by echocardiography and natriuretic peptidesin patients with heart failure. The elevation of hs-TnT levels in heart failure may represent cardiac dysfunction due to minor and ongoing myocardial injury.
Copyright © 2012. Published by Elsevier Ltd.
The coiled coil motif in polymer drug delivery systems.
Abstract
The coiled coil is a superhelical structural protein motif that has been thoroughly investigated in recent years. Because of the relatively well-understood principles that determine the properties of coiled coil peptides and proteins, macromolecular systems containing the coiled coil motif have been suggested for various applications. This short review focuses on hybrid polymer coiled coil systems designed for drug delivery purposes. After a short introduction, the most important features of the coiled coils (stability, association number, oligomerization selectivity and orientation of helices) are described, and the factors influencing these characteristics are discussed. Several examples of the most interesting biomedical applications of the polymer-coiled coil systems (according to the authors' opinion) are presented.
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