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1

Structure and function of cholera toxin and the related Escherichia coli heat-labile enterotoxin.  

PubMed Central

Cholera and the related Escherichia coli-associated diarrheal disease are important problems confronting Third World nations and any area where water supplies can become contaminated. The disease is extremely debilitating and may be fatal in the absence of treatment. Symptoms are caused by the action of cholera toxin, secreted by the bacterium Vibrio cholerae, or by a closely related heat-labile enterotoxin, produced by Escherichia coli, that causes a milder, more common traveler's diarrhea. Both toxins bind receptors in intestinal epithelial cells and insert an enzymatic subunit that modifies a G protein associated with the adenylate cyclase complex. The consequent stimulated production of cyclic AMP, or other factors such as increased synthesis of prostaglandins by intoxicated cells, initiates a metabolic cascade that results in the excessive secretion of fluid and electrolytes characteristic of the disease. The toxins have a very high degree of structural and functional homology and may be evolutionarily related. Several effective new vaccine formulations have been developed and tested, and a growing family of endogenous cofactors is being discovered in eukaryotic cells. The recent elucidation of the three-dimensional structure of the heat-labile enterotoxin has provided an opportunity to examine and compare the correlations between structure and function of the two toxins. This information may improve our understanding of the disease process itself, as well as illuminate the role of the toxin in studies of signal transduction and G-protein function. Images

Spangler, B D

1992-01-01

2

Functional Diversity of Heat-labile Toxins (LT) Produced by Enterotoxigenic Escherichia coli  

PubMed Central

Heat-labile toxins (LTs) have ADP-ribosylation activity and induce the secretory diarrhea caused by enterotoxigenic Escherichia coli (ETEC) strains in different mammalian hosts. LTs also act as adjuvants following delivery via mucosal, parenteral, or transcutaneous routes. Previously we have shown that LT produced by human-derived ETEC strains encompass a group of 16 polymorphic variants, including the reference toxin (LT1 or hLT) produced by the H10407 strain and one variant that is found mainly among bacterial strains isolated from pigs (LT4 or pLT). Herein, we show that LT4 (with six polymorphic sites in the A (K4R, K213E, and N238D) and B (S4T, A46E, and E102K) subunits) displays differential in vitro toxicity and in vivo adjuvant activities compared with LT1. One in vitro generated LT mutant (LTK4R), in which the lysine at position 4 of the A subunit was replaced by arginine, showed most of the LT4 features with an ?10-fold reduction of the cytotonic effects, ADP-ribosylation activity, and accumulation of intracellular cAMP in Y1 cells. Molecular dynamic studies of the A subunit showed that the K4R replacement reduces the N-terminal region flexibility and decreases the catalytic site crevice. Noticeably, LT4 showed a stronger Th1-biased adjuvant activity with regard to LT1, particularly concerning activation of cytotoxic CD8+ T lymphocytes when delivered via the intranasal route. Our results further emphasize the relevance of LT polymorphism among human-derived ETEC strains that may impact both the pathogenicity of the bacterial strain and the use of these toxins as potential vaccine adjuvants.

Rodrigues, Juliana F.; Mathias-Santos, Camila; Sbrogio-Almeida, Maria Elisabete; Amorim, Jaime H.; Cabrera-Crespo, Joaquim; Balan, Andrea; Ferreira, Luis C. S.

2011-01-01

3

Preexisting antibodies to homologous colonization factors and heat-labile toxin in serum, and the risk to develop enterotoxigenic Escherichia coli-associated diarrhea  

Microsoft Academic Search

Preexisting serum immunoglobulin (Ig) A and IgG titers against colonization factors and heat-labile toxin of enterotoxigenic Escherichia coli (ETEC) were examined in young adults who subsequently developed ETEC-associated diarrhea and in healthy matched controls. The data suggest an inverse association between the antibody titers against colonization factors, but not heat-labile toxin, and development of ETEC-associated diarrhea.

Joshua Tobias; Kerstin Andersson; Anya Bialik; Dani Cohen

2008-01-01

4

Ingestion of transgenic carrots expressing the Escherichia coli heat-labile enterotoxin B subunit protects mice against cholera toxin challenge.  

PubMed

Diarrheal diseases caused by Vibrio cholerae and enterotoxigenic Escherichia coli (ETEC) are worldwide health problems that might be prevented with vaccines based on edible plants expressing the B subunit from either the cholera toxin (CTB) or the E. coli heat labile toxin (LTB). In this work we analyzed the immunity induced in Balb/c mice by ingestion of three weekly doses of 10 mug of LTB derived from transgenic carrot material. Although the anti-LTB serum immunoglobulin G (IgG) and intestinal IgA antibody responses were higher with 10 mug-doses of pure bacterial recombinant LTB (rLTB), the transgenic carrot material also elicited significant serum and intestinal antibody responses. Serum anti-LTB IgG1 antibodies predominated over IgG2a antibodies, suggesting that mainly Th2 responses were induced. A decrease of intestinal fluid accumulation after cholera toxin challenge was observed in mice immunized with either rLTB or LTB-containing carrot material. These results demonstrate that ingestion of carrot-derived LTB induces antitoxin systemic and intestinal immunity in mice and suggest that transgenic carrots expressing LTB may be used as an effective edible vaccine against cholera and ETEC diarrhea in humans. PMID:17874110

Rosales-Mendoza, Sergio; Soria-Guerra, Ruth Elena; López-Revilla, Rubén; Moreno-Fierros, Leticia; Alpuche-Solís, Angel Gabriel

2007-09-15

5

Expression and immunogenicity of enterotoxigenic Escherichia coli heat-labile toxin B subunit in transgenic rice callus.  

PubMed

Enterotoxigenic Escherichia coli is one of the leading causes of diarrhea in developing countries, and the disease may be fatal in the absence of treatment. Enterotoxigenic E. coli heat-labile toxin B subunit (LTB) can be used as an adjuvant, as a carrier of fused antigens, or as an antigen itself. The synthetic LTB (sLTB) gene, optimized for plant codon usage, has been introduced into rice cells by particle bombardment-mediated transformation. The integration and expression of the sLTB gene were observed via genomic DNA PCR and western blot analysis, respectively. The binding activity of LTB protein expressed in transgenic rice callus to G(M1)-ganglioside, a receptor for biologically active LTB, was confirmed by G(M1)-ELISA. Oral inoculation of mice with lyophilized transgenic rice calli containing LTB generated significant IgG antibody titers against bacterial LTB, and the sera of immunized mice inhibited the binding of bacterial LTB to G(M1)-ganglioside. Mice orally immunized with non-transgenic rice calli failed to generate detectable anti-LTB IgG antibody titers. Mice immunized with plant-produced LTB generated higher IgG1 antibody titers than IgG2a, indicating a Th2-type immune response. Mice orally immunized with lyophilized transgenic rice calli containing LTB elicited higher fecal IgA antibody titers than mice immunized with non-transgenic rice calli. These experimental results demonstrate that LTB proteins produced in transgenic rice callus and given to mice by oral administration induce humoral and secreted antibody immune responses. We suggest that transgenic rice callus may be suitable as a plant-based edible vaccine to provide effective protection against enterotoxigenic E. coli heat-labile toxin. PMID:19657748

Kim, Tae-Geum; Kim, Bang-Geul; Kim, Mi-Young; Choi, Jae-Kwon; Jung, Eun-Sun; Yang, Moon-Sik

2009-08-06

6

Multiplex PCR for detection of the heat-labile toxin gene and shiga-like toxin I and II genes in Escherichia coli isolated from natural waters.  

PubMed Central

A triplex PCR method was developed to simultaneously amplify a heat-labile toxin sequence (LT) of 258 bp, a shiga-like toxin I sequence (SLT I) of 130 bp, and a shiga-like toxin II sequence (SLT II) of 346 bp from toxigenic strains of Escherichia coli. This method was used to screen 377 environmental E. coli isolates from marine waters or estuaries located in Southern California and North Carolina for enterotoxigenic or enterohemorrhagic E. coli strains. Of the 377 E. coli screened, one isolate was found to belong to the enterotoxigenic group, since it contained a LT homologous sequence, and one isolate was found to belong to the enterohemorrhagic group, since it contained a SLT I homologous sequence. None was found to contain SLT II homologous sequences. The pathogenicity of the positive environmental E. coli isolates was confirmed by standard bioassays with Y-1 adrenal cells and Vero cells to confirm toxin production. Our results suggest that toxigenic E. coli occurs infrequently in environmental waters and that there is a low public health risk from toxigenic E. coli in coastal waters. Images

Lang, A L; Tsai, Y L; Mayer, C L; Patton, K C; Palmer, C J

1994-01-01

7

Cytopathic effect of heat-labile toxin of Bordetella parapertussis on aortic smooth muscle cells from pigs or guinea pigs.  

PubMed

The in vitro effect of the heat-labile toxin (HLT) of Bordetella parapertussis on HeLa, baby hamster kidney (BHK), chinese hamster ovary (CHO), myeloma (Pa-NS-1), human embryonic lung (HEL-R66) cells, erythrocytes, adipocytes and lymphocytes from guinea pigs, mice or rats, or aortic smooth muscle cells from pigs or guinea pigs was examined. Within 8, 6, 4, 2, and 2 hr after the exposure to 1, 3, 10, 30, and 100 MNDs/ml of HLT, respectively, the cultured smooth muscle cells only showed a cytopathic change. When the cells exposed to HLT were washed out within 60 min post-exposure, the change could be induced with an extend period of lag. Histamine, KCl or norepinephrine caused similar change in the cells, but the period of lag was within 30 min. The HLT activity was neutralized by an anti-B. parapertussis- or B. bronchiseptica-HLT guinea pig IgG. HLT had no effects on any other cells tested. PMID:3393100

Endoh, M; Nagai, M; Ueda, T; Yoshida, Y; Nakase, Y

1988-01-01

8

Neutralization of enterotoxigenic escherichia coli heat?labile toxin by chicken egg yolk immunoglobulin Y and its antigen?binding fragments  

Microsoft Academic Search

The protective effect of chicken egg yolk immunoglobulin Y (IgY) and its antigen?binding FAb’ fragments was studied by their neutralization of heat?labile toxin (LT) produced by enterotoxigenic Escherichia coli (ETEC) strain H10407. High levels of specific antibodies against LT were produced and maintained over a period of 8 months in eggs of hyper?immunized hens. The FAb’ fragment produced by peptic

E. M. Akita; S. Nakai

1998-01-01

9

Cholera toxin, E. coli heat-labile toxin, and non-toxic derivatives induce dendritic cell migration into the follicle-associated epithelium of Peyer's patches  

PubMed Central

The follicle-associated epithelium (FAE) of Peyer's patches (PPs) transports antigens and microorganisms into mucosal lymphoid tissues where they are captured by subepithelial dendritic cells (DCs). Feeding of cholera toxin (CT) induced migration of subepithelial DCs to interfollicular T-cell areas within 24 h. This study investigated short-term effects of CT, Escherichia coli heat-labile toxin, and non-toxic derivatives on DC migration. CT or CTB injected into ligated intestinal loops induced significant increase in CD11c + DCs within the FAE within 90 min. In mice fed CT intragastrically, DC numbers in the FAE increased by 1 h, were maximal by 2 h, declined between 8 and 12 h, and were reversed by 24 h. Feeding of native LT, recombinant CTB, dibutyryl cyclic AMP, and to a lesser extent mutated CT(E29H) or mutated LT(R192G) had the same effect. Thus, both A and B subunits of enterotoxins, presumably acting through distinct signaling pathways, may promote capture of incoming antigens and pathogens by PP DCs.

Anosova, NG; Chabot, S; Shreedhar, V; Borawski, JA; Dickinson, BL; Neutra, MR

2008-01-01

10

Low-Dose Exposure and Immunogenicity of Transgenic Maize Expressing the Escherichia coli Heat-Labile Toxin B Subunit  

PubMed Central

Background Transgenic maize, which produces the nontoxic B subunit of the Escherichia coli heat-labile toxin (LT-B) in seed, has proven to be an effective oral immunogen in mice. Currently, there is considerable concern over accidental consumption of transgenic maize expressing LT-B by humans and domestic animals. We have yet to define nonimmunogenic levels of transgenic LT-B when ingested. Objectives Our goal in this study was to determine the highest dose of LT-B orally administered in mice that does not result in a measurable immune response. We defined an immune response as specific serum or mucosal IgG or IgA significantly greater than background after three feedings (0.0002–20 ?g) or a priming response induced by the intermittent feeding. Methods We fed transgenic maize pellets on days 0, 7, 21, and 49 and collected serum and fecal samples weekly. Serum was analyzed for LT-B–specific IgG and IgA, and feces was analyzed for LT-B–specific IgA. Results We observed a dose-dependent anti-LT-B antibody response with high specific antibody concentrations in groups fed high doses (0.2, 2, 20 ?g) of LT-B maize. Mice fed 0.02 ?g LT-B demonstrated immune priming in 62.5% of the animals. Mice that were fed ? 0.002 ?g LT-B showed no increase in specific antibody nor did they demonstrate immune priming, indicating that 0.002 ?g LT-B was the highest nonimmunogenic dose tested. Conclusion Our results demonstrate that LT-B derived from transgenic maize is immunogenic at nanogram levels when orally administered to mice.

Beyer, April J.; Wang, Kan; Umble, Amber N.; Wolt, Jeffrey D.; Cunnick, Joan E.

2007-01-01

11

Synthesis of hybrid molecules between heat-labile enterotoxin and cholera toxin B subunits: potential for use in a broad-spectrum vaccine.  

PubMed Central

Three variants of the cholera toxin B subunit (CTB) were generated by site-specific mutagenesis in which regions of the mature protein were altered to the composition found at the corresponding positions of the closely related B subunit of the heat-labile enterotoxin of enterotoxigenic Escherichia coli (LTB). The mutant proteins were expressed in Vibrio cholerae and purified from the growth medium. In the first of the mutant proteins, the first 25 amino acids corresponded to the sequence found in LTB, and in the second, changes were made at positions 94 and 95 of the mature protein. The third mutant protein combined the changes made in the first two. Analysis of the immunological properties of these novel proteins by using monoclonal antibodies and absorbed polyclonal antiserum demonstrated that they had acquired LTB-specific epitopes. Immunizations with the mutant proteins resulted in antisera containing LTB-specific as well as CTB-specific and cross-reactive antibodies. The sera were also found to be more strongly cross-reactive in the in vitro neutralization of both cholera toxin and heat-labile enterotoxin than were antisera raised against either CTB or LTB. The results suggest that such hybrid CTB-LTB proteins may be useful in a broad-spectrum vaccine against enterotoxin-induced diarrhea.

Lebens, M; Shahabi, V; Backstrom, M; Houze, T; Lindblad, N; Holmgren, J

1996-01-01

12

Generation and Characterization of a Live Attenuated Enterotoxigenic Escherichia coli Combination Vaccine Expressing Six Colonization Factors and Heat-Labile Toxin Subunit B?  

PubMed Central

Live attenuated oral enterotoxigenic Escherichia coli (ETEC) vaccines have been demonstrated to be safe and immunogenic in human volunteers and to provide a viable approach to provide protection against this important pathogen. This report describes the construction of new ETEC vaccine candidate strains from recent clinical isolates and their characterization. All known genes for ETEC toxins were removed, and attenuating deletion mutations were made in the aroC, ompC, and ompF chromosomal genes. An isolate expressing coli surface antigen 2 (CS2), CS3, heat-labile toxin (LT), heat-stable toxin (ST), and enteroaggregative Escherichia coli heat-stable toxin 1 (EAST1) was attenuated to generate ACAM2007. The subsequent insertion of the operon encoding CS1 created ACAM2017, and this was further modified by the addition of an expression cassette containing the eltB gene, encoding a pentamer of B subunits of LT (LTB), to generate ACAM2027. Another isolate expressing CS5, CS6, LT, ST, and EAST1 was attenuated to generate ACAM2006, from which a lysogenic prophage was deleted to create ACAM2012 and an LTB gene was introduced to form ACAM2022. Finally, a previously described vaccine strain, ACAM2010, had the eltB gene incorporated to generate ACAM2025. All recombinant genes were incorporated into the chromosomal sites of the attenuating mutations to ensure maximal genetic stability. The expression of the recombinant antigens and the changes in plasmids accompanying the deletion of toxin genes are described. Strains ACAM2025, ACAM2022, and ACAM2027 have been combined to create the ETEC vaccine formulation ACE527, which has recently successfully completed a randomized, double-blind, placebo-controlled phase I trial and is currently undergoing a randomized, double-blind placebo-controlled phase II challenge trial, both in healthy adult volunteers.

Turner, Arthur K.; Stephens, Jonathan C.; Beavis, Juliet C.; Greenwood, Judith; Gewert, Cornelia; Randall, Roger; Freeman, Donna; Darsley, Michael J.

2011-01-01

13

Expression of an Escherichia coli antigenic fusion protein comprising the heat labile toxin B subunit and the heat stable toxin, and its assembly as a functional oligomer in transplastomic tobacco plants.  

PubMed

Enterotoxigenic Escherichia coli (ETEC) strains are important pathogens in developing countries. Some vaccine formulations containing the heat labile toxin B subunit (LTB) have been used in clinical trials; however, the induction of neutralizing antibodies against the heat-stable toxin (ST), a poor immunogenic peptide, is necessary, as most ETEC strains can produce both toxins. In this study, a plant optimized synthetic gene encoding for the LTB-ST fusion protein has been introduced into plastids of tobacco leaf tissues, using biolistic microprojectile bombardment, in an effort to develop a single plant-based candidate vaccine against both toxins. Transplastomic tobacco plants carrying the LTB-ST transgene have been recovered. Transgene insertion into the plastid was confirmed by both PCR and Southern blot analysis. GM1-ELISA revealed that the LTB-ST fusion protein retained its oligomeric structure, and displayed antigenic determinants for both LTB and ST. Western blot analysis, using LTB antisera, confirmed the presence of a 17-KDa protein in transplastomic lines, with the correct antigenicity of the fusion protein. Expression levels of this fusion protein in different lines reached up to 2.3% total soluble protein. Oral immunization of mice with freeze-dried transplastomic tobacco leaves led to the induction of both serum and mucosal LTB-ST specific antibodies. Following cholera toxin challenge, a decrease of intestinal fluid accumulation was observed in mice immunized with LTB-ST-containing tobacco. These findings suggest that tobacco plants expressing LTB-ST could serve as a plant-based candidate vaccine model providing broad-spectrum protection against ETEC-induced diarrhoeal disease. PMID:18764920

Rosales-Mendoza, Sergio; Alpuche-Solís, Angel Gabriel; Soria-Guerra, Ruth Elena; Moreno-Fierros, Leticia; Martínez-González, Luzmila; Herrera-Díaz, Areli; Korban, Schuyler S

2008-09-30

14

Selection of Escherichia coli heat-labile toxin (LT) inhibitors using both the GM1-ELISA and the cAMP vero cell assay.  

PubMed

Weaned piglets are very susceptible to diarrhea caused by enterotoxigenic Escherichia coli. In the past, various natural components were proposed to have beneficial effects by reducing the effects of diarrheal infectious diseases in humans and animals, and thus may represent an alternative for the use of (prophylactic) antibiotics. Alternatives may inactivate enterotoxigenic Escherichia coli heat-labile toxin (LT) by interfering with toxin binding to the cellular receptor GM1. In this study, various plants and other natural substances were tested for inhibitory properties, in the GM1 binding assay, and in the LT-induced cAMP production in Vero cells. The toxic dose of each compound was determined in a cell viability assay, and the highest nontoxic concentrations were used in the GM1 and cAMP assays. Results demonstrated that only d-(+)-galactose, lactose, N-acetyl-d-galactosamine, and two tea extracts were able to inhibit the binding of LT to its GM1 receptor. In the cAMP assay, only the two tea extracts showed inhibitory activity. This shows that d-(+)-galactose, lactose, and N-acetyl-d-galactosamine can indeed inhibit LT binding to GM1 based on structural homology with GM1 in the absence of living cells. However, in the cAMP assay, d-(+)-galactose, and lactose, N-acetyl-d-galactosamine are apparently metabolized to below their effective inhibitory concentration, likely predicting limited practical applicability in vivo. Both tea extracts maintained their activity in the presence of cells. The active compounds in both are probably polyphenols, which are not easily metabolized, and most likely work by aggregating the toxin. In conclusion, the combination of methods used here is a convenient and fast method for preselecting natural substances containing potentially toxin-binding compounds. Furthermore, if antidiarrhea activity is attributed to compounds found inactive here, their activity is unlikely based on interference with toxin binding. PMID:23692076

Verhelst, Roderick; Schroyen, Martine; Buys, Nadine; Niewold, Theo

2013-05-21

15

Characterization of Fluorescent Chimeras of Cholera Toxin and Escherichia coli Heat-Labile Enterotoxins Produced by Use of the Twin Arginine Translocation System  

PubMed Central

Cholera toxin (CT) is an AB5 toxin responsible for the profuse secretory diarrhea resulting from Vibrio cholerae infection. CT consists of a pentameric, receptor-binding B subunit (CTB) and a monomeric A subunit (CTA) that has latent enzymatic activity. In addition to its enterotoxicity, CT has potent mucosal adjuvant activity and can also function as a carrier molecule with many potential applications in cell biology. In earlier studies, the toxic CTA1 domain was replaced by several other antigenic protein domains to produce holotoxin-like chimeras for use as potential mucosal vaccines. In the present study we utilized the twin arginine translocation (tat) system to produce fluorescent CT chimeras, as well as fluorescent chimeras of Escherichia coli heat-labile toxins LTI and LTIIb. Fusion proteins containing either green fluorescent protein (GFP) or monomeric red fluorescent protein (mRFP) and the A2 domain of CT, LTI, or LTIIb were transported to the periplasm of E. coli by the tat system, and the corresponding B polypeptides of CT, LTI, and LTIIb were transported to the periplasm by the sec system. The fluorescent fusion proteins were shown to assemble spontaneously and efficiently with the corresponding B polypeptides in the periplasm to form chimeric holotoxin-like molecules, and these chimeras bound to and entered cultured cells in a manner similar to native CT, LTI, or LTIIb. The GFP and mRFP derivatives of CT, LT, and LTIIb developed here are useful tools for studies on the cell biology of trafficking of the CT/LT family of bacterial enterotoxins. In addition, these constructs provide proof in principle for the development of novel chimeric CT-like or LT-like vaccine candidates containing CTA2 fusion proteins that cannot be delivered to the periplasm of E. coli by use of the sec secretion pathway.

Tinker, Juliette K.; Erbe, Jarrod L.; Holmes, Randall K.

2005-01-01

16

Characterization of fluorescent chimeras of cholera toxin and Escherichia coli heat-labile enterotoxins produced by use of the twin arginine translocation system.  

PubMed

Cholera toxin (CT) is an AB(5) toxin responsible for the profuse secretory diarrhea resulting from Vibrio cholerae infection. CT consists of a pentameric, receptor-binding B subunit (CTB) and a monomeric A subunit (CTA) that has latent enzymatic activity. In addition to its enterotoxicity, CT has potent mucosal adjuvant activity and can also function as a carrier molecule with many potential applications in cell biology. In earlier studies, the toxic CTA(1) domain was replaced by several other antigenic protein domains to produce holotoxin-like chimeras for use as potential mucosal vaccines. In the present study we utilized the twin arginine translocation (tat) system to produce fluorescent CT chimeras, as well as fluorescent chimeras of Escherichia coli heat-labile toxins LTI and LTIIb. Fusion proteins containing either green fluorescent protein (GFP) or monomeric red fluorescent protein (mRFP) and the A(2) domain of CT, LTI, or LTIIb were transported to the periplasm of E. coli by the tat system, and the corresponding B polypeptides of CT, LTI, and LTIIb were transported to the periplasm by the sec system. The fluorescent fusion proteins were shown to assemble spontaneously and efficiently with the corresponding B polypeptides in the periplasm to form chimeric holotoxin-like molecules, and these chimeras bound to and entered cultured cells in a manner similar to native CT, LTI, or LTIIb. The GFP and mRFP derivatives of CT, LT, and LTIIb developed here are useful tools for studies on the cell biology of trafficking of the CT/LT family of bacterial enterotoxins. In addition, these constructs provide proof in principle for the development of novel chimeric CT-like or LT-like vaccine candidates containing CTA(2) fusion proteins that cannot be delivered to the periplasm of E. coli by use of the sec secretion pathway. PMID:15908392

Tinker, Juliette K; Erbe, Jarrod L; Holmes, Randall K

2005-06-01

17

The Adjuvant Double Mutant Escherichia coli Heat Labile Toxin Enhances IL-17A Production in Human T Cells Specific for Bacterial Vaccine Antigens  

PubMed Central

The strong adjuvant activity and low enterotoxicity of the novel mucosal adjuvant double mutant Escherichia coli heat labile toxin, LT(R192G/L211A) or dmLT, demonstrated in mice, makes this molecule a promising adjuvant candidate. However, little is known about the mechanisms responsible for the adjuvant effect of dmLT or whether dmLT also has an adjuvant function in humans. We investigated the effect of dmLT on human T cell responses to different bacterial vaccine antigens: the mycobacterial purified protein derivative (PPD) antigen, tested in individuals previously vaccinated with Bacillus Calmette-Guérin, the LT binding subunit (LTB), evaluated in subjects immunised with oral inactivated whole cell vaccines against enterotoxigenic Escherichia coli, and Streptococcus pneumoniae whole cell vaccine antigens, tested in subjects naturally exposed to pneumococci. We found that dmLT enhanced the production of IL-17A by peripheral blood mononuclear cells in response to all antigens tested. dmLT had comparable effects on IL-17A responses to PPD as the single mutant LT(R192G) adjuvant, which has demonstrated clinical adjuvant activity in humans. Neutralisation of IL-1? and IL-23, but not IL-6, suppressed the IL-17A-enhancing effect of dmLT. Furthermore, CD4+ T cells produced higher levels of IL-17A when stimulated with monocytes pulsed with PPD and dmLT compared to PPD alone, supporting an important role of antigen presenting cells in enhancing IL-17A responses. dmLT also potentiated mitogen-induced IL-17A and IL-13 production. However, dmLT had variable influences on IFN-? responses to the different stimuli tested. Our demonstration of a potent ability of dmLT to enhance human Th17 type T cell responses to bacterial vaccine antigens encourages further evaluation of the adjuvant function of dmLT in humans.

Leach, Susannah; Clements, John D.; Kaim, Joanna; Lundgren, Anna

2012-01-01

18

Humoral and cellular immune responses in the murine respiratory tract following oral immunization with cholera toxin or Escherichia coli heat-labile enterotoxin.  

PubMed

Cholera toxin (CT) and Escherichia coli heat-labile enterotoxin (LT) are the strongest mucosal immunogens identified to date and are also good adjuvants when given orally together in combination with unrelated antigens. We used these potent immunogens to monitor local and systemic immune responses following oral immunization of BALB/c mice, and compared their action on the following: (a) immunoglobulin production rates (IgG, IgM and IgA) in mucosal inductive (Peyer's patches-PPs), effector (intestinal lamina propria-LP, respiratory tract) and systemic (spleen) sites; (b) analysis of systemic antigen-specific antibodies (IgG subclasses, IgA and IgE); (c) time monitoring of fecal anti-CT and anti-LT antibodies, and (d) in vivo relevance of interleukin-6 (IL-6) to mucosal responses. Both mucosal immunogens elicited specific antibody responses (IgA, IgG) not only in the gastrointestinal tract (PP's and intestinal LP), but also in the respiratory tract and spleens of orally immunized mice. These mucosal responses were accompained by elevated secretion of IL-6 in all investigated tissues, indicating involvement of this cytokine in B-cell maturation processes. Furthermore, oral immunization with CT and LT induced elevated serum titers of IgG1 followed by IgG2a, IgG2b, IgG3 and IgA, while high antigen-specific IgA and IgG1 responses were found in fecal extracts. These findings illustrate the action of orally administered CT and LT, respectively, on several humoral and cellular immune responses not only at the gastrointestinal tract, the application site, but also in distant mucosal effector sites such as the respiratory tract. These data suggest the potential use of these mucosal adjuvants in oral immunization strategies to improve the local immune response in remote mucosal tissues, in accordance with the concept of a common mucosa-associated immune system. PMID:8817827

Ruedl, C; Rieser, C; Kofler, N; Wick, G; Wolf, H

1996-06-01

19

Alkaline pH Is a Signal for Optimal Production and Secretion of the Heat Labile Toxin, LT in Enterotoxigenic Escherichia Coli (ETEC)  

PubMed Central

Enterotoxigenic Escherichia coli (ETEC) cause secretory diarrhea in children and travelers to endemic areas. ETEC spreads through the fecal-oral route. After ingestion, ETEC passes through the stomach and duodenum before it colonizes the lower part of the small intestine, exposing bacteria to a wide range of pH and environmental conditions. This study aimed to determine the impact of external pH and activity of the Cyclic AMP receptor protein (CRP) on the regulation of production and secretion of heat labile (LT) enterotoxin. ETEC strain E2863wt and its isogenic mutant E2863?CRP were grown in LBK media buffered to pH 5, 7 and 9. GM1 ELISA, cDNA and cAMP analyses were carried out on bacterial pellet and supernatant samples derived from 3 and 5 hours growth and from overnight cultures. We confirm that CRP is a repressor of LT transcription and production as has been shown before but we show for the first time that CRP is a positive regulator of LT secretion both in vitro and in vivo. LT secretion increased at neutral to alkaline pH compared to acidic pH 5 where secretion was completely inhibited. At pH 9 secretion of LT was optimal resulting in 600 percent increase of secreted LT compared to unbuffered LBK media. This effect was not due to membrane leakage since the bacteria were viable at pH 9. The results indicate that the transition to the alkaline duodenum and/or exposure to high pH close to the epithelium as well as activation of the global transcription factor CRP are signals that induce secretion of the LT toxin in ETEC.

Gonzales, Lucia; Ali, Zahra Bagher; Nygren, Erik; Wang, Zhiyun; Karlsson, Stefan; Zhu, Baoli; Quiding-Jarbrink, Marianne; Sjoling, Asa

2013-01-01

20

Parenteral Adjuvant Activities of Escherichia coli Heat-Labile Toxin and Its B Subunit for Immunization of Mice against Gastric Helicobacter pylori Infection  

PubMed Central

The heat-labile toxin (LT) of Escherichia coli is a potent mucosal adjuvant that has been used to induce protective immunity against Helicobacter felis and Helicobacter pylori infection in mice. We studied whether recombinant LT or its B subunit (LTB) has adjuvant activity in mice when delivered with H. pylori urease antigen via the parenteral route. Mice were immunized subcutaneously or intradermally with urease plus LT, recombinant LTB, or a combination of LT and LTB prior to intragastric challenge with H. pylori. Control mice were immunized orally with urease plus LT, a regimen shown previously to protect against H. pylori gastric infection. Parenteral immunization using either LT or LTB as adjuvant protected mice against H. pylori challenge as effectively as oral immunization and enhanced urease-specific immunoglobulin G (IgG) responses in serum as effectively as aluminum hydroxide adjuvant. LT and LTB had adjuvant activity at subtoxic doses and induced more consistent antibody responses than those observed with oral immunization. A mixture of a low dose of LT and a high dose of LTB stimulated the highest levels of protection and specific IgG in serum. Urease-specific IgG1 and IgG2a antibody subclass responses were stimulated by all immunization regimens tested, but relative levels were dependent on the adjuvant used. Compared to parenteral immunization with urease alone, LT preferentially enhanced IgG1, while LTB or the LT-LTB mixture preferentially enhanced IgG2a. Parenteral immunization using LT or LTB as adjuvant also induced IgA to urease in the saliva of some mice. These results show that LT and LTB stimulate qualitatively different humoral immune responses to urease but are both effective parenteral adjuvants for immunization of mice against H. pylori infection.

Weltzin, Richard; Guy, Bruno; Thomas, William D.; Giannasca, Paul J.; Monath, Thomas P.

2000-01-01

21

Enhancement of Helicobacter pylori outer inflammatory protein DNA vaccine efficacy by co-delivery of interleukin-2 and B subunit heat-labile toxin gene encoded plasmids.  

PubMed

Development of an effective vaccine for controlling H. pylori-associated infection, which is present in about half the people in the world, is a priority. The H. pylori outer inflammatory protein (oipA) has been demonstrated to be a potential antigen for a vaccine. In the present study, use of oipA gene encoded construct (poipA) for C57BL/6 mice vaccination was investigated. Whether co-delivery of IL-2 gene encoded construct (pIL-2) and B subunit heat-labile toxin of Escherichia coli gene encoded construct (pLTB) can modulate the immune response and enhance DNA vaccine efficacy was also explored. Our results demonstrated that poipA administered intradermally ('gene gun' immunization) promoted a strong Th2 immune response, whereas co-delivery of either pIL-2 or pLTB adjuvant elicited a Th1-biased immune response. PoipA administered with both pIL-2 and pLTB adjuvants promoted a strong Th1 immune response. Regardless of the different immune responses promoted by the various vaccination regimes, all immunized mice had smaller bacterial loads after H. pylori challenge than did PBS negative and pVAX1 mock controls. Co-delivery of adjuvant(s) enhances poipA DNA vaccine efficacy by shifting the immune response from being Th2 to being Th1-biased, which results in a greater reduction in bacterial load after H. pylori challenge. Both prophylactic and therapeutic vaccination can achieve sterile immunity in some subjects. PMID:22150716

Chen, Jiansen; Lin, Liping; Li, Neng; She, Feifei

2012-02-01

22

Nanoparticulated heat-stable (STa) and heat-labile B subunit (LTB) recombinant toxin improves vaccine protection against enterotoxigenic Escherichia coli challenge in mouse.  

PubMed

Enterotoxigenic Escherichia coli (ETEC) remains a major cause of diarrheic disease in developing areas, for which there is no effective vaccine available. In this study, we genetically engineered a recombinant heat-stable enterotoxin (STa) coupled to the subunit B of heat-labile enterotoxin (LTB). This fusion protein, STa-LTB, possesses a single amino acid substitution at position 14 of STa. Our data demonstrates that the enterotoxicity of STa in STa-LTB was dramatically reduced. A gelatin nanovaccine candidate was prepared using the purified STa-LTB fusion protein characterized with an entrapment efficiency of 84.88 ± 6.37% and smooth spheres size ranges of 80-200 nm. Antigen-specific antibody responses against STa-LTB and STa in the sera and the intestinal mucus respectively were used to test the immunogenicity of the nanovaccine. This vaccine was further screened in mice by its ability to elicit neutralizing antibodies against STa and protect animals from the challenge with ETEC in mice. The STa-LTB nanoparticles delivered demonstrated a capacity to induce significantly higher and long-lasting antibody responses and increased immune protection against ETEC challenge relative to the control STa-LTB vaccine absorbed in conventional aluminum hydrate salt (p < 0.01). These results warrant the further studies of the development of a novel nanoparticulate vaccine as a broad-spectrum vaccine against ETEC infection. PMID:23040995

Deng, Guangcun; Zeng, Jin; Jian, Minjie; Liu, Wenmiao; Zhang, Zhong; Liu, Xiaoming; Wang, Yujiong

2012-10-05

23

A Functional Antigen in a Practical Crop: LT-B Producing Maize Protects Mice against Escherichia coli Heat Labile Enterotoxin (LT) and Cholera Toxin (CT)  

Microsoft Academic Search

We have produced a functional heat labile enterotoxin (LT-) B subunit of Escherichia coli in maize. LT-B is a multimeric protein that presents an ideal model for an edible vaccine, displaying stability in the gut and inducing mucosal and systemic immune responses. Transgenic maize was engineered to synthesize the LT-B polypeptides, which assembled into oligomeric structures with affinity for GM1

Rachel Chikwamba; Joan Cunnick; Diane Hathaway; Jennifer McMurray; Hugh Mason; Kan Wang

2002-01-01

24

A functional antigen in a practical crop: LT-B producing maize protects mice against Escherichia coli heat labile enterotoxin (LT) and cholera toxin (CT)  

Microsoft Academic Search

We have produced a functional heat labile enterotoxin (LT-) B subunit of Escherichia coli in maize. LT-B is a multimeric protein that presents an ideal model for an edible vaccine, displaying stability in the gut and inducing mucosal and systemic immune responses. Transgenic maize was engineered to synthesize the LT-B polypeptides, which assembled into oligomeric structures with affinity for GM1

Rachel Chikwamba; Joan Cunnick; Diane Hathaway; Jennifer McMurray; Hugh Mason

2002-01-01

25

Intranasal Administration of 2\\/6-Rotavirus-Like Particles with Mutant Escherichia coli Heat-Labile Toxin (LTR192G) Induces Antibody-Secreting Cell Responses but Not Protective Immunity in Gnotobiotic Pigs  

Microsoft Academic Search

We investigated the immunogenicity of recombinant double-layered rotavirus-like particle (2\\/6-VLPs) vac- cines derived from simian SA11 or human (VP6) Wa and bovine RF (VP2) rotavirus strains. The 2\\/6-VLPs were administered to gnotobiotic pigs intranasally (i.n.) with a mutant Escherichia coli heat-labile toxin, LT-R192G (mLT), as mucosal adjuvant. Pigs were challenged with virulent Wa (P1A(8),G1) human rotavirus at post- inoculation day

LIJUAN YUAN; ANNELISE GEYER; DOUGLAS C. HODGINS; ZHIQIAN FAN; YUAN QIAN; KYEONG-OK CHANG; SUE E. CRAWFORD; VIVIANA PARRENO; LUCY A. WARD; MARY K. ESTES; MARGARET E. CONNER; LINDA J. SAIF

2000-01-01

26

Immunoregulatory role of H-2 and intra-H-2 alleles on antibody responses to recombinant preparations of B-subunits of Escherichia coli heat-labile enterotoxin (rEtxB) and cholera toxin (rCtxB)  

Microsoft Academic Search

The immunoregulatory role of H-2 and intra-H-2 alleles on antibody responses to recombinant preparations of B-subunits of Escherichia coli heat-labile enterotoxin (rEtxB) and cholera toxin (rCtxB) is reported. Oral delivery of rEtxB to congenic mice of several different H-2 haplotypes resulted in H-2 dependent serum IgG responses (H-2d>H-2b=H-2q>H-2a>H-2k) and a similar spectrum of intestinal IgA responses in those strains tested.

Toufic O. Nashar; Timothy R. Hirst

1995-01-01

27

Safety and immunogenicity of bacterial and tobacco plant cell line derived recombinant native and mutant Escherichia coli heat-labile toxin in chickens  

Microsoft Academic Search

The safety and immunogenicity of the mammalian mucosal adjuvants, Escherichia coli wild-type heat-labile holotoxin (LT) and E. coli mutant LT (LTA-K63\\/LTB), were examined in 1-day-old chicks and 10-day-old to 21-day-old broilers. Biologically active, E. coli recombinant wild-type LT and recombinant LTA-K63\\/LTB produced in a transgenic Nicotiana tabacum (NT-1) tobacco cell line (SLT102) were tested for safety and antigenicity following various

Tim Miller; Matthew Fanton; Stephanie Nickleson; Hugh Mason; Steven Webb

2012-01-01

28

Ability of SPI2 mutant of S. typhi to effectively induce antibody responses to the mucosal antigen enterotoxigenic E. coli heat labile toxin B subunit after oral delivery to humans  

PubMed Central

We have evaluated an oral vaccine based on an Salmonella enteric serovar typhi (S. typhi) Ty2 derivative TSB7 harboring deletion mutations in ssaV (SPI-2) and aroC together with a chromosomally integrated copy of eltB encoding the B subunit of enterotoxigenic Escherichia coli heat labile toxin (LT-B) in volunteers. Two oral doses of 108 or 109 CFU were administered to two groups of volunteers and both doses were well tolerated, with no vaccinemia, and only transient stool shedding. Immune responses to LT-B and S. typhi lipopolysaccharide were demonstrated in 67 and 97% of subjects, respectively, without evidence of anti-carrier immunity preventing boosting of LT-B responses in many cases. Further development of this salmonella-based (spi-VEC) system for oral delivery of heterologous antigens appears warranted.

Khan, S.; Chatfield, S.; Stratford, R.; Bedwell, J.; Bentley, M.; Sulsh, S.; Giemza, R.; Smith, S.; Bongard, E.; Cosgrove, C.A.; Johnson, J.; Dougan, G.; Griffin, G.E.; Makin, J.; Lewis, D.J.M.

2007-01-01

29

Safety and Immunogenicity of a Single Oral Dose of Recombinant Double Mutant Heat-Labile Toxin Derived from Enterotoxigenic Escherichia coli.  

PubMed

Enterotoxigenic Escherichia coli (ETEC) is a primary cause of traveler's diarrhea for which there is no licensed vaccine. This phase 1 trial determined the safety and immunogenicity of a recombinantly produced double mutant heat-labile enterotoxin (dmLT) of ETEC. It was administered as a single oral dose of dmLT in escalating doses of 5 ?g, 25 ?g, 50 ?g, and 100 ?g, followed by a 72-h inpatient observation, outpatient visits at 8, 14, and 28 days, and telephone calls at 2 and 6 months postvaccination. Safety was assessed by frequency of adverse events, and immune responses determined after immunization included dmLT-specific serum IgA and IgG, fecal IgA, antibody-secreting cells (ASC), and antibodies in lymphocyte supernatant (ALS) responses. All doses were well tolerated by the 36 healthy adults enrolled. Immune responses were limited in the 5- and 25-?g dose recipients. The 50-?g dose recipients trended toward stronger responses than the 100-?g dose recipients by serum IgA (67% versus 33%, P = 0.22), serum IgG (58% versus 33%, P = 0.41), and fecal IgA (58% versus 33%, P = 0.41). By day 14 postvaccination, there were significantly more positive responders (?4-fold increase from baseline) among the 50- versus 100-?g dose recipients for serum IgA (P = 0.036) but not serum IgG (P = 0.21). In conclusion, a single oral dose of dmLT was well tolerated and immunogenic, with immune responses plateauing at the 50-?g dose. (This clinical trial is registered at www.clinicaltrials.gov, registration number NCT01147445.). PMID:24049109

El-Kamary, Samer S; Cohen, Mitchell B; Bourgeois, A Louis; Van De Verg, Lillian; Bauers, Nicole; Reymann, Mardi; Pasetti, Marcela F; Chen, Wilbur H

2013-09-18

30

Functional diversity of heat-labile toxins (LT) produced by enterotoxigenic Escherichia coli: differential enzymatic and immunological activities of LT1 (hLT) AND LT4 (pLT).  

PubMed

Heat-labile toxins (LTs) have ADP-ribosylation activity and induce the secretory diarrhea caused by enterotoxigenic Escherichia coli (ETEC) strains in different mammalian hosts. LTs also act as adjuvants following delivery via mucosal, parenteral, or transcutaneous routes. Previously we have shown that LT produced by human-derived ETEC strains encompass a group of 16 polymorphic variants, including the reference toxin (LT1 or hLT) produced by the H10407 strain and one variant that is found mainly among bacterial strains isolated from pigs (LT4 or pLT). Herein, we show that LT4 (with six polymorphic sites in the A (K4R, K213E, and N238D) and B (S4T, A46E, and E102K) subunits) displays differential in vitro toxicity and in vivo adjuvant activities compared with LT1. One in vitro generated LT mutant (LTK4R), in which the lysine at position 4 of the A subunit was replaced by arginine, showed most of the LT4 features with an ?10-fold reduction of the cytotonic effects, ADP-ribosylation activity, and accumulation of intracellular cAMP in Y1 cells. Molecular dynamic studies of the A subunit showed that the K4R replacement reduces the N-terminal region flexibility and decreases the catalytic site crevice. Noticeably, LT4 showed a stronger Th1-biased adjuvant activity with regard to LT1, particularly concerning activation of cytotoxic CD8(+) T lymphocytes when delivered via the intranasal route. Our results further emphasize the relevance of LT polymorphism among human-derived ETEC strains that may impact both the pathogenicity of the bacterial strain and the use of these toxins as potential vaccine adjuvants. PMID:21135101

Rodrigues, Juliana F; Mathias-Santos, Camila; Sbrogio-Almeida, Maria Elisabete; Amorim, Jaime H; Cabrera-Crespo, Joaquim; Balan, Andrea; Ferreira, Luís C S

2010-12-06

31

Bile and Unsaturated Fatty Acids Inhibit the Binding of Cholera Toxin and Escherichia coli Heat-Labile Enterotoxin to GM1 Receptor  

Microsoft Academic Search

Cholera toxin (CT) is an archetypal bacterial toxin that binds with a high affinity to the receptor ganglioside GM1 on the intestinal epithelial surface and that causes the severe watery diarrhea characteristic of the disease cholera. Blockage of the interaction of CT with the GM1 receptor is an attractive approach for therapeutic intervention. We report here that crude bile prevents

Arpita Chatterjee; Rukhsana Chowdhury

2008-01-01

32

Structure and mucosal adjuvanticity of cholera and Escherichia coli heat-labile enterotoxins  

Microsoft Academic Search

Escherichia coli heat-labile enterotoxin and cholera toxin are potent mucosal immunogens and adjuvants in animal models. Non-toxic mutants retaining adjuvant activity are useful tools to dissect the mechanism of mucosal adjuvanticity and promising candidates for development of human vaccines and immunotherapy. Clinical trials are expected to proceed in the near future.

Rino Rappuoli; Mariagrazia Pizza; Gill Douce; Gordon Dougan

1999-01-01

33

Evaluation of the adjuvant effect of Salmonella-based Escherichia coli heat-labile toxin B subunits on the efficacy of a live Salmonella-delivered avian pathogenic Escherichia coli vaccine.  

PubMed

The present study evaluated the adjuvant effect of live attenuated salmonella organisms expressing the heat-labile toxin of Escherichia coli B subunit (LTB) on the efficacy of an avian pathogenic Escherichia coli (APEC) vaccine. The Asd(+) (aspartate semialdehyde dehydrogenase) plasmid pMMP906 containing the LTB gene was introduced into a Salmonella enterica Typhimurium strain lacking the lon, cpxR and asd genes to generate the adjuvant strain. Live recombinant Salmonella-delivered APEC vaccine candidates were used for this study. The birds were divided into three groups: group A, non-vaccinated controls; group B, immunized with vaccine candidates only; and group C, immunized with vaccine candidates and the LTB strain. The immune responses were measured and the birds were challenged at 21 days of age with a virulent APEC strain. Group C showed a significant increase in plasma IgG and intestinal IgA levels and a significantly higher lymphocyte proliferation response compared with the other groups. Upon challenge with the virulent APEC strain, group C showed effective protection whereas group B did not. We also attempted to optimize the effective dose of the adjuvant. The birds were immunized with the vaccine candidates together with 1×10? or 1×10? colony-forming units of the LTB strain and were subsequently challenged at 3 weeks of age. The 1×10? colony-forming units of the LTB strain showed a greater adjuvant effect with increased levels of serum IgG, intestinal IgA and a potent lymphocyte proliferation response, and yielded higher protection against challenge. Overall, the LTB strain increased the efficacy of the Salmonella -delivered APEC vaccine, indicating that vaccination for APEC along with the LTB strain appears to increase the efficacy for protection against colibacillosis in broiler chickens. PMID:23815619

Chaudhari, Atul A; Lee, John Hwa

2013-07-01

34

In Vivo Expression and Immunoadjuvancy of a Mutant of Heat-Labile Enterotoxin of Escherichia coli in Vaccine and Vector Strains of Vibrio cholerae  

Microsoft Academic Search

Vibrio cholerae secretes cholera toxin (CT) and the closely related heat-labile enterotoxin (LT) of Escherichia coli, the latter when expressed in V. cholerae. Both toxins are also potent immunoadjuvants. Mutant LT molecules that retain immunoadjuvant properties while possessing markedly diminished enterotoxic activities when expressed by E. coli have been developed. One such mutant LT molecule has the substitution of a

EDWARD T. RYAN; THOMAS I. CREAN; MANOHAR JOHN; JOAN R. BUTTERTON; JOHN D. CLEMENTS; STEPHEN B. CALDERWOOD

35

Comparative Analysis of the Mucosal Adjuvanticity of the Type II Heat-Labile Enterotoxins LT-IIa and LT-IIb  

Microsoft Academic Search

Cholera toxin (CT) and the heat-labile enterotoxin of Escherichia coli (LT-I) are members of the serogroup I heat-labile enterotoxins (HLT) and can serve as systemic and mucosal adjuvants. However, information is lacking with respect to the structurally related but antigenically distinct serogroup II HLT, LT-IIa and LT-IIb, which have different binding specificities for ganglioside receptors. The purpose of this study

MICHAEL MARTIN; DANIEL J. METZGER; SUZANNE M. MICHALEK; TERRY D. CONNELL; MICHAEL W. RUSSELL

2000-01-01

36

Construction and immunogenicity evaluation of an epitope-based antigen against swine influenza A virus using Escherichia coli heat-labile toxin B subunit as a carrier-adjuvant.  

PubMed

Influenza A virus causes a highly contagious respiratory disease in a variety of avian and mammalian hosts, including humans and pigs. The primary means for preventing influenza epidemics is vaccination. Epitope-based vaccine represents a new approach to achieve protective immunity. The objective of this study was to construct and evaluate the immunogenicity of an epitope-based antigen for its potential application in future influenza vaccine development. The antigen, comprised of a set of consensus influenza A virus epitopes (IAVe), was genetically linked to a subunit of the bacterial heat-labile enterotoxin (LTB) as an adjuvant. Immunogenicity of this LTB-IAVe antigen was evaluated in a pig model. Despite an inability to detect neutralizing antibodies directed toward the whole virus, humoral immunity against the IAVe was demonstrated in both serum (IgA and IgG) and mucosal secretions (IgG) of immunized pigs. Specific cellular immunity was also induced after LTB-IAVe immunization, as evidenced by up-regulating of IL-1?, IL-8, and IL-4 expression in peripheral blood mononuclear cells (PBMCs) of vaccinated pigs. In comparison to the non-immunized pigs, pigs immunized with the LTB-IAVe showed improved protection against a pathogenic H1N1 swine influenza virus challenge, with about 50% decrease of pneumonic lesions and 10-fold reduction of the viral load in lung and nasal secretion at five days post challenge. This study establishes a platform for future construction of epitope-based vaccines against influenza A virus infection. PMID:23497910

Sun, Zhi; Lawson, Steven; Langenhorst, Robert; McCormick, Kara L; Brunick, Colin; Opriessnig, Tanja; Baker, Rodney; Yoon, Kyoung-Jin; Zhang, Weiping; Huber, Victor C; Fang, Ying

2013-02-26

37

Escherichia coli heat-labile toxin subunit B fusions with Streptococcus sobrinus antigens expressed by Salmonella typhimurium oral vaccine strains: importance of the linker for antigenicity and biological activities of the hybrid proteins.  

PubMed Central

A set of vectors possessing the genes for aspartate semialdehyde dehydrogenase (asd) and the B subunit of the heat-labile enterotoxin of Escherichia coli (LT-B) has been developed. These vectors allow operon or gene fusions of foreign gene epitopes at the C-terminal end of LT-B. Two groups of vectors have been constructed with and without leader sequences to facilitate placing of the foreign antigen in different cell compartments. Two Streptococcus sobrinus genes coding for principal colonization factors, surface protein antigen A (SpaA), and dextranase (Dex), have been fused into the 3' end of the LT-B gene. Resulting protein fusions of approximately 120 to 130 kDa are extremely well recognized by antibodies directed against both SpaA and Dex as well as against LT-B domains and retain the enzymatic activity of dextranase and the biological activity of LT-B in that they bind to GM1 gangliosides. Maximum antigenicity was obtained with the vector possessing an intervening linker of at least six amino acids with two proline residues. Some of the fusion proteins also exhibited another property of LT-B in that they were exported into the periplasm where they oligomerized. LT-B-SpaA and LT-B-Dex hybrid proteins are expressed stably and at a high level in avirulent Salmonella typhimurium vaccine strains which are being used to investigate their immunogenicity and types of induced immune responses. The fusion vectors will also be useful for production and purification of LT-B fusion antigens to be used and evaluated in other vaccine compositions. Images

Jagusztyn-Krynicka, E K; Clark-Curtiss, J E; Curtiss, R

1993-01-01

38

Toll-Like Receptor 2 Mediates Cellular Activation by the B Subunits of Type II Heat-Labile Enterotoxins  

Microsoft Academic Search

The type II heat-labile enterotoxins (LT-IIa and LT-IIb) of Escherichia coli have an AB5 subunit structure similar to that of cholera toxin (CT) and other type I enterotoxins, despite significant differences in the amino acid sequences of their B subunits and different ganglioside receptor specificities. LT-II holotoxins and their nontoxic B subunits display unique properties as immunological adjuvants distinct from

George Hajishengallis; Richard I. Tapping; Michael H. Martin; Hesham Nawar; Elizabeth A. Lyle; Michael W. Russell; Terry D. Connell

2005-01-01

39

Assay for heat-labile Escherichia coli enterotoxin using sandwich erythroimmunoassay.  

PubMed

We investigated the possibility of using a sheep erythrocyte-antibody conjugate as reagent in a sandwich erythroimmunoassay (SERIA) procedure to detect and titrate Escherichia coli heat-labile enterotoxin (LT) with the naked eye. In this assay, which is based on the immunological similarity between Vibrio cholerae toxin (CT) and LT, rabbit anti-CT IgG was used as immunosorbent, and sheep erythrocytes, sensitized with the rabbit anti-CT antibodies, were used as indicator. The sensitivity of the test was demonstrated by a comparative study using an enzyme-linked immunosorbent assay (ELISA). The results obtained by SERIA with 130 samples correlated well with those of a Vero cell assay and a GM1-ELISA. The test is easy, relatively cheap and as sensitive as other standard techniques; it is particularly suited for field laboratories, especially in tropical countries, and a large number of strains may be examined daily. PMID:3553884

Germani, Y; Begaud, E; Guesdon, J L

1987-01-01

40

Factors Affecting Release of Heat-Labile Enterotoxin by Enterotoxigenic Escherichia coli  

PubMed Central

Various conditions affecting the release of heat-labile enterotoxin (LT) by enterotoxigenic Escherichia coli have been examined. The pH of a defined medium containing three amino acids, M-9 salts, and 0.5% glucose decreased to less than 7.0 in early log phase of growth, and no extracellular LT was detected. Adjustment of the pH at 8 h from 6.0 to 8.0 resulted in a concomitant increase in LT activity in culture supernatants. The release of cell-associated LT was significantly reduced by preincubation with protease inhibitors and increased by preincubation with trypsin. Cell-associated LT was not released by pH adjustment of cells grown at 21°C; however, polymyxin B treatment released a toxin species active in only the pigeon erythrocyte lysate (PEL) assay system. As the growth temperature was increased, polymyxin B released toxin species which exhibited both PEL and Y-1 adrenal tumor cell activity. Polymyxin B extracts of enterotoxigenic E. coli in early log phase grown at 37°C possessed only PEL activity, whereas extracts from cells in late-log and stationary phases had biological activity in both assay systems. Also, LT released by pH adjustment from mid-log to stationary phase was active in both PEL and Y-1 adrenal tumor cell assays. Gel electrophoresis of polymyxin B extracts revealed at least three molecular weight species active in either the PEL (22,000 daltons and 30,000 daltons) or both the PEL and the Y-1 adrenal tumor cell assay (72,000 daltons), depending on the growth temperature. These observations may help to explain the chemical and biological heterogeneity of most LT preparations and facilitate purification of LT by increasing the yield of enterotoxin.

Kunkel, Steven L.; Robertson, Donald C.

1979-01-01

41

Inhibition of Escherichia coli heat-labile enterotoxin-induced diarrhea by Chaenomeles speciosa.  

PubMed

Enterotoxigenic Escherichia coli (ETEC) is responsible for millions of deaths in developing countries. Heat-labile enterotoxin (LT), the virulence factor of ETEC, induces diarrhea by initially binding to the G(M1) on the surface of intestinal epithelial cells and consequently leading to the massive loss of fluid and ions from cells. Fruit of Chaenomeles (FC), the dried fruit of Chaenomeles speciosa, has been used for diarrhea in China. However, the anti-diarrheal mechanism of FC is still unclear. In this study, we demonstrated that FC extract (FCE) inhibited the LT-induced diarrhea in mice by blocking the binding of the B subunit of LT (LTB) to G(M1). The ethyl acetate (EA) soluble fraction was the most active fraction of FC that significantly abolished the LTB and G(M1) interaction. Furthermore, the oleanolic acid, ursolic acid, and betulinic acid from EA fraction, blocked the toxin binding effects, resulting in the suppression of LT-induced diarrhea. Moreover, by docking techniques, these compounds fitted LTB well via hydrogen bonds and hydrophobic contacts with amino acid residues of LTB. In conclusion, our findings suggested that oleanolic acid, ursolic acid, and betulinic acid were the active constituents from FC and might be considered as lead therapeutic agents in the treatment of LT-induced diarrhea. PMID:17624704

Chen, Jaw-Chyun; Chang, Yuan-Shiun; Wu, Shih-Lu; Chao, De-Cheng; Chang, Chih-Shiang; Li, Chia-Cheng; Ho, Tin-Yun; Hsiang, Chien-Yun

2007-06-07

42

Escherichia coli heat-labile enterotoxin preferentially interacts with blood group A-active glycolipids from pig intestinal mucosa and A- and B-active glycolipids from human red cells compared to H-active glycolipids  

Microsoft Academic Search

The capacity of cholera toxin (CT) and of the heat-labile enterotoxin produced by Escherichia coli isolated from humans (LTh) to interact with glycolipids bearing ABO(H) blood group determinants isolated from different sources and separated by thin layer chromatography was studied. Toxin binding to the ABO(H)-related glycolipids depends on the glycolipid source, the type of the blood group activity, and the

Jose L. Barra; Clara G. Monferran; Luis E. Balanzino; Federico A. Cumar

1992-01-01

43

Isolation and epidemiological characterization of heat-labile enterotoxin-producing Escherichia fergusonii from healthy chickens.  

PubMed

Escherichia fergusonii has been associated with a wide variety of intestinal and extraintestinal infections in both humans and animals. The aim of this study was to demonstrate the presence of heat-labile enterotoxin (LT)-producing E. fergusonii in healthy chickens and its plasmid-mediated LT toxin gene transfer to other Enterobacteriaceae. We tested faecal samples from 184 chicken flocks (consisting of 109 broilers and 75 layers) of 78 commercial chicken farms for the presence of the LT gene using a polymerase chain reaction-based screening and identified samples from 43 flocks (23.4%) as positive for the LT gene. We subsequently isolated and identified E. fergusonii harboring the LT gene from all LT-positive samples and observed 21 various biochemical types. The plasmids encoding LT in 16 (37.2%) of the 43 isolates were conjugally transferred to the recipient strain Escherichia coli J53. Southern hybridization showed that all plasmids from the transconjugants carried the eltAB gene (Ent plasmid) and belonged to the narrow-host-range IncF type. In addition, all the E. fergusonii strains identified were classified into 17 pulsed-field gel electrophoresis (PFGE) types, and it is likely that there was an association between the PFGE types and geographical location or breed of flocks. In conclusion, this is the first study to demonstrate that LT-producing E. fergusonii strains were present in the faeces of healthy chickens and that plasmid-mediated virulence genes can be transferred to E. coli and may have a great potential to cause human disease. PMID:22771038

Oh, Jae-Young; Kang, Min-Su; An, Byung-Ki; Shin, Eun-Gyeong; Kim, Mi-Jin; Kwon, Jun-Hun; Kwon, Yong-Kuk

2012-06-01

44

EXPRESSION OF A SYNTHETIC E. COLI HEAT LABILE ENTEROTOXIN B SUBUNIT (LTB) IN MAIZE  

Technology Transfer Automated Retrieval System (TEKTRAN)

We have produced the B sub-unit of the enterotoxigenic Escherischia coli (ETEC) heat labile enterotoxin (LT-B) in transgenic maize seed. LT-B is a model antigen that induces a strong immune response upon oral administration and enhances immune responses to conjugated and co-administered antigens. ...

45

Residues of Heat-Labile Enterotoxin Involved in Bacterial Cell Surface Binding  

Microsoft Academic Search

Enterotoxigenic Escherichia coli (ETEC) is a leading cause of traveler's diarrhea worldwide. One major virulence factor released by this pathogen is the heat-labile enterotoxin LT, which upsets the balance of electrolytes in the intestine. After export, LT binds to lipopolysaccharide (LPS) on the bacterial surface. Although the residues responsible for LT's binding to its host receptor are known, the portion

Benjamin Mudrak; Daniel L. Rodriguez; Meta J. Kuehn

2009-01-01

46

Expression of Functional Pentameric Heat-Labile Enterotoxin B Subunit of Escherichia coli in Saccharomyces cerevisiae  

Microsoft Academic Search

Although the Escherichia coli heat-labile enterotoxin B subunit (LTB) has already been expressed in several different systems, including prokaryotic and eukaryotic organisms, studies regarding the synthesis of LTB into oligomeric structures of pentameric size in the budding yeast Saccharomyces cerevisiae have been limited. Therefore, this study used a functional signal peptide of the amylase 1A protein from rice to direct

Jung-Gu Lim; Jung-Ae Kim; Hea-Jong Chung; Tae-Geum Kim; Jung-Mi Kim; Kyung-Ryul Lee; Seung-Moon Park; Moon-Sik Yang; Dae-Hyuk Kim

2009-01-01

47

Heat-labile bacterial alkaline phosphatase from a marine Vibrio sp  

Microsoft Academic Search

Psychrophilic organisms have successfully adapted to various low-temperature environments such as cold ocean waters. Catalysts with increased catalytic efficiencies are produced, generally at the expense of thermal stability due to fewer non-covalent stabilizing interactions. A marine bacterial strain producing a particularly heat-labile alkaline phosphatase was selected from a total of 232 strains isolated from North-Atlantic coastal waters. From partial 16S

Jónas B. Hauksson; Ólafur S. Andrésson; Bjarni Ásgeirsson

2000-01-01

48

Heat-Labile- and Heat-Stable-Toxoid Fusions (LTR192G-STaP13F) of Human Enterotoxigenic Escherichia coli Elicit Neutralizing Antitoxin Antibodies ?  

PubMed Central

Enterotoxigenic Escherichia coli (ETEC) strains are a major cause of diarrheal disease in humans and animals. Adhesins and enterotoxins, including heat-labile (LT) and heat-stable (STa) toxins, are the key virulence factors. Antigenic adhesin and LT antigens have been used in developing vaccines against ETEC diarrhea. However, STa has not been included because of its poor immunogenicity and potent toxicity. Our recent study showed that porcine-type STa toxoids became immunogenic and elicited neutralizing anti-STa antibodies after being genetically fused to a full-length porcine-type LT toxoid, LTR192G (W. Zhang et al., Infect. Immun. 78:316-325, 2010). In this study, we mutated human-type LT and STa genes, which are highly homologous to porcine-type toxin genes, for a full-length LT toxoid (LTR192G) and a full-length STa toxoid (STaP13F) and genetically fused them to produce LT192-STa13 toxoid fusions. Mice immunized with LT192-STa13 fusion antigens developed anti-LT and anti-STa IgG (in serum and feces) and IgA antibodies (in feces). Moreover, secretory IgA antibodies from immunized mice were shown to neutralize STa and cholera toxins in T-84 cells. In addition, we fused the STa13 toxoid at the N terminus and C terminus, between the A1 and A2 peptides, and between the A and B subunits of LT192 to obtain different fusions in order to explore strategies for enhancing STa immunogenicity. This study demonstrated that human-type LT192-STa13 fusions induce neutralizing antitoxin antibodies and provided important information for developing toxoid vaccines against human ETEC diarrhea.

Liu, Mei; Ruan, Xiaosai; Zhang, Chengxian; Lawson, Steve R.; Knudsen, David E.; Nataro, James P.; Robertson, Donald C.; Zhang, Weiping

2011-01-01

49

Type II Heat-Labile Enterotoxins from 50 Diverse Escherichia coli Isolates Belong Almost Exclusively to the LT-IIc Family and May Be Prophage Encoded  

PubMed Central

Some enterotoxigenic Escherichia coli (ETEC) produce a type II heat-labile enterotoxin (LT-II) that activates adenylate cyclase in susceptible cells but is not neutralized by antisera against cholera toxin or type I heat-labile enterotoxin (LT-I). LT-I variants encoded by plasmids in ETEC from humans and pigs have amino acid sequences that are ?95% identical. In contrast, LT-II toxins are chromosomally encoded and are much more diverse. Early studies characterized LT-IIa and LT-IIb variants, but a novel LT-IIc was reported recently. Here we characterized the LT-II encoding loci from 48 additional ETEC isolates. Two encoded LT-IIa, none encoded LT-IIb, and 46 encoded highly related variants of LT-IIc. Phylogenetic analysis indicated that the predicted LT-IIc toxins encoded by these loci could be assigned to 6 subgroups. The loci corresponding to individual toxins within each subgroup had DNA sequences that were more than 99% identical. The LT-IIc subgroups appear to have arisen by multiple recombinational events between progenitor loci encoding LT-IIc1- and LT-IIc3-like variants. All loci from representative isolates encoding the LT-IIa, LT-IIb, and each subgroup of LT-IIc enterotoxins are preceded by highly-related genes that are between 80 and 93% identical to predicted phage lysozyme genes. DNA sequences immediately following the B genes differ considerably between toxin subgroups, but all are most closely related to genomic sequences found in predicted prophages. Together these data suggest that the LT-II loci are inserted into lambdoid type prophages that may or may not be infectious. These findings raise the possibility that production of LT-II enterotoxins by ETEC may be determined by phage conversion and may be activated by induction of prophage, in a manner similar to control of production of Shiga-like toxins by converting phages in isolates of enterohemmorhagic E. coli.

Jobling, Michael G.; Holmes, Randall K.

2012-01-01

50

Serotype-related differences in production and type of heat-labile hemolysin and heat-labile cytotoxin of Actinobacillus (Haemophilus) pleuropneumoniae.  

PubMed Central

Reference strains of serotypes 1 to 12 of Actinobacillus (Haemophilus) pleuropneumoniae were cultured in Eagle minimal essential medium with 10% Serum Plus. Culture supernatants were examined for cytotoxicity to alveolar macrophages and for the ability to hemolyze sheep erythrocytes. All strains except the reference strain of serotype 6 produced cytotoxin, whereas only serotypes 1, 5, 9, 10, and 11 produced hemolysin. Both cytotoxin and hemolysin appeared to be heat labile. Antisera were raised against cytotoxin- and hemolysin-containing culture supernatants of serotypes 1 to 11. Cross-neutralization studies revealed that the hemolysins were serologically homogeneous. In contrast, four serologically different cytotoxins were distinguished. One cytotoxin was produced by serotypes 1, 5, 9, and 11, and a second was produced by serotypes 2, 3, 4, and 8. A third cytotoxin was produced by serotypes 7 and 12; this cytotoxin was related to the cytotoxins of serotypes 1, 2, 4, 5, 9, and 11. A fourth cytotoxin, produced by serotype 10, was related to the cytotoxin of serotypes 1, 5, 9, and 11. Seventy field strains belonging to serotypes 2, 3, 7, 8, 9, and 11 were also tested for production of cytotoxin and hemolysin. All strains belonging to serotypes 9 and 11 produced hemolysin and cytotoxin, whereas all strains of serotypes 2, 3, 7, and 8 produced only cytotoxin. Hemolysins and cytotoxins of both the field strains and the corresponding serotype reference strains were comparably neutralized. These findings strongly suggest that the observed differences in production and type of hemolysin and cytotoxin were related to serotype and not to strain.

Kamp, E M; van Leengoed, L A

1989-01-01

51

Efficacy of the Heat-Labile Enterotoxin from Escherichia Coli as an Adjuvant for a HSV-2 Inactivated Oral Vaccine.  

National Technical Information Service (NTIS)

This project examined the efficacy of the heat-labile enterotoxin from Escherichia coli (LT) as an adjuvant for an inactivated HSV-2 vaccine. Using 5-week-old BAB/c mice, three oral doses of inactivated HSV-2/LT (25 ug/25 ug) vaccine given at weekly inter...

A. J. Pinto

1996-01-01

52

Expression of the B Subunit of E. coli Heat-labile Enterotoxin in the Chloroplasts of Plants and its Characterization  

Microsoft Academic Search

Transgenic chloroplasts have become attractive systems for heterologous gene expressions because of unique advantages. Here, we report a feasibility study for producing the nontoxic B subunit of Escherichia coli heat-labile enterotoxin (LTB) via chloroplast transformation of tobacco. Stable site-specific integration of the LTB gene into chloroplast genome was confirmed by PCR and genomic Southern blot analysis in transformed plants. Immunoblot

Tae-Jin Kang; Nguyen-Hoang Loc; Mi-Ok Jang; Yong-Suk Jang; Young-Sook Kim; Jo-Eun Seo; Moon-Sik Yang

2003-01-01

53

Expression of the B subunit of Escherichia coli heat-labile enterotoxin as a fusion protein in transgenic tomato  

Microsoft Academic Search

Epitopes often require co-delivery with an adjuvant or targeting protein to enable recognition by the immune system. This paper reports the ability of transgenic tomato plants to express a fusion protein consisting of the B subunit of the Escherichia coli heat-labile enterotoxin (LTB) and an immunocontraceptive epitope. The fusion protein was found to assemble into pentamers, as evidenced by its

A. M. Walmsley; M. L. Alvarez; Y. Jin; D. D. Kirk; S. M. Lee; J. Pinkhasov; M. M. Rigano; C. J. Arntzen; H. S. Mason

2003-01-01

54

Oral immunization of mice with attenuated Salmonella enteritidis containing a recombinant plasmid which codes for production of the B subunit of heat-labile Escherichia coli enterotoxin.  

PubMed Central

We used Salmonella enteritidis serotype dublin strain SL1438, a nonreverting, aromatic-dependent, histidine-requiring mutant, as a recipient for a recombinant plasmid coding for production of the nontoxic B subunit of the heat-labile Escherichia coli enterotoxin. The S. enteritidis derivative EL23 produced heat-labile enterotoxin subunit B that was indistinguishable from heat-labile enterotoxin subunit B produced by strains of E. coli or Salmonella typhi harboring the same plasmid. Mice immunized orally with strain EL23 developed progressively increasing mucosal and serum antibody responses to both heat-labile enterotoxin subunit B and to the lipopolysaccharide of the vaccine strain. The mucosal antibody response was shown to be immunoglobulin A specific and to be capable of neutralizing the biological activities of both E. coli heat-labile enterotoxin and cholera enterotoxin in vitro. Images

Clements, J D; Lyon, F L; Lowe, K L; Farrand, A L; el-Morshidy, S

1986-01-01

55

Adjuvant Activity of a Nontoxic Mutant of Escherichia coli Heat-Labile Enterotoxin on Systemic and Mucosal Immune Responses Elicited against a Heterologous Antigen Carried by a Live Salmonella enterica Serovar Typhimurium Vaccine Strain  

PubMed Central

Systemic and mucosal antibody responses against both the major subunit of colonization factor antigen I (CFA/I) of enterotoxigenic Escherichia coli (ETEC) and the somatic lipopolysaccharide expressed by recombinant bivalent Salmonella vaccine strains were significantly enhanced by coadministration of a detoxified derivative with preserved adjuvant effects of the ETEC heat-labile toxin, LT(R192G). The results further support the adjuvant effects of LT(R192G) and represent a simple alternative to improve responses against passenger antigens expressed by orally delivered Salmonella vaccine strains.

Guillobel, Heloisa C. R.; Carinhanha, Joana I.; Cardenas, Lucia; Clements, John D.; de Almeida, Darcy F.; Ferreira, Luis C. S.

2000-01-01

56

Secretory IgA-mediated protection against V. cholerae and heat-labile enterotoxin-producing enterotoxigenic Escherichia coli by rice-based vaccine  

PubMed Central

Cholera and enterotoxigenic Escherichia coli (ETEC) are among the most common causes of acute infantile gastroenteritis globally. We previously developed a rice-based vaccine that expressed cholera toxin B subunit (MucoRice-CTB) and had the advantages of being cold chain–free and providing protection against cholera toxin (CT)–induced diarrhea. To advance the development of MucoRice-CTB for human clinical application, we investigated whether the CTB-specific secretory IgA (SIgA) induced by MucoRice-CTB gives longstanding protection against diarrhea induced by Vibrio cholerae and heat-labile enterotoxin (LT)–producing ETEC (LT-ETEC) in mice. Oral immunization with MucoRice-CTB stored at room temperature for more than 3 y provided effective SIgA-mediated protection against CT- or LT-induced diarrhea, but the protection was impaired in polymeric Ig receptor–deficient mice lacking SIgA. The vaccine gave longstanding protection against CT- or LT-induced diarrhea (for ?6 months after primary immunization), and a single booster immunization extended the duration of protective immunity by at least 4 months. Furthermore, MucoRice-CTB vaccination prevented diarrhea in the event of V. cholerae and LT-ETEC challenges. Thus, MucoRice-CTB is an effective long-term cold chain–free oral vaccine that induces CTB-specific SIgA-mediated longstanding protection against V. cholerae– or LT-ETEC–induced diarrhea.

Tokuhara, Daisuke; Yuki, Yoshikazu; Nochi, Tomonori; Kodama, Toshio; Mejima, Mio; Kurokawa, Shiho; Takahashi, Yuko; Nanno, Masanobu; Nakanishi, Ushio; Takaiwa, Fumio; Honda, Takeshi; Kiyono, Hiroshi

2010-01-01

57

Thermo-osmoregulation of heat-labile enterotoxin expression by Escherichia coli.  

PubMed

Enterotoxigenic Escherichia coli causes diarrhea by producing several virulence factors including heat-labile enterotoxin (LT). LT is maximally expressed at 37 degrees C. The histone-like nucleoid structuring protein (H-NS) appears to inhibit LT expression by binding to a downstream regulatory element (DRE) at low temperatures. An hns+ E. coli strain, X7026, carrying an LT-beta-galactosidase translational fusion plasmid (pLT-lac) was shown to be responsive to varying amounts of sodium chloride (NaCl) as well as sucrose or lithium chloride. Maximal responsiveness to the various osmolytes was obtained with cells grown at 37 degrees C under microaerophilic conditions. Temperature-osmotic upshift experiments demonstrate LT expression is thermo-osmoregulated. pLT-lac was tested in an hns strain or its congenic hns+ strain for its response to NaCl. LT expression is elevated in the hns strain regardless of NaCl concentration and retains its osmoresponsiveness. The response of the DRE deletion plasmid (pLT-lacDeltaNC) to NaCl is similar to that of the undeleted plasmid. PMID:15486710

Trachman, Julie D; Yasmin, Munira

2004-11-01

58

Effect of stress on production of heat labile enterotoxin by Escherichia coli.  

PubMed

Enterotoxigenic Escherichia coli (ETEC) is an important pathogen responsible for secretory diarrhoea. The production of heat labile enterotoxin (LT), by ETEC, is largely responsible for the pathogenesis of diarrhoea. In the present study we investigated the effect of stress factors such as temperature, pH, osmotic stress and nutritional limitation on the production of LT by ETEC using in-house GMI-ELISA. Four strains of E. coli consisting, one standard strain MTCC 723 and three clinical isolates were used in the study. Maximum amount of LT (OD 3.285) was produced at 37 0 C followed by 40 0 C (OD 3.305). Growth of E. coli in medium with pH 8.6 resulted in maximum amount of LT production (OD 3.489). LT was not detectable when bacteria were grown in medium with pH < or =7.2 and > or = 9.2. Sodium chloride concentration of 0.2 M stimulated maximum amount of LT production. Maximum amount of LT was produced when the bacteria were grown in medium containing 2.5 g/l of glucose. All the stress factors had a significant effect on the LT production by E. coli , though quantitative differences in the various strains were observed. PMID:19736401

Hegde, A; Bhat, G K; Mallya, S

59

Edible vaccine protects mice against Escherichia coli heat-labile enterotoxin (LT): potatoes expressing a synthetic LT-B gene  

Microsoft Academic Search

The authors have designed and constructed a plant-optimized synthetic gene encoding the Escherichia coli heat-labile enterotoxin B subunit (LT-B), for use in transgenic plants as an edible vaccine against enterotoxigenic E. coli. Expression of the synthetic LT-B gene in potato plants under the control of a constitutive promoter yielded increased accumulation of LT-B in leaves and tubers, as compared to

Hugh S. Mason; Tariq A. Haq; John D. Clements; Charles J. Arntzen

1998-01-01

60

Inhibition of T-cell Response by Escherichia coli Heat-Labile Enterotoxin-Treated Epithelial Cells  

Microsoft Academic Search

Escherichia coli heat-labile enterotoxin (LT) is an extensively studied adjuvant of mucosal responses. Nevertheless, its mode of action as an adjuvant remains incompletely understood. In this study, we describe a simplified in vitro model with which to look at some aspects of immunoregulation by LT. The interaction of LT with the apical surface of a monolayer of CaCo-2 epithelial cells

LUCIENE M. LOPES; ASHER MAROOF; GORDON DOUGAN; BENJAMIN M. CHAIN

2000-01-01

61

Detection of Heat-Labile Escherichia coli Enterotoxin with the Use of Adrenal Cells in Tissue Culture  

Microsoft Academic Search

Cell-free culture filtrates of heat-labile enterotoxin-producing strains of Escherichia coli are capable of inducing morphological changes and steroidogenesis in monolayer cultures of adrenal cells. These tissue culture changes are similar to those induced by cholera enterotoxin and cannot be effected by culture filtrates of other enterotoxigenic or enteropathogenic types of bacteria. The results of the tissue culture studies correlated well

Sam T. Donta; Harley W. Moon; Shannon C. Whipp

1974-01-01

62

Expression of the Escherichia coli heat-labile enterotoxin B subunit in transgenic watercress ( Nasturtium officinale L . )  

Microsoft Academic Search

A gene encoding the B subunit of the enterotoxigenic Escherichia coli heat-labile enterotoxin (LTB) was adapted to the optimized plant coding sequence, and fused to the endoplasmic reticulum\\u000a retention signal SEKDEL in order to enhance its expression level and protein assembly in plants. The synthetic LTB (sLTB)\\u000a gene was placed into a plant expression vector under the control of the

Nguyen Hoang Loc; Nguyen Van Song; Nguyen Quang Duc Tien; Tang Thuy Minh; Phan Thi Quynh Nga; Tae-Geum Kim; Moon-Sik Yang

2011-01-01

63

Real-Time Fluorescence PCR Assays for Detection and Characterization of Heat-Labile I and Heat-Stable I Enterotoxin Genes from Enterotoxigenic Escherichia coli  

Microsoft Academic Search

To facilitate the diagnosis of enterotoxigenic Escherichia coli (ETEC) infections in humans, we developed and evaluated real-time fluorescence PCR assays for the Roche LightCycler (LC) against the enterotoxin genes commonly present in strains associated with human illness. Separate LC-PCR assays with identical cycling conditions were designed for the type I heat-labile enterotoxin (LT I) and the type I heat-stable enterotoxin

Udo Reischl; Mohammad T. Youssef; Hans Wolf; Eija Hyytia-Trees; Nancy A. Strockbine

2004-01-01

64

Marine neurotoxins: Envenomations and contact toxins  

Microsoft Academic Search

Opinion statement  Familiarity with the appearance and habitat of venomous sea creatures, the location of their stinging apparatus, and surveillance\\u000a of population concentrations within recreational waters are essential in avoiding envenomations. Compared with the thermo-stable\\u000a low molecular weighted ingestible seafood toxins, venomous toxins are often large molecular weight proteins and many are heat\\u000a labile, which provides opportunity for therapeutic intervention. Heat

Michael R. Watters; Elijah W. Stommel

2004-01-01

65

Toxicity and Immunogenicity of Enterotoxigenic Escherichia coli Heat-Labile and Heat-Stable Toxoid Fusion 3xSTaA14Q-LTS63K/R192G/L211A in a Murine Model  

PubMed Central

Diarrhea is the second leading cause of death to young children. Enterotoxigenic Escherichia coli (ETEC) are the most common bacteria causing diarrhea. Adhesins and enterotoxins are the virulence determinants in ETEC diarrhea. Adhesins mediate bacterial attachment and colonization, and enterotoxins including heat-labile (LT) and heat-stable type Ib toxin (STa) disrupt fluid homeostasis in host cells that leads to fluid hyper-secretion and diarrhea. Thus, adhesins and enterotoxins have been primarily targeted in ETEC vaccine development. A recent study reported toxoid fusions with STa toxoid (STaP13F) fused at the N- or C-terminus, or inside the A subunit of LTR192G elicited neutralizing antitoxin antibodies, and suggested application of toxoid fusions in ETEC vaccine development (Liu et al., Infect. Immun. 79:4002-4009, 2011). In this study, we generated a different STa toxoid (STaA14Q) and a triple-mutant LT toxoid (LTS63K/R192G/L211A, tmLT), constructed a toxoid fusion (3xSTaA14Q-tmLT) that carried 3 copies of STaA14Q for further facilitation of anti-STa immunogenicity, and assessed antigen safety and immunogenicity in a murine model to explore its potential for ETEC vaccine development. Mice immunized with this fusion antigen showed no adverse effects, and developed antitoxin antibodies particularly through the IP route. Anti-LT antibodies were detected and were shown neutralizing against CT in vitro. Anti-STa antibodies were also detected in the immunized mice, and serum from the IP immunized mice neutralized STa toxin in vitro. Data from this study indicated that toxoid fusion 3xSTaA14Q-tmLT is safe and can induce neutralizing antitoxin antibodies, and provided helpful information for vaccine development against ETEC diarrhea.

Zhang, Chengxian; Knudsen, David E.; Liu, Mei; Robertson, Donald C.; Zhang, Weiping

2013-01-01

66

Toxicity and Immunogenicity of Enterotoxigenic Escherichia coli Heat-Labile and Heat-Stable Toxoid Fusion 3xSTaA14Q-LTS63K/R192G/L211A in a Murine Model.  

PubMed

Diarrhea is the second leading cause of death to young children. Enterotoxigenic Escherichia coli (ETEC) are the most common bacteria causing diarrhea. Adhesins and enterotoxins are the virulence determinants in ETEC diarrhea. Adhesins mediate bacterial attachment and colonization, and enterotoxins including heat-labile (LT) and heat-stable type Ib toxin (STa) disrupt fluid homeostasis in host cells that leads to fluid hyper-secretion and diarrhea. Thus, adhesins and enterotoxins have been primarily targeted in ETEC vaccine development. A recent study reported toxoid fusions with STa toxoid (STaP13F) fused at the N- or C-terminus, or inside the A subunit of LTR192G elicited neutralizing antitoxin antibodies, and suggested application of toxoid fusions in ETEC vaccine development (Liu et al., Infect. Immun. 79:4002-4009, 2011). In this study, we generated a different STa toxoid (STaA14Q) and a triple-mutant LT toxoid (LTS63K/R192G/L211A, tmLT), constructed a toxoid fusion (3xSTaA14Q-tmLT) that carried 3 copies of STaA14Q for further facilitation of anti-STa immunogenicity, and assessed antigen safety and immunogenicity in a murine model to explore its potential for ETEC vaccine development. Mice immunized with this fusion antigen showed no adverse effects, and developed antitoxin antibodies particularly through the IP route. Anti-LT antibodies were detected and were shown neutralizing against CT in vitro. Anti-STa antibodies were also detected in the immunized mice, and serum from the IP immunized mice neutralized STa toxin in vitro. Data from this study indicated that toxoid fusion 3xSTaA14Q-tmLT is safe and can induce neutralizing antitoxin antibodies, and provided helpful information for vaccine development against ETEC diarrhea. PMID:24146989

Zhang, Chengxian; Knudsen, David E; Liu, Mei; Robertson, Donald C; Zhang, Weiping

2013-10-11

67

Membrane-wall interrelationship in Gaffkya homari: sulfhydryl sensitivity and heat lability of nascent peptidoglycan incorporation into walls.  

PubMed Central

Membrane-walls from Gaffkya homari require a specific interrelationship between membrane and wall that functions in the incorporation of nascent peptidoglycan into the preexisting peptidoglycan of the wall. Two different methods were used to inhibit selectively this incorporation process: (i) sensitivity to sulfhydryl reagents and (ii) heat inactivation. Of the sulfhydryl reagents tested, 2.2 mM iodoacetamide inhibited the synthesis of wall peptidoglycan 50%, whereas greater than 100 mM was required to inhibit the synthesis of sodium dodecyl sulfate (SDS)-soluble peptidoglycan. Heat treatment at 37 degrees C (t 1/2 = 5.7 min) inhibited wall peptidoglycan synthesis without affecting SDS-soluble peptidoglycan synthesis. Inhibition of LD-carboxypeptidase by iodoacetamide and heat gave 50% inhibition and t 1/2 values similar to those observed for the incorporation process. Thus, it is suggested that the LD-carboxypeptidase may be one of the enzymes responsible for the sulfhydryl sensitivity and heat lability and that this enzyme may play a role in the relationship between membrane and wall in G. homari.

Neuhaus, F C; Tobin, C E; Ahlgren, J A

1980-01-01

68

Expression of the B subunit of E. coli heat-labile enterotoxin in tobacco using a herbicide resistance gene as a selection marker  

Microsoft Academic Search

The B subunit of Escherichia coli heat-labile enterotoxin (LTB) has been transformed to plants for use as an edible vaccine. We have developed a simple and reliable Agrobacterium-mediated transformation method to express synthetic LTB gene in N. tabacum using a phosphinothricin acetyltransferase (bar) gene as a selectable marker. The synthetic LTB gene adapted to the coding sequence of tobacco plants

Tae-Jin Kang; So-Chon Han; Moon-Sik Yang

2005-01-01

69

Evaluation of heat-labile enterotoxins type IIa and type IIb in the pathogenicity of enterotoxigenic Escherichia coli for neonatal pigs  

Technology Transfer Automated Retrieval System (TEKTRAN)

Type II heat-labile enterotoxins (LT-II) have been reported in Escherichia coli isolates from humans, animals, food and water samples. The roles of the antigenically distinguishable LT-IIa and LT-IIb subtypes in pathogenesis and virulence of enterotoxigenic E. coli (ETEC) have not been previously re...

70

Studies on a Heat-Labile Variola Virus Inhibitor in Normal Sera. I. Detection by the Variola Focus Reduction Assay and its General Characteristics  

Microsoft Academic Search

Summary A heat-labile inhibitor (HLI) capable of neutralizing the infectivity of variola virus, as measured by reduction of focus-forming and plaque-forming activity, was detected in normal human, guinea pig, rabbit and monkey sera. HLI lost its activity on incubation at 56° for 30 min, and showed different behaviors from complement in heat inactivation curves as well as in specific absorption

Takashi Kitamura; Yoshiko Miyagawa; Yukië Tanaka

1973-01-01

71

Heat-stable toxin production by strains of Bacillus cereus, Bacillus firmus, Bacillus megaterium, Bacillus simplex and Bacillus licheniformis  

Microsoft Academic Search

Strains of Bacillus cereus can produce a heat-stable toxin (cereulide). In this study, 101 Bacillus strains representing 7 Bacillus species were tested for production of heat-stable toxins. Strains of B. megaterium, B. firmus and B. simplex were found to produce novel heat-stable toxins, which showed varying levels of toxicity. B. cereus strains (18 out of 54) were positive for toxin

Janice M. W. Taylor; Alastair D. Sutherland; Kofi E. Aidoo; Niall A. Logan

2005-01-01

72

Immunocytochemical localization of calmodulin and a heat-labile calmodulin-binding protein (CaM-BP80) in basal ganglia of mouse brain  

PubMed Central

Antisera to calmodulin, a Ca2%-dependent modulator protein, and a heat- labile calmodulin-binding protein have been used to localize these proteins in mouse caudate-putamen. The two proteins appear to be located at identical sites in this brain area. At the light microscopic level, calmodulin and calmodulin-binding protein are found within the cytoplasm and processes of large cells. At the electron microscopic level the proteins are associated with neuronal elements only, primarily at postsynaptic sites within neuronal somata and dendrites. Within the dendrites the immunocytochemical label is associated predominantly with the postsynaptic density and dendritic microtubules. These results are in accord with recent biochemical and immunihistochemical studies of calmodulin in brain and in dividing cells. Thus, calmodulin and the heat-labile calmodulin-binding protein may play a role in the nervous system at the site of neurotransmitter action and at the level of microtubular function.

1980-01-01

73

Antigen B of the vaccine strains of Marek's disease virus and herpesvirus of turkeys presents heat-labile group and serotype specific epitopes  

Microsoft Academic Search

Summary Antigen B of Marek's disease virus (MDV) vaccine strains CVI988 and SB1 (serotypes 1 and 2) and herpesvirus of turkeys (HVT) (serotype 3) is formed of oligomeric molecules that are detergent-stable and heat-labile. Immunoblots of native membranal extracts of HVT- and MDV-infected chick embryo fibroblasts (CEF) probed with avian monoserotypic antisera, murine monoclonal antibodies (mAb) to the three serotypes

M. Malkinson; I. Davidson; Y. Becker

1992-01-01

74

Production of a heat-labile enterotoxin B subunit-porcine epidemic diarrhea virus-neutralizing epitope fusion protein in transgenic lettuce ( Lactuca sativa )  

Microsoft Academic Search

Plant-based vaccines have been produced in transgenic plants including tobacco, potatoes, corn, and rice. However, these plants\\u000a are not suitable for administration without cooking. To overcome this obstacle, a fusion gene encoding the synthetic enterotoxigenic\\u000a Escherichia coli heat-labile enterotoxin B subunit genetically fused with a synthetic neutralizing epitope of porcine epidemic diarrhea virus\\u000a (sLTB-sCOE) was introduced into lettuce cells (Lactuca

Nguyen-Xuan Huy; Young-Sook Kim; Sang-Chel Jun; Zhewu Jin; Seung-Moon Park; Moon-Sik Yang; Tae-Geum Kim

2009-01-01

75

Expression of a synthetic neutralizing epitope of porcine epidemic diarrhea virus fused with synthetic B subunit of Escherichia coli heat labile enterotoxin in rice endosperm  

Microsoft Academic Search

Epitopes often require co-delivery with adjuvant and targeting proteins to enable recognition by the immune system, and this\\u000a approach may also increase the efficacy of the antigen. In this study, we assess and describe the ability of transgenic rice\\u000a plants to express a fusion protein consisting of the B-subunit of the Escherichia coli heat-labile enterotoxin (LTB) and a synthetic core-neutralizing

Maria Oszvald; Tae-Jin Kang; Sandor Tomoskozi; Cecilia Tamas; Laszlo Tamas; Tae-Geum Kim; Moon-Sik Yang

2007-01-01

76

Expression of synthetic neutralizing epitope of porcine epidemic diarrhea virus fused with synthetic B subunit of Escherichia coli heat-labile enterotoxin in tobacco plants  

Microsoft Academic Search

The pentameric B subunit of Escherichia coli heat-labile enterotoxin (LTB) can be used as an efficient mucosal carrier of either immunogenic or tolerogenic T-cell epitopes. Co-delivery of therapeutic proteins with carrier proteins could increase the effectiveness of the antigen. This paper reports the ability of transgenic tobacco plants to express a fusion protein consisting of the synthetic LTB and a

Tae-Jin Kang; So-Chon Han; Moon-Sik Yang; Yong-Suk Jang

2006-01-01

77

Serotyping of Campylobacter jejuni by slide agglutination based on heat-labile antigenic factors.  

PubMed Central

A serotyping scheme for Campylobacter jejuni was developed based on slide agglutination of live bacteria with whole cell antisera absorbed with homologous heated and heterologous unheated cross-reactive antigens. Among 815 isolates from human and nonhuman sources, 21 serogroups were recognized. Of the 615 isolates from human cases of gastroenteritis, 529 (86%) were typable; 455 strains agglutinated in 20 single antisera, whereas 74 isolates agglutinated in various pairs of antisera, allowing subdivision of some main serogroups into subserogroups. Of the 200 isolates of C. jejuni from nonhuman sources (chicken, swine, etc.), 166 (83%) were typable, 145 cultures agglutinated in various single antisera, and 21 strains agglutinated with different pairs of antisera. Among isolates from all sources, 8 serogroups (1, 2, 4, 5, 7, 8, 9, and 11) were encountered most frequently. Serogroups 1, 2, 4, 5, 7, 9, and 11 were most common among human isolates; the majority of the chicken and all of the swine isolates belonged to the same serogroups identified from human cases. Very good serological correlation was obtained in 20 family outbreaks and 4 community outbreaks.

Lior, H; Woodward, D L; Edgar, J A; Laroche, L J; Gill, P

1982-01-01

78

Both enzymatic and non-enzymatic properties of heat-labile enterotoxin are responsible for LT-enhanced adherence of enterotoxigenic Escherichia coli to porcine IPEC-J2 cells.  

PubMed

Previous studies in piglets indicate that heat labile enterotoxin (LT) expression enhances intestinal colonization by K88 adhesin-producing enterotoxigenic Escherichia coli (ETEC) as wild-type ETEC adhered to intestinal epithelium in substantially greater numbers than did non-toxigenic constructs. Enzymatic activity of the toxin was also shown to contribute to the adhesion of ETEC and non-ETEC bacteria to epithelial cells in culture. To further characterize the contribution of LT to host cell adhesion, a nontoxigenic, K88-producing E. coli was transformed with either the gene encoding for LT holotoxin, a catalytically-attenuated form of the toxin [LT(R192G)], or LTB subunits, and resultant changes in bacterial adherence to IPEC-J2 porcine intestinal epithelial cells were measured. Strains expressing LT holotoxin or mutants were able to adhere in significantly higher numbers to IPEC-J2 cells than was an isogenic, toxin-negative construct. LT+ strains were also able to significantly block binding of a wild-type LT+ ETEC strain to IPEC-J2 cells. Adherence of isogenic strains to IPEC-J2 cells was unaltered by cycloheximide treatment, suggesting that LT enhances ETEC adherence to IPEC-J2 cells independent of host cell protein synthesis. However, pretreating IPEC-J2 cells with LT promoted adherence of negatively charged latex beads (a surrogate for bacteria which carry a negative change), which adherence was inhibited by cycloheximide, suggesting LT may induce a change in epithelial cell membrane potential. Overall, these data suggest that LT may enhance ETEC adherence by promoting an association between LTB and epithelial cells, and by altering the surface charge of the host plasma membrane to promote non-specific adherence. PMID:23517763

Fekete, Peter Z; Mateo, Kristina S; Zhang, Weiping; Moxley, Rodney A; Kaushik, Radhey S; Francis, David H

2013-02-28

79

Inhibition of Cronobacter sakazakii by Heat Labile Bacteriocins Produced by Probiotic LAB Isolated from Healthy Infants.  

PubMed

Cronobacter sakazakii is an opportunistic pathogen that can cause bacteremia, meningitis, and necrotizing enterocolitis, most often in neonates with case-fatality rates that may reach 80%. The antimicrobial activity of lactic acid bacteria against a wide range of foodborne pathogens is well-established in different types of food products. The objective of the current study was to investigate the antibacterial activity of Lactobacillus acidophilus and L. casei isolated from feces of healthy infants against different strains of C. sakazakii in agar and a rehydrated infant milk formula (RIMF) model. The inhibition zones of C. sakazakii around L. acidophilus or L. casei ranged from 22 to 32 mm on eMan Rogosa Sharpe (MRS) agar under aerobic conditions, while a slight reduction in antibacterial activity was noted on modified MRS (0.2% glucose) under anaerobic conditions. It was observed that pH-neutralized cell-free supernatant (CFS) of L. acidophilus or L. casei was inhibitory against tested C. sakazakii strains. The inhibition zones of neutralized CFS were lower than the antibacterial activities of live cultures. The antibacterial activity of CFS was abolished when CFS from L. acidophilus or L. casei was heated at 60 or 80 °C for either 10 min or 2 h, or treated with trypsin or pepsin. This was considered strong evidence that the inhibition was due to the production of bacteriocins by L. casei and L. acidophilus. Both the CFS and active growing cells of L. casei and L. acidophilus were able to reduce the viability of C. sakazakii in the RIMF model. The results may extend the use of natural antimicrobials instead of conventional preservation methods to improve the safety of RIMF. PMID:23924352

Awaisheh, Saddam S; Al-Nabulsi, Anas A; Osaili, Tareq M; Ibrahim, Salam; Holley, Richard

2013-08-07

80

Identification of a point mutation resulting in a heat-labile adenosine deaminase (ADA) in two unrelated children with partial ADA deficiency.  

PubMed Central

We have determined the mutation in a child with partial adenosine deaminase (ADA) deficiency who is phenotypically homozygous for a mutant ADA gene encoding a heat-labile enzyme (Am. J. Hum. Genet. 38: 13-25). Sequencing of cDNA demonstrated a C to A transversion that results in the replacement of a proline by a glutamine residue at codon 297. As this mutation generated a new recognition site in exon 10 of genomic DNA for the enzyme Alu I, Southern blot analysis was used to establish that this child was indeed homozygous for the mutation. The abnormal restriction fragment generated by this mutation was also found in a second partially ADA-deficient patient who phenotypically is a genetic compound and also expresses a heat-labile ADA (in addition to a more acidic than normal ADA) (Am. J. Hum. Genet. 38: 13-25). Sequencing of cDNA clones from the second patient established the identical codon 297 mutation. Transfection of the mutant cDNA into heterologous cells resulted in expression of a heat-labile ADA of normal electrophoretic mobility and isoelectric point, properties exhibited by the ADA in the patients' cells. Images

Hirschhorn, R; Tzall, S; Ellenbogen, A; Orkin, S H

1989-01-01

81

Effect of Escherichia coli heat-labile enterotoxin on the myoelectric activity of the duodenum in weaned pigs.  

PubMed

The objective of the present study was to elucidate the effect of subclinical doses of Escherichia coli heat-labile enterotoxin (LT) on the antro-duodenal myoelectric activities of weaned pigs. Twelve weaned pigs were surgically implanted with three pairs of electrodes on the antrum 3 cm before the pylorus, 5 and 20 cm after the pylorus on the duodenum, respectively. An infusion cannula was inserted into the duodenum between duodenal electrodes. Using a wireless telemetry recording system, an electromyography (EMG) tracing lasting at least 24 h was recorded as the control, then another 24-h EMG recording was performed with a bolus intraduodenal infusion of LT (0.1 and 0.5 microg/kg b.w.). After a 1- to 2-day break, a 5-fold higher dose of LT was administered using the same protocol. In the antrum, LT administration barely modified the EMG signal. However, in the duodenum it prolonged the duration of phase II and the migrating myoelectric complex (MMC) cycle when compared with the control. The number of duodenal MMC cycles was also significantly diminished. Moreover, the migrating velocity of phase III was increased. The migrating action potential complex (MAPC) was present both without and with LT, but occurred more frequently following LT administration. In conclusion, LT caused a dose-dependent, lagged alteration in the duodenal MMC in weaned pigs, involving a reduction of the MMC number by lengthening phase II, increased phase III migration velocity, and increased MAPC frequency. The disturbances did not, however, result in diarrhoea and may reflect the induction of a local protection mechanism of the gut to expel unwanted foreign content from the lumen of the upper gut. PMID:15214849

Yao, G; Woli?ski, J; Zabielski, R

2004-04-01

82

A mutant cholera toxin B subunit that binds GM1- ganglioside but lacks immunomodulatory or toxic activity  

Microsoft Academic Search

GM1-ganglioside receptor binding by the B subunit of cholera toxin (CtxB) is widely accepted to initiate toxin action by triggering uptake and delivery of the toxin A subunit into cells. More recently, GM1 binding by isolated CtxB, or the related B subunit of Escherichia coli heat-labile enterotoxin (EtxB), has been found to modulate leukocyte function, resulting in the down-regulation of

A. T. Aman; S. Fraser; E. A. Merritt; C. Rodigherio; M. Kenny; M. Ahn; W. G. J. Hol; N. A. Williams; W. I. Lencer; T. R. Hirst

2001-01-01

83

Oral immunisation of mice with a recombinant rabies virus vaccine incorporating the heat-labile enterotoxin B subunit of Escherichia coli in an attenuated Salmonella strain  

Microsoft Academic Search

To investigate effective new rabies vaccines, a fusion protein consisting of the rabies virus (RV) glycoprotein and the heat-labile enterotoxin B subunit of Escherichia coli (LTB) was successfully constructed and delivered in a live attenuated Salmonella strain LH430. Mice were immunised with LH430 carrying pVAX1-G, pVAX1-G-LTB or pVAX1-ori-G-LTB. The antibody titres of mice immunised with oral LH430 carrying pVAX1-G-LTB or

Xuelin Wang; Juan Liu; Xiuping Wu; Lu Yu; Haiying Chen; Heng Guo; Huiping Li; Xue Liu; Shumin Sun; Lijing Zhao; Lixin Chu; Duo Xu; Mingyuan Liu

84

Antibody responses in volunteers induced by nasal influenza vaccine combined with Escherichia coli heat-labile enterotoxin B subunit containing a trace amount of the holotoxin  

Microsoft Academic Search

Evaluation of the efficacy of nasal influenza vaccine combined with Escherichia coli heat-labile enterotoxin B subunit (LTB) containing a trace amount of the holotoxin (LT) in inducing antibody responses among volunteers, which was conducted during the winter season of 1993–1994, is reported. A trivalent inactivated vaccine, composed of A\\/Yamagata\\/32\\/89 (H1N1), A\\/Kitakyusyu\\/159\\/93 (H3N2) and B\\/Bangkok\\/163\\/90 influenza virus strains, was used alone

Kazuhiro Hashigucci; Hiroshi Ogawa; Takeo Ishidate; Ryoko Yamashita; Hitoshi Kamiya; Kouji Watanabe; Nobuaki Hattori; Takaaki Sato; Yujiro Suzuki; Takashi Nagamine; Chikara Aizawa; Shin-ichi Tamura; Takeshi Kurata; Akira Oya

1996-01-01

85

Real-Time Fluorescence PCR Assays for Detection and Characterization of Heat-Labile I and Heat-Stable I Enterotoxin Genes from Enterotoxigenic Escherichia coli  

PubMed Central

To facilitate the diagnosis of enterotoxigenic Escherichia coli (ETEC) infections in humans, we developed and evaluated real-time fluorescence PCR assays for the Roche LightCycler (LC) against the enterotoxin genes commonly present in strains associated with human illness. Separate LC-PCR assays with identical cycling conditions were designed for the type I heat-labile enterotoxin (LT I) and the type I heat-stable enterotoxin (ST I) genes, using the LC hybridization probe format. A duplex assay for ST I with two sets of amplification primers and three hybridization probes was required to detect the major nucleotide sequence variants of ST I, ST Ia and ST Ib. LC-PCR findings from the testing of 161 E. coli isolates of human origin (138 ETEC and 23 non-ETEC) were compared with those obtained by block cycler PCR analysis. The sensitivities and specificities of the LC-PCR assays were each 100% for the LT I and ST I genes. The LC-PCR and block cycler PCR assays were also compared for their abilities to detect LT I and ST I genes in spiked stool specimens with different methods of sample preparation. Findings from these experiments revealed that the limits of detection for the LC-PCR assays were the same or substantially lower than those observed for the block cycler PCR assay. Melting curve analysis of the amplified LT I and ST I genes revealed sequence variation within each gene, which for the ST I genes correlated with the presence of ST Ia and ST Ib. The rapidity, sensitivity, and specificity of the LC-PCR assays make them attractive alternatives to block cycler PCR assays for the detection and characterization of ETEC.

Reischl, Udo; Youssef, Mohammad T.; Wolf, Hans; Hyytia-Trees, Eija; Strockbine, Nancy A.

2004-01-01

86

Influence of host interleukin-10 polymorphisms on development of traveler's diarrhea due to heat-labile enterotoxin-producing Escherichia coli in travelers from the United States who are visiting Mexico.  

PubMed

Up to 60% of U.S. visitors to Mexico develop traveler's diarrhea (TD), mostly due to enterotoxigenic Escherichia coli (ETEC) strains that produce heat-labile (LT) and/or heat-stable (ST) enterotoxins. Distinct single-nucleotide polymorphisms (SNPs) within the interleukin-10 (IL-10) promoter have been associated with high, intermediate, or low production of IL-10. We conducted a prospective study to investigate the association of SNPs in the IL-10 promoter and the occurrence of TD in ETEC LT-exposed travelers. Sera from U.S. travelers to Mexico collected on arrival and departure were studied for ETEC LT seroconversion by using cholera toxin as the antigen. Pyrosequencing was performed to genotype IL-10 SNPs. Stools from subjects who developed diarrhea were also studied for other enteropathogens. One hundred twenty-one of 569 (21.3%) travelers seroconverted to ETEC LT, and among them 75 (62%) developed diarrhea. Symptomatic seroconversion was more commonly seen in subjects who carried a genotype producing high levels of IL-10; it was seen in 83% of subjects with the GG genotype versus 54% of subjects with the AA genotype at IL-10 gene position -1082 (P, 0.02), in 71% of those with the CC genotype versus 33% of those with the TT genotype at position -819 (P, 0.005), and in 71% of those with the CC genotype versus 38% of those with the AA genotype at position -592 (P, 0.02). Travelers with the GCC haplotype were more likely to have symptomatic seroconversion than those with the ATA haplotype (71% versus 38%; P, 0.002). Travelers genetically predisposed to produce high levels of IL-10 were more likely to experience symptomatic ETEC TD. PMID:18579697

Flores, Jose; DuPont, Herbert L; Lee, Stephanie A; Belkind-Gerson, Jaime; Paredes, Mercedes; Mohamed, Jamal A; Armitige, Lisa Y; Guo, Dong-Chuan; Okhuysen, Pablo C

2008-06-25

87

Heat-stable toxin production by strains of Bacillus cereus, Bacillus firmus, Bacillus megaterium, Bacillus simplex and Bacillus licheniformis.  

PubMed

Strains of Bacillus cereus can produce a heat-stable toxin (cereulide). In this study, 101 Bacillus strains representing 7 Bacillus species were tested for production of heat-stable toxins. Strains of B. megaterium, B. firmus and B. simplex were found to produce novel heat-stable toxins, which showed varying levels of toxicity. B. cereus strains (18 out of 54) were positive for toxin production. Thirteen were of serovar H1, and it was of interest that some were of clinical origin. Two were of serovars 17B and 20, which are not usually implicated in the emetic syndrome. Partial purification of the novel B. megaterium, B. simplex and B. firmus toxins showed they had similar physical characteristics to the B. cereus emetic toxin, cereulide. PMID:15621453

Taylor, Janice M W; Sutherland, Alastair D; Aidoo, Kofi E; Logan, Niall A

2005-01-15

88

Humoral immune response to the heat-labile enterotoxin of Escherichia coli in naturally acquired diarrhea and antitoxin determination by passive immune hemolysis.  

PubMed Central

Acute- and convalescent-phase sera from 132 students attending a university in rural Mexico were assayed for antibody against the heat-labile enterotoxin (LT) of Escherichia coli by neutralization of LT activity in the Y-1 adrenal cell assay and by passive immune hemolysis of LT-sensitized sheep erythrocytes. The two titration methods produced comparable results with respect to antitoxin responses detected. An inverse relationship was found between acute geometric mean antitoxin titer and the occurrence of diarrhea associated with LT-producing E. coli, especially in newly arrived students from the U.S.A. A significant correlation (P less than 0.00 5) was found between a rise in antitoxin titer detectable by the passive immune hemolysis technique and diarrhea with LT-producing E. coli isolated. Thus, humoral antitoxin titers appear to be a useful indicator of immune status with respect to enterotoxigenic (LT) E. coli diarrhea.

Evans, D J; Ruiz-Palacios, G; Evans, D E; DuPont, H L; Pickering, L K; Olarte, J

1977-01-01

89

Relative Importance of Heat-Labile Enterotoxin in the Causation of Severe Diarrheal Disease in the Gnotobiotic Piglet Model by a Strain of Enterotoxigenic Escherichia coli That Produces Multiple Enterotoxins  

Microsoft Academic Search

Enterotoxigenic Escherichia coli (ETEC) strains that produce multiple enterotoxins are important causes of severe dehydrating diarrhea in human beings and animals, but the relative importance of these enterotoxins in the pathogenesis is poorly understood. Gnotobiotic piglets were used to study the importance of heat-labile enterotoxin (LT) in infection with an ETEC strain that produces multiple enterotoxins. LT (eltAB) and complemented

Emil M. Berberov; You Zhou; David H. Francis; Michael A. Scott; Stephen D. Kachman; Rodney A. Moxley

2004-01-01

90

Influence of host interleukin-10 polymorphisms on development of traveler's diarrhea due to heat-labile enterotoxin-producing Escherichia coli in travelers from the United States who are visiting Mexico  

Microsoft Academic Search

Up to 60% of U.S. visitors to Mexico develop traveler's diarrhea (TD), mostly due to enterotoxigenic Escherichia coli (ETEC) strains that produce heat-labile (LT) and\\/or heat-stable (ST) enterotoxins. Distinct single-nucleotide polymorphisms (SNPs) within the interleukin-10 (IL-10) promoter have been associated with high, intermediate, or low production of IL-10. We conducted a prospective study to investigate the association of SNPs in

Jose Flores; Herbert L. DuPont; Stephanie A. Lee; Jaime Belkind-Gerson; Mercedes Paredes; Jamal A. Mohamed; Lisa Y. Armitige; Dong-Chuan Guo; Pablo C. Okhuysen

2008-01-01

91

A biomarker for the identification of cattle fecal pollution in water using the LTIIa toxin gene from enterotoxigenic Escherichia coli  

Microsoft Academic Search

This research describes a method based on PCR to identify cattle fecal pollution in water using a portion of the heat labile toxin IIA (LTIIa) gene from enterotoxigenic Escherichia coli (ETEC). We describe the development of the primers and target. DNA extracts (221) from different animal fecal and human sewage samples were screened and showed no cross-reactivity. Minimum detection limits

L. A. Khatib; Y. L. Tsai; B. H. Olson

2002-01-01

92

Protection against Lethal Leptospirosis after Vaccination with LipL32 Coupled or Coadministered with the B Subunit of Escherichia coli Heat-Labile Enterotoxin  

PubMed Central

Leptospirosis, a worldwide zoonosis, lacks an effective, safe, and cross-protective vaccine. LipL32, the most abundant, immunogenic, and conserved surface lipoprotein present in all pathogenic species of Leptospira, is a promising antigen candidate for a recombinant vaccine. However, several studies have reported a lack of protection when this protein is used as a subunit vaccine. In an attempt to enhance the immune response, we used LipL32 coupled to or coadministered with the B subunit of the Escherichia coli heat-labile enterotoxin (LTB) in a hamster model of leptospirosis. After homologous challenge with 5× the 50% lethal dose (LD50) of Leptospira interrogans, animals vaccinated with LipL32 coadministered with LTB and LTB::LipL32 had significantly higher survival rates (P < 0.05) than animals from the control group. This is the first report of a protective immune response afforded by a subunit vaccine using LipL32 and represents an important contribution toward the development of improved leptospirosis vaccines.

Grassmann, Andre A.; Felix, Samuel R.; Ximendes dos Santos, Carolina; Amaral, Marta G.; Seixas Neto, Amilton C. P.; Fagundes, Michel Q.; Seixas, Fabiana K.; da Silva, Everton F.; Conceicao, Fabricio R.

2012-01-01

93

Oral immunisation of mice with a recombinant rabies virus vaccine incorporating the heat-labile enterotoxin B subunit of Escherichia coli in an attenuated Salmonella strain.  

PubMed

To investigate effective new rabies vaccines, a fusion protein consisting of the rabies virus (RV) glycoprotein and the heat-labile enterotoxin B subunit of Escherichia coli (LTB) was successfully constructed and delivered in a live attenuated Salmonella strain LH430. Mice were immunised with LH430 carrying pVAX1-G, pVAX1-G-LTB or pVAX1-ori-G-LTB. The antibody titres of mice immunised with oral LH430 carrying pVAX1-G-LTB or pVAX1-ori-G-LTB were significantly higher than those of pVAX1-G-immunised mice. The results of the challenge with the rabies virus standard strain (CVS-11) showed that the LH430 strain carrying the G-LTB gene induced immunity and elevated IL-2 levels in immunised mice ((??)P<0.01), whereas LH430 carrying pVAX1-G did not contribute to protection. These results show that LH430 carrying recombinant G-LTB could provide overall immunity against challenge with CVS-11 and should be considered to be a potential rabies vaccine. PMID:22019192

Wang, Xuelin; Liu, Juan; Wu, Xiuping; Yu, Lu; Chen, Haiying; Guo, Heng; Zhang, Maolin; Li, Huiping; Liu, Xue; Sun, Shumin; Zhao, Lijing; Zhang, Xinyue; Gao, Lifang; Liu, Mingyuan

2011-10-21

94

Heat-labile enterotoxin-induced activation of NF-?B and MAPK pathways in intestinal epithelial cells impacts enterotoxigenic Escherichia coli (ETEC) adherence  

PubMed Central

Summary Enterotoxigenic Escherichia coli (ETEC) causes human morbidity and mortality in developing nations and is an emerging threat to food safety in developed nations. The ETEC heat-labile enterotoxin (LT) not only causes diarrheal disease by deregulating host adenylate cyclase, but also enhances ETEC adherence to intestinal epithelial cells. The mechanism governing this LT pro-adherence phenotype is unclear. Here we investigated intestinal epithelial cell signal transduction pathways activated by ETEC and quantified the relative importance of these host pathways to LT-induced ETEC adherence. We show that ETEC activates both NF-?B and mitogen-activated protein kinase (MAPK) signaling pathways through mechanisms that are primarily dependent upon LT. LT-induced NF-?B activation depends upon the cAMP-dependent activation of the Ras-like GTPase Rap1 but is independent of protein kinase A (PKA). By using inhibitors of these pathways, we demonstrate that inhibiting the p38 MAPK prevents LT from increasing ETEC adherence. By contrast, the LT pro-adherence phenotype appears unrelated to both LT-induced Rap1 activity and to subsequent NF-?B activation. We speculate that LT may alter host signal transduction to induce the presentation of ligands for ETEC adhesins in such a way that promotes ETEC adherence. Our findings provide insight into previously unexplored functions of LT and their relative importance to ETEC virulence.

Wang, Xiaogang; Gao, Xiaofei; Hardwidge, Philip R.

2012-01-01

95

Chemical studies of H chondrites-10 : contents of thermally labile trace elements are unaffected by late heating.  

SciTech Connect

We have used radiochemical neutron activation analysis (RNAA) to determine 15 trace elements, including 10 moderately and highly volatile ones - Rb, Ag, Se, Cs, Te, Zn, Cd, Bi, Tl, In (in increasing volatility order) - in 6 H chondrite falls with low 3He contents. These plus prior RNAA data provide a compositional database of 92 H4-6 chondrite falls. Three suites of samples can be identified from their noble gas contents: 44 with 'normal' contents, and, therefore, 'normal' orbits and cosmic ray exposure histories; 8 that lost radiogenic gases, presumably by shock late in their histories; and 17 that lost cosmogenic gases by heating during close solar approach. We used the standard multivariate statistical techniques of linear discriminant analysis and logistic regression to compare contents of the 10 moderately and highly volatile trace elements, listed above, in these 3 suites. We found no significant differences. This contrasts sharply with similar comparisons involving random falls and H4-6 chondrites that landed on Earth at specific time intervals. Apparently, contents of volatile trace elements in H4-6 chondrites were established early in their histories and they are so retentively sited that loss during later heating episodes did not occur.

Wang, M.-S.; Wolf, S. F.; Lipschutz, M. E.; Chemical Engineering; Purdue Univ.

1999-09-01

96

Temperature Regulation of Heat-Labile Enterotoxin (LT) Synthesis in Escherichia coli Is Mediated by an Interaction of H-NS Protein with the LT A-Subunit DNA  

Microsoft Academic Search

Protein and mRNA levels of heat-labile enterotoxin (LT) of Escherichia coli are highest at 37°C, and they de- crease gradually as temperature is decreased. This temperature effect is eliminated in an Hns 2 mutant. De- letion of portions of DNA coding for the LT A subunit also results in an increase in LT expression at low temperatures, suggesting that the

JULIE D. TRACHMAN; WERNER K. MAAS

1998-01-01

97

Protection against Helicobacter pylori infection in mice by intragastric vaccination with H. pylori antigens is achieved using a non-toxic mutant of E. coli heat-labile enterotoxin (LT) as adjuvant  

Microsoft Academic Search

We have previously shown that infection of mice with H. pylori can be prevented by oral immunization with H. pylori antigens given together with E. coli heat-labile enterotoxin (LT) as adjuvant. Since LT cannot be used in humans because of its unacceptable toxicity, we investigated whether protection of mice could be achieved by co-administration of antigens with non-toxic LT mutants.

Marta Marchetti; Michela Rossi; Valentina Giannelli; Marzia M Giuliani; Mariagrazia Pizza; Stefano Censini; Antonello Covacci; Paola Massari; Cristina Pagliaccia; Roberto Manetti; John L Telford; Gill Douce; Gordon Dougan; Rino Rappuoli; Paolo Ghiara

1998-01-01

98

Bacteria and their toxins tamed for immunotherapy.  

PubMed

Bacterial toxins share the ability to enter host cells to target various intracellular proteins and to modulate host immune responses. Over the last 20 years, toxins and their mutated variants, as well as live attenuated bacteria, have been exploited for vaccination and immunotherapy of various infectious, malignant and autoimmune diseases. The ability of Bordetella pertussis adenylate cyclase toxin to translocate its adenylate cyclase domain across the host cell membrane, as well as the pathways of intracellular trafficking of Bacillus anthracis lethal and edema toxins, Shigella dysenteriae shiga toxin or Escherichia coli shiga-like toxin, have been repeatedly exploited for the delivery of antigenic epitopes into host cells and for stimulation of antigen-specific T cell responses. Similarly, E. coli ?-hemolysin, or effector proteins of Yersinia and Salmonella secreted by the type III secretion systems, were used to facilitate the delivery of fused heterologous proteins or peptides for antigenic presentation. Vibrio cholerae cholera toxin, E. coli heat-labile enterotoxin, B. pertussis pertussis toxin or the Cry1A protein of Bacillus thuringiensis have shown a great potential to act as adjuvants and to stimulate mucosal as well as systemic immune responses. The immunotherapeutic potential of some toxins, like Clostridium perfringens perfringolysin O, Streptococcus intermedius intermedilysin, or Streptococcus pneumoniae pneumolysin needs to be evaluated further. The Bordetella adenylate cyclase toxoid used as a vaccine delivery tool, or Corynebacterium diphtheriae diphtheria toxin and Pseudomonas aeruginosa exotoxin A-based immunotoxins, are currently in various phases of clinical trials for cancer immunotherapy, as are some antigen-delivering Salmonella and Listeria monocytogenes strains. PMID:22339216

Adkins, Irena; Holubova, Jana; Kosova, Martina; Sadilkova, Lenka

2012-06-01

99

Attenuated Salmonella Gallinarum secreting an Escherichia coli heat-labile enterotoxin B subunit protein as an adjuvant for oral vaccination against fowl typhoid.  

PubMed

In our previous study, we constructed a vaccine candidate (JOL916) for fowl typhoid (FT). A live adjuvant Salmonella Gallinarum (SG) strain was generated in the present study to facilitate efficacious oral vaccination with this vaccine. The Escherichia coli eltB gene secreting heat-labile enterotoxin B subunit (LTB) was cloned into an Asd(+) plasmid pJHL65. This was transformed into a ?lon ?cpxR ?asd SG strain and the resulting strain was designated JOL1229. Secretion of LTB from JOL1229 was confirmed with an immunoblot assay. To determine the optimal dose of the strain, 50 six-week-old female chickens were divided into five groups (Groups A-E, n=10 per group) and orally inoculated with various doses of JOL1229 and JOL916. In Group B (consisting of four parts JOL916 and one part JOL1229), significant cell-mediated immune responses, plasma IgG levels and intestinal secretary IgA levels were induced after inoculation with both strains. On challenge with the wild-type strain, significant reductions in mortality were observed in the group. In addition, after inoculation the LTB strain was not recovered in feces samples, and resulted in no, or very mild, gross lesions in the liver and spleen. Both CD4(+) and CD8(+) T-cells were significantly increased in peripheral blood samples from the chickens immunized with the LTB strain. Expression of the interleukin-6 (IL-6) gene in splenocytes was induced in the chickens immunized with the LTB strain. These results suggest that oral immunization with the LTB-adjuvant strain, in particular with the four parts JOL916 and one part JOL1229 mixture, increased the immune response and provided efficient protection against FT in chickens. PMID:23083937

Jeon, Byung Woo; Jawale, Chetan V; Kim, Seung Hwan; Lee, John Hwa

2012-09-13

100

Use of a patch containing heat-labile toxin from Escherichia coli against travellers' diarrhoea: a phase II, randomised, double-blind, placebo-controlled fi eld trial  

Microsoft Academic Search

Methods In this phase II study, healthy adults (aged 18-64 years) who planned to travel to Mexico or Guatemala and had access to a US regional vaccination centre were eligible. A centralised randomisation code was used for allocation, which was masked to participants and site staff . Primary endpoints were to investigate the fi eld rate of ETEC diarrhoea, and

Sarah A Frech; Herbert L DuPont; A Louis Bourgeois; Robin McKenzie; Jaime Belkind-Gerson; Jose F Figueroa; Pablo C Okhuysen; Francisco G Martinez-Sandoval; Juan H M Meléndez-Romero; Zhi-Dong Jiang; Edwin J Asturias; Jane Halpern; Olga R Torres; Christina P Villar; Raniya N Kassem; David C Flyer; Bo H Andersen; Kazem Kazempour; Sally A Breisch; Gregory M Glenn; Z-D Jiang

101

The expression of biologically active cholera toxin in Escherichia coli.  

PubMed Central

Chromosomal DNA from Vibrio cholerae El Tor strain 1621 was digested with Hind III and the products fractionated by centrifugation through a sucrose gradient. A 15kb fragment containing the toxin gene of V. cholerae was identified by its homology with the heat labile toxin (LT) gene of toxigenic E. coli. This fragment was cloned in E. coli using pAT153 and subsequently characterised by digestion with different restriction endonucleases. Sequences homologous to the LT gene were identified by hybridisation and then sub-cloned using either pAT153 or pACYC184. Expression of the cloned CT gene in E. coli was detected using both cell culture and ELISA assays. One recombinant plasmid coded for the synthesis of an immunologically active but biologically inactive derivative of CT. Images

Gennaro, M L; Greenaway, P J; Broadbent, D A

1982-01-01

102

Construction of recombinant lactobacilli expressing the core neutralizing epitope (COE) of porcine epidemic diarrhea virus and a fusion protein consisting of COE and Escherichia coli heat-labile enterotoxin B, and comparison of the immune responses by orogastric immunization.  

PubMed

The core neutralizing epitope (COE) region of porcine epidemic diarrhea virus (PEDV) plays an important role in the development of the subunit vaccine against PEDV infection. To enhance the vaccine's immunogenicity, Escherichia coli heat-labile enterotoxin B (LTB) has usually been adopted as a molecular adjuvant. In this study, the COE and LTB-COE genes were engineered into the Lactobacillus -Escherichia coli shuttle vectors pSAPG1 (surface-displaying) and pSAPG2 (secreting) followed by electrotransformation into Lactobacillus casei (Lc) to yield the following recombinant strains: Lc:PG1-LTB-COE, Lc:PG2-LTB-COE, Lc:PG1-COE, and Lc:PG2-COE. Our results showed that mice immunized orogastrically with L. casei expressing COE or LTB-COE produced secretory immunoglobulin A and immunoglobulin G with the ability to neutralize PEDV in sera and mucus. Moreover, higher levels of interleukin-4 and gamma interferon were also exhibited compared with negative control. These data displayed the tendency of Lc:PG2-LTB-COE > Lc:PG1-LTB-COE > Lc:PG2-COE > Lc:PG1-COE at the same time point. Taken together, LTB-COE is more suitable for Lactobacillus expressing system to engineer mucosal vaccine against PEDV infection. PMID:23145823

Ge, Jun-Wei; Liu, Di-Qiu; Li, Yi-Jing

2012-10-30

103

Rapid simultaneous ultrasensitive immunodetection of five bacterial toxins.  

PubMed

Rapid ultrasensitive detection of gastrointestinal pathogens presents a great interest for medical diagnostics and epidemiologic services. Though conventional immunochemical and polymerase chain reaction (PCR)-based methods are sensitive enough for many applications, they usually require several hours for assay, whereas as sensitive but more rapid methods are needed in many practical cases. Here, we report a new microarray-based analytical technique for simultaneous detection of five bacterial toxins: the cholera toxin, the E. coli heat-labile toxin, and three S. aureus toxins (the enterotoxins A and B and the toxic shock syndrome toxin). The assay involves three major steps: electrophoretic collection of toxins on an antibody microarray, labeling of captured antigens with secondary biotinylated antibodies, and detection of biotin labels by scanning the microarray surface with streptavidin-coated magnetic beads in a shear-flow. All the stages are performed in a single flow cell allowing application of electric and magnetic fields as well as optical detection of microarray-bound beads. Replacement of diffusion with a forced transport at all the recognition steps allows one to dramatically decrease both the limit of detection (LOD) and the assay time. We demonstrate here that application of this "active" assay technique to the detection of bacterial toxins in water samples from natural sources and in food samples (milk and meat extracts) allowed one to perform the assay in less than 10 min and to decrease the LOD to 0.1-1 pg/mL for water and to 1 pg/mL for food samples. PMID:22724559

Shlyapnikov, Yuri M; Shlyapnikova, Elena A; Simonova, Maria A; Shepelyakovskaya, Anna O; Brovko, Fedor A; Komaleva, Ravilya L; Grishin, Eugene V; Morozov, Victor N

2012-06-18

104

Recombinant expression of in silico identified Bcell epitope of epsilon toxin of Clostridium perfringens in translational fusion with a carrier protein  

PubMed Central

Epsilon toxin secreted by Clostridium perfringens types B and D has been directly implicated as the causative agent of fatal enterotoxemia in domestic animals. The aim of the present study is to use in silico approach for identification of B-cell epitope(s) of epsilon toxin, and its expression in fusion with a carrier protein to analyze its potential as vaccine candidate(s). Using different computational analyses and bioinformatics tools, a number of antigenic determinant regions of epsilon toxin were identified. One of the B cell epitopes of epsilon toxin comprising the region (amino acids 40-62) was identified as a promising antigenic determinant. This Etx epitope (Etx40-62) was cloned and expressed as a translational fusion with B-subunit of heat labile enterotoxin (LTB) of E. coli in a secretory expression system. Similar to the native LTB, the recombinant fusion protein retained the ability to pentamerize and bind to GM1 ganglioside receptor of LTB. The rLTB.Etx40-62 could be detected both with anti-Etx and anti-LTB antisera. The rLTB.Etx40-62 fusion protein thus can be evaluated as a potential vaccine candidate against C. perfringens. Abbreviations aa - amino acid(s), Etx - epsilon toxin of Clostridium perfringens, LTB - B-subunit of heat labile enterotoxin of E. coli.

Kaushik, Himani; Deshmukh, Sachin; Mathur, Deepika Dayal; Tiwari, Archana; Garg, Lalit C

2013-01-01

105

The A Subunit of Escherichia coli Heat-Labile Enterotoxin Functions as a Mucosal Adjuvant and Promotes IgG2a, IgA, and Th17 Responses to Vaccine Antigens  

PubMed Central

Enterotoxigenic Escherichia coli (ETEC) produces both heat-labile (LT) and heat-stable (ST) enterotoxins and is a major cause of diarrhea in infants in developing countries and in travelers to those regions. In addition to inducing fluid secretion, LT is a powerful mucosal adjuvant capable of promoting immune responses to coadministered antigens. In this study, we examined purified A subunit to further understand the toxicity and adjuvanticity of LT. Purified A subunit was enzymatically active but sensitive to proteolytic degradation and unable to bind gangliosides, and even in the presence of admixed B subunit, it displayed low cyclic AMP (cAMP) induction and no enterotoxicity. Thus, the AB5 structure plays a key role in protecting the A subunit from proteolytic degradation and in delivering the enzymatic signals required for secretion. In contrast, the A subunit alone was capable of activating dendritic cells and enhanced immune responses to multiple antigens following intranasal immunization; therefore, unlike toxicity, LT adjuvanticity is not dependent on the AB5 holotoxin structure or the presence of the B subunit. However, immune responses were maximal when signals were received from both subunits either in an AB5 structure or with A and B admixed. Furthermore, the quality of the immune response (i.e., IgG1/IgG2 balance and mucosal IgA and IL-17 secretion) was determined by the presence of an A subunit, revealing for the first time induction of Th17 responses with the A subunit alone. These results have important implications for understanding ETEC pathogenesis, unraveling immunologic responses induced by LT-based adjuvants, and developing new mucosal vaccines.

Norton, Elizabeth B.; Lawson, Louise B.; Mahdi, Zaid; Freytag, Lucy C.

2012-01-01

106

Metal Complexes and Free Radical Toxins Produced by Pfiesteria piscicida  

SciTech Connect

Metal-containing organic toxins produced by Pfiesteria piscicida were characterized, for the first time, by corroborating data obtained from five distinct instrumental methods: nuclear magnetic resonance spectroscopy (NMR), inductively coupled plasma mass spectrometry (ICP-MS), liquid chromatography particle beam glow discharge mass spectrometry (LC/PB-GDMS), electron paramagnetic resonance spectroscopy (EPR), and X-ray absorption spectroscopy (XAS). The high toxicity of the metal-containing toxins is due to metal-mediated free radical production. This mode of activity explains the toxicity of Pfiesteria, as well as previously reported difficulty in observing the molecular target, due to the ephemeral nature of radical species. The toxins are highly labile in purified form, maintaining activity for only 2-5 days before all activity is lost. The multiple toxin congeners in active extracts are also susceptible to decomposition in the presence of white light, pH variations, and prolonged heat. These findings represent the first formal isolation and characterization of a radical forming toxic organic-ligated metal complex isolated from estuarine/marine dinoflagellates. These findings add to an increased understanding regarding the active role of metals interacting with biological systems in the estuarine environment, as well as their links and implications to human health.

Moeller,P.; Beauchesne, K.; Huncik, K.; Davis, W.; Christopher, S.; Riggs-Gelasco, P.; Gelasco, A.

2007-01-01

107

Metal Complexes And Free Radical Toxins Produced By Pfiesteria Piscicida  

SciTech Connect

Metal-containing organic toxins produced by Pfiesteria piscicida were characterized, for the first time, by corroborating data obtained from five distinct instrumental methods: nuclear magnetic resonance spectroscopy (NMR), inductively coupled plasma mass spectrometry (ICPMS), liquid chromatography particle beam glow discharge mass spectrometry (LC/PB-GDMS), electron paramagnetic resonance spectroscopy (EPR), and X-ray absorption spectroscopy (XAS). The high toxicity of the metal-containing toxins is due to metal-mediated free radical production. This mode of activity explains the toxicity of Pfiesteria, as well as previously reported difficulty in observing the molecular target, due to the ephemeral nature of radical species. The toxins are highly labile in purified form, maintaining activity for only 2-5 days before all activity is lost. The multiple toxin congeners in active extracts are also susceptible to decomposition in the presence of white light, pH variations, and prolonged heat. These findings represent the first formal isolation and characterization of a radical forming toxic organic-ligated metal complex isolated from estuarine/marine dinoflagellates. These findings add to an increased understanding regarding the active role of metals interacting with biological systems in the estuarine environment, as well as their links and implications to human health.

Moeller, P.D.R.; Beauchesne, K.R.; Huncik, K.M.; Davis, W.C.; Christopher, S.J.; Riggs-Gelasco, P.; Gelasco, A.K.

2009-06-03

108

Oral immunization with an attenuated Salmonella Gallinarum mutant as a fowl typhoid vaccine with a live adjuvant strain secreting the B subunit of Escherichia coli heat-labile enterotoxin  

PubMed Central

Background The Salmonella Gallinarum (SG) lon/cpxR deletion mutant JOL916 was developed as a live vaccine candidate for fowl typhoid (FT), and a SG mutant secreting an Escherichia coli heat-labile enterotoxin B subunit (LTB), designated JOL1229, was recently constructed as an adjuvant strain for oral vaccination against FT. In this study, we evaluated the immunogenicity and protective properties of the SG mutant JOL916 and the LTB adjuvant strain JOL1229 in order to establish a prime and boost immunization strategy for each strain. In addition, we compared the increase in body weight, the immunogenicity, the egg production rates, and the bacteriological egg contamination of these strains with those of SG 9R, a widely used commercial vaccine. Results Plasma IgG, intestinal secretory IgA (sIgA), and cell-mediated responses were significantly induced after a boost inoculation with a mixture of JOL916 and JOL1229, and significant reductions in the mortality of chickens challenged with a wild-type SG strain were observed in the immunized groups. There were no significant differences in increases in body weight, cell-mediated immune responses, or systemic IgG responses between our vaccine mixture and the SG 9R vaccine groups. However, there was a significant elevation in intestinal sIgA in chickens immunized with our mixture at 3 weeks post-prime-immunization and at 3 weeks post-boost-immunization, while sIgA levels in SG 9R-immunized chickens were not significantly elevated compared to the control. In addition, the SG strain was not detected in the eggs of chickens immunized with our mixture. Conclusion Our results suggest that immunization with the LTB-adjuvant strain JOL1229 can significantly increase the immune response, and provide efficient protection against FT with no side effects on body weight, egg production, or egg contamination.

2013-01-01

109

Orientation of cholera toxin bound to model membranes.  

PubMed Central

The orientation of cholera toxin bound to its cell-surface receptor, ganglioside GM1, in a supporting lipid membrane was determined by electron microscopy of negatively stained toxin-lipid samples. Image analysis of two dimensional crystalline arrays has shown previously that the B-subunits of cholera toxin orient at the membrane surface as a pentameric ring with a central channel (Reed, R. A., J. Mattai, and G.G. Shipley. 1987. Biochemistry. 26:824-832; Ribi, H. O., D. S. Ludwig, K. L. Mercer, G. K. Schoolnik, and R. D. Kornberg. 1988. Science (Wash, DC). 239:1272-1276). We recorded images of negatively stained cholera toxin and isolated B-pentamers oriented perpendicular to the lipid surface so that the pentamer ring is viewed from the side. The pentamer dimensions, estimated from the average of 100 molecules, are approximately 60 by 30 A. Images of side views of whole cholera toxin clearly show density above the pentamer ring away from the lipid layer. On the basis of difference maps between averages of side views of whole toxin and B-pentamers, this density above the pentamer has been identified as a portion of the A-subunit. The A-subunit may also extend into the pore of the pentamer. In addition, Fab fragments from a monoclonal antibody to the A-subunit were mixed with the toxin prior to binding to GM1. Density from the Fab was localized to the region of toxin above the pentamer ring confirming the location of the A-subunit. The structure determined for the homologous heat-labile enterotoxin from Escherichia coli shows that the A-subunit lies mostly on one face of this pentamer with a small region penetrating the pentamer pore (Sixma, T. K., S. E. Pronk, K. H. Kalk, E. S. Wartna, B. A. M. van Zanten, B. Witholt,and W. G. J. Hol. 1991. Nature (Lond.). 351:371-377). The putative GM1 binding sites are located on the opposite face of the B-pentamer. Cholera toxin, therefore appears to bind to a model membrane with its GM1 binding surface adjacent to the membrane. Low resolution density maps were constructed from the x-ray coordinates of the E. coli toxin and compared with the electron microscopy-derived maps. Images FIGURE 1 FIGURE 2 FIGURE 3 FIGURE 4

Cabral-Lilly, D.; Sosinsky, G. E.; Reed, R. A.; McDermott, M. R.; Shipley, G. G.

1994-01-01

110

Crystal structure of cholera toxin B-pentamer bound to receptor GM1 pentasaccharide.  

PubMed Central

Cholera toxin (CT) is an AB5 hexameric protein responsible for the symptoms produced by Vibrio cholerae infection. In the first step of cell intoxication, the B-pentamer of the toxin binds specifically to the branched pentasaccharide moiety of ganglioside GM1 on the surface of target human intestinal epithelial cells. We present here the crystal structure of the cholera toxin B-pentamer complexed with the GM1 pentasaccharide. Each receptor binding site on the toxin is found to lie primarily within a single B-subunit, with a single solvent-mediated hydrogen bond from residue Gly 33 of an adjacent subunit. The large majority of interactions between the receptor and the toxin involve the 2 terminal sugars of GM1, galactose and sialic acid, with a smaller contribution from the N-acetyl galactosamine residue. The binding of GM1 to cholera toxin thus resembles a 2-fingered grip: the Gal(beta 1-3)GalNAc moiety representing the "forefinger" and the sialic acid representing the "thumb." The residues forming the binding site are conserved between cholera toxin and the homologous heat-labile enterotoxin from Escherichia coli, with the sole exception of His 13. Some reported differences in the binding affinity of the 2 toxins for gangliosides other than GM1 may be rationalized by sequence differences at this residue. The CTB5:GM1 pentasaccharide complex described here provides a detailed view of a protein:ganglioside specific binding interaction, and as such is of interest not only for understanding cholera pathogenesis and for the design of drugs and development of vaccines but also for modeling other protein:ganglioside interactions such as those involved in GM1-mediated signal transduction.

Merritt, E. A.; Sarfaty, S.; van den Akker, F.; L'Hoir, C.; Martial, J. A.; Hol, W. G.

1994-01-01

111

Cholera Toxin B Subunits Assemble into Pentamers - Proposition of a Fly-Casting Mechanism  

PubMed Central

The cholera toxin B pentamer (CtxB5), which belongs to the AB5 toxin family, is used as a model study for protein assembly. The effect of the pH on the reassembly of the toxin was investigated using immunochemical, electrophoretic and spectroscopic methods. Three pH-dependent steps were identified during the toxin reassembly: (i) acquisition of a fully assembly-competent fold by the CtxB monomer, (ii) association of CtxB monomer into oligomers, (iii) acquisition of the native fold by the CtxB pentamer. The results show that CtxB5 and the related heat labile enterotoxin LTB5 have distinct mechanisms of assembly despite sharing high sequence identity (84%) and almost identical atomic structures. The difference can be pinpointed to four histidines which are spread along the protein sequence and may act together. Thus, most of the toxin B amino acids appear negligible for the assembly, raising the possibility that assembly is driven by a small network of amino acids instead of involving all of them.

Zrimi, Jihad; Ng Ling, Alicia; Giri-Rachman Arifin, Ernawati; Feverati, Giovanni; Lesieur, Claire

2010-01-01

112

Cholera toxin B subunits assemble into pentamers--proposition of a fly-casting mechanism.  

PubMed

The cholera toxin B pentamer (CtxB(5)), which belongs to the AB(5) toxin family, is used as a model study for protein assembly. The effect of the pH on the reassembly of the toxin was investigated using immunochemical, electrophoretic and spectroscopic methods. Three pH-dependent steps were identified during the toxin reassembly: (i) acquisition of a fully assembly-competent fold by the CtxB monomer, (ii) association of CtxB monomer into oligomers, (iii) acquisition of the native fold by the CtxB pentamer. The results show that CtxB(5) and the related heat labile enterotoxin LTB(5) have distinct mechanisms of assembly despite sharing high sequence identity (84%) and almost identical atomic structures. The difference can be pinpointed to four histidines which are spread along the protein sequence and may act together. Thus, most of the toxin B amino acids appear negligible for the assembly, raising the possibility that assembly is driven by a small network of amino acids instead of involving all of them. PMID:21203571

Zrimi, Jihad; Ng Ling, Alicia; Giri-Rachman Arifin, Ernawati; Feverati, Giovanni; Lesieur, Claire

2010-12-21

113

LT-IIc, a new member of the type II heat-labile enterotoxin family, exhibits potent immunomodulatory properties that are different from those induced by LT-IIa or LT-IIb  

PubMed Central

A plethora of human pathogens invade and/or colonize mucosal surfaces. Elaboration of strong, protective immune responses against those pathogens by mucosal vaccination, however, is hampered by endogenous regulatory systems in the mucosae that dampen responses to foreign antigens (Ag). To overcome those natural barriers, mucosal adjuvants must be employed. Using a mouse mucosal immunization model and AgI/II, a weak immunogen from Streptococcus mutans, LT-IIc, a new member of the type II subgroup of the heat-labile enterotoxin family, was shown to have potent mucosal adjuvant properties. In comparison to mice intranasally immunized only with AgI/II, co-administration of AgI/II with LT-IIc enhanced production of Ag-specific IgA antibodies in the saliva and vaginal fluids and Ag-specific IgA and IgG in the serum. Secretion of IL-2, IL-6, IL-17, IFN-?, and TNF-? was enhanced in cultures of AgI/II-stimulated splenic cells isolated from mice that had received LT-IIc as a mucosal adjuvant. In contrast, secretion of IL-10 was suppressed in those cells. This pattern of cytokine secretion suggested that LT-IIc stimulates both Th1 and Th2 immune responses. In contrast to LT-IIa and LT-IIb, the original members of the type II subgroup that also are mucosal adjuvants, LT-IIc dramatically enhanced secretion of IL-1? and IL-1? in peritoneal macrophages that had been co-cultured with LPS. Furthermore, the B pentameric subunit of LT-IIc augmented uptake of Ag by bone marrow-derived dendritic cells to levels that exceeded those attained by use of LPS or by the B pentamers of LT-IIa or LT-IIb. These data confirmed that LT-IIc is a strong mucosal adjuvant with immunomodulatory properties that are distinguishable from those of LT-IIa and LT-IIb and which has immunomodulatory properties that may be exploitable in vaccine development.

Nawar, Hesham F.; Greene, Christopher J.; Lee, Chang Hoon; Mandell, Lorrie; Connell, Terry D.

2010-01-01

114

Toxin Production  

Microsoft Academic Search

Staphylococci have developed a highly regulated system of toxin production that researchers are only beginning to understand. These toxin control systems respond to a wide range of environmental conditions, from catabolite and oxygen concentrations to bacterial cell density. Understanding the mechanisms of toxin regulation and production and how these systems might be manipulated to prevent toxin production will greatly enhance

Jeremy M. Yarwood; Patrick M. Schlievert

115

Cytolethal Distending Toxin of Haemophilus ducreyi Induces Apoptotic Death of Jurkat T Cells  

PubMed Central

The immune response to Haemophilus ducreyi is mediated in part by T cells infiltrating the site of infection. In this study, we show that H. ducreyi antigen preparations inhibited the proliferation of peripheral blood mononuclear cells and primary human T-cell lines. H. ducreyi also inhibited Jurkat T-cell proliferation and induced apoptosis of Jurkat T cells, confirmed through the detection of DNA degradation and membrane unpacking. The cytotoxic product(s) was present in cell-free culture supernatant and whole-cell preparations of H. ducreyi and was heat labile. H. ducreyi produces two known heat-labile toxins, a hemolysin and a cytolethal distending toxin (CDT). Whole cells and supernatants prepared from a hemolysin-deficient mutant had the same inhibitory and apoptotic effects on Jurkat T cells as did its isogenic parent. Preparations made from an H. ducreyi cdtC mutant were less toxic and induced less apoptosis than the parent. The toxic activity of the cdtC mutant was restored by complementation in trans. CdtC-neutralizing antibodies also inhibited H. ducreyi-induced toxicity and apoptosis. The data suggest that CDT may interfere with T-cell responses to H. ducreyi by induction of apoptosis.

Gelfanova, Valentina; Hansen, Eric J.; Spinola, Stanley M.

1999-01-01

116

Heat-stable enterotoxin from Escherichia coli: factors involved in growth and toxin production.  

PubMed Central

Six enterotoxigenic strains of Escherichia coli produced variable levels of heat-stable enterotoxin (ST) when grown under pH control at 8.5 in a simple synthetic medium containing neither amino acids nor vitamins. Bacterial growth and ST production were at levels as high as or higher than those observed in complex media. ST elaboration was detectable in the early logarithmic phase of growth and appeared to be related to disappearance of glucose in the growth medium. The results of this study did not suggest pH-dependent release of ST. Imposition of pH control in complex media resulted in increased growth rates, earlier detectable ST synthesis, and elevated levels of ST. In synthetic medium, attainment of the stationary growth phase was followed by a significant decrease in culture density and a concomitant increase in ST. Cellular autolysis experiments revealed that as much as 20% of the total ST activity was present in a cell-associated form.

Johnson, W M; Lior, H; Johnson, K G

1978-01-01

117

Millipede toxin  

MedlinePLUS

... toxin) if they are threatened or if you handle them roughly. Millipedes can squirt toxin several inches ... Schwartz RA. Arthropod bites and stings. In: Wolff K, Goldsmith LA, Katz SI, et al., eds. Fitzpatrick’s ...

118

Labile Factor Depression in Scorbutic Guinea Pigs.  

National Technical Information Service (NTIS)

The hemorrhagic manifestations of scurvy are caused by both increased capillary fragility and abnormal blood coagulation. Guinea pigs fed a vitamin C-deficient diet developed a moderately severe deficiency of labile factor (V) and fatty metamorphoses of t...

M. B. Garvey L. H. Dennis M. E. Conrad

1969-01-01

119

Toward the development of a stable, freeze-dried formulation of Helicobacter pylori killed whole cell vaccine adjuvanted with a novel mutant of Escherichia coli heat-labile toxin  

Microsoft Academic Search

No vaccine exists for the prevention of infection with the ubiquitous gastric pathogen Helicobacter pylori, and drug therapy for the infection is complicated by poor patient compliance, the high cost of treatment, and ineffectiveness against drug-resistant strains. A new medical advancement is required to reduce the incidence of peptic ulcer disease and stomach cancer, two conditions caused by infection with

Nancy A. Summerton; Richard W. Welch; Laureano Bondoc; Huei-Hsiung Yang; Brett Pleune; Naryaswamy Ramachandran; Andrea M. Harris; Desiree Bland; W. James Jackson; John D. Clements; Gary S. Nabors

2010-01-01

120

Pilot study of whole-blood gamma interferon response to the Vibrio cholerae toxin B subunit and resistance to enterotoxigenic Escherichia coli-associated diarrhea.  

PubMed

Enterotoxigenic Escherichia coli (ETEC), which produces heat-labile toxin (LT), is a common cause of travelers' diarrhea (TD). The B subunit of ETEC LT is immunologically related to the B subunit of Vibrio cholerae toxin (CT). In this pilot study we evaluated the whole-blood gamma interferon response to CT B in 17 U.S. adults traveling to Mexico. Only one of nine subjects who demonstrated a cellular immune response as determined by whole-blood gamma interferon production to CT B on arrival to Mexico developed diarrhea, whereas five of eight without a cellular response developed diarrhea. Markers of the cellular immune response to ETEC LT could help in identifying individuals immune to ETEC LT, and these markers deserve additional study. PMID:20219880

Flores, Jose; DuPont, Herbert L; Paredes-Paredes, Mercedes; Aguirre-Garcia, M Magdalena; Rojas, Araceli; Gonzalez, Alexei; Okhuysen, Pablo C

2010-03-10

121

Botulinum toxin.  

PubMed

Botulinum toxin is regarded as the most lethal substance known. It is estimated that the human LD50 for inhalation botulism is 1 to 3 nanograms of toxin/kilogram body mass. Although only three cases of inhalational botulism have been described, an understanding of the pathophysiology of food-borne outbreaks, wound botulism, and infant botulism, and their therapies, enables the medical community to plan treatment in the event of an aerosol release of botulinum toxin. Antitoxin, vaccine, and F(ab')2 immune fragment therapies are discussed as adjuncts to supportive therapy. PMID:16168317

Horowitz, B Zane

2005-10-01

122

Labile Serum Factor and Its Effect on Arbovirus Neutralization  

PubMed Central

Enhancement of neutralization of Sindbis, Venezuelan equine encephalitis, Eastern equine encephalitis, Western equine encephalitis, and St. Louis encephalitis viruses by labile serum factor (LSF) in human serum and plasma was demonstrated. Human serum and plasma could be diluted 1:8 and 1:16 and still retain some LSF activity. Satisfactory storage temperatures for retention of LSF activity were ?20 or ?56 C. Repeated freeze-thaw cycles of serum did not alter LSF activity, but the activity was completely eliminated by heating at 56 C for 5 min. LSF of human serum equally enhanced neutralization by Sindbis immune mouse and rabbit sera; these results suggest a lack of species specificity. Rehydrated lyophilized gunea pig complement did not restore LSF activity to heated human plasma. Serum components responsible for LSF activity were not dialyzable. Discovery of fresh serum without LSF activity established the need to pretest all sera used as LSF sources.

Chappell, W. A.; Sasso, D. R.; Toole, Roberta F.; Monath, Thomas P.

1971-01-01

123

Marine Toxins  

MedlinePLUS

... by marine toxins? General guidelines for safe seafood consumption: Although any person eating fish or shellfish containing ... same food safety regulations as seafood for human consumption. Back to Top What is the government doing ...

124

BOTULINUM TOXIN  

PubMed Central

Botulinum toxin, one of the most poisonous biological substances known, is a neurotoxin produced by the bacterium Clostridium botulinum. C. botulinum elaborates eight antigenically distinguishable exotoxins (A, B, C1, C2, D, E, F and G). All serotypes interfere with neural transmission by blocking the release of acetylcholine, the principal neurotransmitter at the neuromuscular junction, causing muscle paralysis. The weakness induced by injection with botulinum toxin A usually lasts about three months. Botulinum toxins now play a very significant role in the management of a wide variety of medical conditions, especially strabismus and focal dystonias, hemifacial spasm, and various spastic movement disorders, headaches, hypersalivation, hyperhidrosis, and some chronic conditions that respond only partially to medical treatment. The list of possible new indications is rapidly expanding. The cosmetological applications include correction of lines, creases and wrinkling all over the face, chin, neck, and chest to dermatological applications such as hyperhidrosis. Injections with botulinum toxin are generally well tolerated and side effects are few. A precise knowledge and understanding of the functional anatomy of the mimetic muscles is absolutely necessary to correctly use botulinum toxins in clinical practice.

Nigam, P K; Nigam, Anjana

2010-01-01

125

Attenuated Escherichia coli strains expressing the colonization factor antigen I (CFA/I) and a detoxified heat-labile enterotoxin (LThK63) enhance clearance of ETEC from the lungs of mice and protect mice from intestinal ETEC colonization and LT-induced fluid accumulation.  

PubMed

Although enterotoxigenic Escherichia coli (ETEC) infections are important causes of infantile and traveler's diarrhea there is no licensed vaccine available for those at-risk. Our goal is to develop a safe, live attenuated ETEC vaccine. We used an attenuated E. coli strain (O157:H7, ?-intimin, Stx1-neg, Stx2-neg) as a vector (ZCR533) to prepare two vaccine strains, one strain expressing colonization factor antigen I (ZCR533-CFA/I) and one strain expressing CFA/I and a detoxified heat-labile enterotoxin (ZCR533-CFA/I+LThK63) to deliver ETEC antigens to mucosal sites in BALB/c mice. Following intranasal and intragastric immunization with the vaccine strains, serum IgG and IgA antibodies were measured to the CFA/I antigen, however, only serum IgG antibodies were detected to the heat-labile enterotoxin. Intranasal administration of the vaccine strains induced respiratory and intestinal antibody responses to the CFA/I and LT antigens, while intragastric administration induced only intestinal antibody responses with no respiratory antibodies detected to the CFA/I and LT antigens. Mice immunized intranasally with the vaccine strains showed enhanced clearance of wild-type (wt) ETEC bacteria from the lungs. Mice immunized intranasally and intragastrically with the vaccine strains were protected from intestinal colonization following oral challenge with ETEC wt bacteria. Mice immunized intragastrically with the ZCR533-CFA/I+LThK63 vaccine strain had less fluid accumulate in their intestine following challenge with ETEC wt bacteria or with purified LT as compared to the sham mice indicating that the immunized mice were protected from LT-induced intestinal fluid accumulation. Thus, mice intragastrically immunized with the ZCR533-CFA/I+LThK63 vaccine strain were able to effectively neutralize the activity of the LT enterotoxin. However, no difference in intestinal fluid accumulation was detected in the mice immunized intranasally with the vaccine strain as compared to the sham mice as the immunized mice induced insufficient intestinal anti-LT antibody to neutralize the activity of the enterotoxin. These results show that our ETEC vaccine induced serum and mucosal antibody responses to CFA/I and LT after mucosal administration which then acted to protect the immunized mice against lung and intestinal colonization, as well as, intestinal fluid accumulation. PMID:23122616

Byrd, Wyatt; Boedeker, Edgar C

2012-10-05

126

Botulinum Toxin.  

National Technical Information Service (NTIS)

Botulism is a disease caused by anaerobic, spore-forming bacteria found in soil. Disease results from the actions of chemical toxins produced by these bacteria. The most common forms of human botulism include foodborne, infant, and wound. The main etiolog...

A. M. Katos J. Anderson M. Krasna P. T. Williams W. Burrows

2009-01-01

127

Legionella Toxin.  

National Technical Information Service (NTIS)

The presence of a Legionella pneumophila toxin has been clinically suspected since 1978. A common 3,400 molecular weight protein has been found in the cell free extracts of sonicated L. pneumophila organisms serotype 1, as well as L. dumoffii, L. bozemani...

K. W. Hedlund

1981-01-01

128

Lability criteria in diffusive gradients in thin films.  

PubMed

The penetration of metal complexes into the resin layer of DGT (diffusive gradients in thin films) devices greatly influences the measured metal accumulation, unless the complexes are either totally inert or perfectly labile. Lability criteria to predict the contribution of complexes in DGT measurements are reported. The key role of the resin thickness is highlighted. For complexes that are partially labile to the DGT measurement, their dissociation inside the resin domain is the main source of metal accumulation. This phenomenon explains the practical independence of the lability degree of a complex in a DGT device with respect to the ligand concentration. Transient DGT regimes, reflecting the times required to replenish the gel and resin domains up to the steady-state profile of the complex, are also examined. Low lability complexes (lability degree between 0.1 and 0.2) exhibit the longest transient regimes and therefore require longer deployment times to ensure accurate DGT measurements. PMID:22404162

Puy, Jaume; Uribe, Ramiro; Mongin, Sandrine; Galceran, Josep; Cecília, Joan; Levy, Jacqueline; Zhang, Hao; Davison, William

2012-03-27

129

Botulinum Toxins  

Microsoft Academic Search

\\u000a In minute doses, purified BTX-A injected into facial muscles causes temporary chemodenervation. Partial or complete paralysis\\u000a of selected muscles of facial expression reduces hyperdynamic wrinkles, improves the position or shape of the brow and mouth,\\u000a and even contours the face. There are discussions on the mechanisms of action of botulinum toxin, clinical effects, anatomy,\\u000a indications, facial assessment, and general techniques.

Peter M. Prendergast

130

Serum Dihydrolipoamide Dehydrogenase Is a Labile Enzyme.  

PubMed

Dihydrolipoamide dehydrogenase (DLDH) is a multifunctional oxidoreductase and is well known as an essential component of four mammalian mitochondrial multienzyme complexes: pyruvate dehydrogenase, ?-ketoglutarate dehydrogenase, branched chain ?-keto acid dehydrogenase, and the glycine cleavage system. However, existence of extracellular DLDH in mammals, if any, has not been clearly defined. The present article reports identification and biochemical characterization of serum DLDH. Proteomic analysis of rat serum using blue native polyacrylamide gel electrophoresis (BN-PAGE) and mass spectrometry peptide sequencing led to generation of 6 tryptic peptides in one band that matched to mitochondrial DLDH, indicating the existence of DLDH in rat serum. Measurement of enzymatic activity also indicated the existence of DLDH in human and mouse serum. Further biochemical analysis of rat serum DLDH revealed that this enzyme lacked diaphorase activity and could not be detected on Western blots probed with antibodies that recognized mitochondrial DLDH. Moreover, both ammonium sulfate fractioning and gel filtration of serum samples rendered a great loss in DLDH activity, indicating that the enzyme activity of this serum protein, unlike that of mitochondrial DLDH, is very labile. When DTT was supplemented in the buffer used for gel filtration, DLDH activity was found to be largely preserved; indicating that serum DLDH is susceptible to air-implicated inactivation. Results of the present study indicate that serum DLDH differs from mitochondrial DLDH in that it is a very labile enzyme. PMID:23646291

Yan, Liang-Jun; Thangthaeng, Nopporn; Sumien, Nathalie; Forster, Michael J

2013-03-01

131

The 2.3 {angstrom} crystal structure of cholera toxin B subunit pentamer: Choleragenoid  

SciTech Connect

Cholera toxin, a heterohexameric AB{sub 5} enterotoxin released by Vibrio cholera, induces a profuse secretory diarrhea in susceptible hosts. Choleragenoid, the B subunit pentamer of cholera toxin, directs the enzymatic A subunit to its target by binding to GM{sub 1} gangliosides exposed on the luminal surface of intestinal epithelial cells. We have solved the crystal structure of choleragenoid at 2.3 {Angstrom} resolution by combining single isomorphous replacement with non-crystallographic symmetry averaging. The structure of the B subunits, and their pentameric arrangement, closely resembles that reported for the intact holotoxin (choleragen), the heat-labile enterotoxin from E. coli, and for a choleragenoid-GM{sub 1} pentasaccharide complex. In the absence of the A subunit the central cavity of the B pentamer is a highly solvated channel. The binding of the A subunit or the receptor pentasaccharide to choleragenoid has only a modest effect on the local stereochemistry and does not perceptibly alter the subunit interface.

Zhang, Rong-Guang; Westbrook, M.L. [Argonne National Lab., IL (United States); Maulik, P.R.; Reed, R.A.; Shipley, G. [Boston Univ., MA (United States). School of Medicine; Westbrook, E.M. [Argonne National Lab., IL (United States)]|[Northwestern Univ., Evanston, IL (United States); Scott, D.L.; Otwinowski, Z. [Yale Univ., New Haven, CT (United States)

1996-02-01

132

Suicidal ideation, affective lability, and religion in depressed adults  

Microsoft Academic Search

Suicidal ideation is a strong precursor to suicidal acts and like depression is complex with many risk and protective factors. The purpose of this study is to determine if affect lability, positive and negative religion\\/spirituality (RS) are related to suicidal ideation and if RS mediates the relationship between affect lability and suicidal ideation. RS are used synonymously to reflect a

Marilyn Baetz; Rudy Bowen

2010-01-01

133

Suicidal ideation, affective lability, and religion in depressed adults  

Microsoft Academic Search

Suicidal ideation is a strong precursor to suicidal acts and like depression is complex with many risk and protective factors. The purpose of this study is to determine if affect lability, positive and negative religion\\/spirituality (RS) are related to suicidal ideation and if RS mediates the relationship between affect lability and suicidal ideation. RS are used synonymously to reflect a

Marilyn Baetz; Rudy Bowen

2011-01-01

134

Identification of labile zn sites in drug-target proteins.  

PubMed

Labile Zn fingers (Zfs) in proteins contain Zn-bound thiolates that can react with electrophilic agents, causing Zn(2+) ejection and protein unfolding. Such labile Zfs have been shown to be Cys4 or Cys3His cores whose Zn-bound Cys have no hydrogen bonds. Our aim here is to identify labile Zfs in proteins that are promising drug targets using these features. To prove the strategy used, we showed that five proteins with predicted labile Zfs reacted with Zn-ejecting agents, whereas five proteins with no or inert Zfs did not. The comprehensive set of labile Zfs provides new drug targets and guidelines to redesign Zn-ejecting compounds with improved specificity. PMID:24010488

Lee, Yu-Ming; Wang, Yi-Ting; Duh, Yulander; Yuan, Hanna S; Lim, Carmay

2013-09-11

135

Sublingually administered Bacillus subtilis cells expressing tetanus toxin C fragment induce protective systemic and mucosal antibodies against tetanus toxin in mice.  

PubMed

Sublingual (SL) immunization against infectious agents or bacterial toxins is not a common route for antigen delivery. However, in our continued search for a needle-free platform for vaccine administration, we evaluated the efficacy of SL immunization with Bacillus subtilis engineered to express tetanus toxin fragment C (TTFC). We compared the results obtained with those for intranasal (IN) immunization with the same vaccine, which we recently reported to induce complete protection in mice against a 2×LD100 challenge of tetanus toxin (Lee et al., Vaccine 28:6658-65). Groups of animals received 3-4 immunizations of 10(9)B. subtilis vegetative cells expressing TTFC given IN or SL. Other SL immunized groups received either purified recombinant TTFC (rTTFC) or B. subtilis placebo. A non-toxic mutant of Escherichia coli heat labile enterotoxin (mLT) was included as adjuvant in some of the studies. Mice inoculated by either IN or SL administration developed protective IgG antibodies against tetanus toxin challenge. Similar of higher IgA levels in saliva, vaginal wash and feces were detected in animals immunized SL with B. subtilis cells expressing TTFC compared with IN-immunized mice or mice immunized SL with rTTFC. SL immunization promoted a mixed Th1/Th2 response, based on cytokine analysis (IL-2, IL-4, IL-10 and INF?). Antigen-stimulated tissues (lung, intestine, spleen and lymph nodes) revealed a dramatic increase in the density of MHC class II+ expressing cells compared to all other groups. The antibody response to TTFC was superior when the adjuvant mLT was excluded from IN and SL immunizations. However, SL administration of mLT induced strong systemic and mucosal antibody responses, indicating that successful use of this route of immunization is not specific to tetanus toxin. We conclude that SL immunization is a promising, effective, safe, non-invasive and convenient method for mucosal delivery of B. subtilis cells expressing tetanus vaccine and, potentially, other immunogens. SL immunization appears to induce both systemic and mucosal immune responses. PMID:21565244

Amuguni, J Hellen; Lee, Sangun; Kerstein, Kathryn O; Brown, David W; Belitsky, Boris R; Herrmann, John E; Keusch, Gerald T; Sonenshein, Abraham L; Tzipori, Saul

2011-05-10

136

The ? Toxin Induces a Set of Protective Responses and Dormancy  

PubMed Central

The ?? module consists of a labile antitoxin protein, ?, which in dimer form (?2) interferes with the action of the long-living monomeric ? phosphotransferase toxin through protein complex formation. Toxin ?, which inhibits cell wall biosynthesis and may be bactericide in nature, at or near physiological concentrations induces reversible cessation of Bacillus subtilis proliferation (protective dormancy) by targeting essential metabolic functions followed by propidium iodide (PI) staining in a fraction (20–30%) of the population and selects a subpopulation of cells that exhibit non-inheritable tolerance (1–5×10?5). Early after induction ? toxin alters the expression of ?78 genes, with the up-regulation of relA among them. RelA contributes to enforce toxin-induced dormancy. At later times, free active ? decreases synthesis of macromolecules and releases intracellular K+. We propose that ? toxin induces reversible protective dormancy and permeation to PI, and expression of ?2 antitoxin reverses these effects. At later times, toxin expression is followed by death of a small fraction (?10%) of PI stained cells that exited earlier or did not enter into the dormant state. Recovery from stress leads to de novo synthesis of ?2 antitoxin, which blocks ATP binding by ? toxin, thereby inhibiting its phosphotransferase activity.

Tabone, Mariangela; Gonzalez-Pastor, Jose E.; Daugelavicius, Rimantas; Ayora, Silvia; Alonso, Juan C.

2012-01-01

137

A common antigenic determinant found in two functionally unrelated toxins  

PubMed Central

The heat-stable enterotoxin ST Ib produced by enterotoxigenic E. coli strains shares a sequence homology with the sea snail neurotoxin, conotoxin GI. Rabbit antisera were raised against synthetic analogs of these toxins and to a six-residue peptide representing the region common to both toxins. Results from enzyme-linked immunosorbent assays indicate that the homologous region of both toxins represents part of their antigenic site. The lack of cross-reactivity exhibited by the six- residue common domain with serum directed against either toxin suggests that this region probably retains a similar conformation in the intact toxins but not in the isolated fragment.

1984-01-01

138

Micellar electrokinetic chromatography with acid labile surfactant.  

PubMed

We present a study of a degradable surfactant, sodium 4-[(2-methyl-2-undecyl-1,3-dioxolan-4-yl)methoxy]-1-propane sulfonate that is also known as an acid-labile surfactant (ALS). The performance of ALS as a pseudostationary phase is assessed and compared with established pseudostationary phases such as sodium dodecyl sulphate (SDS), volatile surfactants and polymeric micelles. ALS achieves separation efficiency of 100,000-145,000 theoretical plates and relative standard deviation (RSD) of electrophoretic mobility (n=5) of less than 3%. Retention factors with ALS are strongly correlated with those with SDS. This is shown by the R2=0.79 for all eleven analytes and an R2=0.992 for specifically the non-hydrogen bonding (NHB) analytes. However, ALS displays different selectivity than SDS for hydrogen bond donor (HBD) and hydrogen bond acceptor (HBA) solutes (R2 of 0.74 and 0.88, respectively). ALS is degraded to less surface active compounds in acidic solution. These less surface-active compounds are more compatible with the electrospray ionization mass spectrometry (ESI-MS). ALS has a half-life of 48 min at pH 4. ALS has the potential to couple micellar electrokinetic chromatography (MEKC) with the ESI-MS. ALS can be used as a pseudostationary phase for a high efficiency separation and later acid hydrolyzed to enable an ESI-MS analysis. PMID:22018715

Stanley, Bob; Lucy, Charles A

2011-09-29

139

Meloidogyne javanica surface proteins: characterization and lability.  

PubMed

Characterization of surface coat (SC) proteins including carbohydrate-binding proteins and glycoproteins of the plant-parasitic nematode Meloidogyne javanica 2nd-stage juvenile (J2) is reported. Extraction of surface proteins with sodium dodecyl sulfate (SDS) and separation by denaturing polyacrylamide gel electrophoresis (SDS-PAGE) results with bands at 6, 9, 14, 22, 26, 31, 46, 49, 58, 66, 80, 205 and 250 kDa. On Western blots, the neoglycoprotein, fucosylated-, mannosylated- and glucosylated-bovine serum albumin, reacted with the 14, 22, 26, 58 and 66 kDa bands. The lectins, Concanavalin A and wheat-germ agglutinin (WGA) labelled surface protein bands of 6, 9, 14, 31, 58 and 66 kDa; WGA also labelled the 22 and 26 kDA bands. Biotin reagents were used to specifically trace surface proteins on live J2. SDS-PAGE of biotinylated J2 extracts revealed only 2 specific biotin-protein bands at 46 and 49 kDa. The labile and transitory nature of Meloidogyne javanica SC was demonstrated by the dynamics of human red blood cells (HRBC) adherence to J2 of different ages. HRBC adherence was also used to demonstrate the SC recovery of detergent-treated J2, which was further exhibited in the SDS-PAGE profiles. PMID:9368902

Spiegel, Y; Kahane, I; Cohen, L; Sharon, E

1997-11-01

140

Staphylococcus hyicus-skin reactions in piglets caused by crude extracellular products and by partially purified exfoliative toxin.  

PubMed

Staphylococcus hyicus may cause a spontaneous generalized exudative epidermitis in piglets. The progression and regression of macroscopical and histopathological lesions in piglet skin after subcutaneous injection of sterile concentrated culture supernatant (CCS) from one virulent and one avirulent strain of S. hyicus was studied every 24 h until 144 h post-injection. CCS from the virulent strain caused local alterations of the epidermis comparable to those of spontaneous exudative epidermitis: exfoliation, crust formation, exocytosis, formation of vesicles, and pustules and acanthosis. CCS from the avirulent strain only caused a transient erythema of the skin and no histopathological alterations of the epidermis. Additionally, proteins in CCS from the virulent strain were fractionated by column chromatography. Skin reactions similar to those caused by CCS from the virulent strain were induced by one fraction of proteins that contained eight protein bands in SDS-PAGE analysis. Two of these protein bands, with molecular weights of approximately 27 kDa and 30 kDa, were unique to the virulent strain compared to the avirulent strain. The results of this study indicate that one of these two proteins or both is a heat-labile exfoliative toxin, and that the toxin is a significant factor in the pathogenesis of exudative epidermitis in piglets. PMID:8271921

Andresen, L O; Wegener, H C; Bille-Hansen, V

1993-09-01

141

Botox (Botulinum Toxin)  

MedlinePLUS

... people when there are many effective and safe cosmetic procedures that can temporarily reduce a very prominent ... form of botulinum toxin is Type A (Botox® Cosmetic, Allergan, Inc). Botulinum toxin, what we will now ...

142

Cell Motility by Labile Association of Molecules  

PubMed Central

This article summarizes our current views on the dynamic structure of the mitotic spindle and its relation to mitotic chromosome movements. The following statements are based on measurements of birefringence of spindle fibers in living cells, normally developing or experimentally modified by various physical and chemical agents, including high and low temperatures, antimitotic drugs, heavy water, and ultraviolet microbeam irradiation. Data were also obtained concomitantly with electron microscopy employing a new fixative and through measurements of isolated spindle protein. Spindle fibers in living cells are labile dynamic structures whose constituent filaments (microtubules) undergo cyclic breakdown and reformation. The dynamic state is maintained by an equilibrium between a pool of protein molecules and their linearly aggregated polymers, which constitute the microtubules or filaments. In living cells under physiological conditions, the association of the molecules into polymers is very weak (absolute value of ?F25°C < 1 kcal), and the equilibrium is readily shifted to dissociation by low temperature or by high hydrostatic pressure. The equilibrium is shifted toward formation of polymer by increase in temperature (with a large increase in entropy: ?S25°C ? 100 eu) or by the addition of heavy water. The spindle proteins tend to polymerize with orienting centers as their geometrical foci. The centrioles, kinetochores, and cell plate act as orienting centers successively during mitosis. Filaments are more concentrated adjacent to an orienting center and yield higher birefringence. Astral rays, continuous fibers, chromosomal fibers, and phragmoplast fibers are thus formed by successive reorganization of the same protein molecules. During late prophase and metaphase, polymerization takes place predominantly at the kinetochores; in metaphase and anaphase, depolymerization is prevalent near the spindle poles. When the concentration of spindle protein is high, fusiform bundles of polymer are precipitated out even in the absence of obvious orienting centers. The shift of equilibrium from free protein molecules to polymer increases the length and number of the spindle microtubules or filaments. Slow depolymerization of the polymers, which can be brought about by low concentrations of colchicine or by gradual cooling, allows the filaments to shorten and perform work. The dynamic equilibrium controlled by orienting centers and other factors provides a plasusible mechanism by which chromosomes and other organelles, as well as the cell surface, are deformed or moved by temporarily organized arrays of microtubules or filaments.

Inoue, Shinya; Sato, Hidemi

1967-01-01

143

Esterification makes retinol more labile to photolysis.  

PubMed

Because retinyl palmitate was reported to be more stable to oxidation than retinol, we wondered if retinyl palmitate was also more resistant to photolysis as compared to free alcohol. We investigated the resistance of ethanolic solutions of retinol, retinyl palmitate, or both to air oxidation and (or) photolysis using fluorescent light. The initial concentrations were all-trans-retinol, 14 mumol/L, and all-trans-retinyl palmitate, 14 mumol/L. The concentrations of retinol and retinyl palmitate were determined by HPLC and are expressed as a percentage of their original concentrations. After 4 h of exposure to an 18 W fluorescent lamp at 15 cm from the solution, the means (SD) of the surviving analytes were 64% (3%) for retinol and 5% (2%) for retinyl palmitate in a solution containing both retinol and retinyl palmitate. Taking account of the cis isomer arising from retinyl palmitate, 29% (3%) of the retinyl palmitate survived after 4 h of photolysis. Degradation of retinyl palmitate might occur after the conversion of trans isomer to cis isomer during photolysis, however, trans isomer could be degraded with a lesser extent of isomerization. After 4 h of bubbling air through the solution in the dark, 49% (6%) of retinol and 69% (4%) of retinyl palmitate survived. Exposing retinol or retinyl palmitate separately to air oxidation, bubbling air through the solution, or photolysis, exposing them to light, we found that retinyl palmitate could retard the air oxidation of retinol (p < 0.001), but it had no effect on the light-induced degradation of retinol. We also studied the effect of the addition of approximately 1,560 mumol/L alpha-tocopherol, approximately 190 mumol/L beta-carotene and approximately 2,000 mumol/L ascorbic acid as antioxidants. In the presence of 156 mumol/L alpha-tocopherol, 87% (1%) of the retinol and 91% (4%) of the retinyl palmitate remained after air oxidation. Although the photolysis of retinol and retinyl palmitate was also inhibited by 190 mumol/L beta-carotene, alpha-tocopherol and ascorbic acid did not exert inhibiting effects. We conclude that retinyl palmitate is physico-chemically more labile to photolysis but is more resistant to air oxidation than retinol. PMID:10524354

Ihara, H; Hashizume, N; Hirase, N; Suzue, R

1999-06-01

144

Pharmacology of botulinum toxin  

Microsoft Academic Search

Background: Botulinum toxin has a well-defined role among dermatologists for the treatment of facial wrinkling, brow position, and palmar and axillary hyperhidrosis. Objective: The purpose of this study is to educate dermatologists on the pharmacology of botulinum toxin. Methods: A retrospective review of the literature on botulinum toxin from 1962 to the present was conducted. We examined the clinical applications

Wilber Huang; Jill A. Foster; Arlene S. Rogachefsky

2000-01-01

145

Detection of Protein Toxins  

Technology Transfer Automated Retrieval System (TEKTRAN)

We have focused on ricin, shiga-like toxin, botulinum neurotoxin (BoNT), and staphylococcal enterotoxin A (SEA), developing sensitive test methods for toxins and marker compounds in food matrices. Although animal models provide the best means for risk assessment, especially for crude toxins in compl...

146

Toxines botuliques : utilisation pratique  

Microsoft Academic Search

Botulinum toxins (A and B) are neurotoxins derived from Clostridium botulinum. Clostridium are anaerobic bacteria. C. botulinum produces exotoxins (A to G) with distinct antigenicities. The neurotoxins inhibit the release of the neurotransmitter acetylcholine from the axon terminals of motor neurons. Botulinum toxin is officially used in clinic for the treatment of muscular hyperactivity (strabismus, blepharospam, cervical dystonia). Botulinum toxins

A Durand; G Serment

2003-01-01

147

A Labile Pool of IQGAP1 Disassembles Endothelial Adherens Junctions  

PubMed Central

Adhesion molecules are known to play an important role in endothelial activation and angiogenesis. Here we determined the functional role of IQGAP1 in the regulation of endothelial adherens junctions. VE-cadherin is found to be associated with actin filaments and thus stable, but IQGAP1 at intercellular junctions is not bound to actin filaments and thus labile. Expression of GFP labeled VE-?-catenin is shown to increase the electrical resistance across HUVEC monolayers and diminishes endogenous labile IQGAP1 at the intercellular junctions. Knockdown of endogenous IQGAP1 enhances intercellular adhesion in HUVECs by increasing the association of VE-cadherin with P120 and ?-catenin. IQGAP1 knockdown also decreases the interaction of N-cadherin with P120 and ?-catenin. Together, these results suggest that a labile pool of IQGAP1 at intercellular junctions disassembles adherens junctions and thus impairs endothelial cell-cell adhesion.

Yuan, Zhiguo; Zhang, Wentao; Tan, Wen

2013-01-01

148

A Labile Pool of IQGAP1 Disassembles Endothelial Adherens Junctions.  

PubMed

Adhesion molecules are known to play an important role in endothelial activation and angiogenesis. Here we determined the functional role of IQGAP1 in the regulation of endothelial adherens junctions. VE-cadherin is found to be associated with actin filaments and thus stable, but IQGAP1 at intercellular junctions is not bound to actin filaments and thus labile. Expression of GFP labeled VE-?-catenin is shown to increase the electrical resistance across HUVEC monolayers and diminishes endogenous labile IQGAP1 at the intercellular junctions. Knockdown of endogenous IQGAP1 enhances intercellular adhesion in HUVECs by increasing the association of VE-cadherin with P120 and ?-catenin. IQGAP1 knockdown also decreases the interaction of N-cadherin with P120 and ?-catenin. Together, these results suggest that a labile pool of IQGAP1 at intercellular junctions disassembles adherens junctions and thus impairs endothelial cell-cell adhesion. PMID:23807500

Yuan, Zhiguo; Zhang, Wentao; Tan, Wen

2013-06-27

149

Repeated Labilization-Reconsolidation Processes Strengthen Declarative Memory in Humans  

PubMed Central

The idea that memories are immutable after consolidation has been challenged. Several reports have shown that after the presentation of a specific reminder, reactivated old memories become labile and again susceptible to amnesic agents. Such vulnerability diminishes with the progress of time and implies a re-stabilization phase, usually referred to as reconsolidation. To date, the main findings describe the mechanisms associated with the labilization-reconsolidation process, but little is known about its functionality from a biological standpoint. Indeed, two functions have been proposed. One suggests that destabilization of the original memory after the reminder allows the integration of new information into the background of the original memory (memory updating), and the other suggests that the labilization-reconsolidation process strengthens the original memory (memory strengthening). We have previously reported the reconsolidation of human declarative memories, demonstrating memory updating in the framework of reconsolidation. Here we deal with the strengthening function attributed to the reconsolidation process. We triggered labilization-reconsolidation processes successively by repeated presentations of the proper reminder. Participants learned an association between five cue-syllables and their respective response-syllables. Twenty-four hours later, the paired-associate verbal memory was labilized by exposing the subjects to one, two or four reminders. The List-memory was evaluated on Day 3 showing that the memory was improved when at least a second reminder was presented in the time window of the first labilization-reconsolidation process prompted by the earlier reminder. However, the improvement effect was revealed on Day 3, only when at least two reminders were presented on Day2 and not as a consequence of only retrieval. Therefore, we propose central concepts for the reconsolidation process, emphasizing its biological role and the parametrical constrains for this function to be operative.

Forcato, Cecilia; Rodriguez, Maria L. C.; Pedreira, Maria E.

2011-01-01

150

Repeated Labilization-Reconsolidation Processes Strengthen Declarative Memory in Humans  

Microsoft Academic Search

The idea that memories are immutable after consolidation has been challenged. Several reports have shown that after the presentation of a specific reminder, reactivated old memories become labile and again susceptible to amnesic agents. Such vulnerability diminishes with the progress of time and implies a re-stabilization phase, usually referred to as reconsolidation. To date, the main findings describe the mechanisms

Cecilia Forcato; María L. C. Rodríguez; María E. Pedreira

2011-01-01

151

Neuropsychological Correlates of Emotional Lability in Children with ADHD  

ERIC Educational Resources Information Center

|Background: Emotional lability (EL) is commonly seen in patients with attention-deficit/hyperactivity disorder (ADHD). The reasons for this association remain currently unknown. To address this question, we examined the relationship between ADHD and EL symptoms, and performance on a range of neuropsychological tasks to clarify whether EL symptoms…

Banaschewski, Tobias; Jennen-Steinmetz, Christine; Brandeis, Daniel; Buitelaar, Jan K.; Kuntsi, Jonna; Poustka, Luise; Sergeant, Joseph A.; Sonuga-Barke, Edmund J.; Frazier-Wood, Alexis C.; Albrecht, Bjorn; Chen, Wai; Uebel, Henrik; Schlotz, Wolff; van der Meere, Jaap J.; Gill, Michael; Manor, Iris; Miranda, Ana; Mulas, Fernando; Oades, Robert D.; Roeyers, Herbert; Rothenberger, Aribert; Steinhausen, Hans-Christoph; Faraone, Stephen V.; Asherson, Philip

2012-01-01

152

Stabilization of Labile Carbonyl Addition Intermediates by a Synthetic Receptor  

Microsoft Academic Search

Products of unfavorable chemical equilibria are not readily observed because their high energy and increased reactivity result in low concentrations. Biological macromolecules use binding forces to access unfavorable equilibria and stabilize reactive intermediates by isolating them from the medium. In a similar vein, we describe here a synthetic receptor that allows direct observation of labile tetrahedral intermediates: hemiaminals formed in

Tetsuo Iwasawa; Richard J. Hooley; Julius Rebek

2007-01-01

153

Contribution of partially labile complexes to the DGT metal flux.  

PubMed

Penetration of complexes into the resin layer can dramatically increase the contribution of complexes to the metal flux measured with a DGT (diffusive gradients in thin films) sensor, but equations to describe this phenomenon were not available. Here, simple approximate analytical expressions for the metal flux, the lability degree and the concentration profiles in a DGT experiment are reported. Together with the thickness of the reaction layer in the gel domain, the effective penetration distance into the resin layer that would be necessary for full dissociation of the complex (?(ML)) plays a key role in determining the metal flux. An increase in the resin-layer thickness (r) effectively increases the metal flux and the lability degree until r ? 3?(ML). For the usual DGT configuration, where the thickness of the gel layer exceeds that of the resin layer, the complex is labile if r > (D(ML)/k(d))½, where D(ML) is the diffusion coefficient of the metal complex and k(d) its dissociation rate constant. A general procedure for estimating the lability of any complex in a standard DGT configuration is provided. PMID:21608530

Uribe, Ramiro; Mongin, Sandrine; Puy, Jaume; Cecília, Joan; Galceran, Josep; Zhang, Hao; Davison, William

2011-05-24

154

Comparison of Labile Soil Organic Matter Fractionation Techniques  

Microsoft Academic Search

to microbial degradation because of low chemical recal- citrance of its components, lack of stabilization onto Labile soil organic carbon (SOCL), soil organic carbon with a rela- clay mineral surfaces, or lack of physical protection in- tively short turnover time, is an important source of energy for the belowground portion of ecosystems and is sensitive to land manage- side soil

Kendra K. McLauchlan; Sarah E. Hobbie

2004-01-01

155

[Hemolysis of Scolopendra toxins].  

PubMed

The hemolysis of toxins from alive Scolopendra subspinipes mutilans, medicinal material of Scolopendra subspimipes mutilans and S. multidens have been compared. The result shows that all the toxins have hemolytic activity. The hemolytic activity of the toxin from the medicinal materials of S. subspinipes mutilans is obviously lower than that from alive ones, and that from fresh medicinal materials are twice as high that from old ones, and that from S. multidens is higher than that from S. subspinipes multilans. PMID:12572496

Deng, F; Fang, H; Wang, K

1997-01-01

156

STUDIES ON THE TOXIN PRODUCTION OF THE SHIGA BACILLI  

PubMed Central

1. The S, R, and Rn variants of the Shiga bacillus are equally toxic. 2. The effect of the toxin upon rabbits is the same, whether it is derived from filtrates of broth cultures (3 to 6 days old), or is obtained by autolysis of the killed bacteria, grown on agar surface. Rabbits show in both cases prostration, loss in weight, paralysis, and diarrhea. 3. When the toxin is heated to 80°C. for 1 hour, its poisonous effect nearly disappears, but its immunizing ability is unaltered. This heated toxin induces a formation of antitoxin, which can protect against the unheated toxins. 4. The anatomical changes observed in the spinal cord (degeneration of the motor neurons) and in the cecum (hyperemia and hemorrhages) are in agreement with the statements of previous authors. Furthermore, the toxin causes hyperemia and hemorrhages in the heart, hyperemia and degeneration in the kidneys and the liver.

Waaler, Erik

1936-01-01

157

Application of a chemical leach technique for estimating labile particulate aluminum, iron, and manganese in the Columbia River plume and coastal waters off Oregon and Washington  

NASA Astrophysics Data System (ADS)

In order to determine the total concentration of bioavailable trace metals in seawater, measurement of both the dissolved and labile particulate fractions is necessary. Comparison of labile particulate metal concentrations from various researchers is limited because of differing definitions of the fraction that is potentially available to phytoplankton on a time frame of generations. A comparison experiment was conducted on coastal and riverine suspended particulate matter to determine the difference between several commonly used techniques that operationally define the labile particulate trace metal fraction. Furthermore, we compared two leach techniques for surface transect samples from within the Columbia River plume and water offshore of Oregon and Washington, United States. The particulate trace metal concentration in the leachate was determined by high-resolution inductively coupled plasma-mass spectrometry. From this comparison, one chemical leach was chosen to best define the labile particulate fraction of Al, Fe, and Mn: a weak acid leach (25% acetic acid at pH 2) with a mild reducing agent (0.02 M hydroxylamine hydrochloride) and a short heating step (10 min 90-95°C). This leach was applied to three surface transects within the Columbia River plume. These coastal waters were found to be rich in labile particulate trace metals that are directly delivered from the Columbia River and indirectly supplied via resuspension from upwelling over a broad continental shelf.

Berger, Carolyn J. M.; Lippiatt, Sherry M.; Lawrence, Michael G.; Bruland, Kenneth W.

2008-02-01

158

Land Use Effects on the Distribution of Labile Organic Carbon Fractions through Soil Profiles  

Microsoft Academic Search

Labile fractions of organic matter can respond rapidly to changes in C supply and are considered to be important indicators of soil quality. However, much less is known on the impact of different land use systems and depth on labile organic matter fractions. The objective of this study was to estimate land use effects on a distribution of labile fraction

Zhang Jinbo; Song Changchun; Yang Wenyan

2006-01-01

159

Suckling mouse model for detection of heat-stable Escherichia coli enterotoxin: characteristics of the model.  

PubMed Central

Although the suckling mouse assay is widely used for the detection of heat-stable Escherichia coli enterotoxin (ST), few data have been published concerning the reproducibility, optimal growth, and test conditions of this assay. Four strains of toxigenic E. coli known to elaborate both heat-labile enterotoxin and ST or ST alone were used to study these parameters. ST activity after heat treatment and the effect of purified choleragen were also examined. ST production was optimal in Casamino Acids-yeast extract media, but both Trypticase soy and brain heart infusion broths resulted in several false negative reactions. Growing cultures in roller tubes was the most reliable method of ST production. Shaking-flask cultures and stationary-grown cultures resulted in suboptimal ST production in several strains. Optimal mouse incubation time was 3 h, and fluid secretion did not rise thereafter. Adequate toxin production occurred after 16 to 24 h of incubation. The coefficient of variation of various toxins tested on many occasions varied between 10.5 and 15.7%. Toxin activity was stable for 6 months when frozen at - 20 C. There was no decrease in ST activity when heated at 65 C for 15 min, but a small decrease was observed in two of four strains after heating at 100 C for 30 min. Choleragen, tested at various doses and at multiple times, gave uniformly negative results. These studies indicate that when done under the proper conditions, the suckling mouse assay is a simple, rapid, and reproducible assay for E. coli ST.

Giannella, R A

1976-01-01

160

HC-toxin.  

PubMed

HC-toxin is a cyclic tetrapeptide of structure cyclo(D-Pro-L-Ala-D-Ala-L-Aeo), where Aeo stands for 2-amino-9,10-epoxi-8-oxodecanoic acid. It is a determinant of specificity and virulence in the interaction between the producing fungus, Cochliobolus carbonum, and its host, maize. HC-toxin qualifies as one of the few microbial secondary metabolites whose ecological function in nature is understood. Reaction to C. carbonum and to HC-toxin is controlled in maize by the Hm1 and Hm2 loci. These loci encode HC-toxin reductase, which detoxifies HC-toxin by reducing the 8-carbonyl group of Aeo. HC-toxin is an inhibitor of histone deacetylases (HDACs) in many organisms, including plants, insects, and mammals, but why inhibition of HDACs during infection by C. carbonum leads to disease is not understood. The genes for HC-toxin biosynthesis (collectively known as the TOX2 locus) are loosely clustered over >500 kb in C. carbonum. All of the known TOX2 genes are present in multiple, functional copies and are absent from natural toxin non-producing isolates. The central enzyme in HC-toxin biosynthesis is a 570-kDa non-ribosomal synthetase encoded by a 15.7-kb open reading frame. Other genes known to be required for HC-toxin encode alpha and beta subunits of fatty acid synthase, which are presumed to contribute to the synthesis of Aeo; a pathway-specific transcription factor; an efflux carrier; a predicted branched-chain amino acid aminotransferase; and an alanine racemase. PMID:16839576

Walton, Jonathan D

2006-07-12

161

Toxin-induced hyperthermic syndromes.  

PubMed

Toxin-induced hyperthermic syndromes are important to consider in the differential diagnosis of patients presenting with fever and muscle rigidity. If untreated, toxin-induced hyperthermia may result in fatal hyperthermia with multisystem organ failure. All of these syndromes have at their center the disruption of normal thermogenic mechanisms, resulting in the activation of the hypothalamus and sympathetic nervous systems.The result of this thermogenic dysregulation is excess heat generation combined with impaired heat dissipation. Although many similarities exist among the clinical presentations and pathophysiologies of toxin-induced hyperthermic syndromes, important differences exist among their triggers and treatments. Serotonin syndrome typically occurs within hours of the addition ofa new serotonergic agent or the abuse of stimulants such as MDMA or methamphetamine. Treatment involves discontinuing the offending agent and administering either a central serotonergic antagonist, such as cyproheptadine or chlorpromazine, a benzodiazepine, or a combination of the two. NMS typically occurs over hours to days in a patient taking a neuroleptic agent; its recommended treatment is generally the combination of a central dopamine agonist, bromocriptine or L-dopa, and dantrolene. In those patients in whom it is difficult to differentiate between serotonin and neuroleptic malignant syndromes, the physical examination may be helpful:clonus and hyperreflexia are more suggestive of serotonin syndrome,whereas lead-pipe rigidity is suggestive of NMS. In patients in whom serotonin syndrome and NMS cannot be differentiated, benzodiazepines represent the safest therapeutic option. MH presents rapidly with jaw rigidity, hyperthermia, and hypercarbia. Although it almost always occurs in the setting of surgical anesthesia, cases have occurred in susceptible individuals during exertion. The treatment of MH involves the use of dantrolene. Future improvements in understanding the pathophysiology and clinical presentations of these syndromes will undoubtedly result in earlier recognition and better treatment strategies. PMID:16227063

Rusyniak, Daniel E; Sprague, Jon E

2005-11-01

162

Lability of metal complexes at spherical sensors. Dynamic voltammetric measurements.  

PubMed

The diffusive-kinetic steady-state (dkss) approximation is applied to the case of a metal ion reaching a transforming/consuming spherical surface (sensor) when the ion is involved in a complexation reaction in solution. Simple time-dependent expressions for the surface metal flux, the lability degree and the half-wave potential are presented, valid for any value of the ratio of concentrations at the surface and the sensor radius. The solution presented is compared with other theoretical approaches, such as the kinetic steady state (kss) and the total steady state (tss), pointing out that the easy dkss approach is much more accurate than the tss one to study the metal flux and the lability degree for any value of the radius, from ultramicro to planar sensors. PMID:20358128

Molina, Angela; Martínez-Ortiz, Francisco; Laborda, Eduardo; Puy, Jaume

2010-04-01

163

Photo-lability of deep ocean dissolved black carbon  

NASA Astrophysics Data System (ADS)

Dissolved black carbon (DBC), defined here as condensed aromatics isolated from seawater via PPL solid phase extraction and quantified as benzene polycarboxylic acid oxidation products, is a significant component of the oceanic dissolved organic carbon (DOC) pool. These condensed aromatics are widely distributed in the open ocean and appear to be tens of thousands of years old. As such DBC is regarded as highly refractory. In the current study, the photo-lability of DBC, DOC and coloured dissolved organic matter (CDOM; ultraviolet-visible absorbance) were determined over the course of a 28 d irradiation of North Atlantic Deep Water under a solar simulator. During the irradiation DBC fell from 1044 ± 164 nM C to 55 ± 15 nM C, a 20-fold decrease in concentration. Dissolved black carbon photo-degradation was more rapid and more extensive than for bulk CDOM and DOC. Further, the photo-lability of components of the DBC pool increased with their degree of aromatic condensation. These trends indicate that a continuum of compounds of varying photo-lability exists within the marine DOC pool. In this continuum, photo-lability scales with aromatic character, specifically the degree of condensation. Scaling the rapid photo-degradation of DBC to rates of DOC photo-mineralisation for the global ocean leads to an estimated photo-chemical half-life for oceanic DBC of less than 800 yr. This is more than an order of magnitude shorter than the apparent age of DBC in the ocean. Photo-degradation is therefore posited as the primary sink for oceanic DBC and the survival of DBC molecules in the oceans for millennia appears to be facilitated not by their inherent inertness but by the rate at which they are cycled through the surface ocean's photic zone.

Stubbins, A.; Niggemann, J.; Dittmar, T.

2012-01-01

164

Labile complexes facilitate cadmium uptake by Caco-2 cells.  

PubMed

The Free Ion Activity Model (FIAM) predicts that metal uptake in biota is related to the free ion activity in the external solution and that metal complexes do not contribute. However, studies with plants have shown that labile metal complexes enhance metal bioavailability when the uptake is rate-limited by transport of the free ion in solution to the uptake site. Here, the role of labile complexes of Cd on metal bioavailability was assessed using Caco-2 cells, the cell model for intestinal absorption. At low Cd(2+) concentration (1 nM), the CdCl(n)(2-n) complexes contributed to the uptake almost to the same extent as the free ion. At large Cd(2+) concentration (10 ?M), the contribution of the complexes was much smaller. At constant Cd(2+) concentration, Cd intake in the cells from solutions containing synthetic ligands such as EDTA increased as the dissociation rate of the cadmium complexes increased, and correlated well with the Cd diffusion flux in solution measured with the Diffusive Gradient in Thin Films technique (DGT). The Cd intake fluxes in the cells were well predicted assuming that the specific uptake is limited by diffusion of the free Cd(2+) ion to the cell surface. Our results underline that speciation of Cd has a major effect on its uptake by intestinal cells, but the availability is not simply related to the free ion concentration. Labile complexes of Cd enhance metal bioavailability in these cells, likely by alleviating diffusive limitations. PMID:22503671

Verheyen, L; Degryse, F; Niewold, T; Smolders, E

2012-04-12

165

Labile disulfide bonds are common at the leucocyte cell surface  

PubMed Central

Redox conditions change in events such as immune and platelet activation, and during viral infection, but the biochemical consequences are not well characterized. There is evidence that some disulfide bonds in membrane proteins are labile while others that are probably structurally important are not exposed at the protein surface. We have developed a proteomic/mass spectrometry method to screen for and identify non-structural, redox-labile disulfide bonds in leucocyte cell-surface proteins. These labile disulfide bonds are common, with several classes of proteins being identified and around 30 membrane proteins regularly identified under different reducing conditions including using enzymes such as thioredoxin. The proteins identified include integrins, receptors, transporters and cell–cell recognition proteins. In many cases, at least one cysteine residue was identified by mass spectrometry as being modified by the reduction process. In some cases, functional changes are predicted (e.g. in integrins and cytokine receptors) but the scale of molecular changes in membrane proteins observed suggests that widespread effects are likely on many different types of proteins including enzymes, adhesion proteins and transporters. The results imply that membrane protein activity is being modulated by a ‘redox regulator’ mechanism.

Metcalfe, Clive; Cresswell, Peter; Ciaccia, Laura; Thomas, Benjamin; Barclay, A. Neil

2011-01-01

166

Method for detecting biological toxins  

Microsoft Academic Search

Biological toxins are indirectly detected by using polymerase chain reaction to amplify unique nucleic acid sequences coding for the toxins or enzymes unique to toxin synthesis. Buffer, primers coding for the unique nucleic acid sequences and an amplifying enzyme are added to a sample suspected of containing the toxin. The mixture is then cycled thermally to exponentially amplify any of

F. S. Ligler; J. R. Campbell

1992-01-01

167

Clostridium Difficile Toxin  

MedlinePLUS

... Anxiety , Tips on Blood Testing , Tips to Help Children through Their Medical Tests , and Tips to Help the Elderly through ... Updated). Stool C. difficile toxin. Medlineplus Health Information, Medical ... Centers for Disease Control and Prevention. Clostridium difficile Infections: ...

168

Topical Botulinum Toxin  

PubMed Central

Nanotechnology is a rapidly growing discipline that capitalizes on the unique properties of matter engineered on the nanoscale. Vehicles incorporating nanotechnology have led to great strides in drug delivery, allowing for increased active ingredient stability, bioavailability, and site-specific targeting. Botulinum toxin has historically been used for the correction of neurological and neuromuscular disorders, such as torticollis, blepharospasm, and strabismus. Recent dermatological indications have been for the management of axillary hyperhydrosis and facial rhytides. Traditional methods of botulinum toxin delivery have been needle-based. These have been associated with increased pain and cost. Newer methods of botulinum toxin formulation have yielded topical preparations that are bioactive in small pilot clinical studies. While there are some risks associated with topical delivery, the refinement and standardization of delivery systems and techniques for the topical administration of botulinum toxin using nanotechnology is anticipated in the near future.

Collins, Ashley

2010-01-01

169

Action of chelators in iron-loaded cardiac cells: accessibility to intracellular labile iron and functional consequences  

Microsoft Academic Search

Labile iron in hemosiderotic plasma and tissue are sources of iron toxicity. We compared the iron chelators deferox- amine, deferiprone, and deferasirox as scavengers of labile iron in plasma and cardiomyocytes at therapeutic concentra- tions. This comprised chelation of labile plasma iron (LPI) in samples from thalas- semia patients; extraction of total cellular iron; accessing labile iron accumulated in organelles

Hava Glickstein; Rinat Ben El; Gabi Link; William Breuer; Abraham M. Konijn; Chaim Hershko; Hanspeter Nick; Z. Ioav Cabantchik; Charles E. Smith

2006-01-01

170

[Natural toxin poisoning].  

PubMed

Natural toxin poisoning often occurs when amateur who has no expert knowledge of food collects and cooks the wrong material. In many cases, the symptoms of natural toxin poisoning are mild and the patients recover from illness within a day. However, if the patients have respiratory or neurological symptoms after several hours of intake, the patients must go to hospital immediately. Mushroom poisoning is often reported and puffer fish poisoning is sometimes reported in Japan. PMID:22894079

Tsunematsu, Satoshi

2012-08-01

171

INTERACTION OF CHOLERA TOXIN AND TOXIN DERIVATIVES WITH LYMPHOCYTES  

PubMed Central

The interaction of cholera toxin and a number of toxin derivatives, containing different proportions of light and heavy toxin-composing subunits (L and H), with mouse lymphocytes was studied. Experiments with [125I]toxin showed that a single cell can rapidly, within minutes, bind up to 40,000 molecules of toxin, the association constant was estimated to 7 ± 4 x 108 liters/mol, and binding was found to be very similar at 37°C and 5°C. Immunofluorescence studies revealed that the toxin attachment is located on the cell surface, and that purified L subunit but not H subunit binds to the cells. A natural cholera toxoid, built up by aggregated L subunits, showed almost identical binding properties as toxin to the cells. Pure GM1 ganglioside, the proposed membrane receptor structure for toxin, prevented entirely the cellular binding of both toxin and toxoid. Cholera toxin in concentrations down to approximately 5 x 10–11 mol/liter (corresponding to 10 bound molecules/cell) inhibited thymus cells from being stimulated to DNA synthesis by concanavalin A (con A), and spleen cells from such stimulation by phytohemagglutinin. The GM1 ganglioside but not a series of other pure structurally related gangliosides and neutral glycosphingolipids neutralized this toxin activity. Toxin derivatives which, in similarity with toxin, possessed H as well as L subunits but in other proportions, were potent inhibitors of con A-induced thymocyte stimulation, whereas the natural toxoid (aggregated L subunits), purified toxin L subunit and purified toxin H subunit were up to 300-fold less active on a weight basis. The capacity of cholera proteins to inhibit con A-induced thymocyte stimulation correlated well with their activity in the rabbit intradermal toxicity assay. The inhibitory action of cholera toxin on con A-induced thymocyte stimulation did not depend on decreased cell viability from the toxin treatment, nor was it caused by a reaction between toxin and con A. [125I]con A bound equally well to the cells when toxin was present as when it was absent, which proves that the toxin did not compete for cellular con A receptors. Nor did the toxin seem to disturb the general mobility of membrane receptors or their ability to accumulate in caps. It is concluded that the L type of subunit confers rapid and firm binding of cholera toxin to lymphocyte membranes, probably to GM1 ganglioside receptors. For biologic activity the additional presence of H subunit is important. One manifestation of toxin action on lymphocytes is inhibition of lectin-induced DNA synthesis; probably this effect relates to the ability of cholera toxin to raise the levels of intracellular cyclic 3'5'-adenosine monophosphate.

Holmgren, J.; Lindholm, L.; Lonnroth, I.

1974-01-01

172

Construction of nontoxic derivatives of cholera toxin and characterization of the immunological response against the A subunit.  

PubMed Central

Using computer modelling, we have identified some of the residues of the A subunit of cholera toxin (CT) and heat-labile toxin that are involved in NAD binding, catalysis, and toxicity. Here we describe the site-directed mutagenesis of the CT gene and the construction of CT mutants. Nine mutations of the A subunit gene were generated. Six of them encoded proteins that were fully assembled in the AB5 structure and were nontoxic; these proteins were CT-D53 (Val-53-->Asp), CT-K63 (Ser-63-->Lys), CT-K97 (Val-97-->Lys), CT-K104 (Tyr-104-->Lys), CT-S106 (Pro-106-->Ser), and the double mutant CT-D53/K63 (Val-53-->Asp, Ser-63-->Lys). Two of the mutations encoded proteins that were assembled into the AB5 structure but were still toxic; these proteins were CT-H54 (Arg-54-->His) and CT-N107 (His-107-->Asn). Finally, one of the mutant proteins, CT-E114 (Ser-114-->Glu), was unable to assemble the A and the B subunits and produced only the B oligomer. The six nontoxic mutants were purified from the culture supernatants of recombinant Vibrio cholerae strains and further characterized. The CT-K63 mutant, which was the most efficient in assembly of the AB5 structure, was used to immunize rabbits and was shown to be able to induce neutralizing antibodies against both the A and B subunits. This molecule may be useful for the construction of improved vaccines against cholera.

Fontana, M R; Manetti, R; Giannelli, V; Magagnoli, C; Marchini, A; Olivieri, R; Domenighini, M; Rappuoli, R; Pizza, M

1995-01-01

173

A labile point in mutant amphotericin polyketide synthases.  

PubMed

Streptomyces nodosus produces the antifungal polyene amphotericin B. Numerous modifications of the amphotericin polyketide synthase have yielded new analogues. However, previous inactivation of the ketoreductase in module 10 resulted in biosynthesis of truncated polyketides. Here we show that modules downstream of this domain remain intact. Therefore, loss of ketoreductase-10 activity is sufficient to cause early chain termination. This modification creates a labile point in cycle 11 of the polyketide biosynthetic pathway. Non-extendable intermediates are released to accumulate as polyenyl-pyrones. PMID:21267757

Khan, Naseem; Rawlings, Bernard; Caffrey, Patrick

2011-01-26

174

Koilocytes are enriched for alkaline-labile sites  

PubMed Central

This study investigated possible variations in the chromatin structure of koilocytes resulting from human papillomavirus (HPV) infection. Alkaline-labile sites (ALS) were detected with the DNA breakage detection–fluorescence in situ hybridization (DBD-FISH) technique using a whole human genome DNA probe obtained from individuals without koilocytosis. The variable levels of ALS present were measured quantitatively using image analysis after whole-genome DNA hybridization. A significant increase in the number of ALS was observed in koilocytes compared with normal cells. We demonstrated that the presence of ALS could be an indicator of chromatin change in koilocytes caused by HPV infection.

Cortes-Gutierrez, E.I.; Davila-Rodriguez, M.I.; Fernandez, J.L.; Lopez-Fernandez, C.; Gosalvez, J.

2010-01-01

175

Stabilization of labile carbonyl addition intermediates by a synthetic receptor.  

PubMed

Products of unfavorable chemical equilibria are not readily observed because their high energy and increased reactivity result in low concentrations. Biological macromolecules use binding forces to access unfavorable equilibria and stabilize reactive intermediates by isolating them from the medium. In a similar vein, we describe here a synthetic receptor that allows direct observation of labile tetrahedral intermediates: hemiaminals formed in the reaction of an aldehyde carbonyl group with amines. The receptor encapsulates alkyl-substituted primary amines, then orients them toward a covalently tethered aldehyde function. The hemiaminal intermediates appear at high concentration, confined from the bulk solution and observable at ambient temperature by conventional nuclear magnetic resonance spectroscopy. PMID:17656719

Iwasawa, Tetsuo; Hooley, Richard J; Rebek, Julius

2007-07-27

176

Photo-lability of deep ocean dissolved black carbon  

NASA Astrophysics Data System (ADS)

Dissolved black carbon (DBC), defined here as condensed aromatics isolated from seawater via PPL solid phase extraction and quantified as benzenepolycarboxylic acid (BPCA) oxidation products, is a significant component of the oceanic dissolved organic carbon (DOC) pool. These condensed aromatics are widely distributed in the open ocean and appear to be tens of thousands of years old. As such DBC is regarded as highly refractory. In the current study, the photo-lability of DBC, DOC and coloured dissolved organic matter (CDOM; ultraviolet-visible absorbance) were determined over the course of a 28 day irradiation of North Atlantic Deep Water under a solar simulator. During the irradiation DBC fell from 1044 ± 164 nM-C to 55 ± 15 nM-C, a 20-fold decrease in concentration. Dissolved black carbon photo-degradation was more rapid and more extensive than for bulk CDOM and DOC. The concentration of DBC correlated with CDOM absorbance and the quality of DBC indicated by the ratios of different BPCAs correlated with CDOM absorbance spectral slope, suggesting the optical properties of CDOM may provide a proxy for both DBC concentrations and quality in natural waters. Further, the photo-lability of components of the DBC pool increased with their degree of aromatic condensation. These trends indicate that a continuum of compounds of varying photo-lability exists within the marine DOC pool. In this continuum, photo-lability scales with aromatic character, specifically the degree of condensation. Scaling the rapid photo-degradation of DBC to rates of DOC photo-mineralisation for the global ocean leads to an estimated photo-chemical half-life for oceanic DBC of less than 800 years. This is more than an order of magnitude shorter than the apparent age of DBC in the ocean. Consequently, photo-degradation is posited as the primary sink for oceanic DBC and the apparent survival of DBC molecules in the oceans for millennia appears to be facilitated not by their inherent inertness but by the rate at which they are cycled through the surface ocean's photic zone.

Stubbins, A.; Niggemann, J.; Dittmar, T.

2012-05-01

177

Immunologic Interrelationships of Coliform Heat-Labile and Heat-Stable Enterotoxins.  

National Technical Information Service (NTIS)

The goal of these studies is the development of an immunization program to prevent diarrheal disease due to intestinal contamination by enterotoxigenic strains of coliform bacteria. We have found that immunization with the polymyxin-release form of Escher...

F. A. Klipstein

1980-01-01

178

Immunological Interrelationships of Coliform Heat-Labile and Heat-Stable Enterotoxins.  

National Technical Information Service (NTIS)

Investigations conducted during the four period (1977 to 1981) of support by the USAMRDC have accomplished the following. (1) The enterotoxigenicity of certain coliform species which contaminate the small bowel in different diarrheal disorders has been es...

F. A. Klipstein

1981-01-01

179

The wing-patterning network in the wingless castes of Myrmicine and Formicine ant species is a mix of evolutionarily labile and non-labile genes.  

PubMed

Wing polyphenism in ants is the ability of a single genome to produce winged or wingless castes in a colony in response to environmental cues. Although wing polyphenism is a universal and homologous feature of ants, the gene network underlying wing polyphenism is conserved in the winged castes, but is labile in the wingless castes, that is, the network is interrupted at different points in the wingless castes of different ant species. Because the expression of all genes sampled so far in this network in the wingless castes is evolutionarily labile across species, an important question is whether all "interruption points" in the network are evolutionarily labile or are there interruption points that are evolutionarily non-labile. Here we show that in the wingless castes, the expression of the gene brinker (brk), which mediates growth, patterning, and apoptosis in the Drosophila wing disc, is non-labile; it is absent in vestigial wing discs of four ants species. In contrast, the expression of engrailed (en), a gene upstream of brk is labile; it is present in some species but absent in others. In the winged castes, both brk and en expression are conserved relative to their expression in Drosophila wing discs. The differential lability of genes in the network in wingless castes may be a general feature of networks underlying polyphenic traits. This raises the possibility that some genes, like brk, may be under stabilizing selection while most others, like en, may be evolving via directional selection or neutral drift. PMID:23225600

Shbailat, Seba Jamal; Abouheif, Ehab

2012-12-06

180

Acid-Labile Polyvinylamine Micro- and Nanogel Capsules  

PubMed Central

Hollow nanoparticles represent an emerging area of development for the encapsulation of active ingredients. Expanding the capabilities of these nanomaterials will require continued efforts to infill properties such as size control, biodegradability, and environmental responsiveness. Acid-labile poly(N-vinylformamide) (PNVF) nanocapsules were synthesized by free radical polymerization of N-vinylformamide on the surface of silica nanoparticles. Polymerization in the presence of a novel crosslinker that contains an acid-labile ketal facilitated stable etching of silica nanoparticle templates using sodium hydroxide and recovery of degradable PNVF nanocapsules. The formamido side group of PNVF was then hydrolyzed by extended exposure to sodium hydroxide to produce polyvinylamine (PVAm) micro- and nanocapsules. Both capsule types demonstrated an increasing dissolution rate as pH decreased. In addition, PVAm nanocapsules exhibited swelling in proportion to the relative charge density of the PVAm network (a function of the degree of formamide hydrolysis and pH), presumably due to the repulsion of positively charged amino groups within the elastic shell network. The synthetic approaches reported provide methods to endow nanocapsules with key attributes such as size control, pH sensitive degradation, swelling in response to pH, and amine functionality.

Shi, Lianjun; Berkland, Cory

2008-01-01

181

Ciguatera Toxin Information Website  

NSDL National Science Digital Library

This website provides information about the marine toxin disease Ciguatera, which is caused by the consumption of fish that have accumulated ciguatoxin in their tissues. The toxin is produced by a microscopic dinoflagellate (Gambierdiscus toxicus) that lives on the surfaces of macroalgae in coral reef ecosystems. The dinoflagellates are inadvertently consumed by herbivorous fish during grazing and the toxins bioaccumulate in the food chain, attaining highest levels in carnivores. The site includes an introduction to ciguatera, information about the symptoms with links to reported cases and medical treatments, non-medical solutions, an education section, list of retailers, news releases, related links, and more. The site is published by ToxiTech, suppliers of Cigua-CheckÃ, which is a commercially available test kit for screening fish for ciguatoxin prior to consumption.

Toxitech; Oceanit

182

Urological Applications of Botulinum Toxin  

Microsoft Academic Search

\\u000a Botulinum toxin is a neurotoxin produced by the Gram-positive, rod-shaped anaerobic bacterium Clostridium botulinum (1). First discovered in 1897 by Professor Pierre Emile van Ermengem of Ellezelles, Belgium botulinum toxin is the most poisonous\\u000a naturally occurring toxin known to man (2). Seven immunologically distinct antigenic subtypes of botulinum toxin have been isolated: A, B, C1, D, E, F, and G

Courtenay K. Moore; Howard B. Goldman

183

Integrated optical toxin sensor  

NASA Astrophysics Data System (ADS)

We have developed a method for simple and highly sensitive detection of multivalent proteins using an optical waveguide sensor. The optical biosensor is based on optically tagged glycolipid receptors imbedded within a fluid phospholipid bilayer membrane formed on the surface of a planar optical waveguide. The binding of multivalent toxin initiates a fluorescence resonance energy transfer resulting in a distinctive spectral signature that is monitored by measuring emitted luminescence above the waveguide surface. The sensor methodology is highly sensitive and specific, and requires no additional reagents or washing steps. Demonstration of the utility of protein-receptor recognition using planar optical waveguides is shown here by the detection of cholera toxin.

Kelly, Dan; Song, Xuedong; Frayer, Daniel K.; Mendes, Sergio B.; Peyghambarian, Nasser; Swanson, Basil I.; Grace, Karen M.

1999-12-01

184

Uremia Toxin Assay.  

National Technical Information Service (NTIS)

The purpose of the research was to find assay systems which could be used in attempts to isolate the supposed toxins of uremia. A total of 14 enzyme assay systems were tested against fractions of plasma, dialysate, and urine from both uremic subjects unde...

C. E. Cook

1970-01-01

185

Diffusion of Botulinum Toxins  

PubMed Central

Background It is generally agreed that diffusion of botulinum toxin occurs, but the extent of the spread and its clinical importance are disputed. Many factors have been suggested to play a role but which have the most clinical relevance is a subject of much discussion. Methods This review discusses the variables affecting diffusion, including protein composition and molecular size as well as injection factors (e.g., volume, dose, injection method). It also discusses data on diffusion from comparative studies in animal models and human clinical trials that illustrate differences between the available botulinum toxin products (onabotulinumtoxinA, abobotulinumtoxinA, incobotulinumtoxinA, and rimabotulinumtoxinB). Results Neither molecular weight nor the presence of complexing proteins appears to affect diffusion; however, injection volume, concentration, and dose all play roles and are modifiable. Both animal and human studies show that botulinum toxin products are not interchangeable, and that some products are associated with greater diffusion and higher rates of diffusion-related adverse events than others. Discussion Each of the botulinum toxins is a unique pharmacologic entity. A working knowledge of the different serotypes is essential to avoid unwanted diffusion-related adverse events. In addition, clinicians should be aware that the factors influencing diffusion may range from properties intrinsic to the drug to accurate muscle selection as well as dilution, volume, and dose injected.

Brodsky, Matthew A.; Swope, David M.; Grimes, David

2012-01-01

186

The bacterial toxin toolkit  

Microsoft Academic Search

Pathogenic bacteria and higher eukaryotes have spent a long time together, leading to a precise understanding of one another's way of functioning. Through rapid evolution, bacteria have engineered increasingly sophisticated weapons to hit exactly where it hurts, interfering with fundamental host functions. However, toxins are not only useful to the bacteria — they have also become an essential asset for

Giampietro Schiavo; F. Gisou van der Goot

2001-01-01

187

The role of labile sulfur compounds in thermochemical sulfate reduction  

USGS Publications Warehouse

The reduction of sulfate to sulfide coupled with the oxidation of hydrocarbons to carbon dioxide, commonly referred to as thermochemical sulfate reduction (TSR), is an important abiotic alteration process that most commonly occurs in hot carbonate petroleum reservoirs. In the present study we focus on the role that organic labile sulfur compounds play in increasing the rate of TSR. A series of gold-tube hydrous pyrolysis experiments were conducted with n-octane and CaSO4 in the presence of reduced sulfur (e.g. H2S, S??, organic S) at temperatures of 330 and 356 ??C under a constant confining pressure. The in-situ pH was buffered to 3.5 (???6.3 at room temperature) with talc and silica. For comparison, three types of oil with different total S and labile S contents were reacted under similar conditions. The results show that the initial presence of organic or inorganic sulfur compounds increases the rate of TSR. However, organic sulfur compounds, such as 1-pentanethiol or diethyldisulfide, were significantly more effective in increasing the rate of TSR than H2S or elemental sulfur (on a mole S basis). The increase in rate is achieved at relatively low concentrations of 1-pentanethiol, less than 1 wt% of the total n-octane, which is comparable to the concentration of organic S that is common in many oils (???0.3 wt%). We examined several potential reaction mechanisms to explain the observed reactivity of organic LSC. First, the release of H2S from the thermal degradation of thiols was discounted as an important mechanism due to the significantly greater reactivity of thiol compared to an equivalent amount of H2S. Second, we considered the generation of olefines in association with the elimination of H2S during thermal degradation of thiols because olefines are much more reactive than n-alkanes during TSR. In our experiments, olefines increased the rate of TSR, but were less effective than 1-pentanethiol and other organic LSC. Third, the thermal decomposition of organic LSC creates free-radicals that in turn might initiate a radical chain-reaction that creates more reactive species. Experiments involving radical initiators, such as diethyldisulfide and benzyldisulfide, did not show an increase in reactivity compared to 1-pentanethiol. Therefore, we conclude that none of these can sufficiently explain our observations of the initial stages of TSR; they may, however, be important in the later stages. In order to gain greater insight into the potential mechanism for the observed reactivity of these organic sulfur compounds during TSR, we applied density functional theory-based molecular modeling techniques to our system. The results of these calculations indicate that 1-pentanethiol or its thermal degradation products may directly react with sulfate and reduce the activation energy required to rupture the first S-O bond through the formation of a sulfate ester. This study demonstrates the importance of labile sulfur compounds in reducing the onset timing and temperature of TSR. It is therefore essential that labile sulfur concentrations are taken into consideration when trying to make accurate predictions of TSR kinetics and the potential for H2S accumulation in petroleum reservoirs. ?? 2008.

Amrani, A.; Zhang, T.; Ma, Q.; Ellis, G. S.; Tang, Y.

2008-01-01

188

The role of labile sulfur compounds in thermochemical sulfate reduction  

NASA Astrophysics Data System (ADS)

The reduction of sulfate to sulfide coupled with the oxidation of hydrocarbons to carbon dioxide, commonly referred to as thermochemical sulfate reduction (TSR), is an important abiotic alteration process that most commonly occurs in hot carbonate petroleum reservoirs. In the present study we focus on the role that organic labile sulfur compounds play in increasing the rate of TSR. A series of gold-tube hydrous pyrolysis experiments were conducted with n-octane and CaSO 4 in the presence of reduced sulfur (e.g. H 2S, S°, organic S) at temperatures of 330 and 356 °C under a constant confining pressure. The in-situ pH was buffered to 3.5 (˜6.3 at room temperature) with talc and silica. For comparison, three types of oil with different total S and labile S contents were reacted under similar conditions. The results show that the initial presence of organic or inorganic sulfur compounds increases the rate of TSR. However, organic sulfur compounds, such as 1-pentanethiol or diethyldisulfide, were significantly more effective in increasing the rate of TSR than H 2S or elemental sulfur (on a mole S basis). The increase in rate is achieved at relatively low concentrations of 1-pentanethiol, less than 1 wt% of the total n-octane, which is comparable to the concentration of organic S that is common in many oils (˜0.3 wt%). We examined several potential reaction mechanisms to explain the observed reactivity of organic LSC. First, the release of H 2S from the thermal degradation of thiols was discounted as an important mechanism due to the significantly greater reactivity of thiol compared to an equivalent amount of H 2S. Second, we considered the generation of olefines in association with the elimination of H 2S during thermal degradation of thiols because olefines are much more reactive than n-alkanes during TSR. In our experiments, olefines increased the rate of TSR, but were less effective than 1-pentanethiol and other organic LSC. Third, the thermal decomposition of organic LSC creates free-radicals that in turn might initiate a radical chain-reaction that creates more reactive species. Experiments involving radical initiators, such as diethyldisulfide and benzyldisulfide, did not show an increase in reactivity compared to 1-pentanethiol. Therefore, we conclude that none of these can sufficiently explain our observations of the initial stages of TSR; they may, however, be important in the later stages. In order to gain greater insight into the potential mechanism for the observed reactivity of these organic sulfur compounds during TSR, we applied density functional theory-based molecular modeling techniques to our system. The results of these calculations indicate that 1-pentanethiol or its thermal degradation products may directly react with sulfate and reduce the activation energy required to rupture the first S-O bond through the formation of a sulfate ester. This study demonstrates the importance of labile sulfur compounds in reducing the onset timing and temperature of TSR. It is therefore essential that labile sulfur concentrations are taken into consideration when trying to make accurate predictions of TSR kinetics and the potential for H 2S accumulation in petroleum reservoirs.

Amrani, Alon; Zhang, Tongwei; Ma, Qisheng; Ellis, Geoffrey S.; Tang, Yongchun

2008-06-01

189

Labile dissolved organic carbon supply limits hyporheic denitrification  

NASA Astrophysics Data System (ADS)

We used an in situ steady state 15N-labeled nitrate (15NO3-) and acetate (AcO-) well-to-wells injection experiment to determine how the availability of labile dissolved organic carbon (DOC) as AcO-influences microbial denitrification in the hyporheic zone of an upland (third-order) agricultural stream. The experimental wells receiving conservative (Cl- and Br) and reactive (15NO3-) solute tracers had hyporheic median residence times of 7.0 to 13.1 h, nominal flowpath lengths of 0.7 to 3.7 m, and hypoxic conditions (<1.5 mg O2 L-1). All receiving wells demonstrated 15N2 production during ambient conditions, indicating that the hyporheic zone was an environment with active denitrification. The subsequent addition of AcO- stimulated more denitrification as evidenced by significant ?15N2 increases by factors of 2.7 to 26.1 in receiving wells and significant decreases of NO3- and DO in the two wells most hydrologically connected to the injection. The rate of nitrate removal in the hyporheic zone increased from 218 kg ha-1 yr-1 to 521 kg ha-1 yr-1 under elevated AcO- conditions. In all receiving wells, increases of bromide and 15N2 occurred without concurrent increases in AcO-, indicating that 100% of AcO- was retained or lost in the hyporheic zone. These results support the hypothesis that denitrification in anaerobic portions of the hyporheic zone is limited by labile DOC supply.

Zarnetske, Jay P.; Haggerty, Roy; Wondzell, Steven M.; Baker, Michelle A.

2011-12-01

190

The Renal Tubular Handling of Aldosterone and Its Acid-Labile Conjugate.  

National Technical Information Service (NTIS)

Stop-flow studies using infusions of aldosterone-3H or its 3H acid-labile conjugate were done on five rhesus monkeys. The aldosterone-3H urine-to-plasma (U/P) ratio decreased in the same distal urine samples as sodium. The 3H acid-labile conjugate U/P-to-...

M. T. Scurry L. Shear K. G. Barry

1967-01-01

191

Fast labile carbon turnover obscures sensitivity of heterotrophic respiration from soil to temperature: A model analysis  

Microsoft Academic Search

Labile carbon, although often a small fraction of soil organic carbon (SOC), significantly affects heterotrophic respiration at short timescales because of its rapid decomposition. However, in the current literature, most soil respiration measurements are interpreted without simultaneous information on labile carbon pool dynamics. Sensitivity of soil respiration to temperature is routinely derived directly from field observations, and such relationships have

Lianhong Gu; Wilfred M. Post; Anthony W. King

2004-01-01

192

Harnessing Labile Bonds between Nanogels Particles to Create Self-Healing Materials  

Microsoft Academic Search

Using computational modeling, we demonstrate the self-healing behavior of novel materials composed of nanoscopic gel particles that are interconnected into a macroscopic network by both stable and labile bonds. Under mechanical stress, the labile bonds between the nanogels can break and readily reform with reactive groups on neighboring units. This breaking and reforming allows the units in the network to

German V. Kolmakov; Krzysztof Matyjaszewski; Anna C. Balazs

2009-01-01

193

Labile iron in parenteral iron formulations: a quantitative and comparative study  

Microsoft Academic Search

Background. Evidence of iron-mediated oxidative stress, neutrophil dysfunction and enhanced bacterial growth after intravenous (IV) iron administration has been ascribed to a labile or bioactive iron fraction present in all IV iron agents. Methods. To quantify and compare the size of the labile fraction in several classes of IV iron agents, we examined iron donation to transferrin (Tf) in vitro

David Van Wyck; Jaime Anderson; Kevin Johnson

194

Whole-ecosystem labile carbon production in a north temperate deciduous forest  

Microsoft Academic Search

Labile carbon (C), which is principally comprised of non-structural carbohydrates, is an essential intermediary between C assimilation and structural growth in deciduous forests. We developed a new approach that combined meteorological and biometric C cycling data for a mixed deciduous forest in Michigan, USA, to provide novel estimates of whole-ecosystem labile C production and reallocation to structural net primary production

Christopher M. Gough; Charles E. Flower; Christoph S. Vogel; Danilo Dragoni; Peter S. Curtis

2009-01-01

195

Response of labile soil organic matter to changes in forest vegetation in subtropical regions  

Microsoft Academic Search

Labile soil organic matter (SOM) can sensitively respond to changes in land use and management practices, and has been suggested as an early and sensitive indicator of SOM. However, knowledge of effects of forest vegetation type on labile SOM is still scarce, particularly in subtropical regions. Soil microbial biomass C and N, water-soluble soil organic C and N, and light

Qingkui Wang; Silong Wang

2011-01-01

196

Glaciers as a source of ancient and labile organic matter to the marine environment  

Microsoft Academic Search

Riverine organic matter supports of the order of one-fifth of estuarine metabolism. Coastal ecosystems are therefore sensitive to alteration of both the quantity and lability of terrigenous dissolved organic matter (DOM) delivered by rivers. The lability of DOM is thought to vary with age, with younger, relatively unaltered organic matter being more easily metabolized by aquatic heterotrophs than older, heavily

Eran Hood; Jason Fellman; Robert G. M. Spencer; Peter J. Hernes; Rick Edwards; David D'Amore; Durelle Scott

2009-01-01

197

Toxins of cyanobacteria.  

PubMed

Blue-green algae are found in lakes, ponds, rivers and brackish waters throughout the world. In case of excessive growth such as bloom formation, these bacteria can produce inherent toxins in quantities causing toxicity in mammals, including humans. These cyanotoxins include cyclic peptides and alkaloids. Among the cyclic peptides are the microcystins and the nodularins. The alkaloids include anatoxin-a, anatoxin-a(S), cylindrospermopsin, saxitoxins (STXs), aplysiatoxins and lyngbyatoxin. Both biological and chemical methods are used to determine cyanotoxins. Bioassays and biochemical assays are nonspecific, so they can only be used as screening methods. HPLC has some good prospects. For the subsequent detection of these toxins different detectors may be used, ranging from simple UV-spectrometry via fluorescence detection to various types of MS. The main problem in the determination of cyanobacterial toxins is the lack of reference materials of all relevant toxins. In general, toxicity data on cyanotoxins are rather scarce. A majority of toxicity data are known to be of microcystin-LR. For nodularins, data from a few animal studies are available. For the alkaloids, limited toxicity data exist for anatoxin-a, cylindrospermopsin and STX. Risk assessment for acute exposure could be relevant for some types of exposure. Nevertheless, no acute reference doses have formally been derived thus far. For STX(s), many countries have established tolerance levels in bivalves, but these limits were set in view of STX(s) as biotoxins, accumulating in marine shellfish. Official regulations for other cyanotoxins have not been established, although some (provisional) guideline values have been derived for microcystins in drinking water by WHO and several countries. PMID:17195276

van Apeldoorn, Marian E; van Egmond, Hans P; Speijers, Gerrit J A; Bakker, Guido J I

2007-01-01

198

Lability of trace metals in submerged soils: a column study  

NASA Astrophysics Data System (ADS)

The reduction of Fe (III) and Mn (IV) and the decomposition of organic matter exert a great influence on the biogeochemical cycles of many trace metals and nutrients in the environment. In the particular case of intermittently submerged soils, metals associated with Fe and Mn oxides become readily available due to the reductive dissolution of Fe and Mn oxides. The effects of oxido-reductive conditions on the release of Cu and Zn from heavy metal contaminated soils and the changes in their chemical speciation were studied. Column experiments were performed, using Rhizon soil moisture samplers inserted at different heights to monitor the mobility and transport of metals in the submerged soil samples. Cu was released in solution immediately, in the first red-ox cycle, either due to the solubilization of Fe and Mn oxides, or to the oxidation of organic matter with which Cu is commonly complexed, or both. During the following reductive half-cycles, the amount of Cu extracted from the soil solution decreased. However, the concentration of Cu in the solution leached from the column, which was percolated in aerobic conditions, increased. Since in the successive red-ox cycles the Eh decreases faster and to lower values, it is possible that Cu might have been removed from pore water by sulfide precipitation during the anaerobic half-cycle and released during the aerobic half-cycle, due to the oxidation of sulfides to sulfates. The release of Zn was similar to the dissolution of Fe and Mn oxyhydroxydes, and the amount extracted by Rhizon and by leaching increased during the four red-ox cycles. The chemical fractionation of the soils was also studied and the results showed that the alternate oxidative-reductive conditions cause, in general, an increase in the lability of trace metals. While Zn speciation suffers little change, Cu showed a much higher exchangeable fraction in the submerged soils, as compared to the initial, not submerged ones. The results of this study indicate that intermittent submergence of contaminated soils not only causes the release of trace metals previously bound to Fe and Mn oxides and to organic matter, but also leads to an increase in their lability, rending them more readily available to be released into the environment.

Nimirciag, Ramona; Ajmone-Marsan, Franco

2013-04-01

199

Method for detecting biological toxins  

SciTech Connect

Biological toxins are indirectly detected by using polymerase chain reaction to amplify unique nucleic acid sequences coding for the toxins or enzymes unique to toxin synthesis. Buffer, primers coding for the unique nucleic acid sequences and an amplifying enzyme are added to a sample suspected of containing the toxin. The mixture is then cycled thermally to exponentially amplify any of these unique nucleic acid sequences present in the sample. The amplified sequences can be detected by various means, including fluorescence. Detection of the amplified sequences is indicative of the presence of toxin in the original sample. By using more than one set of labeled primers, the method can be used to simultaneously detect several toxins in a sample.

Ligler, F.S.; Campbell, J.R.

1992-01-01

200

Capturing labile sulfenamide and sulfinamide serum albumin adducts of carcinogenic arylamines by chemical oxidation.  

PubMed

Aromatic amines and heterocyclic aromatic amines (HAAs) are a class of structurally related carcinogens that are formed during the combustion of tobacco or during the high temperature cooking of meats. These procarcinogens undergo metabolic activation by N-oxidation of the exocyclic amine group to produce N-hydroxylated metabolites, which are critical intermediates implicated in toxicity and DNA damage. The arylhydroxylamines and their oxidized arylnitroso derivatives can also react with cysteine (Cys) residues of glutathione or proteins to form, respectively, sulfenamide and sulfinamide adducts. However, sulfur-nitrogen linked adducted proteins are often difficult to detect because they are unstable and undergo hydrolysis during proteolytic digestion. Synthetic N-oxidized intermediates of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), a carcinogenic HAA produced in cooked meats, and 4-aminobiphenyl, a carcinogenic aromatic amine present in tobacco smoke, were reacted with human serum albumin (SA) and formed labile sulfenamide or sulfinamide adducts at the Cys(34) residue. Oxidation of the carcinogen-modified SA with m-chloroperoxybenzoic acid (m-CPBA) produced the arylsulfonamide adducts, which were stable to heat and the chemical reduction conditions employed to denature SA. The sulfonamide adducts of PhIP and 4-ABP were identified, by liquid chromatography/mass spectrometry, in proteolytic digests of denatured SA. Thus, selective oxidation of arylamine-modified SA produces stable arylsulfonamide-SA adducts, which may serve as biomarkers of these tobacco and dietary carcinogens. PMID:23240913

Peng, Lijuan; Turesky, Robert J

2012-12-28

201

[Botulinum toxin: the misguided path].  

PubMed

Botulinum toxin is widely used and has become a popular mass phenomenon in aesthetic medicine. Considerable scientific data concerning the biopsychosocial impact of botulinum toxin use have become available. The bidirectional interaction of mimic and emotion, described as the facial feedback hypothesis, is particularly influenced, as is mimicry. Furthermore, botulinum toxin can cause dysfunction of face harmony including false laughing or the "frozen face". As a result, complex psychosocial disturbances can occur and may affect social interaction and cause flattening of affect. Thus one must ask whether in the future botulinum toxin will continue to be employed in aesthetic dermatology or perhaps be regarded as a misguided path. PMID:23636411

Harth, W

2013-06-01

202

Functional role of intracellular labile zinc in pulmonary endothelium.  

PubMed

After iron, zinc is the most abundant essential trace metal. Intracellular zinc ([Zn](i)) is maintained across a wide range of cells and species in a tight quota (100 to 500 ?M) by a dynamic process of transport, intracellular vesicular storage, and binding to a large number of proteins (estimated at 3-10% of human proteome). As such, zinc is an integral component of numerous metalloenzymes, structural proteins, and transcription factors. It is generally assumed that a vanishingly small component of [Zn](i,) referred to as free or labile zinc, and operationally defined as the pool sensitive to chelation (by agents such as N, N, N', N'-tetrakis [2-pyridylmethyl] ethylenediamine [TPEN]) and capable of detection by a variety of chemical and genetic sensors, participates in signal transduction pathways. Zinc deficiencies, per se, can arise from acquired (malnutrition, alcoholism) or genetic (mutations in molecules affecting zinc homeostasis, the informative and first example being acrodermatitis enteropathica) factors or as a component of various diseases (e.g., sickle cell disease, cystic fibrosis, sepsis). Hypozincemia has profound effects on developing humans, and all facets of physiological function (neuronal, endocrine, immunological) are affected, although considerably less is known regarding cardiovascular pathophysiology. In this review, we provide an update on current knowledge of molecular and cellular aspects of zinc homeostasis and then focus on implications of zinc signaling in pulmonary endothelium as it relates to programmed cell death, altered contractility, and septic and aseptic injury to this segment of the lung. PMID:23372928

Thambiayya, Kalidasan; Kaynar, A Murat; St Croix, Claudette M; Pitt, Bruce R

2012-10-01

203

Labile disulfide bonds in human placental insulin receptor  

SciTech Connect

The disulfide crosslinking pattern of human placental insulin receptor was investigated using selective reduction with tributylphosphine followed by alkylation with N-({sup 3}H)ethylmaleimide. Insulin receptor contains a single sulfhydryl group in each {beta} subunit whose alkylation with N-({sup 3}H)ethylmaleimide inhibits receptor autophosphorylation. Alkylation is partially inhibited by ATP or the nonhydrolyzable substrate analog adenosine 5{prime}-({beta},{gamma}-imido)triphosphate when the nucleotides are added as MN{sup 2+} complexes. Neither insulin nor 6 M guanidinium chloride renders additional sulfhydryl groups accessible to alkylation. When the receptor is reduced under drastic conditions with tributylphosphine in guanidinium chloride, 32 or the 37 sulfhydryl groups in the receptor's {alpha} subunit can be alkylated with N-({sup 3}H)ethylmaleimide. Surprisingly only three of the 10 cysteines in the {beta} subunit become titratable under identical conditions. By using highly selective reducing conditions, the authors were able to determine quantitatively the maximum number of disulfide bridges that link the two {alpha}{beta} halves to form the tetrameric structures and those that couple the {alpha} to the {beta} subunits. Liberation of two sulfhydryl groups in the {alpha} and one in the {beta} subunit resulted in formation of {alpha}{beta} dimers. Free {beta} subunit was formed when additional disulfide bond was reduced. Three models of the arrangement of the labile disulfide bonds, consistent with these findings, are proposed.

Finn, F.M.; Ridge, K.D.; Hofmann, K. (Univ. of Pittsburgh School of Medicine, PA (USA))

1990-01-01

204

Ratcheting up protein translocation with anthrax toxin  

PubMed Central

Energy-consuming nanomachines catalyze the directed movement of biopolymers in the cell. They are found both dissolved in the aqueous cytosol as well as embedded in lipid bilayers. Inquiries into the molecular mechanism of nanomachine-catalyzed biopolymer transport have revealed that these machines are equipped with molecular parts, including adjustable clamps, levers, and adaptors, which interact favorably with substrate polypeptides. Biological nanomachines that catalyze protein transport, known as translocases, often require that their substrate proteins unfold before translocation. An unstructured protein chain is likely entropically challenging to bind, push, or pull in a directional manner, especially in a way that produces an unfolding force. A number of ingenious solutions to this problem are now evident in the anthrax toxin system, a model used to study protein translocation. Here we highlight molecular ratchets and current research on anthrax toxin translocation. A picture is emerging of proton-gradient-driven anthrax toxin translocation, and its associated ratchet mechanism likely applies broadly to other systems. We suggest a cyclical thermodynamic order-to-disorder mechanism (akin to a heat-engine cycle) is central to underlying protein translocation: peptide substrates nonspecifically bind to molecular clamps, which possess adjustable affinities; polypeptide substrates compress into helical structures; these clamps undergo proton-gated switching; and the substrate subsequently expands regaining its unfolded state conformational entropy upon translocation.

Feld, Geoffrey K; Brown, Michael J; Krantz, Bryan A

2012-01-01

205

Ratcheting up protein translocation with anthrax toxin.  

PubMed

Energy-consuming nanomachines catalyze the directed movement of biopolymers in the cell. They are found both dissolved in the aqueous cytosol as well as embedded in lipid bilayers. Inquiries into the molecular mechanism of nanomachine-catalyzed biopolymer transport have revealed that these machines are equipped with molecular parts, including adjustable clamps, levers, and adaptors, which interact favorably with substrate polypeptides. Biological nanomachines that catalyze protein transport, known as translocases, often require that their substrate proteins unfold before translocation. An unstructured protein chain is likely entropically challenging to bind, push, or pull in a directional manner, especially in a way that produces an unfolding force. A number of ingenious solutions to this problem are now evident in the anthrax toxin system, a model used to study protein translocation. Here we highlight molecular ratchets and current research on anthrax toxin translocation. A picture is emerging of proton-gradient-driven anthrax toxin translocation, and its associated ratchet mechanism likely applies broadly to other systems. We suggest a cyclical thermodynamic order-to-disorder mechanism (akin to a heat-engine cycle) is central to underlying protein translocation: peptide substrates nonspecifically bind to molecular clamps, which possess adjustable affinities; polypeptide substrates compress into helical structures; these clamps undergo proton-gated switching; and the substrate subsequently expands regaining its unfolded state conformational entropy upon translocation. PMID:22374876

Feld, Geoffrey K; Brown, Michael J; Krantz, Bryan A

2012-03-30

206

Photolytic Lability of Bromo, Chloro and Fluoro Substituents in Dialkyl Phenylphosphonates.  

National Technical Information Service (NTIS)

Examples of dihalobenzene photolyses are reported in which synthetically important carbon-chlorine and carbon-fluorine bond lability is observed. The photolyses were carried out in the presence of trimethyl phosphites and resulted in the formation of halo...

R. Obrycki C. E. Griffin

1966-01-01

207

Biogeochemical implications of labile phosphorus in forest soils determined by the Hedley fractionation procedure  

Microsoft Academic Search

Forest ecologists and biogeochemists have used a variety of extraction techniques to assess labile vs. non-labile soil P pools in chronosequences, the balance between biological vs. geochemical control of P transformations across a wide range of soil orders, the role of plants with either N-fixing or mycorrhizal symbionts in controlling soil P fractions, and to make inferences about plant-available P.

Arthur H. Johnson; Jaqueline Frizano; David R. Vann

2003-01-01

208

Effects of forest conversion on soil labile organic carbon fractions and aggregate stability in subtropical China  

Microsoft Academic Search

Soil labile fractions play an important role in improving soil quality due to its ability of maintaining soil fertility and\\u000a minimizing negative environmental impacts. The objective of this study was to evaluate the effects of forest transition (conversion\\u000a of natural broadleaf forests into monoculture tree plantations) on soil labile fractions (light fraction organic carbon, particulate\\u000a organic carbon, and microbial biomass

Yusheng Yang; Jianfen Guo; Guangshui Chen; Yunfeng Yin; Ren Gao; Chengfang Lin

2009-01-01

209

Repression of the heavy ferritin chain increases the labile iron pool of human K562 cells.  

PubMed Central

The role of ferritin in the modulation of the labile iron pool was examined by repressing the heavy subunit of ferritin in K562 cells transfected with an antisense construct. Repression of the heavy ferritin subunit evoked an increase in the chemical levels and pro-oxidant activity of the labile iron pool and, in turn, caused a reduced expression of transferrin receptors and increased expression of the light ferritin subunit.

Kakhlon, O; Gruenbaum, Y; Cabantchik, Z I

2001-01-01

210

Peptide antagonists of superantigen toxins  

Microsoft Academic Search

Superantigens produced by Staphylococcus aureus and Streptococcus pyogenes are among the most lethal of toxins. Toxins in this large family trigger an excessive cellular immune response leading to toxic shock. Superantigens are secreted by the bacteria as diverse natural mixtures, a complexity that demands development of broad-spectrum countermeasures. We used a rational approach to design short peptides with homology to

Raymond Kaempfer

2004-01-01

211

Botulinum toxin: bioweapon & magic drug.  

PubMed

Botulinum neurotoxins, causative agents of botulism in humans, are produced by Clostridium botulinum, an anaerobic spore-former Gram positive bacillus. Botulinum neurotoxin poses a major bioweapon threat because of its extreme potency and lethality; its ease of production, transport, and misuse; and the need for prolonged intensive care among affected persons. A single gram of crystalline toxin, evenly dispersed and inhaled, can kill more than one million people. The basis of the phenomenal potency of botulinum toxin is enzymatic; the toxin is a zinc proteinase that cleaves neuronal vesicle associated proteins responsible for acetylcholine release into the neuromuscular junction. As a military or terrorist weapon, botulinum toxin could be disseminated via aerosol or by contamination of water or food supplies, causing widespread casualties. A fascinating aspect of botulinum toxin research in recent years has been development of the most potent toxin into a molecule of significant therapeutic utility . It is the first biological toxin which is licensed for treatment of human diseases. In the late 1980s, Canada approved use of the toxin to treat strabismus, in 2001 in the removal of facial wrinkles and in 2002, the FDA in the United States followed suit. The present review focuses on both warfare potential and medical uses of botulinum neurotoxin. PMID:21149997

Dhaked, Ram Kumar; Singh, Manglesh Kumar; Singh, Padma; Gupta, Pallavi

2010-11-01

212

The Clostridium perfringens?-toxin  

Microsoft Academic Search

The gene encoding the ?-(cpa) is present in all strains of Clostridium perfringens , and the purified ?-toxin has been shown to be a zinc-containing phospholipase C enzyme, which is preferentially active towards phosphatidylcholine and sphingomyelin. The ?-toxin is haemolytic as a result if its ability to hydrolyse cell membrane phospholipids and this activity distinguishes it from many other related

Richard W Titball; Claire E Naylor; Ajit K Basak

1999-01-01

213

Botulinum toxin: Bioweapon & magic drug  

PubMed Central

Botulinum neurotoxins, causative agents of botulism in humans, are produced by Clostridium botulinum, an anaerobic spore-former Gram positive bacillus. Botulinum neurotoxin poses a major bioweapon threat because of its extreme potency and lethality; its ease of production, transport, and misuse; and the need for prolonged intensive care among affected persons. A single gram of crystalline toxin, evenly dispersed and inhaled, can kill more than one million people. The basis of the phenomenal potency of botulinum toxin is enzymatic; the toxin is a zinc proteinase that cleaves neuronal vesicle associated proteins responsible for acetylcholine release into the neuromuscular junction. As a military or terrorist weapon, botulinum toxin could be disseminated via aerosol or by contamination of water or food supplies, causing widespread casualties. A fascinating aspect of botulinum toxin research in recent years has been development of the most potent toxin into a molecule of significant therapeutic utility. It is the first biological toxin which is licensed for treatment of human diseases. In the late 1980s, Canada approved use of the toxin to treat strabismus, in 2001 in the removal of facial wrinkles and in 2002, the FDA in the United States followed suit. The present review focuses on both warfare potential and medical uses of botulinum neurotoxin.

Dhaked, Ram Kumar; Singh, Manglesh Kumar; Singh, Padma; Gupta, Pallavi

2010-01-01

214

Selective trapping of labile S3 in a porous coordination network and the direct X-ray observation.  

PubMed

S3 is one of the basic allotropes of sulfur but is still a mysterious labile species. We selectively trapped S3 in a pore of a thermally stable coordination network and determined S3 structure by ab initio X-ray powder diffraction analysis. S3 in a pore has a C2v bent structure. The network containing trapped S3 is remarkably stable under ambient conditions and is inert to photoirradiation. S3 in the network could be transformed to S6 by mechanical grinding or heating in the presence of NH4X (X = Cl or Br). S6 could be reverse-transformed to S3 by photoirradiation. We also determined the structure of the network containing S6 by ab initio X-ray powder diffraction analysis. PMID:23879312

Ohtsu, Hiroyoshi; Choi, Wanuk; Islam, Nazrul; Matsushita, Yoshitaka; Kawano, Masaki

2013-07-25

215

The labile brain. I. Neuronal transients and nonlinear coupling.  

PubMed

In this, the first of three papers, the nature of, and motivation for, neuronal transients is described in relation to characterizing brain dynamics. This paper deals with some basic aspects of neuronal dynamics, interactions, coupling and implicit neuronal codes. The second paper develops neuronal transients and nonlinear coupling in the context of dynamic instability and complexity, and suggests that instability or lability is necessary for adaptive self-organization. The final paper addresses the role of neuronal transients through information theory and the emergence of spatio-temporal receptive fields and functional specialization. By considering the brain as an ensemble of connected dynamic systems one can show that a sufficient description of neuronal dynamics comprises neuronal activity at a particular time and its recent history This history constitutes a neuronal transient. As such, transients represent a fundamental metric of neuronal interactions and, implicitly, a code employed in the functional integration of brain systems. The nature of transients, expressed conjointly in distinct neuronal populations, reflects the underlying coupling among populations. This coupling may be synchronous (and possibly oscillatory) or asynchronous. A critical distinction between synchronous and asynchronous coupling is that the former is essentially linear and the latter is nonlinear. The nonlinear nature of asynchronous coupling enables the rich, context-sensitive interactions that characterize real brain dynamics, suggesting that it plays a role in functional integration that may be as important as synchronous interactions. The distinction between linear and nonlinear coupling has fundamental implications for the analysis and characterization of neuronal interactions, most of which are predicated on linear (synchronous) coupling (e.g. cross-correlograms and coherence). Using neuromagnetic data it is shown that nonlinear (asynchronous) coupling is, in fact, more abundant and can be more significant than synchronous coupling. PMID:10724457

Friston, K J

2000-02-29

216

Elution of Labile Fluorescent Dye from Nanoparticles during Biological Use  

PubMed Central

Cells act as extremely efficient filters for elution of unbound fluorescent tags or impurities associated with nanoparticles, including those that cannot be removed by extensive cleaning. This has consequences for quantification of nanoparticle uptake and sub-cellular localization in vitro and in vivo as a result of the presence of significant amount of labile dye even following extensive cleaning by dialysis. Polyacrylamide gel electrophoresis (PAGE) can be used to monitor the elution of unbound fluorescent probes from nanoparticles, either commercially available or synthesized in-house, and to ensure their complete purification for biological studies, including cellular uptake and sub-cellular localisation. Very different fluorescence distribution within cells is observed after short dialysis times versus following extensive dialysis against a solvent in which the free dye is more soluble, due to the contribution from free dye. In the absence of an understanding of the presence of residual free dye in (most) labeled nanoparticle solutions, the total fluorescence intensity in cells following exposure to nanoparticle solutions could be mis-ascribed to the presence of nanoparticles through the cell, rather than correctly assigned to either a combination of free-dye and nanoparticle-bound dye, or even entirely to free dye depending on the exposure conditions (i.e. aggregation of the particles etc). Where all of the dye is nanoparticle-bound, the particles are highly localized in sub-cellular organelles, likely lysosomes, whereas in a system containing significant amounts of free dye, the fluorescence is distributed through the cell due to the free diffusion of the molecule dye across all cellular barriers and into the cytoplasm.

Tenuta, Tiziana; Monopoli, Marco P.; Kim, JongAh; Salvati, Anna; Dawson, Kenneth A.; Sandin, Peter; Lynch, Iseult

2011-01-01

217

Distribution and lability of dissolved iron in surface waters of marginal seas in southeastern Asia  

NASA Astrophysics Data System (ADS)

More than eighty surface water samples from marginal seas in southeastern Asia, including the South China Sea, East China Sea, Western Philippine Sea, and the Taiwan Strait, were collected in order to assess the sources and transport of iron in this region. Dissolved Fe (Chelex-labile and total dissolved) concentrations were determined. Additionally, samples were collected from near-shore waters along the west coast of Taiwan during two different seasons and analyzed for potential lability of Fe. Although total dissolved Fe concentrations were, in general, replete in coastal waters and decreasing seaward, the proportions of the dissolved labile (Chelex extractable) and non-labile Fe fractions showed substantial spatial variability. Results from dissolved Fe distributions indicate that Fe in estuarine and coastal regimes forms highly stable non-labile complexes, which are removed quickly, resulting in moderate to low dissolved concentrations offshore. Most of the Fe-replete river plumes contain a large proportion of dissolved non-labile Fe species that also show a low potential 'bio-reactivity' and seasonally variable concentrations, making biological production in the coastal and adjacent marginal seas temporally dependent on the potential chemical reactivity of the different Fe fractions in the source waters. Regional flow patterns in the study area led to localized supplies of Fe-enriched waters in the northern Taiwan Strait and southern East China Sea waters.

Jiann, Kuo-Tung; Wen, Liang-Saw

2012-03-01

218

Toxin-Based Therapeutic Approaches  

PubMed Central

Protein toxins confer a defense against predation/grazing or a superior pathogenic competence upon the producing organism. Such toxins have been perfected through evolution in poisonous animals/plants and pathogenic bacteria. Over the past five decades, a lot of effort has been invested in studying their mechanism of action, the way they contribute to pathogenicity and in the development of antidotes that neutralize their action. In parallel, many research groups turned to explore the pharmaceutical potential of such toxins when they are used to efficiently impair essential cellular processes and/or damage the integrity of their target cells. The following review summarizes major advances in the field of toxin based therapeutics and offers a comprehensive description of the mode of action of each applied toxin.

Shapira, Assaf; Benhar, Itai

2010-01-01

219

Immunogenicity of Staphylococcus aureus delta-toxin.  

PubMed Central

Studies were conducted to determine the immunogenicity of purified Staphylococcus aureus delta-toxin. Rabbits and guinea pigs immunized with delta-toxin incorporated into a multiple antibody, whereas animals given toxin in saline or toxin in saline with Tween 80 did not produce antibody. The immunoglobulin G (IgG) fraction isolated by chromatography on protein A-Sepharose was examined for the presence of anti-delta-toxin antibody by immunoelectrophoresis, immunodiffusion, quantitative precipitation tests, affinity chromatography, and toxin neutralization tests. Although delta-toxin-specific IgG precipitated the toxin in agar gels, the antibody did not neutralize the toxin's hemolytic activity. Delta-toxin binding to human erythrocyte membranes was demonstrated by indirect immunofluorescent staining of toxin-treated erythrocytes. Images

Nolte, F S; Kapral, F A

1981-01-01

220

Inflammatory events induced by brown spider venom and its recombinant dermonecrotic toxin: a pharmacological investigation.  

PubMed

Accidents involving Brown spider (Loxosceles sp.) venom produce a massive inflammatory response in injured region. This venom has a complex mixture of different toxins, and the dermonecrotic toxin is the major contributor to toxic effects. The ability of Loxosceles intermedia venom and a recombinant isoform of dermonecrotic toxin to induce edema and increase in vascular permeability was investigated. These toxins were injected into hind paws and caused a marked dose and time-dependent edema and increase in vascular permeability in mice. Furthermore, the enzymatic activity of venom toxins may be primal for these effects. A mutated recombinant isoform of dermonecrotic toxin, that has only residual enzymatic activity, was not able to induce these inflammatory events. Besides the previous heating of toxins markedly reduced the paw edema and vascular permeability showing that thermolabile constituents can trigger these effects. In addition, the ability of these venom toxins to evoke inflammatory events was partially reduced in compound 48/80-pretreated animals, suggesting that mast cells may be involved in these responses. Pretreating mice with histamine (prometazine and cetirizine) and serotonin (methysergide) receptor antagonists significantly attenuated toxins induced edema and vascular permeability. Moreover, HPLC analysis of whole venom showed the presence of histamine sufficient to induce inflammatory responses. In conclusion, these inflammatory events may result from the activation of mast cells, which in turn release bioamines and may be related to intrinsic histamine content of venom. PMID:19041422

Paludo, Katia Sabrina; Biscaia, Stellee Marcela Petris; Chaim, Olga Meiri; Otuki, Michel Fleith; Naliwaiko, Katya; Dombrowski, Patrícia Andréia; Franco, Célia Regina Cavichiolo; Veiga, Silvio Sanches

2008-11-13

221

The three-dimensional crystal structure of cholera toxin  

SciTech Connect

The clinical manifestations of cholera are largely attributable to the actions of a secreted hexameric AB{sub 5} enterotoxin (choleragen). We have solved the three-dimensional structure of choleragen at 2.5 {Angstrom} resolution and compared the refined coordinates with those of choleragenoid (isolated B pentamer) and the heat-labile enterotoxin from Escherichia coli (LT). The crystalline coordinates provide a detailed view of the stereochemistry implicated in binding to GM1 gangliosides and in carrying out ADP-ribosylation. The A2 chain of choleragen, in contrast to that of LT, is a nearly continuous {alpha}-helix with an interpretable carboxyl tail.

Zhang, Rong-Guang; Westbrook, M.L.; Nance, S.; Spangler, B.D. [Argonne National Lab., IL (United States); Scott, D.L. [Yale Univ., New Haven, CT (United States). Dept. of Molecular Biophysics and Biochemistry; Westbrook, E.M. [Northwestern Univ., Evanston, IL (United States)

1996-02-01

222

Effectiveness of botulinum toxin A in treatment of refractory erythromelalgia.  

PubMed

Erythromelalgia is characterized by intense burning pain, erythema, and heat in affected areas after precipitating factors such as warm temperature or stress. It is refractory to treatment in some situations. We describe a woman with adenosquamous cell carcinoma of the lung and medically refractory erythromelalgia. The symptoms of erythromelalgia presented as refractory to any medical treatment. Due to the unresponsive nature of her condition, botulinum toxin type A (onabotulinumtoxin A) was injected over both of her cheeks, periodically for six cycles. Her symptoms responded dramatically to subcutaneous and intradermal injection of botulinum toxin type A. Repetitive injection demonstrated consistent and reproducible responses, and the efficacy was maintained for approximately 1 month. No adverse effects or complications were noted. Botulinum toxin type A might be safe and effective as an alternative treatment for refractory erythromelalgia, but further large-scale studies are required. PMID:23683264

Lin, Kuan-Hsiang; Wang, Shuu-Jiun; Fuh, Jong-Ling; Chen, Shih-Pin

2013-03-17

223

Lincomycin-induced over-expression of mature recombinant cholera toxin B subunit and the holotoxin in Escherichia coli.  

PubMed

Cholera toxin (CT) B subunit (CTB) was overproduced using a novel expression system in Escherichia coli. An expression plasmid was constructed by inserting the gene encoding the full-length CTB and the Shine-Dalgarno (SD) sequence derived from CTB or from the heat-labile enterotoxin B subunit (LTB) of enterotoxigenic E. coli into the lacZalpha gene fragment in the pBluescript SK(+) vector. The E. coli strain MV1184 was transformed with each plasmid and then cultured in CAYE broth containing lincomycin. Recombinant CTB (rCTB) was purified from each cell extract. rCTB was overproduced in both transformants without obvious toxicity and was structurally and biologically identical to that of CT purified from Vibrio cholerae, indicating that the original SD and CTB signal sequences were also sufficient to express rCTB in E. coli. Lincomycin-induced rCTB expression was inhibited by mutating the lac promoter, suggesting that lincomycin affects the lactose operon. Based on these findings, we constructed a plasmid that contained the wild-type CT operon and successfully overproduced CT (rCT) using the same procedure for rCTB. Although rCT had an intact A subunit, the amino-terminal modifications and biological properties of the A and B subunits of rCT were identical to those of CT. These results suggest that this novel rCTB over-expression system would also be useful to generate both wild-type and mutant CT proteins that will facilitate further studies on the characteristics of CT, such as mucosal adjuvant activity. PMID:19410003

Arimitsu, Hideyuki; Tsukamoto, Kentaro; Ochi, Sadayuki; Sasaki, Keiko; Kato, Michio; Taniguchi, Koki; Oguma, Keiji; Tsuji, Takao

2009-05-04

224

Multiple Properties of Cl. Botulinum Toxin.  

National Technical Information Service (NTIS)

Testing Cl. botulinum toxin type A at various times after its preparation it was found that the toxin was not always toxic to the same degree for albino mice and guinea pigs. With the aging of toxin, the toxin's titer decreased to a greater extent for mic...

I. N. Morgunov S. M. Minervin

1966-01-01

225

Chemical toxins that cause seizures.  

PubMed

Seizurogenic chemicals include a variety of toxic agents, including chemical warfare agents, toxic industrial chemicals, and natural toxins. Chemical weapons such as sarin and VX, and pesticides such as parathion and carbaryl cause hyperstimulation of cholinergic receptors and an increase in excitatory neurotransmission. Glutamatergic hyperstimulation can occur after exposure to excitatory amino acid toxins such as the marine toxin domoic acid. Other pesticides such as lindane and strychnine do not affect excitatory neurotransmission directly, but rather, they block the inhibitory regulation of neurotransmission by antagonism of inhibitory GABA and glycine synapses. In this paper, chemicals that cause seizures by a variety of molecular mechanisms and pathways are discussed. PMID:23085523

Jett, David A

2012-10-18

226

Airway obstruction lability helps distinguish levels of disease activity in asthma.  

PubMed

Classifying disease activity in asthma relies on clinical and physiological variables, but these variables do not capture all aspects of asthma that distinguish levels of disease activity. We used data from two pivotal trials of montelukast in asthma to classify disease activity as "high" or "low". We performed a principal component analysis (PCA) of disease activity using 21 efficacy outcome variables, including several novel derived outcome variables reflecting clinical and airway obstruction lability. Then we performed discriminant analysis (DA) based on disease activity classification. PCA revealed 6 factors (daytime asthma control, nighttime-predominant asthma control, airway obstruction, exacerbations, clinical lability, airway obstruction lability) that explained 76% of the variance between outcome variables. Although airway obstruction lability (comprising both diurnal variability in peak expiratory flow and diurnal variability in ?-agonist use) accounted for only 6% of the explained variance in PCA, in DA it was more accurate (canonical coefficient 0.75) than traditional measures of asthma severity such as obstruction (-0.54) and daytime control (-0.56) in distinguishing between high and low disease activity. We conclude that airway obstruction lability, a parameter not typically captured in clinical trials, may contribute to more complete assessment of asthma disease activity and may define an emerging clinical target of future therapy. PMID:22301379

Greenberg, Steven; Liu, Nancy; Kaur, Amarjot; Lakshminarayanan, Mani; Zhou, Yijie; Nelsen, Linda M; Smugar, Steven S; Noonan, Gertrude; Reiss, Theodore F; Knorr, Barbara A

2012-01-31

227

Concentration, Structure, and Lability of Dissolved Organic Matter Across 16 Major Rivers in North America  

NASA Astrophysics Data System (ADS)

The riverine transport of carbon is an important component of the net terrestrial and oceanic carbon cycles. The proportion of carbon that is available for remineralization is critical for estimates of net ecosystem production on a large scale. In rivers, microbial communities alter the structure and composition of organic carbon as it progresses toward the coast. This in-stream processing directly affects carbon lability, which is important for secondary production and ecosystem health. The presence of labile carbon can increase the remineralization of inorganic nutrients and contribute to the production of algal and detrital DOC. An assessment of the fraction of labile organic carbon across 16 of the largest rivers in North America is presented. Hydrophobic organic acid fractions, hydrophobic neutral fractions, low molecular weight hydrophilic fractions and transphilic organic acid fractions were isolated in parallel to each lability experiment and relationships between lability and organic matter structure will be explored and presented. Organic matter fluorescence and absorbance measurements were made and highlight the differences seen across these large watersheds. This research is in collaboration with the United Station Geological Surveys National Stream Quality Accounting Network (NASQAN) program.

Butman, D. E.; Raymond, P. A.; Aiken, G.; Butler, K.

2009-12-01

228

Botulinum toxin in clinical practice  

PubMed Central

Botulinum toxin, the most potent biological toxin, has become a powerful therapeutic tool for a growing number of clinical applications. This review draws attention to new findings about the mechanism of action of botulinum toxin and briefly reviews some of its most frequent uses, focusing on evidence based data. Double blind, placebo controlled studies, as well as open label clinical trials, provide evidence that, when appropriate targets and doses are selected, botulinum toxin temporarily ameliorates disorders associated with excessive muscle contraction or autonomic dysfunction. When injected not more often than every three months, the risk of blocking antibodies is slight. Long term experience with this agent suggests that it is an effective and safe treatment not only for approved indications but also for an increasing number of off-label indications.

Jankovic, J

2004-01-01

229

Yeast Killer Toxins Technology Transfer  

Microsoft Academic Search

\\u000a Among the different competitive mechanisms which microorganisms can use to multiply and survive in natural communities, the\\u000a production of antimicrobial toxins represents a common, efficient and specific ecological way to eliminate competitor strains\\/species\\u000a from the same habitat. By killing or severely reducing the fitness of sensitive strains, toxin-producing microorganisms which\\u000a are self-immune can be selected and so dominate in specific

Walter Magliani; Stefania Conti; Laura Giovati; Luciano Polonelli

230

Methods for determining renal toxins  

US Patent & Trademark Office Database

The present invention is based on the elucidation of the global changes in gene expression and the identification of toxicity markers in tissues or cells exposed to a known renal toxin. The genes may be used as toxicity markers in drug screening and toxicity assays. The invention includes a database of genes characterized by toxin-induced differential expression that is designed for use with microarrays and other solid-phase probes.

Mendrick; Donna (Gaithersburg, MD); Porter; Mark (Gaithersburg, MD); Johnson; Kory (Gaithersburg, MD); Higgs; Brandon (Gaithersburg, MD); Castle; Arthur (Gaithersburg, MD); Elashoff; Michael (Gaithersburg, MD)

2008-09-16

231

Harnessing Labile Bonds between Nanogels Particles to Create Self-Healing Materials  

NASA Astrophysics Data System (ADS)

Using computational modeling, we demonstrate the self-healing behavior of novel materials composed of nanoscopic gel particles that are interconnected into a macroscopic network by both stable and labile bonds. Under mechanical stress, the labile bonds between the nanogels can break and readily reform with reactive groups on neighboring units. This breaking and reforming allows the units in the network to undergo a structural rearrangement that preserves the mechanical integrity of the sample. The stable bonds between the nanogels play an essential role by forming a backbone that provides a mechanical strength to the material. The simulations show that just a relatively small fraction of such labile bonds (roughly 15%) are needed to prevent the catastrophic failure of the sample. The findings provide guidelines for creating high-strength, self-healing materials.

Kolmakov, German; Matyjaszewski, Krzysztof; Balazs, Anna

2009-03-01

232

Susceptibility of Skeletal Muscle to Coxsackie A2 Virus Infection: Effects of Botulinum Toxin and Denervation  

NASA Astrophysics Data System (ADS)

Coxsackie A viruses can infect denervated but not innervated mature skeletal muscles. The role of synaptic transmission in preventing susceptibility to Coxsackievirus infection was studied by surgically denervating leg muscles of mice or injecting the muscles with botulinum toxin to block quantal release of acetylcholine. Control muscles were injected with heat-inactivated toxin. Subsequent injection of Coxsackie A2 virus resulted in extensive virus replication and tissue destruction in the denervated and botulinum toxin-treated muscles, while the control muscles showed only minimal changes. This suggests that the susceptibility of skeletal muscle to Coxsackievirus infection is regulated by synaptic transmission.

Andrew, Clifford G.; Drachman, Daniel B.; Pestronk, Alan; Narayan, Opendra

1984-02-01

233

Induction of apoptosis by Shiga toxins  

PubMed Central

Shiga toxins comprise a family of structurally and functionally related protein toxins expressed by Shigella dysenteriae serotype 1 and multiple serotypes of Escherichia coli. While the capacity of Shiga toxins to inhibit protein synthesis by catalytic inactivation of eukaryotic ribosomes has been well described, it is also apparent that Shiga toxins trigger apoptosis in many cell types. This review presents evidence that Shiga toxins induce apoptosis of epithelial, endothelial, leukocytic, lymphoid and neuronal cells. Apoptotic signaling pathways activated by the toxins are reviewed with an emphasis on signaling mechanisms that are shared among different cell types. Data suggesting that Shiga toxins induce apoptosis through the endoplasmic reticulum stress response and clinical evidence demonstrating apoptosis in humans infected with Shiga toxin-producing bacteria are briefly discussed. The potential for use of Shiga toxins to induce apoptosis in cancer cells is briefly reviewed.

Tesh, Vernon L

2010-01-01

234

Escherichia Coli Heat-Labile Enterotoxin, an Oral Adjuvant for Protection Against Mucosal Pathogens.  

National Technical Information Service (NTIS)

Vaccinology, including adjuvant design, has focused on parenteral routes of immunization and parenteral IgO antibody as a measure of success. Moreover, most pathogens attack their animal hosts at mucosal surfaces where parenteral IgG serves as an ineffici...

J. A. Majde O. Pavlovskis S. Baqar J. M. Katz R. I. Walker

1995-01-01

235

Targeted Toxins in Brain Tumor Therapy  

PubMed Central

Targeted toxins, also known as immunotoxins or cytotoxins, are recombinant molecules that specifically bind to cell surface receptors that are overexpressed in cancer and the toxin component kills the cell. These recombinant proteins consist of a specific antibody or ligand coupled to a protein toxin. The targeted toxins bind to a surface antigen or receptor overexpressed in tumors, such as the epidermal growth factor receptor or interleukin-13 receptor. The toxin part of the molecule in all clinically used toxins is modified from bacterial or plant toxins, fused to an antibody or carrier ligand. Targeted toxins are very effective against cancer cells resistant to radiation and chemotherapy. They are far more potent than any known chemotherapy drug. Targeted toxins have shown an acceptable profile of toxicity and safety in early clinical studies and have demonstrated evidence of a tumor response. Currently, clinical trials with some targeted toxins are complete and the final results are pending. This review summarizes the characteristics of targeted toxins and the key findings of the important clinical studies with targeted toxins in malignant brain tumor patients. Obstacles to successful treatment of malignant brain tumors include poor penetration into tumor masses, the immune response to the toxin component and cancer heterogeneity. Strategies to overcome these limitations are being pursued in the current generation of targeted toxins.

Li, Yan Michael; Hall, Walter A.

2010-01-01

236

Biotic and abiotic controls on diurnal fluctuations in labile soil phosphorus of a wet tropical forest.  

PubMed

The productivity of many tropical wet forests is generally limited by bioavailable phosphorus (P). Microbial activity is a key regulator of P availability in that it determines both the supply of P through organic matter decomposition and the depletion of bioavailable P through microbial uptake. Both microbial uptake and mineralization occur rapidly, and their net effect on P availability varies with soil moisture, temperature, and soil organic matter quantity and quality. Exploring the mechanisms driving P availability at fine temporal scales can provide insight into the coupling of carbon, water, and nutrient cycles, and ultimately, the response of tropical forests to climate change. Despite the recognized importance of P cycling to the dynamics of wet tropical forests and their potential sensitivity to short-term fluctuations in bioavailable P, the diurnal pattern of P remains poorly understood. This study quantifies diurnal fluctuations in labile soil P and evaluates the importance of biotic and abiotic factors in driving these patterns. To this end, measurements of labile P were made every other hour in a Costa Rican wet tropical forest oxisol. Spatial and temporal variation in Bray-extractable P were investigated in relation to ecosystem carbon flux, soil CO2 efflux, soil moisture, soil temperature, solar radiation, and sap-flow velocity. Spatially averaged bi-hourly (every two hours) labile P ranged from 0.88 to 2.48 microg/g across days. The amplitude in labile P throughout the day was 0.61-0.82 microg/g (41-54% of mean P concentrations) and was characterized by a bimodal pattern with a decrease at midday. Labile P increased with soil CO2 efflux and soil temperature and declined with increasing sap flow and solar radiation. Together, soil CO2 efflux, soil temperature, and sap flow explained 86% of variation in labile P. PMID:19769132

Vandecar, Karen L; Lawrence, Deborah; Wood, Tana; Oberbauer, Steven F; Das, Rishiraj; Tully, Katherine; Schwendenmann, Luitgard

2009-09-01

237

Inositol hexakisphosphate-dependent processing of Clostridium sordellii lethal toxin and Clostridium novyi alpha-toxin.  

PubMed

Clostridium sordellii lethal toxin and Clostridium novyi ?-toxin, which are virulence factors involved in the toxic shock and gas gangrene syndromes, are members of the family of clostridial glucosylating toxins. The toxins inactivate Rho/Ras proteins by glucosylation or attachment of GlcNAc (?-toxin). Here, we studied the activation of the autoproteolytic processing of the toxins by inositol hexakisphosphate (InsP(6)) and compared it with the processing of Clostridium difficile toxin B. In the presence of low concentrations of InsP(6) (<1 ?M), toxin fragments consisting of the N-terminal glucosyltransferase (or GlcNAc-transferase) domains and the cysteine protease domains (CPDs) of C. sordellii lethal toxin, C. novyi ?-toxin, and C. difficile toxin B were autocatalytically processed. The cleavage sites of lethal toxin (Leu-543) and ?-toxin (Leu-548) and the catalytic cysteine residues (Cys-698 of lethal toxin and Cys-707 of ?-toxin) were identified. Affinity of the CPDs for binding InsP(6) was determined by isothermal titration calorimetry. In contrast to full-length toxin B and ?-toxin, autocatalytic cleavage and InsP(6) binding of full-length lethal toxin depended on low pH (pH 5) conditions. The data indicate that C. sordellii lethal toxin and C. novyi ?-toxin are InsP(6)-dependently processed. However, full-length lethal toxin, but not its short toxin fragments consisting of the glucosyltransferase domain and the CPD, requires a pH-sensitive conformational change to allow binding of InsP(6) and subsequent processing of the toxin. PMID:21385871

Guttenberg, Gregor; Papatheodorou, Panagiotis; Genisyuerek, Selda; Lü, Wei; Jank, Thomas; Einsle, Oliver; Aktories, Klaus

2011-03-08

238

Emetic toxin-producing strains of Bacillus cereus show distinct characteristics within the Bacillus cereus group  

Microsoft Academic Search

One hundred representative strains of Bacillus cereus were selected from a total collection of 372 B. cereus strains using two typing methods (RAPD and FT-IR) to investigate if emetic toxin-producing hazardous B. cereus strains possess characteristic growth and heat resistance profiles. The strains were classified into three groups: emetic toxin (cereulide)-producing strains (n=17), strains connected to diarrheal foodborne outbreaks (n=40)

Frédéric Carlin; Martina Fricker; Annemarie Pielaat; Simon Heisterkamp; Ranad Shaheen; Mirja Salkinoja Salonen; Birgitta Svensson; Christophe Nguyen-the; Monika Ehling-Schulz

2006-01-01

239

Emetic toxin-producing strains of Bacillus cereus show distinct characteristics within the Bacillus cereus group  

Microsoft Academic Search

One hundred representative strains of Bacillus cereus were selected from a total collection of 372 B. cereus strains using two typing methods (RAPD and FT-IR) to investigate if emetic toxin-producing hazardous B. cereus strains possess characteristic growth and heat resistance profiles. The strains were classified into three groups: emetic toxin (cereulide)-producing strains (n=17), strains connected to diarrheal foodborne outbreaks (n=40)

Frédéric Carlin; Martina Fricker; Annemarie Pielaat; Simon Heisterkamp; Ranad Shaheen; Mirja Salkinoja Salonen; Birgitta Svensson; Christophe Nguyen-the; Monika Ehling-Schulz

2007-01-01

240

Long-term time course of affective lability after subthalamic deep brain stimulation electrode implantation.  

PubMed

The mechanism and time course of emotional side effects of subthalamic deep brain stimulation in Parkinson's disease are a matter for discussion. We report a 53-month follow-up of a patient with affective lability. Postoperative lesion plus bilateral stimulation strongly influenced mood in the first week in terms of laughing behavior, while voltage changes had only minor long-term impact up to 37 months on negative emotion, possibly caused by the right electrode stimulating the subthalamic nucleus and adjacent fiber tracts involving the internal capsule. Thus we conclude that affective lability can occur with different temporal dynamics of microlesion, and early and chronic stimulation. PMID:21707232

Wojtecki, Lars; Timmermann, Lars; Groiss, Stefan Jun; Elben, Saskia; Reck, Christiane; Südmeyer, Martin; Sturm, Volker; Schnitzler, Alfons

2011-06-27

241

Factors Contributing to Heat Resistance of Clostridium perfringens Endospores  

Microsoft Academic Search

The endospores formed by strains of type A Clostridium perfringens that produce the C. perfringens entero- toxin (CPE) are known to be more resistant to heat and cold than strains that do not produce this toxin. The high heat resistance of these spores allows them to survive the cooking process, leading to a large number of food-poisoning cases each year.

Benjamin Orsburn; Stephen B. Melville; David L. Popham

2008-01-01

242

Vaccination with plasmid DNA encoding a mutant toxic shock syndrome toxin-1 ameliorates toxin-induced lethal shock in mice.  

PubMed

Staphylococcal toxic shock syndrome toxin-1 (TSST-1), a superantigenic toxin produced by Staphylococcus (S.) aureus, is a major cause of septic shock and toxic shock syndrome. To investigate whether vaccination with a plasmid DNA encoding a non-toxic mutant TSST-1 (mTSST-1) can protect mice against wild-type TSST-1-induced lethal shock, the mice were intranasally immunized with the plasmid DNA (named pcDNA-mTSST-1) plus a mucosal adjuvant, a non-toxic mutant labile toxin (mLT). After the immunization, the mice were challenged with TSST-1 and lipopolysaccharide (LPS). The survival rate of mice immunized with pcDNA-mTSST-1 plus mLT was higher than that of the control mice immunized with PBS alone, mLT alone, pcDNA-mTSST-1 alone, or a parent plasmid plus mLT. The titers of interferon-? (IFN-?) in the sera of mice immunized with pcDNA-mTSST-1 plus mLT were significantly lower than those of the mLT control mice. Immunization with pcDNA-mTSST-1 plus mLT increased the serum levels of TSST-1-specific antibodies, especially immunoglobulin G1 (IgG1) and IgG2a subclasses. Furthermore, the sera obtained from mice immunized with pcDNA-mTSST-1 plus mLT significantly inhibited the TSST-1-induced secretion of IFN-? and tumor necrosis factor-? (TNF-?) in murine spleen cells in vitro. These results indicate that immunization with pcDNA-mTSST-1 plus mLT provides protection against the lethal toxic shock of mice induced by wild-type TSST-1. The protective effect could be due to TSST-1-specific neutralizing antibodies as well as the inhibition of IFN-? and TNF-? secretions. Since TSST-1 is commonly released by invasive S. aureus, the pcDNA-mTSST-1 should be useful in preventing toxin-induced shock resulting from S. aureus infection. PMID:23985881

Feng, Mao-Hui; Cui, Jing-Chun; Nakane, Akio; Hu, Dong-Liang

2013-01-01

243

Peculiarities of the associative function of the brain in children with high and low lability of the nervous processes  

Microsoft Academic Search

Conclusions 1.According to the psychological data, the level of general development of the children with high and low lability of the nervous processes does not differ appreciably, but the tempo of assignments in the kindergarten group poses difficulties for the inert children and they cannot cope with the tasks in the time allotted.2.Among the children with a low lability the

M. M. Koltsova; É. B. Ayurova; T. A. Borisova

1986-01-01

244

Rapid decomposition of labile soil organic matter inputs obscures sensitivity of heterotrophic respiration to temperature: A model analysis  

Microsoft Academic Search

Labile carbon, although often a small fraction of soil organic matter (SOM), significantly affects heterotrophic respiration at short time scales because of its rapid decomposition. However, in the current literature, most soil respiration measurements are interpreted without simultaneous information on labile carbon pool dynamics. Sensitivity of soil respiration to temperature is routinely derived directly from field observations and such relationships

W. M. Post; L. Gu; A. W. King

2003-01-01

245

Therapy After Exposure to Toxins (I).  

National Technical Information Service (NTIS)

During their duties, military personnel can be exposed to military relevant toxins. Then, efficient therapy is needed. Alternative antibodies, aptamers, can be used to neutralise and remove the toxins from the body. Aptamers are developed by means of the ...

M. Polhuijs A. M. de Vries W. E. Kaman

2005-01-01

246

Mechanism of Action of Tetanus Toxin.  

National Technical Information Service (NTIS)

We have previously reported that tetanus toxin (TT) increased ATP-dependent Calcium (++) uptake by human neutrophil lysosomes, and we hypothesized that the toxin activates the Ca(++) ATPase present in these organelles. However, we have been unable to show...

M. S. Klempner

1989-01-01

247

Double Blind Trial of Divalproex Sodium for Affective Lability and Alcohol Use Following Traumatic Brain Injury.  

National Technical Information Service (NTIS)

A large and under-recognized sub-set of patients suffer from both traumatic brain injury (TBI) and alcohol abuse/dependence (AA/D). This group appears to use alcohol to self-treat fronto-limbic disinhibition, expressed clinically as affective lability, fo...

T. P. Beresford

2010-01-01

248

Double Blind Trial of Divalproex Sodium for Affective Lability and Alcohol Use Following Traumatic Brain Injury.  

National Technical Information Service (NTIS)

A large and under-recognized sub-set of patients suffer from both traumatic brain injury (TBI) and alcohol abuse/dependence (AA/D). This group appears to use alcohol to self-treat fronto-limbic disinhibition, expressed clinically as affective lability, fo...

T. P. Beresford

2009-01-01

249

Environmental factors related to schizophrenia in psychophysiologically labile high-risk males  

Microsoft Academic Search

Research indicates that certain parameters of electrodermal functioning are related to schizophrenia and risk for schizophrenia. The present study investigated childhood environmental factors in 2 subgroups of high-risk 9–20 yr old males (offspring of schizophrenic mothers): those who showed patterns of electrodermal lability in childhood and later became schizophrenic (9 Ss), and a matched subgroup who showed similar patterns of

Walker Elaine; Mednick Sarnoff; Emory Eugene; Schulsinger Fini

1981-01-01

250

Labile compounds in plant litter reduce the sensitivity of decomposition to warming and altered precipitation.  

PubMed

Together, climate and litter quality strongly regulate decomposition rates. Although these two factors and their interaction have been studied across species in continent-scale experiments, few researchers have studied how labile and recalcitrant compounds interact to influence decomposition, or the climate sensitivity of decomposition, within a litter type. Over a period of 3 yr, we studied the effects of warming and altered precipitation on mass loss and compound-specific decomposition using two litter types that possessed similar heteropolymer chemistry, but different proportions of labile and recalcitrant compounds. Climate treatments immediately affected the mass loss of the more recalcitrant litter, but affected the more labile litter only after 2 yr. After 3 yr, although both litter types had lost similar amounts of mass, warming (c. 4°C) and supplemental precipitation (150% of ambient) together accelerated the degradation of alkyl-carbon and lignin only in the more recalcitrant litter, highlighting the role of initial litter quality in determining whether the chemistry of litter residues converges or diverges under different climates. Our finding that labile compounds in litter reduce the climate sensitivity of mass loss and the decomposition of recalcitrant matrix is novel. Our results highlight the potential for litter quality to regulate the effect of climatic changes on the sequestration of litter-derived carbon. PMID:23822593

Suseela, Vidya; Tharayil, Nishanth; Xing, Baoshan; Dukes, Jeffrey S

2013-07-04

251

Simulating decomposition of labile soil organic carbon: Effects of pH  

Microsoft Academic Search

Based on previous studies we suppose common soil carbon turnover modelling approaches to fail to accurately simulate the fate of labile organic carbon in acidic soils possibly because pH effects on decomposition are not accounted for. For mountainous permanent grasslands with higher shares of particulate carbon, turnover times of this fraction were calculated by means of radiocarbon dating and compared

Jens Leifeld; Michael Zimmermann; Jürg Fuhrer

2008-01-01

252

Analysis of the genetic stability of Eucalyptus globulus Labill. somatic embryos by flow cytometry  

Microsoft Academic Search

Flow cytometry was used to measure the nuclear DNA content of Eucalyptus globulus Labill. somatic and zygotic embryos and leaves in order to determine if somatic embryogenesis induces DNA content and ploidy changes in this species. Mature zygotic embryos derived from open-pollination orchard families were collected from a location in the centre of Portugal. One group was kept for nuclear

G. Pinto; J. Loureiro; T. Lopes; C. Santos

2004-01-01

253

Key role of the resin layer thickness in the lability of complexes measured by DGT.  

PubMed

Analysis of the dynamic features of diffusion gradients in thin film devices (DGT) indicates that the penetration of complexes into the resin layer dramatically increases their lability. This should be taken into account when interpreting DGT measurements in terms of the dynamics of solution speciation. The experimental accumulation of Cd by DGT sensors in Cd-NTA systems confirmed these theoretical analyses. A computational code, which allows a rigorous digital simulation of the diffusion-reaction processes in the gel and resin layers, was used to model the results and to demonstrate the effect of the complex penetration into the resin layer on the lability degree. These findings suggest that DGT renders all complexes much more labile than if the resin-diffusive gel interface was considered as a perfect planar sink, explaining why DGT often measures a high proportion of the metal in a natural water. This information is relevant since some studies have stressed the importance of labile complexes as a source of bioaccumulated metal. PMID:21561131

Mongin, Sandrine; Uribe, Ramiro; Puy, Jaume; Cecília, Joan; Galceran, Josep; Zhang, Hao; Davison, William

2011-05-11

254

Solubility and lability of cadmium and zinc in two soils treated with organic matter  

SciTech Connect

The effect of organic matter (pig manure, sus scrofa) addition on solubility and free Cd(II) and Zn(II) speciation was studied in two mineral soils. The soils were extracted with ultra pure 0.01 M KNO{sub 3}, and the extracts were analyzed for total dissolved Cd and Zn by graphite furnace AAS and ICP, respectively, and for labile Cd and Zn by differential pulse anodic stripping voltammetry (DPASV). Based on the assumption that the non-ASV-labile fraction of the total dissolved Cd and Zn was organically bound to fulvic acid (FA), the relative fraction of labile to total dissolved Cd and Zn was used to estimate conditional stability constants (log K) for the formation of Cd-Fulvate (CdFA) and Zn-Fulvate (ZnFA). Species of organically and inorganically associated Cd and Zn, as affected by the addition of pig manure to the two different soil types, were calculated. The addition of organic matter increased the solubility of Cd and Zn in both soils by the formation of organo-metallic complexes. The lability of Zn was, however, reduced substantially, whereas for Cd it was unaffected. The conditional log K values calculated indicate that the stability of organo-metallic complexes with Cd and Zn may be more important than reported previously. This implies that increasing concentrations of dissolved organic acids can increase their solubility, thus leading to the leaching of Cd and Zn into ground water.

Almaas, A.R.; McBride, M.B.; Singh, B.R.

2000-03-01

255

Labile soil organic matter pools in a calciorthent after 18 years of afforestation by different plantations  

Microsoft Academic Search

Labile soil organic matter pools (LSOMs) are the fine indicators of soil quality which are influenced by changes in management practices. The suitability of forest tree species is essential for soil quality improvement of a nutrient deficient calciorthent with very high percentage of free CaCO3 (34%). Six multipurpose tree species were selected to investigate the effect of afforestation after 18

R. Laik; Koushlendra Kumar; D. K. Das; O. P. Chaturvedi

2009-01-01

256

Similar response of labile and resistant soil organic matter pools to changes in temperature  

Microsoft Academic Search

Our understanding of the relationship between the decomposition of soil organic matter (SOM) and soil temperature affects our predictions of the impact of climate change on soil-stored carbon. One current opinion is that the decomposition of soil labile carbon is sensitive to temperature variation whereas resistant components are insensitive. The resistant carbon or organic matter in mineral soil is then

Changming Fang; Pete Smith; John B. Moncrieff; Jo U. Smith

2005-01-01

257

Is resistant soil organic matter more sensitive to temperature than the labile organic matter?  

Microsoft Academic Search

A recent paper by Knorr et al. (2005) suggested that the decomposition of resistant soil organic matter is more temperature sensitive than labile organic matter. In Knorr et al.'s model, the reference decay rate was fixed for all pools of soil carbon. We refit Knorr et al.'s model but allow both the activation energy and the reference decay rate to

C. Fang; P. Smith; J. U. Smith

2005-01-01

258

[Clinical application of botulinum toxin].  

PubMed

The clinical application of botulinum toxin (BoNT) was first proposed by Justinus Kerner in 1822. BoNT was formally accepted as a therapeutic agent in the 1970s, and currently, it is used worldwide for treating diseases as well as for cosmetic conditions. In Japan, Botox® is the only type A formulation that has been officially approved for the treatment of blepharospasm, hemifacial spasm, cervical dystonia, pes equinus of cerebral palsy, adult spasticity of upper and lower limbs, and Botox Vista® is applied for glabellar frown lines. Its effect is symptomatic, but long-lasting remission is noted after treatment in more than 30% of cases with cervical dystonia. Ultrasound guidance is useful and may be even superior to electromyographic monitoring, especially when the obliquus capitis inferior muscle is targeted in rotatocollis, because the vertebral artery or upper cervical nerve root(s) may be injured when the needle penetrates the muscle. BoNT alleviates pain or glandular secretion besides causing a neuromuscular block. After being transported to the axons, BoNT is carried centrally and even to the adjacent neurons via synapses (toxin jump). A direct central action has also been postulated. BoNT is generally safe, but serious adverse reactions may occur very rarely. Individual differences in toxin sensitivity may be considerably greater than assumed, and even the routine clinical dose may be too high in some patients. The future strategy includes clinical application of other types of toxin or chimera toxins, or the use of the toxin as a cargo ("Trojan Horse") carrying some bioactive molecules into the cell. A non-injection procedure for mucosal application or cosmetic use is currently under clinical trials. PMID:21747149

Mezaki, Takahiro

2011-07-01

259

Inputs of total and labile trace metals from wastewater treatment plants effluents to the Seine River  

NASA Astrophysics Data System (ADS)

The Seine river basin has long been impacted by metal inputs from the Paris area, but the water quality has been gradually improving for the last 20 years. Among all metal pollution sources (surface runoff, industries), urban wastewater discharge has been shown to significantly contribute, during low-flow periods, to metal fluxes of the River Seine. This paper assesses the current wastewater contribution to metal inputs in the Seine river basin, based on sampling of nine wastewater treatment plants (WWTPs). Seven metals were targeted (Al, Cd, Cr, Cu, Fe, Ni and Pb) during dry weather periods. Since total and dissolved concentrations alone are not relevant enough for an ecological risk assessment, labile metals (free + weekly complexed) were also measured by means of DGT (diffusive gradient in thin film technique). Results show that WWTPs greatly reduce total metal concentrations but reduce labile metal concentrations only slightly. Estimations made for direct total metal inputs in the River Seine via treated effluent discharge confirm the decrease observed for the 1994-1995 period. Labile metals released by WWTP were also considered by comparing fluxes in the effluent discharge of two different WWTPs to those flowing in the receiving river. Fluxes discharged by the largest plant were similar to those measured in the river during low-flow periods whereas they were negligible for the smaller one. Nevertheless, labile metal concentrations in both discharges were similar and the wastewater discharge's contribution to labile fluxes in receiving waters seems to depend mostly on the relative significance of the discharge flow compared to the receiving water flow.

Buzier, Rémy; Tusseau-Vuillemin, Marie-Hélène; Keirsbulck, Marion; Mouchel, Jean-Marie

260

Determination of various types of labile atmospheric iron over remote oceans  

NASA Astrophysics Data System (ADS)

Atmospheric deposition of iron (Fe) is a major source of the micronutrient to the remote ocean. Most studies have focused on the total atmospheric Fe fluxes to the oceans while fewer studies have focused on the chemistry and chemical speciation of atmospheric Fe. This speciation of Fe in the atmosphere is critical to understanding the fraction of Fe that will be labile in surface waters after deposition and consequently has implications for the bioavailability of this atmospherically derived Fe. In this study, 24-hour aerosol samples were collected using a high-volume dichotomous virtual impactor (HVDVI) that collected coarse (Dp > 2.5 ?m) and fine (Dp< 2.5 ?m) aerosol fractions on two 90-mm Teflon membrane filters, over the tropical and subtropical North Atlantic Ocean. A sequential aqueous extraction procedure using a pH 4.5 buffer solution and a chemical reductant (hydroxylamine hydrochloride (HA)) was used to measure various labile Fe fractions. The extraction procedure was performed immediately after aerosol sample collection and used time series measurements of Fe(II) using long path length absorbance spectroscopy (LPAS) for analysis of Fe(II). The method measured both the quantities of labile Fe and also the dissolution and reduction kinetics of the labile Fe. Comparisons of HA-reducible Fe and photoreducible Fe concentrations were conducted on board and showed that both reduction processes had similar reduction kinetics and final Fe(II) concentrations during the initial 90 min. The average pseudo-first-order rate constants for the increase in Fe(II) were 0.020 and 0.0076 min-1 for the photoreducible Fe extraction and HA-reduction extraction, respectively. This HA-reducible Fe amount could potentially be used to determine the maximum amount of labile atmospheric Fe that is deposited into the ocean.

Chen, Y.; Siefert, R. L.

2003-12-01

261

Glaciers as a source of ancient and labile organic matter to the marine environment.  

PubMed

Riverine organic matter supports of the order of one-fifth of estuarine metabolism. Coastal ecosystems are therefore sensitive to alteration of both the quantity and lability of terrigenous dissolved organic matter (DOM) delivered by rivers. The lability of DOM is thought to vary with age, with younger, relatively unaltered organic matter being more easily metabolized by aquatic heterotrophs than older, heavily modified material. This view is developed exclusively from work in watersheds where terrestrial plant and soil sources dominate streamwater DOM. Here we characterize streamwater DOM from 11 coastal watersheds on the Gulf of Alaska that vary widely in glacier coverage (0-64 per cent). In contrast to non-glacial rivers, we find that the bioavailability of DOM to marine microorganisms is significantly correlated with increasing (14)C age. Moreover, the most heavily glaciated watersheds are the source of the oldest ( approximately 4 kyr (14)C age) and most labile (66 per cent bioavailable) DOM. These glacial watersheds have extreme runoff rates, in part because they are subject to some of the highest rates of glacier volume loss on Earth. We estimate the cumulative flux of dissolved organic carbon derived from glaciers contributing runoff to the Gulf of Alaska at 0.13 +/- 0.01 Tg yr(-1) (1 Tg = 10(12) g), of which approximately 0.10 Tg is highly labile. This indicates that glacial runoff is a quantitatively important source of labile reduced carbon to marine ecosystems. Moreover, because glaciers and ice sheets represent the second largest reservoir of water in the global hydrologic system, our findings indicate that climatically driven changes in glacier volume could alter the age, quantity and reactivity of DOM entering coastal oceans. PMID:20033045

Hood, Eran; Fellman, Jason; Spencer, Robert G M; Hernes, Peter J; Edwards, Rick; D'Amore, David; Scott, Durelle

2009-12-24

262

Botulinum toxin therapy for palmar hyperhidrosis  

Microsoft Academic Search

Background: Severe palmar hyperhidrosis is a chronic disease, resistant to conventional therapy. Botulinum toxin inhibits sweat production by blocking release of acetylcholine from presynaptic membranes. Objective: Our purpose was to evaluate the short- and long-term effectiveness of botulinum toxin therapy in treatment of palmar hyperhidrosis. Methods: Four patients with severe palmar hyperhidrosis were treated with subepidermal injections of botulinum toxin.

W. B. Shelley; N. Y. Talanin; E. D. Shelley

1998-01-01

263

Botulinum toxin treatment in spasmodic torticollis  

Microsoft Academic Search

Botulinum toxin A was administered to 19 patients in a double-blind placebo controlled trial. Toxin was more effective than placebo for improving both head position and pain which was measured by an objective rating scale and videofilm assessments. Following the controlled trial, treatment with botulinum toxin was continued in an open fashion. A total of 60 patients with torticollis received

J D Blackie; A J Lees

1990-01-01

264

Botulinum toxin in spasmodic torticollis  

Microsoft Academic Search

Ten patients with spasmodic torticollis were treated by injection of a total dose of 30 ng of botulinum toxin type A into the affected sternomastoid and posterior cervical muscles. Nine patients reported improvement in head position and control, which was confirmed in seven cases by clinical assessment and \\

R Stell; P D Thompson; C D Marsden

1988-01-01

265

NATURAL TOXINS OF PLANT ORIGIN  

Technology Transfer Automated Retrieval System (TEKTRAN)

Poisonous Plants and the natural toxins therefrom cause significant economic losses to livestock industries throughout the world. Using 1989 figures, it was estimated that poisonous plants cause losses of over #340 million annually to the livestock industry in the seventeen western states of the U....

266

Antibody-based bacterial toxin detection  

NASA Astrophysics Data System (ADS)

Fiber optic evanescent fluorosensors are under investigation in our laboratory for the study of drug-receptor interactions for detection of threat agents and antibody-antigen interactions for detection of biological toxins. In a one step assay, antibodies against Cholera toxin or Staphylococcus Enterotoxin B were noncovalently immobilized on quartz fibers and probed with fluorescein-isothiocyanate (FITC)-labeled toxins. In the two-step assay, Cholera toxin or Botulinum toxoid A was immobilized onto the fiber, followed by incubation in an antiserum or partially purified antitoxin IgG. These were then probed with FITC-anti-IgG antibodies. Unlabeled toxins competed with labeled toxins or antitoxin IgG in a dose-dependent manner and the detection of the toxins was in the nanomolar range.

Menking, Darrell E.; Heitz, Jonathon M.; Anis, Nabil A.; Thompson, Roy G.

1994-03-01

267

The Effect of Multiple Parallel Bonds on the Self-healing of Labile Crosslinked Nanogel Networks  

NASA Astrophysics Data System (ADS)

We develop a hybrid computational approach to examine the mechanical properties and self-healing behavior of nanogel particles that are crosslinked primarily by highly reactive bonds that can break and readily remake (labile bonds). The individual nanogels are modeled via the lattice spring model (LSM). The crosslinks between the nanogels are simulated via a modified Hierarchical Bell Model (HBM), which allows us to capture both the rupturing and reforming of multiple, parallel bonds due to an applied force. Using our hybrid HBM/LSM, we simulate the behavior of the crosslinked nanogels under a tensile deformation. In these simulations, each labile linkage between the nanogels contains at most N parallel bonds. We reveal that while numerous parallel bonds within a linkage enhance the strength of the material, these bonds diminish the ductility and the ability of the material to undergo the structural rearrangements that are necessary for self-repair.

Salib, Isaac G.; Kolmakov, German V.; Gnegy, Chet N.; Matyjaszewski, Krzysztof; Balazs, Anna C.

2011-03-01

268

Effect of hydrogen sulfide on phosphorus lability in lake sediments amended with drinking water treatment residuals.  

PubMed

The use of drinking water treatment residuals (WTRs) to immobilize P in sediments is a novel approach for lake restoration. However, the lability of P in WTRs-amended sediments may vary with many factors, e.g., hydrogen sulfide content. Earlier works in our laboratory have demonstrated that WTRs are effective sorbents for hydrogen sulfide in water. Thus, we hypothesized that the lability of P in WTRs-amended sediments would not be increased by hydrogen sulfide. The results of this work suggested that this hypothesis was tenable. Compared to the raw sediments, the amended sediments had significantly lower P desorption potential in the presence of hydrogen sulfide at different times, pH and concentrations. Moreover, the amended sediments were also better able to adsorb hydrogen sulfide. In the amended sediments, the P, which was easily desorbed due to the effect of hydrogen sulfide, was transformed into the Fe/Al bound P. PMID:23453604

Wang, Changhui; Liu, Juanfeng; Pei, Yuansheng

2013-03-01

269

Decrease of labile Zn and Cd in the rhizosphere of hyperaccumulating Thlaspi caerulescens with time.  

PubMed

By using a rhizobox micro-suction cup technique we studied in-situ mobilization and complexation of Zn and Cd in the rhizosphere of non-hyperaccumulating Thlaspi perfoliatum and two different Thlaspi caerulescens ecotypes, one of them hyperaccumulating Zn, the other Zn and Cd. The dynamic fraction (free metal ions and small labile complexes) of Zn and Cd decreased with time in the rhizosphere solution of the respective hyperaccumulating T. caerulescens ecotypes, and at the end of the experiment, it was significantly smaller than in the other treatments. Furthermore, the rhizosphere solutions of the T. caerulescens ecotypes exhibited a higher UV absorptivity than the solution of the T. perfoliatum rhizosphere and the plant-free soil. Based on our findings we suggest that mobile and labile metal-dissolved soil organic matter complexes play a key role in the rapid replenishment of available metal pools in the rhizosphere of hyperaccumulating T. caerulescens ecotypes, postulated earlier. PMID:19913965

Dessureault-Rompré, Jacynthe; Luster, Jörg; Schulin, Rainer; Tercier-Waeber, Mary-Lou; Nowack, Bernd

2009-11-13

270

Toxin-antitoxin loci vapBC-1 and vapXD contribute to survival and virulence in nontypeable Haemophilus influenzae  

PubMed Central

Background Nontypeable Haemophilus influenzae (NTHi) is a significant human pathogen responsible for respiratory tract infections and the most common cause of recurrent otitis media. Type II toxin-antitoxin (TA) systems are genetic elements that code for a stable protein toxin and a labile antitoxin that are thought to be involved in metabolic regulation of bacteria by enabling a switch to a dormant state under stress conditions. The contribution to infection persistence of the NTHi TA loci vapBC-1 and vapXD was examined in this study. Results Deletions in vapBC-1, vapXD and vapBC-1 vapXD significantly decreased the survival of NTHi co-cultured with primary human respiratory tissue at the air-liquid interface and in the chinchilla model of otitis media. The TA deletions did not affect the growth dynamics of the mutants in rich media, their ultra-structural morphology, or display appreciable synergy during NTHi infections. The toxin and antitoxin proteins of both pairs heterodimerized in vivo. Consistent with our previous findings regarding the VapC-1 toxin, the NTHi VapD toxin also displayed ribonuclease activity. Conclusions We conclude that the vapBC-1 and vapXD TA loci enhance NTHi survival and virulence during infection in vitro and in vivo using a mechanism of mRNA cleavage, and that these conserved TA pairs represent new targets for the prophylaxis and therapy of otitis media and other NTHi-caused mucosal diseases.

2012-01-01

271

Human Acid-Labile Subunit Deficiency: Clinical, Endocrine and Metabolic Consequences  

Microsoft Academic Search

The majority of insulin-like growth factor (IGF)-I and IGF-II circulate in the serum as a complex with the insulin-like growth factor binding protein (IGFBP)-3 or IGFBP-5, and an acid-labile subunit (ALS). The function of ALS is to prolong the half-life of the IGF-I-IGFBP-3\\/IGFBP-5 binary complexes. Fourteen different mutations of the human IGFALS gene have been identified in 17 patients, suggesting

Horacio M. Domené; Vivian Hwa; Jesús Argente; Jan M. Wit; Cecilia Camacho-Hübner; Héctor G. Jasper; Jesús Pozo; Hermine A. van Duyvenvoorde; Shoshana Yakar; Olga V. Fofanova-Gambetti; Ron G. Rosenfeld; A. R. M. M. Hermus; T. B. Twickler; M. J. E. Kempers

2009-01-01

272

Tillage and liming effects on crop and labile soil nitrogen in an acid soil  

Microsoft Academic Search

Limited information is available on soil management effects on crop production and nitrogen (N) cycling in acid soils. The effects of conventional tillage (CT) versus no-till (NT) and liming (0 versus 7.5Mgha?1), and their interaction, on labile N pools in an acid soil were evaluated during the 7th to 10th year of a 3-course small grain rotation. Crop production and

Y. K. Soon; M. A. Arshad

2005-01-01

273

Lability of Proteinaceous Material in Estuarine Seston and Subcellular Fractions of Phytoplankton  

Microsoft Academic Search

The rate of proteolysis of amino acids was used to assess the nutritional lability of various materials making up estuarine seston in 3 Maine, USA, estuaries. Physical separations of subcellular fractions of phytoplankton cells led to higher proteolysis rate constants for the cytoplasmic fraction (>1.2 h(-1)) than for the membrane fraction (0.2 to 1 h(-1)). Whole cells, copepod fecal pellets,

A. K. Laursen; Lawrence Mayer; David Townsend

1996-01-01

274

Profiling of structurally labile oxylipins in plants by in situ derivatization with pentafluorobenzyl hydroxylamine  

Microsoft Academic Search

A GC–MS-based method for the simultaneous quantification of common oxylipins along with labile and highly reactive compounds based on in situ derivatization with pentafluorobenzyl hydroxylamine to the corresponding O-2,3,4,5,6-pentafluorobenzyl oximes (PFB oximes) is presented. The approach covers oxo derivatives such as jasmonic acid (JA), 12-oxophytodienoic acid (OPDA), certain phytoprostanes, unsaturated oxo-acids, oxo-hydroxy acids, and aldehyde fragments from the polar head

Birgit Schulze; Ryan Lauchli; Mesmin Mekem Sonwa; Annika Schmidt; Wilhelm Boland

2006-01-01

275

Optimization of foaming process using triblock polyimides with thermally labile blocks  

Microsoft Academic Search

Triblock polyamic acid was synthesized from the reaction of amine-terminated polystyrene with 4,4?-oxydianiline and pyromellitic dianhydride in N-methyl-2-pyrrolidone. IR and TGA were used to determine optimum curing conditions, in which imidization was completed and the thermally labile polystyrene block was intact. From the thermomechanical analysis (TMA), it was identified that the resulting triblock polyimide film showed contraction at several points

D. W Kim; S. S Hwang; S. M Hong; H. O Yoo; S. P Hong

2001-01-01

276

Decreased Serum Levels of Acid-Labile Subunit in Patients with Anorexia Nervosa  

Microsoft Academic Search

One of the observations in malnutrition is that serum insulin-like growth factor (IGF)-I levels are decreased, and this decrease is as- sociated with an altered profile of IGF binding proteins (IGFBPs). In human circulation, IGFs are mostly present as an approximately 150-kDa ternary protein complex consisting of IGFs, IGFBP-3, and acid-labile subunit (ALS). In the present study, to clarify the

IZUMI FUKUDA; MARI HOTTA; NAOMI HIZUKA; KAZUE TAKANO; YUKIKO ISHIKAWA; KUMIKO ASAKAWA-YASUMOTO; EMINA TAGAMI; HIROSHI DEMURA

277

Effects of labile soil carbon on nutrient partitioning between an arctic graminoid and microbes  

Microsoft Academic Search

We measured partitioning of N and P uptake between soil microorganisms and potted Festuca vivipara in soil from a subarctic heath in response to factorial addition of three levels of labile carbon (glucose) combined with\\u000a two levels of inorganic N and P. The glucose was added to either non-sterilized or sterilized (autoclaved) soils in quantities\\u000a which were within the range

Inger K. Schmidt; Anders Michelsen; Sven Jonasson

1997-01-01

278

Evaluation of potentially labile soil organic carbon and nitrogen fractionation procedures  

Microsoft Academic Search

Particulate organic matter (POM) and light fraction (LF) organic matter are potentially labile (active) fractions of soil organic matter (SOM) that have been shown to be indicators of short-term changes in soil management practices (e.g. tillage, manure and fertilizer applications, and crop rotation). These two fractions consist mainly of partially decomposed plant residues, microbial residues, seeds, and spores forming organo-mineral

Cleiton H. Sequeira; Marcus M. Alley; Brian P. Jones

2011-01-01

279

Management-induced change in labile soil organic matter under continuous corn in eastern Canadian soils  

Microsoft Academic Search

Soil samples taken from four experimental sites that had been cropped to continuous corn for 3–11 years in Ontario and Quebec\\u000a were analyzed to evaluate changes in quantity and quality of labile soil organic carbon under different nitrogen (N) fertility\\u000a and tillage treatments. Addition of fertilizer N above soil test recommendations tended to decrease amounts of water-soluble\\u000a organic carbon (WSOC)

B. C. Liang; A. F. MacKenzie; M. Schnitzer; C. M. Monreal; P. R. Voroney; R. P. Beyaert

1997-01-01

280

Mayolenes: Labile defensive lipids from the glandular hairs of a caterpillar (Pieris rapae)  

PubMed Central

Larvae of the European cabbage butterfly, Pieris rapae (Pieridae), are beset with glandular hairs, bearing droplets of a clear oily secretion at their tip. The fluid consists primarily of a series of chemically labile, unsaturated lipids, the mayolenes, which are derived from 11-hydroxylinolenic acid. In bioassays with the ant Crematogaster lineolata, the secretion was shown to be potently deterrent, indicating that the fluid plays a defensive role in nature.

Smedley, Scott R.; Schroeder, Frank C.; Weibel, Douglas B.; Meinwald, Jerrold; Lafleur, Katie A.; Renwick, J. Alan; Rutowski, Ronald; Eisner, Thomas

2002-01-01

281

Staphylococcus aureus toxins - Their functions and genetics.  

PubMed

The outcome of encounters between Staphylococcus (S.) aureus and its human host ranges from life-threatening infection through allergic reactions to symptom-free colonization. The pan-genome of this bacterial species encodes numerous toxins, known or strongly suspected to cause specific diseases or symptoms. Three toxin families are in the focus of this review, namely (i) pore-forming toxins, (ii) exfoliative toxins and (iii) superantigens. The majority of toxin-encoding genes are located on mobile genetic elements (MGEs), resulting in a pronounced heterogeneity in the endowment with toxin genes of individual S. aureus strains. Recent population genomic analysis have provided a framework for an improved understanding of the temporal and spatial scales of the motility of MGEs and their associated toxin genes. The distribution of toxin genes among clonal lineages within the species S. aureus is not random, and phylogenetic (sub-)lineages within clonal complexes feature characteristic toxin signatures. When studying pathogenesis, this lineage association, which is caused by the clonal nature of S. aureus makes it difficult to discriminate effects of specific toxins from contributions of the genetic background and/or other associated genetic factors. PMID:23541411

Grumann, Dorothee; Nübel, Ulrich; Bröker, Barbara M

2013-03-26

282

Affect Intensity and Lability: The Role of Posttraumatic Stress Disorder Symptoms in Borderline Personality Disorder  

PubMed Central

Background Emotion dysregulation is likely a core psychological process underlying the heterogeneity of presentations in borderline personality disorder (BPD) and is associated with BPD symptom severity. Emotion dysregulation has also been independently associated with posttraumatic stress disorder (PTSD), a disorder that has been found to co-occur with BPD in 30.2% of cases in a nationally representative sample. However, relatively little is known about the specific relationships between emotion dysregulation and PTSD among those diagnosed with BPD. The purpose of the current study was to evaluate relations between PTSD symptom severity and negative affect intensity and affective lability among individuals with BPD. Method Participants were 67 individuals diagnosed with BPD (79% women; Mage = 38, SD = 10), who reported one or more DSM-IV PTSD Criterion A events. Results Hierarchical multiple regression analyses indicated that when examined concurrently with BPD symptom severity, PTSD symptom severity, but not BPD symptom severity, was related to negative affect intensity and affective lability. Reexperiencing symptoms uniquely predicted affective lability, and hyperarousal symptoms uniquely predicted negative affect intensity, lending additional support to emerging literature linking reexperiencing and hyperarousal symptoms with emotion dysregulation. Conclusions PTSD symptom severity among individuals with a BPD diagnosis is related to elevations in emotion dysregulation. It is important to evaluate whether early treatment of PTSD symptoms provided concurrently with BPD treatment leads to enhanced improvements in emotion regulation among individuals with co-occurring PTSD and BPD.

Marshall-Berenz, Erin C.; Morrison, Jay A.; Schumacher, Julie A.; Coffey, Scott F.

2011-01-01

283

Electrodermal lability as an indicator for subjective sleepiness during total sleep deprivation.  

PubMed

The present study addresses the suitability of electrodermal lability as an indicator of individual vulnerability to the effects of total sleep deprivation. During two complete circadian cycles, the effects of 48h of total sleep deprivation on physiological measures (electrodermal activity and body temperature), subjective sleepiness (measured by visual analogue scale and tiredness symptom scale) and task performance (reaction time and errors in a go/no go task) were investigated. Analyses of variance with repeated measures revealed substantial decreases of the number of skin conductance responses, body temperature, and increases for subjective sleepiness, reaction time and error rates. For all changes, strong circadian oscillations could be observed as well. The electrodermal more labile subgroup reported higher subjective sleepiness compared with electrodermal more stable participants, but showed no differences in the time courses of body temperature and task performance. Therefore, electrodermal lability seems to be a specific indicator for the changes in subjective sleepiness due to total sleep deprivation and circadian oscillations, but not a suitable indicator for vulnerability to the effects of sleep deprivation per se. PMID:22150963

Michael, Lars; Passmann, Sven; Becker, Ruth

2011-12-12

284

Effects of chemical amendments on the lability and speciation of metals in anaerobically digested biosolids.  

PubMed

The interaction of inorganic contaminants present in biosolids with iron, aluminum, and manganese oxy/hydroxides has been advocated as a key mechanism limiting their bioavailability. In this study, we investigated whether this is indeed the case, and further, whether it can be exploited to produce optimized biosolids products through the addition of chemical additives during sewage sludge processing. Experiments were conducted to investigate whether the addition of iron- and aluminum-based amendments (at 5 different rates) during the anaerobic digestion phase of wastewater treatment can effectively change the speciation or lability of contaminant metals (copper, zinc and cadmium) in biosolids destined for use in agriculture. The performance of the bioreactors was monitored throughout and the speciation and lability were determined in both fresh and 3-month aged biosolids using X-ray absorption spectroscopy (Cu, Zn) and isotopic dilution ((65)Cu, (65)Zn, (109)Cd). The tested amendments (FeCl3, Al2(SO4)3, and Al-rich water treatment residual) did not cause significant changes in metal speciation and were of limited use for reducing the lability of contaminant metals in good quality biosolids (suitable for use in agriculture), suggesting that high affinity binding sites were already in excess in these materials. However, the use of chemical amendments may offer advantages in terms of treatment process optimization and may also be beneficial when biosolids are used for contaminated site remediation. PMID:23981056

Donner, Erica; Brunetti, Gianluca; Zarcinas, Bernie; Harris, Paul; Tavakkoli, Ehsan; Naidu, Ravi; Lombi, Enzo

2013-09-17

285

Involvement of vasodilator mechanisms in arterial pressure lability after sino-aortic baroreceptor denervation in rat.  

PubMed Central

1. To examine the regional haemodynamic basis of arterial pressure lability seen after sino-aortic baroreceptor denervation (SAD), simultaneous beat-to-beat recordings of arterial pressure and indices of regional blood flows (Doppler probes around the subdiaphragmatic and lower abdominal aortae and the superior mesenteric artery) were performed in the same conscious rats (n = 7) before, 1 and 14 days after SAD. 2. Acute SAD increased arterial pressure, decreased regional blood flows and vascular conductances, and potentiated the depressor and vasodilator effects of ganglionic blockade with trimethaphan, suggesting sympathetic overactivity. All parameters chronically returned to or near normal. 3. Both acute and chronic SAD increased the variability of arterial pressure and of regional conductances. Arterial pressure lability was characterized by a mixture of depressor and pressor events which were associated with regional vasodilatations and vasoconstrictions, respectively. This haemodynamic pattern was not affected by acute beta-adrenoceptor blockade with propranolol. 4. In conscious rats, the baroreceptor reflex acts to buffer the spontaneous variability of regional vascular conductances and thereby stabilizes arterial pressure. Sino-aortic baroreceptor denervation-induced arterial pressure lability does not depend on the level of sympathetic activation, and is determined by the relative contribution of depressor and pressor events accompanied by extensive vasodilatations and vasoconstrictions, respectively. Vasodilatations are not caused by the stimulation of vascular beta 2-adrenoceptors.

Zhang, Z Q; Barres, C; Julien, C

1995-01-01

286

Labile soil carbon inputs mediate the soil microbial community composition and plant residue decomposition rates  

SciTech Connect

Root carbon (C) inputs may regulate decomposition rates in soil, and in this study we ask: how do labile C inputs regulate decomposition of plant residues, and soil microbial communities? In a 14 d laboratory incubation, we added C compounds often found in root exudates in seven different concentrations (0, 0.7, 1.4, 3.6, 7.2, 14.4 and 21.7 mg C g{sup -1} soil) to soils amended with and without {sup 13}C-labeled plant residue. We measured CO{sub 2} respiration and shifts in relative fungal and bacterial rRNA gene copy numbers using quantitative polymerase chain reaction (qPCR). Increased labile C input enhanced total C respiration, but only addition of C at low concentrations (0.7 mg C g{sup -1}) stimulated plant residue decomposition (+2%). Intermediate concentrations (1.4, 3.6 mg C g{sup -1}) had no impact on plant residue decomposition, while greater concentrations of C (> 7.2 mg C g{sup -1}) reduced decomposition (-50%). Concurrently, high exudate concentrations (> 3.6 mg C g{sup -1}) increased fungal and bacterial gene copy numbers, whereas low exudate concentrations (< 3.6 mg C g{sup -1}) increased metabolic activity rather than gene copy numbers. These results underscore that labile soil C inputs can regulate decomposition of more recalcitrant soil C by controlling the activity and relative abundance of fungi and bacteria.

De Graaff, Marie-Anne [ORNL; Classen, Aimee T [University of Tennessee, Knoxville (UTK); Castro Gonzalez, Hector F [ORNL; Schadt, Christopher Warren [ORNL

2010-01-01

287

Emetic toxin-producing strains of Bacillus cereus show distinct characteristics within the Bacillus cereus group.  

PubMed

One hundred representative strains of Bacillus cereus were selected from a total collection of 372 B. cereus strains using two typing methods (RAPD and FT-IR) to investigate if emetic toxin-producing hazardous B. cereus strains possess characteristic growth and heat resistance profiles. The strains were classified into three groups: emetic toxin (cereulide)-producing strains (n=17), strains connected to diarrheal foodborne outbreaks (n=40) and food-environment strains (n=43), these latter not producing the emetic toxin. Our study revealed a shift in growth limits towards higher temperatures for the emetic strains, regardless of their origin. None of the emetic toxin-producing strains were able to grow below 10 degrees Celsius. In contrast, 11% (9 food-environment strains) out of the 83 non-emetic toxin-producing strains were able to grow at 4 degrees Celsius and 49% at 7 degrees Celsius (28 diarrheal and 13 food-environment strains). non-emetic toxin-producing strains. All emetic toxin-producing strains were able to grow at 48 degrees Celsius, but only 39% (16 diarrheal and 16 food-environment strains) of the non-emetic toxin-producing strains grew at this temperature. Spores from the emetic toxin-producing strains showed, on average, a higher heat resistance at 90 degrees Celsius and a lower germination, particularly at 7 degrees Celsius, than spores from the other strains. No difference between the three groups in their growth kinetics at 24 degrees Celsius, 37 degrees Celsius, and pH 5.0, 7.0, and 8.0 was observed. Our survey shows that emetic toxin-producing strains of B. cereus have distinct characteristics, which could have important implication for the risk assessment of the emetic type of B. cereus caused food poisoning. For instance, emetic strains still represent a special risk in heat-processed foods or preheated foods that are kept warm (in restaurants and cafeterias), but should not pose a risk in refrigerated foods. PMID:16503068

Carlin, Frédéric; Fricker, Martina; Pielaat, Annemarie; Heisterkamp, Simon; Shaheen, Ranad; Salonen, Mirja Salkinoja; Svensson, Birgitta; Nguyen-the, Christophe; Ehling-Schulz, Monika

2006-02-24

288

Exfoliative toxins of Staphylococcus aureus.  

PubMed

Staphylococcus aureus is an important pathogen of humans and livestock. It causes a diverse array of diseases, ranging from relatively harmless localized skin infections to life-threatening systemic conditions. Among multiple virulence factors, staphylococci secrete several exotoxins directly associated with particular disease symptoms. These include toxic shock syndrome toxin 1 (TSST-1), enterotoxins, and exfoliative toxins (ETs). The latter are particularly interesting as the sole agents responsible for staphylococcal scalded skin syndrome (SSSS), a disease predominantly affecting infants and characterized by the loss of superficial skin layers, dehydration, and secondary infections. The molecular basis of the clinical symptoms of SSSS is well understood. ETs are serine proteases with high substrate specificity, which selectively recognize and hydrolyze desmosomal proteins in the skin. The fascinating road leading to the discovery of ETs as the agents responsible for SSSS and the characterization of the molecular mechanism of their action, including recent advances in the field, are reviewed in this article. PMID:22069631

Bukowski, Michal; Wladyka, Benedykt; Dubin, Grzegorz

2010-05-25

289

Effect of Electrodermal Lability and Anxiety on the Electrodermal Detection of Deception with a Control Question Technique.  

National Technical Information Service (NTIS)

This exploratory study was designed to examine the effects of individual differences in electrodermal lability and state-trait anxiety on the detection of deception. Eighty-two males participated in this study. Half were assigned to the programmed innocen...

E. M. Ingram

1994-01-01

290

The removal of uremic toxins  

Microsoft Academic Search

The removal of uremic toxins. Three major groups of uremic solutes can be characterized: the small water-soluble compounds, the middle molecules, and the protein-bound compounds. Whereas small water-soluble compounds are quite easily removed by conventional hemodialysis, this is not the case for many other molecules with different physicochemical characteristics. Continuous ambulatory peritoneal dialysis (CAPD) is often characterized by better removal

Annemieke Dhondt; Raymond Vanholder; Wim Van Biesen; Norbert Lameire

2000-01-01

291

Peau, rides et toxine botulique  

Microsoft Academic Search

Objective. – To present an up-to-date analysis about the use of botulinum toxin for treating facial lines and wrinkles.Method. – A systematic search of the literature was conducted to select the most recent or relevant publications on this topic, through Medline.Results. – Out of the 583 articles retrieved, 90 were finally selected for the study.Discussion. – Validity of using botulinum

P. J Nicolau; M Chaouat; M Mimoun

2003-01-01

292

In vivo effects of cnidarian toxins and venoms  

Microsoft Academic Search

Cnidarians (Coelenterates), a very old and diverse animal phylum, possess a wide variety of biologically active substances that can be considered as toxins. Anthozoan toxins can be classified into two chemically very different groups, namely polypeptide toxins isolated from sea anemones and diterpenes isolated from octocorals. Cubozoan and scyphozoan protein toxins have been the most elusive cnidarian toxins to investigate

Dušan Šuput

2009-01-01

293

Pathways followed by ricin and Shiga toxin into cells  

Microsoft Academic Search

The plant toxin ricin and the bacterial toxin Shiga toxin belong to a group of protein toxins that inhibit protein synthesis in cells enzymatically after entry into the cytosol. Ricin and Shiga toxin, which both have an enzymatically active moiety that inactivates ribosomes and a moiety that binds to cell surface receptors, enter the cytosol after binding to the cell

Kirsten Sandvig; Stine Grimmer; Silje Ugland Lauvrak; Maria Lyngaas Torgersen; Grethe Skretting; Bo van Deurs; Tore Iversen

2002-01-01

294

Neutralising Antibodies against Ricin Toxin  

PubMed Central

The Centers for Disease Control and Prevention have listed the potential bioweapon ricin as a Category B Agent. Ricin is a so-called A/B toxin produced by plants and is one of the deadliest molecules known. It is easy to prepare and no curative treatment is available. An immunotherapeutic approach could be of interest to attenuate or neutralise the effects of the toxin. We sought to characterise neutralising monoclonal antibodies against ricin and to develop an effective therapy. For this purpose, mouse monoclonal antibodies (mAbs) were produced against the two chains of ricin toxin (RTA and RTB). Seven mAbs were selected for their capacity to neutralise the cytotoxic effects of ricin in vitro. Three of these, two anti-RTB (RB34 and RB37) and one anti-RTA (RA36), when used in combination improved neutralising capacity in vitro with an IC50 of 31 ng/ml. Passive administration of association of these three mixed mAbs (4.7 µg) protected mice from intranasal challenges with ricin (5 LD50). Among those three antibodies, anti-RTB antibodies protected mice more efficiently than the anti-RTA antibody. The combination of the three antibodies protected mice up to 7.5 hours after ricin challenge. The strong in vivo neutralising capacity of this three mAbs combination makes it potentially useful for immunotherapeutic purposes in the case of ricin poisoning or possibly for prevention.

Prigent, Julie; Panigai, Laetitia; Lamourette, Patricia; Sauvaire, Didier; Devilliers, Karine; Plaisance, Marc; Volland, Herve; Creminon, Christophe; Simon, Stephanie

2011-01-01

295

Cellular and Systemic Effects of Anthrax Lethal Toxin and Edema Toxin  

PubMed Central

Anthrax lethal toxin (LT) and edema toxin (ET) are the major virulence factors of anthrax and can replicate the lethality and symptoms associated with the disease. This review provides an overview of our current understanding of anthrax toxin effects in animal models and the cytotoxicity (necrosis and apoptosis) induced by LT in different cells. A brief reexamination of early historic findings on toxin in vivo effects in the context of our current knowledge is also presented.

Moayeri, Mahtab; Leppla, Stephen H.

2009-01-01

296

The pyrogenic effect of scarlet fever toxin  

Microsoft Academic Search

Scarlet fever toxin was found to liberate leukocytic pyrogen from granulocytesin vitro. In comparative experiments withSalmonella paratyphi B endotoxin and scarlet fever toxin it was tested whether leukocytes from rabbits tolerant to one of these toxins are able\\u000a to synthetize and liberate endogenous pyrogen. Leukocytes from rabbits tolerant to endotoxin liberated leukoeytic pyrogen\\u000a following challenge with endotoxin or with scarlet

V. SCHUI-I; V?ra H?íbalová

1966-01-01

297

The Stable and Radio- Carbon Isotopic Content of Labile and Refractory Carbon in Atmospheric Particulate Matter  

NASA Astrophysics Data System (ADS)

Studies of the isotopic content of atmospheric particulate matter are hampered by difficulties in chemically defining the pools of carbon and analytically isolating the different pools. We are conducting studies on reference materials and atmospheric aerosol samples to develop a method to measure stable and radio- carbon isotopes on the labile and refractory carbon. We are using a flow-through combustion system that allows us to combust, collect and measure the isotopic content of the gases produced at all stages of heating/oxidizing. We compare our results to those measured using a chemothermal oxidation method (CTO) (Gustafsson et al., 2001). In this method, refractory carbon is defined as the material remaining after pre- combusting a sample at 375°C in the presence of oxygen for 24 hours. The reference materials are diesel soot, apple leaves and a hybrid of the two (DiesApple), all from NIST. These provide carbon with two well-defined fractions -- the soot provides refractory carbon that is radiocarbon dead and the apple leaves provide organic carbon that is radiocarbon modern. Radiocarbon results from DiesApple indicate that the "refractory" carbon defined by the CTO method is actually a mixture of old and modern carbon that contains over 25% modern carbon. This suggests that charred material formed from the apples leaves during the pre-combustion step is contributing to the fraction we identify as refractory carbon. We are studying this by analyzing the individual materials and the mixture using our flow-through system. First results with this system indicate that the refractory fraction trapped from the DiesApple contains much less modern carbon than the CTO method, less than 7%. We will present detailed concentration and isotopic results of the generation of carbon dioxide during programmed combustion of each of the reference materials. We studied the radiocarbon content of both the total carbon (TC) and refractory carbon in the fine particulate matter (PM2.5) collected on quartz fiber filters as part of the Southeastern Aerosol Research and Characterization (SEARCH) program. The five samples were collected at two sites (Birmingham, AL and Atlanta, GA) with very different sources of atmospheric particulate matter. In all instances, the refractory carbon contained significantly less radiocarbon than the TC suggesting, not unexpectedly, a source of particulate carbon from the combustion of fossil material. We will present results from the analysis of the same filters in the flow-through system. The implication of our results for the use of radiocarbon in the quantitative apportionment of atmospheric particulate matter sources will be discussed. Gustafsson O., T. Bucheli, Z. Kukulska, M. Andersson, C. Largeau, J-N. Rouzaud, C. Reddy and T. Eglinton (2001) Evaluation of a protocol for the quantification of black carbon in sediments. GBD 15, 881-890.

McNichol, A. P.; Rosenheim, B. E.; Gerlach, D. S.; Hayes, J. M.

2006-12-01

298

Application of Botulinum Toxin in Pain Management  

PubMed Central

Botulinum toxin has been used for the treatment of many clinical disorders by producing temporary skeletal muscle relaxation. In pain management, botulinum toxin has demonstrated an analgesic effect by reducing muscular hyperactivity, but recent studies suggest this neurotoxin could have direct analgesic mechanisms different from its neuromuscular actions. At the moment, botulinum toxin is widely investigated and used in many painful diseases such as myofascial syndrome, headaches, arthritis, and neuropathic pain. Further studies are needed to understand the exact analgesic mechanisms, efficacy and complications of botulinum toxin in chronic pain disorders.

2011-01-01

299

Quantitative Analysis of Cereulide, the Emetic Toxin of Bacillus cereus, Produced under Various Conditions  

Microsoft Academic Search

This paper describes a quantitative and sensitive chemical assay for cereulide, the heat-stable emetic toxin produced by Bacillus cereus. The methods previously available for measuring cereulide are bioassays that give a toxicity titer, but not an accurate concentration. The dose of cereulide causing illness in humans is therefore not known, and thus safety limits for cereulide cannot be indicated. We

M. M Haggblom; Camelia Apetroaie; Maria A. Andersson; Mirja S. Salkinoja-Salonen

2002-01-01

300

Regulation of the Escherichia coli HipBA Toxin-Antitoxin System by Proteolysis  

PubMed Central

Bacterial populations produce antibiotic-tolerant persister cells. A number of recent studies point to the involvement of toxin/antitoxin (TA) modules in persister formation. hipBA is a type II TA module that codes for the HipB antitoxin and the HipA toxin. HipA is an EF-Tu kinase, which causes protein synthesis inhibition and dormancy upon phosphorylation of its substrate. Antitoxins are labile proteins that are degraded by one of the cytosolic ATP-dependent proteases. We followed the rate of HipB degradation in different protease deficient strains and found that HipB was stabilized in a lon- background. These findings were confirmed in an in vitro degradation assay, showing that Lon is the main protease responsible for HipB proteolysis. Moreover, we demonstrated that degradation of HipB is dependent on the presence of an unstructured carboxy-terminal stretch of HipB that encompasses the last 16 amino acid residues. Further, substitution of the conserved carboxy-terminal tryptophan of HipB to alanine or even the complete removal of this 16 residue fragment did not alter the affinity of HipB for hipBA operator DNA or for HipA indicating that the major role of this region of HipB is to control HipB degradation and hence HipA-mediated persistence.

Hansen, Sonja; Vulic, Marin; Min, Jungki; Yen, Tien-Jui; Schumacher, Maria A.; Brennan, Richard G.; Lewis, Kim

2012-01-01

301

Regulation of the Escherichia coli HipBA toxin-antitoxin system by proteolysis.  

PubMed

Bacterial populations produce antibiotic-tolerant persister cells. A number of recent studies point to the involvement of toxin/antitoxin (TA) modules in persister formation. hipBA is a type II TA module that codes for the HipB antitoxin and the HipA toxin. HipA is an EF-Tu kinase, which causes protein synthesis inhibition and dormancy upon phosphorylation of its substrate. Antitoxins are labile proteins that are degraded by one of the cytosolic ATP-dependent proteases. We followed the rate of HipB degradation in different protease deficient strains and found that HipB was stabilized in a lon(-) background. These findings were confirmed in an in vitro degradation assay, showing that Lon is the main protease responsible for HipB proteolysis. Moreover, we demonstrated that degradation of HipB is dependent on the presence of an unstructured carboxy-terminal stretch of HipB that encompasses the last 16 amino acid residues. Further, substitution of the conserved carboxy-terminal tryptophan of HipB to alanine or even the complete removal of this 16 residue fragment did not alter the affinity of HipB for hipBA operator DNA or for HipA indicating that the major role of this region of HipB is to control HipB degradation and hence HipA-mediated persistence. PMID:22720069

Hansen, Sonja; Vuli?, Marin; Min, Jungki; Yen, Tien-Jui; Schumacher, Maria A; Brennan, Richard G; Lewis, Kim

2012-06-15

302

42 CFR 73.3 - HHS select agents and toxins.  

Code of Federal Regulations, 2011 CFR

...toxins: Abrin Botulinum neurotoxins Botulinum neurotoxin producing species of Clostridium Cercopithecine herpesvirus 1 (Herpes B virus) Clostridium perfringens epsilon toxin Coccidioides posadasii/Coccidioides immitis Conotoxins...

2011-10-01

303

Comparison of the relative toxicities of Shiga-like toxins type I and type II for mice.  

PubMed Central

In earlier studies using a streptomycin-treated mouse model of infection caused by enterohemorrhagic Escherichia coli (EHEC), animals fed Shiga-like toxin type II (SLT-II)-producing strains developed acute renal cortical necrosis and died, while mice fed Shiga-like toxin type I (SLT-I)-producing clones did not die (E. A. Wadolkowski, L. M. Sung, J. A. Burris, J. E. Samuel, and A. D. O'Brien, Infect. Immun. 58:3959-3965, 1990). To examine the bases for the differences we noted between the two toxins in the murine infection model, we injected mice with purified toxins and carried out histopathological examinations. Despite the genetic and structural similarities between the two toxins, SLT-II had a 50% lethal dose (LD50) which was approximately 400 times lower than that of SLT-I when injected intravenously or intraperitoneally into mice. Histopathologic examination of toxin-injected mice revealed that detectable damage was limited to renal cortical tubule epithelial cells. Passive administration of anti-SLT-II antibodies protected mice from SLT-II-mediated kidney damage and death. Immunofluorescence staining of normal murine kidney sections incubated with purified SLT-I or SLT-II demonstrated that both toxins bound to cortical tubule and medullary duct epithelial cells. Compared with SLT-I, SLT-II was more heat and pH stable, suggesting that SLT-II is a relatively more stable macromolecule. Although both toxins bound to globotriaosylceramide, SLT-I bound with a higher affinity in a solid-phase binding assay. Differences in enzymatic activity between the two toxins were not detected. These data suggest that structural/functional differences between the two toxins, possibly involving holotoxin stability and/or receptor affinity, may contribute to the differential LD50s in mice. Images

Tesh, V L; Burris, J A; Owens, J W; Gordon, V M; Wadolkowski, E A; O'Brien, A D; Samuel, J E

1993-01-01

304

Interactions between recalcitrant and labile organic carbon in streams - Can stream biofilms mediate a priming effect?  

NASA Astrophysics Data System (ADS)

Inland waters - such as streams, rivers and lakes - are increasingly recognized as important components in the global carbon cycle. Dissolved organic carbon (DOC) in these systems is diverse in structure, origin and reactivity, and a fraction of it is regarded as recalcitrant to microbial degradation. In soils, degradation of recalcitrant carbon is often controlled by the availability of labile carbon sources. This is linked to the priming effect (PE). Mounting evidence suggests that PE is also important in aquatic ecosystems but there are so far very few studies addressing this topic. Biofilms are vital components of aquatic ecosystems. In stream biofilms, heterotrophic bacteria and algae coexist in close proximity, exposing the bacteria to both recalcitrant DOC of terrestrial origin and labile organic carbon from the algae. We hypothesize that this makes stream biofilms hotspots for PE. We used plug-flow bioreactors inoculated with natural stream biofilm bacterial communities to test the potential of a priming effect in aquatic ecosystems. The bioreactors were amended with an isotope-labeled plant extract serving as a model of recalcitrant DOC in streams. Labile carbon sources, in the form of glucose and an algal extract were added to induce PE. Nitrate and phosphate were also added to assess the role of these inorganic nutrients on carbon uptake. Microbial uptake of the different carbon sources was monitored by measuring the concentrations and isotopic ratios of respired CO2, biomass and DOC. Our results suggest that the priming effect plays a role in stream carbon cycling and that it is potentially an important process in other aquatic ecosystems.

Bengtsson, M. M.; Wagner, K.; Herberg, E. R.; Burns, N. R.; Wanek, W.; Battin, T. J.

2012-04-01

305

Coordination assemblies of polyoxomolybdate cluster framework: from labile building blocks to stable functional materials.  

PubMed

Polyoxomolybdates, an important branch in polyoxometalates chemistry, present complicated solution chemistry and unmatched physicochemical properties, which endows us with both great opportunities and considerable challenges in creating new functional materials. This perspective highlights the recent development on the coordination assembly of transition-metal-substituted heteropolymolybdates by using labile lacunary heteropolymolybdates as inorganic multidentate ligands. A series of strategies have been used to stabilize the lacunary heteropolymolybdate building blocks. Finally, we introduce some researches on the modification of polymolybdates by organic groups in aqueous media, which may shed light on the green chemistry of the functionalization of polyoxomolybdates. PMID:21321727

Li, Fengyan; Xu, Lin

2011-02-14

306

Stable and labile components of humus in soddy-podzolic soils  

NASA Astrophysics Data System (ADS)

A mathematical model was proposed to characterize the seasonal dynamics of the humus composition in loamy soddy-podzolic soils. The results of determining the composition of the organic matter during two successive seasons revealed the presence of labile and stable components in almost all the groups and fractions of the humic substances. The seasonal changes in the content of the humic substances, the exchangeable Ca, and the pH value at the equilibrium state of the soil were found to be identical during the successive years.

Drichko, V. F.; Bakina, L. G.; Orlova, N. E.

2013-01-01

307

The influence of weathering and organic matter on heavy metals lability in silicatic, Alpine soils.  

PubMed

We investigated the effect of organic matter and weathering on the lability and solid phase speciation of heavy metals (Cd, Cr, Cu, Ni, Pb, Zn) in two contrasting subalpine regions in the Italian Alps. Cr, Ni and Cu could be linked to weathering. This was not the case for Pb. Since organic matter (OM) influences the solid phase speciation of heavy metals, the total organic C and N content, the C and N content of different density fractions of OM and also of the labile (oxidised by H(2)O(2)) and stable (H(2)O(2)-resistant) fractions were determined. Soil OM stocks were high and soils on north-facing slopes had more OM than the south-facing sites to which they were paired. Density measurements and the H(2)O(2) fractionation indicated that the higher OM content on north-facing sites was due to an accumulation of weakly degraded organic material. Due to higher weathering intensity on north-facing sites, the abundance of the EDTA-extractable heavy metals was higher than on south-facing sites. All EDTA-extractable heavy metals showed a good correlation to the water-soluble phenolic concentrations which indicates that the metals were probably translocated as metal-organic complexes. Pb and Cu correlate not only to the light (density < 1 g/cm(3)) and labile, organic fraction but also to the heavy (density > 2 g/cm(3)) and stable fraction. High-mountain ecosystems like the Alps are sensitive to changing environmental conditions such as global warming. A warmer climate and the more favourable conditions it brings for biological activity, especially at cooler sites, will probably lead in the short- to mid-term to an increased loss of accumulated, weakly degraded OM. As the Pb and Cu content is significantly related to the labile organic matter pools, the risk exists that an increase in OM mineralisation could affect the storage capacity and mobility of these metals in soils. PMID:19879634

Egli, Markus; Sartori, Giacomo; Mirabella, Aldo; Giaccai, Daniele; Favilli, Filippo; Scherrer, Daniel; Krebs, Rolf; Delbos, Evelyne

2009-10-30

308

Destruction of Cyanobacterial Toxins By Ozone  

Microsoft Academic Search

The potential for the oxidant ozone used in water treatment, to destroy the various classes of toxins produced by cyanobacteria (blue-green algae) was investigated. Toxin destruction was determined by chemical analyses or mouse bioassay. Ozone was more effective than chlorine, hydrogen peroxide and potassium permanganate in destroying the peptide hepatotoxin microcystin-LR. Ozone in combination with hydrogen peroxide was more effective

J. Rositano; B. C. Nicholson; P. Pieronne

1998-01-01

309

Plant Insecticidal Toxins in Ecological Networks  

PubMed Central

Plant secondary metabolites play a key role in plant-insect interactions, whether constitutive or induced, C- or N-based. Anti-herbivore defences against insects can act as repellents, deterrents, growth inhibitors or cause direct mortality. In turn, insects have evolved a variety of strategies to act against plant toxins, e.g., avoidance, excretion, sequestration and degradation of the toxin, eventually leading to a co-evolutionary arms race between insects and plants and to co-diversification. Anti-herbivore defences also negatively impact mutualistic partners, possibly leading to an ecological cost of toxin production. However, in other cases toxins can also be used by plants involved in mutualistic interactions to exclude inadequate partners and to modify the cost/benefit ratio of mutualism to their advantage. When considering the whole community, toxins have an effect at many trophic levels. Aposematic insects sequester toxins to defend themselves against predators. Depending on the ecological context, toxins can either increase insects’ vulnerability to parasitoids and entomopathogens or protect them, eventually leading to self-medication. We conclude that studying the community-level impacts of plant toxins can provide new insights into the synthesis between community and evolutionary ecology.

Ibanez, Sebastien; Gallet, Christiane; Despres, Laurence

2012-01-01

310

Cyanobacterial toxins: risk management for health protection  

Microsoft Academic Search

This paper reviews the occurrence and properties of cyanobacterial toxins, with reference to the recognition and management of the human health risks which they may present. Mass populations of toxin-producing cyanobacteria in natural and controlled waterbodies include blooms and scums of planktonic species, and mats and biofilms of benthic species. Toxic cyanobacterial populations have been reported in freshwaters in over

Geoffrey A. Codd; Louise F. Morrison; James S. Metcalf

2005-01-01

311

Molecular Size of Clostridium Botulinum Toxins.  

National Technical Information Service (NTIS)

The molecular size of the various types of Clostridium botulinum toxins in spent culture have been estimated. The estimates were based on the rate of sedimentation of the toxin as measured by mouse assay before and after ultracentrifugation of culture. Th...

E. J. Schantz L. Spero

1966-01-01

312

The scorpion toxin and the potassium channel  

PubMed Central

The structure of a complex containing a toxin bound to a potassium ion channel has been solved for the first time, revealing how scorpions have designed toxins that can recognize and target the filter that controls the movement of potassium ions through these channels.

2013-01-01

313

Competition between tetanus toxoid and toxin  

Microsoft Academic Search

Experiments on albino mice showed that preliminary injection of tetanus toxoid increases the resistance of animals to tetanus toxin, as manifested by an increase in LD50. The effect is enhanced by increasing the dose of toxoid or by giving it in fractional doses. The use of protagon and unpurified mitochondrial fraction, isolated from the brain, as receptor of tetanus toxin

G. N. Kryzhanovskii; A. Ya. Rozanov; O. A. Kirilenko; N. G. Bondarchuk

1975-01-01

314

Brown spider dermonecrotic toxin directly induces nephrotoxicity  

SciTech Connect

Brown spider (Loxosceles genus) venom can induce dermonecrotic lesions at the bite site and systemic manifestations including fever, vomiting, convulsions, disseminated intravascular coagulation, hemolytic anemia and acute renal failure. The venom is composed of a mixture of proteins with several molecules biochemically and biologically well characterized. The mechanism by which the venom induces renal damage is unknown. By using mice exposed to Loxosceles intermedia recombinant dermonecrotic toxin (LiRecDT), we showed direct induction of renal injuries. Microscopic analysis of renal biopsies from dermonecrotic toxin-treated mice showed histological alterations including glomerular edema and tubular necrosis. Hyalinization of tubules with deposition of proteinaceous material in the tubule lumen, tubule epithelial cell vacuoles, tubular edema and epithelial cell lysis was also observed. Leukocytic infiltration was neither observed in the glomerulus nor the tubules. Renal vessels showed no sign of inflammatory response. Additionally, biochemical analyses showed such toxin-induced changes in renal function as urine alkalinization, hematuria and azotemia with elevation of blood urea nitrogen levels. Immunofluorescence with dermonecrotic toxin antibodies and confocal microscopy analysis showed deposition and direct binding of this toxin to renal intrinsic structures. By immunoblotting with a hyperimmune dermonecrotic toxin antiserum on renal lysates from toxin-treated mice, we detected a positive signal at the region of 33-35 kDa, which strengthens the idea that renal failure is directly induced by dermonecrotic toxin. Immunofluorescence reaction with dermonecrotic toxin antibodies revealed deposition and binding of this toxin directly in MDCK epithelial cells in culture. Similarly, dermonecrotic toxin treatment caused morphological alterations of MDCK cells including cytoplasmic vacuoles, blebs, evoked impaired spreading and detached cells from each other and from culture substratum. In addition, dermonecrotic toxin treatment of MDCK cells changed their viability evaluated by XTT and Neutral-Red Uptake methodologies. The present results point to brown spider dermonecrotic toxin cytotoxicity upon renal structures in vivo and renal cells in vitro and provide experimental evidence that this brown spider toxin is directly involved in nephrotoxicity evoked during Loxosceles spider venom accidents.

Chaim, Olga Meiri [Department of Cell Biology, Federal University of Parana, Jardim das Americas, 81531-990, Curitiba, Parana (Brazil); Sade, Youssef Bacila [Department of Cell Biology, Federal University of Parana, Jardim das Americas, 81531-990, Curitiba, Parana (Brazil); Bertoni da Silveira, Rafael [Department of Biochemistry, Federal University of Sao Paulo, Sao Paulo (Brazil); Toma, Leny [Department of Biochemistry, Federal University of Sao Paulo, Sao Paulo (Brazil); Kalapothakis, Evanguedes [Department of Pharmacology, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais (Brazil); Chavez-Olortegui, Carlos [Department of Biochemistry and Immunology, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais (Brazil); Mangili, Oldemir Carlos [Department of Physiology, Federal University of Parana, Curitiba, Parana (Brazil); Gremski, Waldemiro [Department of Cell Biology, Federal University of Parana, Jardim das Americas, 81531-990, Curitiba, Parana (Brazil); Catholic University of Parana, Health and Biological Sciences Institute, Curitiba, Parana (Brazil); Dietrich, Carl Peter von [Department of Biochemistry, Federal University of Sao Paulo, Sao Paulo (Brazil); Nader, Helena B. [Department of Biochemistry, Federal University of Sao Paulo, Sao Paulo (Brazil); Sanches Veiga, Silvio [Department of Cell Biology, Federal University of Parana, Jardim das Americas, 81531-990, Curitiba, Parana (Brazil)]. E-mail: veigass@ufpr.br

2006-02-15

315

Brown spider dermonecrotic toxin directly induces nephrotoxicity.  

PubMed

Brown spider (Loxosceles genus) venom can induce dermonecrotic lesions at the bite site and systemic manifestations including fever, vomiting, convulsions, disseminated intravascular coagulation, hemolytic anemia and acute renal failure. The venom is composed of a mixture of proteins with several molecules biochemically and biologically well characterized. The mechanism by which the venom induces renal damage is unknown. By using mice exposed to Loxosceles intermedia recombinant dermonecrotic toxin (LiRecDT), we showed direct induction of renal injuries. Microscopic analysis of renal biopsies from dermonecrotic toxin-treated mice showed histological alterations including glomerular edema and tubular necrosis. Hyalinization of tubules with deposition of proteinaceous material in the tubule lumen, tubule epithelial cell vacuoles, tubular edema and epithelial cell lysis was also observed. Leukocytic infiltration was neither observed in the glomerulus nor the tubules. Renal vessels showed no sign of inflammatory response. Additionally, biochemical analyses showed such toxin-induced changes in renal function as urine alkalinization, hematuria and azotemia with elevation of blood urea nitrogen levels. Immunofluorescence with dermonecrotic toxin antibodies and confocal microscopy analysis showed deposition and direct binding of this toxin to renal intrinsic structures. By immunoblotting with a hyperimmune dermonecrotic toxin antiserum on renal lysates from toxin-treated mice, we detected a positive signal at the region of 33-35 kDa, which strengthens the idea that renal failure is directly induced by dermonecrotic toxin. Immunofluorescence reaction with dermonecrotic toxin antibodies revealed deposition and binding of this toxin directly in MDCK epithelial cells in culture. Similarly, dermonecrotic toxin treatment caused morphological alterations of MDCK cells including cytoplasmic vacuoles, blebs, evoked impaired spreading and detached cells from each other and from culture substratum. In addition, dermonecrotic toxin treatment of MDCK cells changed their viability evaluated by XTT and Neutral-Red Uptake methodologies. The present results point to brown spider dermonecrotic toxin cytotoxicity upon renal structures in vivo and renal cells in vitro and provide experimental evidence that this brown spider toxin is directly involved in nephrotoxicity evoked during Loxosceles spider venom accidents. PMID:16005484

Chaim, Olga Meiri; Sade, Youssef Bacila; da Silveira, Rafael Bertoni; Toma, Leny; Kalapothakis, Evanguedes; Chávez-Olórtegui, Carlos; Mangili, Oldemir Carlos; Gremski, Waldemiro; von Dietrich, Carl Peter; Nader, Helena B; Sanches Veiga, Silvio

2005-07-11

316

Biological methods for marine toxin detection.  

PubMed

The presence of marine toxins in seafood poses a health risk to human consumers which has prompted the regulation of the maximum content of marine toxins in seafood in the legislations of many countries. Most marine toxin groups are detected by animal bioassays worldwide. Although this method has well known ethical and technical drawbacks, it is the official detection method for all regulated phycotoxins except domoic acid. Much effort by the scientific and regulatory communities has been focused on the development of alternative techniques that enable the substitution or reduction of bioassays; some of these have recently been included in the official detection method list. During the last two decades several biological methods including use of biosensors have been adapted for detection of marine toxins. The main advances in marine toxin detection using this kind of technique are reviewed. Biological methods offer interesting possibilities for reduction of the number of biosassays and a very promising future of new developments. PMID:20458470

Vilariño, Natalia; Louzao, M Carmen; Vieytes, Mercedes R; Botana, Luis M

2010-05-12

317

Crystallization of isoelectrically homogeneous cholera toxin  

SciTech Connect

Past difficulty in growing good crystals of cholera toxin has prevented the study of the crystal structure of this important protein. The authors have determined that failure of cholera toxin to crystallize well has been due to its heterogeneity. They have now succeeded in overcoming the problem by isolating a single isoelectric variant of this oligomeric protein (one A subunit and five B subunits). Cholera toxin purified by their procedure readily forms large single crystals. The crystal form has been described previously. They have recorded data from native crystals of cholera toxin to 3.0-{angstrom} resolution with our electronic area detectors. With these data, they have found the orientation of a 5-fold symmetry axis within these crystals, perpendicular to the screw dyad of the crystal. They are now determining the crystal structure of cholera toxin by a combination of multiple heavy-atom isomorphous replacement and density modification techniques, making use of rotational 5-fold averaging of the B subunits.

Spangler, B.D.; Westbrook, E.M. (Argonne National Laboratory, IL (USA))

1989-02-07

318

Toxins and Secretion Systems of Photorhabdus luminescens  

PubMed Central

Photorhabdus luminescens is a nematode-symbiotic, gram negative, bioluminescent bacterium, belonging to the family of Enterobacteriaceae. Recent studies show the importance of this bacterium as an alternative source of insecticides, as well as an emerging human pathogen. Various toxins have been identified and characterized in this bacterium. These toxins are classified into four major groups: the toxin complexes (Tcs), the Photorhabdus insect related (Pir) proteins, the “makes caterpillars floppy” (Mcf) toxins and the Photorhabdus virulence cassettes (PVC); the mechanisms however of toxin secretion are not fully elucidated. Using bioinformatics analysis and comparison against the components of known secretion systems, multiple copies of components of all known secretion systems, except the ones composing a type IV secretion system, were identified throughout the entire genome of the bacterium. This indicates that Photorhabdus luminescens has all the necessary means for the secretion of virulence factors, thus it is capable of establishing a microbial infection.

Rodou, Athina; Ankrah, Dennis O.; Stathopoulos, Christos

2010-01-01

319

Peptide antagonists of superantigen toxins.  

PubMed

Superantigens produced by Staphylococcus aureus and Streptococcus pyogenes are among the most lethal of toxins. Toxins in this large family trigger an excessive cellular immune response leading to toxic shock. Superantigens are secreted by the bacteria as diverse natural mixtures, a complexity that demands development of broad-spectrum countermeasures. We used a rational approach to design short peptides with homology to various domains in a typical superantigen (staphylococcal enterotoxin B) and screened each peptide for its ability to antagonize, in human peripheral blood mononuclear cells, superantigen-mediated induction of the genes encoding T helper 1 cytokines that mediate shock: interleukin-2, interferon-gamma and tumor necrosis factor. A dodecamer peptide proved a potent antagonist against widely different superantigens. This peptide protected mice from killing by superantigens and it was able to rescue mice undergoing toxic shock. The antagonist peptide shows homology to a beta-strand-hinge-alpha-helix domain that is structurally conserved among superantigens, yet currently of unknown function and remote from the binding sites for the known ligands essential for T cell activation, the major histocompatibility complex class II molecule and T cell receptor. The antagonist activity of this peptide thus identifies a novel domain in superantigens that is critical for their toxic action. The antagonist peptide provides a new tool for understanding the mechanism of excessive human immune response activation by superantigens that occurs during toxic shock and for identification of a novel target ligand that may interact with this superantigen domain. PMID:15209162

Kaempfer, Raymond

2004-01-01

320

Clinical relevance of botulinum toxin immunogenicity.  

PubMed

Botulinum toxin type A is a 150?kD protein produced by Clostridium botulinum, which exists in a complex with up to six additional proteins. The ability of botulinum toxin to inhibit acetylcholine release at the neuromuscular junction has been exploited for use in medical conditions characterized by muscle hyperactivity. As such, botulinum toxin is widely recommended by international treatment guidelines for movement disorders and it has a plethora of other clinical and cosmetic indications. The chronic nature of these conditions requires repeated injections of botulinum toxin, usually every few months. Multiple injections can lead to secondary treatment failure in some patients that may be associated with the production of neutralizing antibodies directed specifically against the neurotoxin. However, the presence of such antibodies does not always render patients non-responsive. The reported prevalence of immunoresistance varies greatly, depending on factors such as study design and treated indication. This review presents what is currently known about the immunogenicity of botulinum toxin and how this impacts upon patient non-response to treatment. The complexing proteins may act as adjuvants and stimulate the immune response. Their role and that of neutralizing and non-neutralizing antibodies in the response to botulinum toxin is discussed, together with an assessment of current neutralizing antibody measurement techniques. Botulinum toxin preparations with different compositions and excipients have been developed. The major commercially available preparations of botulinum toxin are Botox (onabotulinumtoxin A; Allergan, Inc., Ireland), Dysport (abobotulinumtoxin A; Ipsen Ltd, UK), and Xeomin (incobotulinumtoxin A; botulinum toxin type A [150?kD], free from complexing proteins; NT 201; Merz Pharmaceuticals GmbH, Germany). The new preparations of botulinum toxin aim to minimize the risk of immunoresistance in patients being treated for chronic clinical conditions. PMID:22385408

Benecke, Reiner

2012-04-01

321

Relationship between the lability of sediment-bound metals (Cd, Cu, Zn) and their bioaccumulation in benthic invertebrates  

NASA Astrophysics Data System (ADS)

The present study has investigated metal contamination at nine sites (10 sampling stations) from the English Channel to the Mediterranean Sea, including low level and highly contaminated sediments. Both total and labile concentrations of metals were determined in superficial sediments. The influence of different pHs was tested and metal lability at pHs encountered in the gut of invertebrates (the ragworm Nereis diversicolor, the blue mussel Mytilus edulis, the Japanese oyster Crassostrea gigas) was compared with the distribution of metals in various operationally defined geochemical fractions. Cd showed the highest lability and Cu the lowest, whereas Zn lability was intermediate. Metal concentrations were determined in bivalves at six sites and in worms at three sites. Cd in living organisms and labile Cd in sediments increased in proportion over the gradient of contamination. This relationship did not always hold for Cu and Zn and these exceptions are discussed. Even if sediments are not the only source of metal contamination in marine invertebrates, the procedure proposed here to assess metal bioavailability by remobilising sediment-bound metals at physiological pHs, seems a significant improvement of the existing methodologies of risk assessment.

Amiard, J.-C.; Geffard, A.; Amiard-Triquet, C.; Crouzet, C.

2007-04-01

322

Clostridium perfringens Delta Toxin Is Sequence Related to Beta Toxin, NetB, and Staphylococcus Pore-Forming Toxins, but Shows Functional Differences  

PubMed Central

Clostridium perfringens produces numerous toxins, which are responsible for severe diseases in man and animals. Delta toxin is one of the three hemolysins released by a number of C. perfringens type C and possibly type B strains. Delta toxin was characterized to be cytotoxic for cells expressing the ganglioside GM2 in their membrane. Here we report the genetic characterization of Delta toxin and its pore forming activity in lipid bilayers. Delta toxin consists of 318 amino acids, its 28 N-terminal amino acids corresponding to a signal peptide. The secreted Delta toxin (290 amino acids; 32619 Da) is a basic protein (pI 9.1) which shows a significant homology with C. perfringens Beta toxin (43% identity), with C. perfringens NetB (40% identity) and, to a lesser extent, with Staphylococcus aureus alpha toxin and leukotoxins. Recombinant Delta toxin showed a preference for binding to GM2, in contrast to Beta toxin, which did not bind to gangliosides. It is hemolytic for sheep red blood cells and cytotoxic for HeLa cells. In artificial diphytanoyl phosphatidylcholine membranes, Delta and Beta toxin formed channels. Conductance of the channels formed by Delta toxin, with a value of about 100 pS to more than 1 nS in 1 M KCl and a membrane potential of 20 mV, was higher than those formed by Beta toxin and their distribution was broader. The results of zero-current membrane potential measurements and single channel experiments suggest that Delta toxin forms slightly anion-selective channels, whereas the Beta toxin channels showed a preference for cations under the same conditions. C. perfringens Delta toxin shows a significant sequence homolgy with C. perfringens Beta and NetB toxins, as well as with S. aureus alpha hemolysin and leukotoxins, but exhibits different channel properties in lipid bilayers. In contrast to Beta toxin, Delta toxin recognizes GM2 as receptor and forms anion-selective channels.

Manich, Maria; Knapp, Oliver; Gibert, Maryse; Maier, Elke; Jolivet-Reynaud, Colette; Geny, Blandine; Benz, Roland; Popoff, Michel R.

2008-01-01

323

Chemical trapping of labile aldehyde intermediates in the metabolism of propranolol and oxprenolol.  

PubMed

Propranolol is N-dealkylated to N-desisopropylpropranolol (DIP) by microsomal enzymes. DIP was shown in this study to be rapidly deaminated by monoamine oxidase (MAO). Thus, incubation of DIP (10(-4) M) with rat liver mitochondria for 90 min demonstrated 74.8 +/- 4.1% metabolism which was almost completely blocked by the MAO inhibitor pargyline (10(-5) M). The end products of this deamination were 3-(alpha-naphthoxy)-1,2-propylene glycol (Glycol) and 3-(alpha-naphthoxy)lactic acid (NLA). In the presence of excess NADH the Glycol was the major product whereas NLA was the major product in the presence of excess NAD+. The intermediate aldehyde in this deamination reaction, 3-(alpha-naphthoxy)-2-hydroxypropanal (Ald), was extremely labile and decomposed quantitatively to alpha-naphthol when removed from the incubates. However, the addition of methoxyamine hydrochloride directly to the incubates made it possible to chemically trap the intact Ald as an O-methyloxime and prove its structure by gas chromatography-mass spectrometry. The deamination of the primary amine of oxprenolol also gave rise to a labile aldehyde which could be trapped and identified as its O-methyloxime. PMID:7335950

Goldszer, F; Tindell, G L; Walle, U K; Walle, T

1981-11-01

324

Initiation, labile, and stabilization phases of experience-dependent plasticity at neocortical synapses.  

PubMed

Alteration of sensory input can change the strength of neocortical synapses. Selective activation of a subset of whiskers is sufficient to potentiate layer 4-layer 2/3 excitatory synapses in the mouse somatosensory (barrel) cortex, a process that is NMDAR dependent. By analyzing the time course of sensory-induced synaptic change, we have identified three distinct phases for synaptic strengthening in vivo. After an early, NMDAR-dependent phase where selective whisker activation is rapidly translated into increased synaptic strength, we identify a second phase where this potentiation is profoundly reduced by an input-specific, NMDAR-dependent depression. This labile phase is transient, lasting only a few hours, and may require ongoing sensory input for synaptic weakening. Residual synaptic strength is maintained in a third phase, the stabilization phase, which requires mGluR5 signaling. Identification of these three phases will facilitate a molecular dissection of the pathways that regulate synaptic lability and stabilization, and suggest potential approaches to modulate learning. PMID:23658185

Wen, Jing A; DeBlois, Mark C; Barth, Alison L

2013-05-01

325

Two clusters of GABAergic ellipsoid body neurons modulate olfactory labile memory in Drosophila.  

PubMed

In Drosophila, aversive olfactory memory is believed to be stored in a prominent brain structure, the mushroom body (MB), and two pairs of MB intrinsic neurons, the dorsal paired medial (DPM) and the anterior paired lateral (APL) neurons, are found to regulate the consolidation of middle-term memory (MTM). Here we report that another prominent brain structure, the ellipsoid body (EB), is also involved in the modulation of olfactory MTM. Activating EB R2/R4m neurons does not affect the learning index, but specifically eliminates anesthesia-sensitive memory (ASM), the labile component of olfactory MTM. We further demonstrate that approximately two-thirds of these EB neurons are GABAergic and are responsible for the suppression of ASM. Using GRASP (GFP reconstitution across synaptic partners), we reveal potential synaptic connections between the EB and MB in regions covering both the presynaptic and postsynaptic sites of EB neurons, suggesting the presence of bidirectional connections between these two important brain structures. These findings suggest the existence of direct connections between the MB and EB, and provide new insights into the neural circuit basis for olfactory labile memory in Drosophila. PMID:23516283

Zhang, Zhiping; Li, Xiaoting; Guo, Jing; Li, Yan; Guo, Aike

2013-03-20

326

Heterotrophic activity and biodegradation of labile and refractory compounds by groundwater and stream microbial populations.  

PubMed Central

The bacteriology and heterotrophic activity of a stream and of nearby groundwater in Marmot Basin, Alberta, Canada, were studied. Acridine orange direct counts indicated that bacterial populations in the groundwater were greater than in the stream. Bacteria that were isolated from the groundwater were similar to species associated with soils. Utilization of labile dissolved organic material as measured by the heterotrophic potential technique with glutamic acid, phenylalanine, and glycolic acid as substrates was generally greater in the groundwater. In addition, specific activity indices for the populations suggested greater metabolic activity per bacterium in the groundwater. 14C-labeled lignocellulose, preferentially labeled in the lignin fraction by feeding Picea engelmannii [14C]phenylalanine, was mineralized by microorganisms in both the groundwater and the stream, but no more than 4% of the added radioactivity was lost as 14CO2 within 960 h. Up to 20% of [3'-14C]cinnamic acid was mineralized by microorganisms in both environments within 500 h. Both microbial populations appear to influence the levels of labile and recalcitrant dissolved organic material in mountain streams.

Ladd, T I; Ventullo, R M; Wallis, P M; Costerton, J W

1982-01-01

327

Effects of lability of metal complex on free ion measurement using DMT.  

PubMed

Very low concentrations of free metal ion in natural samples can be measured using the Donnan membrane technique (DMT) based on ion transport kinetics. In this paper, the possible effects of slow dissociation of metal complexes on the interpretation of kinetic DMT are investigated both theoretically and experimentally. The expressions of the lability parameter, Lgrangian , were derived for DMT. Analysis of new experimental studies using synthetic solution containing NTA as the ligand and Cu(2+) ions shows that when the ionic strength is low (labile species measured using other dynamic sensors (DGT, GIME) in several freshwaters, it is concluded that in most waters ion transport in DMT is controlled by diffusion in the membrane. Only in very soft waters (<0.7 mM Ca+Mg), the dissociation rate of natural metal complex may influence ion transport in DMT. In this case, neglecting this effect may lead to an underestimation of the free metal ion concentration measured. PMID:20163175

Weng, Liping; Van Riemsdijk, Willem H; Temminghoff, Erwin J M

2010-04-01

328

Evaluation of insulin-like growth factor acid-labile subunit as a potential biomarker of effect for deoxynivalenol-induced proinflammatory cytokine expression.  

PubMed

Consumption of the trichothecene deoxynivalenol (DON) suppresses growth in experimental animals - an adverse effect that was used to establish the tolerable daily intake for this toxin. DON ingestion has been recently found to suppress plasma insulin-like growth factor acid-labile subunit (IGFALS), a protein essential for growth. Studies were conducted to explore the feasibility of using plasma IGFALS as a biomarker of effect for DON. In the first study, weanling mice were fed 0, 1, 2.5, 5 and 10 ppm DON and weight and plasma IGFALS determined at intervals over 9 wk. Reduced body weight gains were detectable beginning at wk 5 in the 10 ppm dose and wk 7 at the 5 ppm dose. Plasma IGFALS was significantly depressed at wk 5 in the 5 and 10 ppm groups at wk 9 in the 10 ppm group. Depressed IGFALS significantly correlated with reduced body weight at wk 5 and 9. Benchmark dose modeling revealed the BMDL and BMD for plasma IGFALS reduction were 1.1 and 3.0 ppm DON and for weight reduction were 2.1 and 4.5 ppm DON. In the second study, it was demonstrated that mice fed 15 ppm DON diet had significantly less plasma IGFALS than mice fed identical amounts of control diet. Thus DON's influence on IGFALS likely reflects the combined effects of reduced food intake as well as its physiological action involving suppressors of cytokine signaling. Taken together, these findings suggest that plasma IGFALS might be a useful biomarker for DON's adverse effects on growth. PMID:23298694

Flannery, Brenna M; Amuzie, Chidozie J; Pestka, James J

2013-01-05

329

Specific roles of alpha-toxin and beta-toxin during Staphylococcus aureus corneal infection.  

PubMed Central

Staphylococcus aureus corneal infection results in extensive inflammation and tissue damage. Our previous studies of bacterial mutants have demonstrated a role for alpha-toxin in corneal virulence. This study analyzes, by genetic rescue experiments, the virulence of mutants affecting alpha-toxin and beta-toxin activity and demonstrates the ocular toxicity of these purified staphylococcal proteins. Three types of isogenic mutants were analyzed: (i) mutants specifically deficient in alpha-toxin (Hla) or beta-toxin (Hlb), (ii) a mutant deficient in both Hla and Hlb, and (iii) a regulatory mutant, deficient in the accessory gene regulator (agr), that produces reduced quantities of multiple exoproteins, including alpha- and beta-toxins. Plasmids coding for Hla and Hlb (pDU1212 and pCU1hlb, respectively) were used to restore toxin activity to mutants specifically deficient in each of these toxins. Either corneas were injected intrastromally with logarithmic-phase S. aureus or purified alpha- or beta-toxins were administered to normal eyes. Ocular pathology was evaluated by slit lamp examination and myeloperoxidase activity of infiltrating polymorphonuclear leukocytes. Corneal homogenates were cultured to determine the CFU per cornea. Eyes infected with the wild-type strain developed significantly greater corneal damage than eyes infected with Agr-, Hlb-, or Hla- strains. Epithelial erosions produced by parent strains were not produced by Agr- or Hla- strains. Hlb+ strains, unlike Hlb- strains, caused scleral edema. Plasmid pDU1212 restored corneal virulence to strain DU1090 (Hla-), and plasmid pCU1hlb restored corneal virulence to strain DU5719 (Hlb-). Application of purified alpha-toxin produced corneal epithelial erosions and iritis, while application of beta-toxin caused scleral inflammation. These studies confirm the role of alpha-toxin as a major virulence factor during S. aureus keratitis and implicate beta-toxin, a mediator of edema, as a lesser contributor to ocular damage.

O'Callaghan, R J; Callegan, M C; Moreau, J M; Green, L C; Foster, T J; Hartford, O M; Engel, L S; Hill, J M

1997-01-01

330

Detection of a cytolytic toxin in the venom of the stonefish (Synanceia trachynis).  

PubMed

The venom of the stonefish, Synanceia trachynis, contains a cytolytic toxin which is antigenic and ammonium sulfate-precipitable, and has a pI of ca 5.7 and an Mr of ca 158,000. The toxin is a potent but narrow-spectrum cytolysin which is lytic in vitro for rabbit, dog, rat, and guinea pig erythrocytes, in that order, but is largely or completely inactive against sheep, cow, human, monkey, mouse, goat, horse, burro and cat erythrocytes. Fractionation of the venom by molecular sieve fast protein liquid chromatography and isoelectric focusing did not separate the haemolytic activity from the venom's lethal and vascular permeability-increasing activities. Also, the three activities were destroyed by heat, proteases, Congo red, potassium permanganate and stonefish antivenoms. The results suggest that the haemolytic, lethal and vascular permeability-increasing activities of stonefish venom are properties of the same molecule, a previously unrecognized, membrane-damaging protein toxin. PMID:1926174

Kreger, A S

1991-01-01

331

Effect of heat-induced aggregation on the IgE binding of patatin (Sol t 1) is dominated by other potato proteins  

Microsoft Academic Search

The interaction of the major potato allergen patatin, Sol t 1, with IgE was investigated on a quantitative level as a function of heat treatment at different temperatures. On the basis of a number of publications, potato is considered to be a heat-labile allergen, but the molecular explanation for this behavior was not given. In this work, heat treatment of

Stef J. Koppelman; Koningsveld van G. A; André C. Knulst; Harry Gruppen; Ingrid G. A. J. Pigmans; Harmen H. J. de Jongh

2002-01-01

332

Painful toxins acting at TRPV1.  

PubMed

Many plant and animal toxins cause aversive behaviors in animals due to their pungent or unpleasant taste or because they cause other unpleasant senstations like pain. This article reviews the current state of knowledge of toxins that act at the TRPV1 ion channel, which is expressed in primary sensory neurons, is activated by multiple painful stimuli and is thought to be a key pain sensor and integrator. The recent finding that painful peptide "vanillotoxin" components of tarantula toxin activate the TRPV1 ion channel to cause pain led us to survey what is known about toxins that act at this receptor. Toxins from plants, spiders and jellyfish are considered. Where possible, structural information about sites of interaction is considered in relation to toxin-binding sites on the Kv ion channel, for which more structural information exists. We discuss a developing model where toxin agonists such as resiniferatoxin and vanillotoxins are proposed to interact with a region of TRPV1 that is homologous to the "voltage sensor" in the Kv1.2 ion channel, to open the channel and activate primary sensory nerves, causing pain. PMID:18061640

Cromer, Brett A; McIntyre, Peter

2007-10-26

333

Insecticidal Toxin Complex Proteins from Xenorhabdus nematophilus  

PubMed Central

Toxin complexes from Xenorhabdus and Photorhabdus spp. bacteria represent novel insecticidal proteins. We purified a native toxin complex (toxin complex 1) from Xenorhabdus nematophilus. The toxin complex is composed of three different proteins, XptA2, XptB1, and XptC1, representing products from class A, B, and C toxin complex genes, respectively. We showed that recombinant XptA2 and co-produced recombinant XptB1 and XptC1 bind together with a 4:1:1 stoichiometry. XptA2 forms a tetramer of ?1,120 kDa that bound to solubilized insect brush border membranes and induced pore formation in black lipid membranes. Co-expressed XptB1 and XptC1 form a tight 1:1 binary complex where XptC1 is C-terminally truncated, resulting in a 77-kDa protein. The ?30-kDa C-terminally cleaved portion of XptC1 apparently only loosely associates with this binary complex. XptA2 had only modest oral toxicity against lepidopteran insects but as a complex with co-produced XptB1 and XptC1 had high levels of insecticidal activity. Addition of co-expressed class B (TcdB2) and class C (TccC3) proteins from Photorhabdus luminescens to the Xenorhabdus XptA2 protein resulted in formation of a hybrid toxin complex protein with the same 4:1:1 stoichiometry as the native Xenorhabdus toxin complex 1. This hybrid toxin complex, like the native toxin complex, was highly active against insects.

Sheets, Joel J.; Hey, Tim D.; Fencil, Kristin J.; Burton, Stephanie L.; Ni, Weiting; Lang, Alexander E.; Benz, Roland; Aktories, Klaus

2011-01-01

334

Labile trace elements in basaltic achondrites: Can they distinguish between meteorites from the Moon, Mars, and V-type asteroids?  

NASA Astrophysics Data System (ADS)

We report data for 14 mainly labile trace elements (Ag, Au, Bi, Cd, Cs, Ga, In, Rb, Sb, Se, Te, Tl, U, and Zn) in eight whole-rock lunar meteorites (Asuka [A-] 881757, Dar al Gani [DaG] 262, Elephant Moraine [EET] 87521, Queen Alexandra Range [QUE] 93069, QUE 94269, QUE 94281, Yamato [Y-] 793169, and Y-981031), and Martian meteorite (DaG 476) and incorporate these into a comparative study of basaltic meteorites from the Moon, Mars, and V-type asteroids. Multivariate cluster analysis of data for these elements in 14 lunar, 13 Martian, and 34 howardite, eucrite, and diogenite (HED) meteorites demonstrate that materials from these three parents are distinguishable using these markers of late, low-temperature episodes. This distinguishability is essentially as complete as that based on markers of high-temperature igneous processes. Concentrations of these elements in 14 lunar meteorites are essentially lognormally distributed and generally more homogeneous than in Martian and HED meteorites. Mean siderophile and labile element concentrations in the 14 lunar meteorites indicate the presence of a CI-equivalent micrometeorite admixture of 2.6% When only feldspathic samples are considered, our data show a slightly higher value of 3.4% consistent with an increasing micrometeorite content in regolith samples of higher maturity. Concentrations of labile elements in the 8 feldspathic samples hint at the presence of a fractionated highly labile element component, possibly volcanic in origin, at a level comparable to the micrometeorite component. Apparently, the process(es) that contributed to establishing lunar meteorite siderophile and labile trace element contents occurred in a system open to highly labile element transport.

Wolf, Stephen F.; Wang, Ming-Sheng; Lipschutz, Michael E.

2009-06-01

335

Paradichlorobenzene (toxin)-induced leucoencephalopathy.  

PubMed

A 40-year-old woman with a history of polysubstance abuse, hypertension, depression and anxiety with panic attacks admitted to the emergency room at the request of her primary physician owing to progressive decline in her mental status associated with anorexia and generalised pruritic skin rashes. Initial outpatient workup and that during two previous hospital admissions including thyroid function and syphilis tests, urine toxicology screen and brain imaging studies were unremarkable. Repeat MRI of the brain during her third hospital admission showed diffuse periventricular and white matter disease. This prompted further questioning of family members which revealed chronic ingestion of mothballs and toilet cakes containing paradichlorobenzene in the patient leading to toxin-induced leucoencephalopathy consistent with her neurological symptoms of altered mental status, ataxic gait, cogwheel rigidity in the arms and characteristic skin rashes. Subsequently, a feeding tube was placed to address her worsening nutritional status and she was discharged home in a stable state. PMID:23608871

Buckman, Francis

2013-04-22

336

[Pharmacology of botulinum toxin drugs].  

PubMed

Botulinum toxin (BT) is used with remarkable success to treat various disorders caused by muscle hyperactivities or exocrine gland overactivity. Its use for treatment of non-muscular pain conditions is currently being explored. In Germany, BT type A is available as Botox®, Dysport® and Xeomin®, BT type B as NeuroBloc®. In aesthetic medicine they are called Vistabel®, Azzalure® and Bocouture®. Numerous other BT drugs are used worldwide. Often, their origin is dubious. BT drugs consist of botulinum neurotoxin, complexing proteins and adjuvants. Their manufacturing process is highly complex. BT drugs vary in many aspects. By no means are they generics. Clinically relevant differences include their potency labeling, antigenicity, presence of complexing proteins, storage conditions, pH value of the reconstituted drug and pharmaceutical preparation. PMID:22669438

Dressler, D

2012-06-01

337

Toxin production by Bacillus pumilus.  

PubMed

Two strains of Bacillus pumilus (M11 and M38) and one strain each of Bacillus cereus (M27), Bacillus subtilis (M67), and Enterobacter agglomerans (M14) were identified from the air of Lancashire cotton mills. These strains were tested for cytopathic effects in Vero cells; B pumilus and B cereus strains were also examined for haemolytic activity, lecithinase production, and proteolytic action on casein. Rounding and clumping of the Vero cells occurred after the addition of supernatants prepared from B pumilus and B cereus strains; finger-like projections developed in the cells treated with B pumilus supernatants. Minimal effects occurred with B subtilis and E agglomerans. After two hours of exposure B pumilus (M11) produced the greatest effect, but treatment with trypan blue showed that most cells exposed to the M11 strain were still alive after 96 hours of exposure; those exposed to the supernatant prepared from the M38 strain of B pumilus were dead. Sheep erythrocytes were lysed more rapidly by B cereus than by B pumilus, B cereus (strongly positive) had a greater effect on lecithin than either of the B pumilus strains (M38 weakly positive, M11 negative). All hydrolised casein but the effect was more rapid with one of the B pumilus (M11) strains. It is concluded that not only do the toxins of B pumilus differ from those of B cereus, but there are also differences between the toxins produced by the two strains of B pumilus (M11 and M38). PMID:2066422

Hoult, B; Tuxford, A F

1991-06-01

338

Structure and action of heteronemertine polypeptide toxins. Primary structure of Cerebratulus lacteus toxin B-IV.  

PubMed

The amino acid sequence of Cerebratulus toxin B-IV, a crustacean-selective axonal toxin occurring in the marine worm C. lacteus, was determined by Edman degradation of the tryptic and staphylococcal protease peptides obtained from the reduced, carboxymethylated toxin. All four of the anticipated maleylated tryptic peptides, ranging in size from 8 to 23 residues, and three staphylococcal protease peptides, ranging from 9 to 35 residues, were isolated in pure form by gel filtration followed by either ion exchange chromatography or preparative paper electrophoresis. The order of the maleylated tryptic peptides was based upon the sequences of the staphylococcal protease peptides. As might be expected, toxin B-IV displays no homology with the elapid nicotinic receptor toxins. In addition, toxin B-IV is structurally unrelated to a group of scorpion neurotoxins which, like B-IV, affect action potential generating mechanisms. PMID:972152

Blumenthal, K M; Kem, W R

1976-10-10

339

Enzyme-linked immunosorbent assay for Clostridium difficile toxin A.  

PubMed Central

Antibodies against Clostridium difficile toxin A were purified by affinity chromatography from antiserum prepared against crude C. difficile toxin preparations. The affinity-purified antibody preparation was free of detectable amounts of antibodies to other C. difficile antigens, as demonstrated by crossed immunoelectrophoresis, and specifically neutralized the cytotoxicity of toxin A. An indirect enzyme-linked immunosorbent assay (ELISA) was subsequently developed using the antibody preparation for the specific detection of toxin A. The ELISA, which could detect 1 ng (5 ng/ml) of toxin A, was used to quantitate the toxin in the culture supernatant fluids of strains of C. difficile. The ELISA values for toxin A closely correlated with the toxin A and B cytotoxic titers of the supernatant fluids. In addition, toxin A was detected by ELISA in human fecal specimens from persons with antibiotic-associated colitis, demonstrating that this toxin is produced during C. difficile colitis. Images

Lyerly, D M; Sullivan, N M; Wilkins, T D

1983-01-01

340

Tetanus toxin blocks the neuromuscular transmission in vitro like botulinum a toxin  

Microsoft Academic Search

1.The blocking effect of tetanus toxin on the neuromuscular junction of the mouse phrenic nervehemidiaphragm preparation exposed to the toxin (0.05–20 µg\\/ml) in the organ bath was studied and compared with the action of botulinum A toxin.2.The time course of the paralysis of the diaphragm could be divided into a latent and a manifest period. Still during the latent period

E. Habermann; F. Dreyer; H. Bigalke

1980-01-01

341

lnhibition of Maize Histone Deacetylases by HC Toxin, the Host-Selective Toxin of Cochliobolus carbonum  

Microsoft Academic Search

HC toxin, the host-selective toxin of the maize pathogen Cochliobolus carbonum, inhibited maize histone deacetylase (HD) at 2 pM. Chlamydocin, a related cyclic tetrapeptide, also inhibited HD activity. The toxins did not affect histone acetyltransferases. After partia1 purification of histone deacetylases HD1-A, HD1-B, and HD2 from germinating maize embryos, we demonstrated that the different enzymes were similarly inhibited by the

Gerald Broschla; Jonathan D. Walton

342

Botulism Due to Clostridium baratii Type F Toxin  

Microsoft Academic Search

Botulism results from consumption of preformed toxin or in vivo toxin elaboration in wounds or intestine. Of U.S. food-borne botulism cases since 1950, the majority were due to toxin A, but a significant number of suspect cases were never confirmed by culture or toxin detection. We report here a possible case of food-borne botulism attributed to toxin F production by

Sydney M. Harvey; Joan Sturgeon; David E. Dassey

2002-01-01

343

Chromatographic analysis of Fusarium toxins in grain samples  

Microsoft Academic Search

A method for the analysis of zearalenone, T-2 toxin, neosolaniol and HT-2 toxin from the grains of barley, wheat and oats has been developed. Toxins are extracted with ethyl acetate, purified on a kieselgel TLC-plate and analysed on a HPTLC-plate. The limits of detection are 0.2 mg\\/kg for zearalenone and T-2 toxin and 5 mg\\/kg for neosolaniol and HT-2 toxin.

T. Ilus; M.-L. Niku-Paavola; T.-M. Enari

1981-01-01

344

The Interactions of Human Neutrophils with Shiga Toxins and Related Plant Toxins: Danger or Safety?  

PubMed Central

Shiga toxins and ricin are well characterized similar toxins belonging to quite different biological kingdoms. Plant and bacteria have evolved the ability to produce these powerful toxins in parallel, while humans have evolved a defense system that recognizes molecular patterns common to foreign molecules through specific receptors expressed on the surface of the main actors of innate immunity, namely monocytes and neutrophils. The interactions between these toxins and neutrophils have been widely described and have stimulated intense debate. This paper is aimed at reviewing the topic, focusing particularly on implications for the pathogenesis and diagnosis of hemolytic uremic syndrome.

Brigotti, Maurizio

2012-01-01

345

Dinoflagellate Toxins Responsible for Ciguatera Poisoning.  

National Technical Information Service (NTIS)

Ciguatera is a syndrome occuring in humans who have become intoxicated from eating poison fish. Fish spontaneously accumulate the toxin through the food chain or directly from eating toxic dinoflagellates. Previous research points to the presence of multi...

D. M. Miller

1988-01-01

346

Mechanism of Action of Tetanus Toxin.  

National Technical Information Service (NTIS)

The mechanism by which tetanus toxin (TT) inhibits the release of neurotransmitters from neurons is unknown. Since secretion of lysosomal contents from monocytes/macrophages (MOs) appears to be similar to neurosecretion, the authors examined the effects o...

M. S. Klempner

1986-01-01

347

Botulinum Toxin Type A Product Approval Information ...  

Center for Drug Evaluation (CDER)

... are Developed and Approved. Types of Applications. ... Proper name: Botulinum Toxin Type A Tradename ... corrugator and/or procerus muscle activity in ... More results from www.fda.gov/drugs/developmentapprovalprocess/howdrugsaredevelopedandapproved

348

Mechanism of Action of Tetanus Toxin.  

National Technical Information Service (NTIS)

The authors examined an in vivo system to explore whether protein kinase C (PKC) activity is diminished when animals become intoxicated with tetanus toxin (TT). Homogenates of brain and spinal cord from mice manifesting generalized tetanus after receiving...

M. S. Klempner

1988-01-01

349

Botulinum Toxin Type A, BOTOX Cosmetic, Allergan  

Center for Drug Evaluation (CDER)

Text Version... Allergan, Inc. to use Botulinurn Toxin Type A (BOTOX COSMETIC) for treatment of glabellar facial lines. Background Allergan's ... More results from www.fda.gov/downloads/drugs/developmentapprovalprocess

350

[Treatment of wrinkles with botulinum toxin].  

PubMed

The use of botulinum toxin A for the treatment of wrinkles is increasing. Botulinum toxin A inhibits exocytosis of acetylcholine from 3 to 12 months, depending on the target tissue. Low-dose botulinum toxin A is used to smooth hyperkinetic facial lines. This is especially successful in the upper facial parts, since the target muscles (procerus, corrugator supracilii, frontalis, orbicularis oculi) all directly overlie the osseous structures of the face. This is not the case for the lower facial parts, and more side effects are encountered when treating, for example, wrinkles around the mouth. Contraindications to the use of botulinum toxin A are diseases affecting neuromuscular signal transduction, allergic reactions to components of the solution, therapy with aminoglycosides or acetylsalicylic acid prior to treatment, infections in the planned treatment area, and pregnancy and lactation. Alternative and complementary treatments include erbium-YAG or CO2 laser, as well as augmentation and surgical plastic procedures. PMID:17823803

Lanzl, I; Merté, R-L

2007-09-01

351

Radioimmunoassay T-2 toxin in biological fluids  

SciTech Connect

A simple radioimmunoassay (RIA) for detection of T-2 toxin in biological fluids was developed. The method, which involves a Sep-Pak C/sub 18/ reverse phase column cleanup step before RIA, can detect 0.5 ppb T-2 toxin in serum and 2.5 ppb T-2 toxin in urine and milk. Recoveries for toxin added to serum and urine or milk samples were 87-106% in the 0.5-20 ppb range and 88-117% in the 2.5-20 ppb range, respectively. If samples were not cleaned up, false positive results prevented positive detection at concentrations less than 2.5 ppb in urine and milk.

Lee, S.; Chu, F.S.

1981-05-01

352

Biosecurity of Select Agents and Toxins.  

National Technical Information Service (NTIS)

The concept of biosecurity as it pertains to Biological Select Agents and Toxins in American biomedical research institutions is explored in some depth. Posing the research question 'How can specific public biomedical research universities securely use an...

T. E. Engells

2005-01-01

353

Dinoflagellate Toxins Responsible for Ciguatera Food Poisoning.  

National Technical Information Service (NTIS)

Ciguatera is a syndrome occurring in humans who have become intoxicated from eating poison fish. Fish spontaneously accumulate the toxin through the food chain or directly from eating toxic dinoflagellates. Previous research points to the presence of mult...

D. L. Miller

1987-01-01

354

Cytolethal distending toxin and use thereof  

US Patent & Trademark Office Database

This invention relates to immunotoxins and their use. Specifically, the invention relates to compositions comprising Cdt toxins or their inhibitors and their use in methods for treating infectious and proliferative diseases.

2012-02-07

355

ADP-ribosylation by cholera toxin: functional analysis of a cellular system that stimulates the enzymic activity of cholera toxin fragment A/sub 1/  

SciTech Connect

The authors have clarified relationships between cholera toxin, cholera toxin substrates, a membrane protein S that is required for toxin activity, and a soluble protein CF that is needed for the function of S. The toxin has little intrinsic ability to catalyze ADP-ribosylations unless it encounters the active form of the S protein, which is S liganded to GTP or to a GTP analogue. In the presence of CF, S x GTP forms readily, though reversibly, but a more permanent active species, S-guanosine 5'-O-(3-thiotriphosphate) (S x GTP..gamma..S), forms over a period of 10-15 min at 37/sup 0/C. Both guanosine 5'-O-(2-thiodiphosphate) and GTP block this quasi-permanent activation. Some S x GTP..gamma..S forms in membranes that are exposed to CF alone and then to GTP..gamma..S, with a wash in between, and it is possible that CF facilitates a G nucleotide exchange. S x GTP..gamma..S dissolved by nonionic detergents persists in solution and can be used to support the ADP-ribosylation of nucleotide-free substrates. In this circumstance, added guanyl nucleotides have no further effect. This active form of S is unstable, especially when heated, but the thermal inactivation above 45/sup 0/C is decreased by GTP..gamma..S. Active S is required equally for the ADP-ribosylation of all of cholera toxin's protein substrates, regardless of whether they bind GTP or not. They suggest that active S interacts directly with the enzymic A/sub 1/ fragments of cholera toxin and not with any toxin substrate. The activation and activity of S are independent of the state, or even the presence, of adenylate cyclase and seem to be involved with the cyclase system only via cholera toxin. S is apparently not related by function to certain other GTP binding proteins, including p21/sup ras/, and appears to be a new GTP binding protein whose physiologic role remains to be identified.

Gill, D.M.; Coburn, J.

1987-10-06

356

Lability of DOC transported by Alaskan rivers to the Arctic Ocean  

NASA Astrophysics Data System (ADS)

Arctic rivers transport huge quantities of dissolved organic carbon (DOC) to the Arctic Ocean. The prevailing paradigm is that DOC in arctic rivers is refractory and therefore of little significance for the biogeochemistry of the Arctic Ocean. We show that there is substantial seasonal variability in the lability of DOC transported by Alaskan rivers to the Arctic Ocean: little DOC is lost during incubations of samples collected during summer, but substantial losses (20-40%) occur during incubations of samples collected during the spring freshet when the majority of the annual DOC flux occurs. We speculate that restricting sampling to summer may have biased past studies. If so, then fluvial inputs of DOC to the Arctic Ocean may have a much larger influence on coastal ocean biogeochemistry than previously realized, and reconsideration of the role of terrigenous DOC on carbon, microbial, and food-web dynamics on the arctic shelf will be warranted.

Holmes, Robert M.; McClelland, James W.; Raymond, Peter A.; Frazer, Breton B.; Peterson, Bruce J.; Stieglitz, Marc

2008-02-01

357

Phosphorus containing mixed anhydrides--their preparation, labile behaviour and potential routes to their stabilisation.  

PubMed

Simple mixed anhydrides are known to pose synthetic difficulties relating to their thermal lability and ways to stabilise such mixed anhydride systems by relying on either electronic or steric effects were therefore explored. Thus, a series of acyloxyphosphines and acylphosphites derived from either propanoic acid or phenylacetic acid were prepared and their in solution stability assessed. These compounds were, where stability allowed, fully characterised using standard analytical techniques. NMR studies, in particular, unearthed interesting coupling behaviour for a number of the acyloxyphosphines and acylphosphites as well as their rearrangement products which could be linked to their chiral nature. Furthermore, the crystal structures for three of the prepared mixed anhydrides were determined using X-ray crystallography and are reported herein. PMID:22466313

Coetzee, Jacorien; Eastham, Graham R; Slawin, Alexandra M Z; Cole-Hamilton, David J

2012-04-02

358

Developmental Change and Intraindividual Variability: Relating Cognitive Aging to Cognitive Plasticity, Cardiovascular Lability, and Emotional Diversity  

PubMed Central

Repeated assessments obtained over years can be used to measure individuals’ developmental change, whereas repeated assessments obtained over a few weeks can be used to measure individuals’ dynamic characteristics. Using data from a burst of measurement embedded in the Berlin Aging Study (BASE: Baltes & Mayer, 1999), we illustrate and examine how long-term changes in cognitive ability are related to short-term changes in cognitive performance, cardiovascular function, and emotional experience. Our findings suggest that “better” cognitive aging over approximately13 years was associated with greater cognitive plasticity, less cardiovascular lability, and less emotional diversity over approximately 2 weeks at age 90 years. The study highlights the potential benefits of multi-time scale longitudinal designs for the study of individual function and development.

Ram, Nilam; Gerstorf, Denis; Lindenberger, Ulman; Smith, Jacqui

2010-01-01

359

The pyrogenic effect of scarlet fever toxin  

Microsoft Academic Search

The scarlet fever toxin is pyrogenically active. The pyretic reaction can be inhibited with antiserum bothin vitro andin vivo. From the quantitative aspect the pyrogenicity neutralization point corresponds approximately to the equivalence point of\\u000a the flocculation reaction. The transmission of tolerance with the serum of tolerant animals failed. Tolerance was of short\\u000a duration; interruption of the series of toxin injections

V. Schuh

1965-01-01

360

REGULATION OF TOXIN SYNTHESIS BY CLOSTRIDIUM DIFFICILE  

Microsoft Academic Search

Clostridium difficile is the leading definable cause of nosocomial diarrhea worldwide due to its virulence, multi-drug resistance, spore-forming ability, and environmental persistence. The incidence of C. difficile infection (CDI) has been increasing exponentially in the last decade. Virulent strains of C. difficile produce either toxin A and\\/or toxin B, which are essential for the pathogenesis of this bacterium. Current methods

Charles Darkoh

2012-01-01

361

Clostridial Rho-Inhibiting Protein Toxins  

Microsoft Academic Search

Rho proteins are master regulators of a large array of cellular functions, including control of cell morphology, cell migration\\u000a and polarity, transcriptional activation, and cell cycle progression. They are the eukaryotic targets of various bacterial\\u000a protein toxins and effectors, which activate or inactivate the GTPases. Here Rhoinactivating toxins and effectors are reviewed,\\u000a including the families of large clostridial cytotoxins and

K. Aktories; I. Just

362

Cytotoxicity Screening for the Cyanobacterial Toxin Cylindrospermopsin  

Microsoft Academic Search

The cell lines C3A, HepG2, NCI-87, HCT-8, HuTu-80, Caco-2, and Vero were screened for sensitivity to the cyanobacterial toxin cylindrospermopsin (CYN), with the aim of determining the most sensitive cells to be used in cytotoxicity tests. Cell lines were chosen to be representative of the organs targeted by the toxin; liver, kidney, intestine, and were expected to have different metabolic

Suzanne M. Froscio; Stella Fanok; Andrew R. Humpage

2009-01-01

363

Apx toxins in Pasteurellaceae species from animals.  

PubMed

Pasteurellaceae species particularly of porcine origin which are closely related to Actinobacillus pleuropneumoniae were analyzed for the presence of analogues to the major A. pleuropneumoniae RTX toxin genes, apxICABD, apxIICA and apxIIICABD and for their expression. Actinobacillus suis contains both apxICABD(var.suis) and apxIICA(var. suis) operons and was shown to produce ApxI and ApxII toxin. Actinobacillus rossii contained the operons apxIICA(var.rossii) and apxIIICABD(var.rossii). However, only the toxin ApxII and not ApxIII could be detected in cultures of A. rossii. The Apx toxins found in A. suis and A. rossi may play a role in virulence of these pathogens. Actinobacillus lignieresii, which was included since it is phylogenetically very closely related to A. pleuropneumoniae, was found to contain a full apxICABD(var.lign.) operon which however lacks the -35 and -10 boxes in the promoter sequences. As expected from these results, no expression of ApxI was detected in A. lignieresii grown under standard culture conditions. Actinobacillus seminis, Actinobacillus equuli, Pasteurella aerogenes, Pasteurella multocida, Haemophilus parasuis, and also Mannheimia (Pasteurella) haemolytica, which is known to secrete leukotoxin, were all shown to be devoid of any of the apx toxin genes and did not produce ApxI, ApxII or ApxIII toxin proteins. However, proteins of slightly lower molecular mass than ApxI, ApxII and ApxIII which showed limited cross-reactions with monospecific, polyclonal anti-ApxI, anti-ApxII and anti-ApxIII were detected on immunoblot analysis of A. equuli, A. seminis and P. aerogenes. The presence of Apx toxins and proteins that imunologically cross react with Apx toxins in porcine Actinobacillus species other than A. pleuropneumoniae can be expected to interfere with serodiagnosis of porcine pleuropneumonia. PMID:10831858

Schaller, A; Kuhnert, P; de la Puente-Redondo, V A; Nicolet, J; Frey, J

2000-06-12

364

Biodegradation of the Polyketide Toxin Cercosporin  

Microsoft Academic Search

Cercosporin is a non-host-specific polyketide toxin produced by many species of plant pathogens belonging to the genus Cercospora. This red-pigmented, light-activated toxin is an important pathogenicity determinant for Cercospora species. In this study, we screened 244 bacterial isolates representing 12 different genera for the ability to degrade cercosporin. Cercosporin degradation was determined by screening for the presence of cleared zones

Thomas K. Mitchell; William Scott Chilton; Margaret E. Daub

2002-01-01

365

Medical Defense Against Protein Toxin Weapons  

Microsoft Academic Search

The term “toxin weapon” has been used to describe poisons, classically of natural origin but increasingly accessible by modern\\u000a synthetic methods, which are suitable for delivery on a battlefield in a form that causes death or severe incapacitation at\\u000a relatively low concentrations (reviewed in ref. 1). Several of the most important toxin weapons are proteins, and these molecules are the

Charles B. Millard

366

The enteric toxins of Clostridium perfringens  

Microsoft Academic Search

The Gram-positive pathogenClostridium perfringens is a major cause of human and veterinary enteric disease largely because this bacterium can produce several toxins when present\\u000a inside the gastrointestinal tract. The enteric toxins of C. perfringens share two common features: (1) they are all single polypeptides of modest (~25—35 kDa) size, although lacking in sequence\\u000a homology, and (2) they generally act by

J. G. Smedley; D. J. Fisher; S. Sayeed; G. Chakrabarti; B. A. McClane

367

The enteric toxins of Clostridium perfringens  

Microsoft Academic Search

The Gram-positive pathogen Clostridium perfringens is a major cause of human and veterinary enteric disease largely because this bacterium can produce several toxins when present inside the gastrointestinal tract. The enteric toxins of C. perfringens share two common features: (1) they are all single polypeptides of modest (~25–35 kDa) size, although lacking in sequence homology, and (2) they generally act by

J. G. Smedley III; D. J. Fisher; S. Sayeed; G. Chakrabarti; B. A. McClane

2004-01-01

368

High lability of sexual system over 250 million years of evolution in morphologically conservative tadpole shrimps  

PubMed Central

Background Sexual system is a key factor affecting the genetic diversity, population structure, genome structure and the evolutionary potential of species. The sexual system androdioecy – where males and hermaphrodites coexist in populations – is extremely rare, yet is found in three crustacean groups, barnacles, a genus of clam shrimps Eulimnadia, and in the order Notostraca, the tadpole shrimps. In the ancient crustacean order Notostraca, high morphological conservatism contrasts with a wide diversity of sexual systems, including androdioecy. An understanding of the evolution of sexual systems in this group has been hampered by poor phylogenetic resolution and confounded by the widespread occurrence of cryptic species. Here we use a multigene supermatrix for 30 taxa to produce a comprehensive phylogenetic reconstruction of Notostraca. Based on this phylogenetic reconstruction we use character mapping techniques to investigate the evolution of sexual systems. We also tested the hypothesis that reproductive assurance has driven the evolution of androdioecy in Notostraca. Results Character mapping analysis showed that sexual system is an extremely flexible trait within Notostraca, with repeated shifts between gonochorism and androdioecy, the latter having evolved a minimum of five times. In agreement with the reproductive assurance hypothesis androdioecious notostracans are found at significantly higher latitudes than gonochoric ones indicating that post glacial re-colonisation may have selected for the higher colonisation ability conferred by androdioecy. Conclusions In contrast to their conserved morphology, sexual system in Notostraca is highly labile and the rare reproductive mode androdioecy has evolved repeatedly within the order. Furthermore, we conclude that this lability of sexual system has been maintained for at least 250 million years and may have contributed to the long term evolutionary persistence of Notostraca. Our results further our understanding of the evolution of androdioecy and indicate that reproductive assurance is a recurrent theme involved in the evolution of this sexual system.

2013-01-01

369

The priming effect: Investigating the role of labile C quantity on subsoil C losses  

NASA Astrophysics Data System (ADS)

In a study examining changes in soil organic carbon storage after clearcut harvesting, we previously reported a 50% decline in soil C stocks approximately 30 years after harvesting, with the greatest losses reported below 20 cm in the mineral soil. Physical and biological separation of organic matter indicated that the decline was greatest in the fractions of organic matter that are conceptually thought to be stable. Stable isotope analyses were consistent with increased mineralization post-harvest and we speculated that the deeper stores of C might have been primed by a flush of labile C post harvest. A recent review (Blagodatskyaya and Kuzyakov, 2008) reported that the direction (positive, negative, neutral) of the priming effect may be dependent not only upon the energy content of the added substrate, but the quantity of C added relative to microbial biomass carbon (MBC). In this study we test this hypothesis using a lab-based incubation of soils collected from the surface (0-10 cm) and subsoil (35-50 cm) of an 80 year old red spruce forest. We added 10, 100 and 1000 % C (glucose) relative to MBC and measured the rate of decomposition (microbial respiration) every 5 h for the first week, every 24 h for the second week, weekly for a month and biweekly for two months. After flushing the headspace with CO2 free air, we measured the rate of microbial respiration and the ?13C of the respired C using a Multiflow prep system with a Gilson autosampler coupled to an Isoprime mass spectrometer. We used an isotope-mixing model to partition the sources of respired C and determine the direction of priming. Our findings suggest that the quantity of added C can affect the direction of priming and that the relative priming effect differs between depths, suggesting that soil organic carbon stores in the subsoil are more sensitive to labile C additions.

Diochon, Amanda; Kellman, Lisa; Beltrami, Hugo

2010-05-01

370

Labile and recalcitrant organic matter utilization by river biofilm under increasing water temperature.  

PubMed

Microbial biofilms in rivers contribute to the decomposition of the available organic matter which typically shows changes in composition and bioavailability due to their origin, seasonality, and watershed characteristics. In the context of global warming, enhanced biofilm organic matter decomposition would be expected but this effect could be specific when either a labile or a recalcitrant organic matter source would be available. A laboratory experiment was performed to mimic the effect of the predicted increase in river water temperature (+4 °C above an ambient temperature) on the microbial biofilm under differential organic matter sources. The biofilm microbial community responded to higher water temperature by increasing bacterial cell number, respiratory activity (electron transport system) and microbial extracellular enzymes (extracellular enzyme activity). At higher temperature, the phenol oxidase enzyme explained a large fraction of respiratory activity variation suggesting an enhanced microbial use of degradation products from humic substances. The decomposition of hemicellulose (?-xylosidase activity) seemed to be also favored by warmer conditions. However, at ambient temperature, the enzymes highly responsible for respiration activity variation were ?-glucosidase and leu-aminopeptidase, suggesting an enhanced microbial use of polysaccharides and peptides degradation products. The addition of labile dissolved organic carbon (DOC; dipeptide plus cellobiose) caused a further augmentation of heterotrophic biomass and respiratory activity. The changes in the fluorescence index and the ratio Abs(250)/total DOC indicated that higher temperature accelerated the rates of DOC degradation. The experiment showed that the more bioavailable organic matter was rapidly cycled irrespective of higher temperature while degradation of recalcitrant substances was enhanced by warming. Thus, pulses of carbon at higher water temperature might have consequences for DOC processing. PMID:22570120

Ylla, Irene; Romaní, Anna M; Sabater, Sergi

2012-05-09

371

Effect of mulching on labile soil organic matter pools, microbial community functional diversity and nitrogen transformations in two hardwood plantations of subtropical Australia  

Microsoft Academic Search

The aims of this study were to: (1) assess the effects of mulching on labile soil organic matter (SOM) pools (water-soluble organic matter, WSOM; hot water extractable organic matter, HWEOM; microbial biomass, MB; acid hydrolysable organic matter, AHOM), microbial community functional diversity and soil nitrogen (N) transformations and (2) quantify the relationships among labile SOM pools, soil N transformations and

Zhiqun Huang; Zhihong Xu; Chengrong Chen

2008-01-01

372

Changing the Receptor Specificity of Anthrax Toxin  

PubMed Central

ABSTRACT The actions of many bacterial toxins depend on their ability to bind to one or more cell-surface receptors. Anthrax toxin acts by a sequence of events that begins when the protective-antigen (PA) moiety of the toxin binds to either one of two cell-surface proteins, ANTXR1 and ANTXR2, and is proteolytically activated. The activated PA self-associates to form oligomeric pore precursors, which, in turn, bind the enzymatic moieties of the toxin and transport them to the cytosol. We introduced a double mutation into domain 4 of PA to ablate its native receptor-binding function and fused epidermal growth factor (EGF) to the C terminus of the mutated protein. The resulting fusion protein transported enzymatic effector proteins into a cell line that expressed the EGF receptor (A431 cells), but not into a line lacking this receptor (CHO-K1 cells). Addition of excess free EGF blocked transport of effector proteins into A431 cells via the fusion protein, but not via native PA. We also showed that fusing the diphtheria toxin receptor-binding domain to the C terminus of the mutated PA channeled effector-protein transport through the diphtheria toxin receptor. PA fusion proteins with altered receptor specificity may be useful in biological research and could have practical applications, including ablation or perturbation of selected populations of cells in vivo.

Mechaly, Adva; McCluskey, Andrew J.; Collier, R. John

2012-01-01

373

Sea Anemone Toxins Affecting Potassium Channels  

NASA Astrophysics Data System (ADS)

The great diversity of K+ channels and their wide distribution in many tissues are associated with important functions in cardiac and neuronal excitability that are now better understood thanks to the discovery of animal toxins. During the past few decades, sea anemones have provided a variety of toxins acting on voltage-sensitive sodium and, more recently, potassium channels. Currently there are three major structural groups of sea anemone K+ channel (SAK) toxins that have been characterized. Radioligand binding and electrophysiological experiments revealed that each group contains peptides displaying selective activities for different subfamilies of K+ channels. Short (35-37 amino acids) peptides in the group I display pore blocking effects on Kv1 channels. Molecular interactions of SAK-I toxins, important for activity and binding on Kv1 channels, implicate a spot of three conserved amino acid residues (Ser, Lys, Tyr) surrounded by other less conserved residues. Long (58-59 amino acids) SAK-II peptides display both enzymatic and K+ channel inhibitory activities. Medium size (42-43 amino acid) SAK-III peptides are gating modifiers which interact either with cardiac HERG or Kv3 channels by altering their voltage-dependent properties. SAK-III toxins bind to the S3C region in the outer vestibule of Kv channels. Sea anemones have proven to be a rich source of pharmacological tools, and some of the SAK toxins are now useful drugs for the diagnosis and treatment of autoimmune diseases.

Diochot, Sylvie; Lazdunski, Michel

374

Sea anemone toxins affecting potassium channels.  

PubMed

The great diversity of K(+) channels and their wide distribution in many tissues are associated with important functions in cardiac and neuronal excitability that are now better understood thanks to the discovery of animal toxins. During the past few decades, sea anemones have provided a variety of toxins acting on voltage-sensitive sodium and, more recently, potassium channels. Currently there are three major structural groups of sea anemone K(+) channel (SAK) toxins that have been characterized. Radioligand binding and electrophysiological experiments revealed that each group contains peptides displaying selective activities for different subfamilies of K(+) channels. Short (35-37 amino acids) peptides in the group I display pore blocking effects on Kv1 channels. Molecular interactions of SAK-I toxins, important for activity and binding on Kv1 channels, implicate a spot of three conserved amino acid residues (Ser, Lys, Tyr) surrounded by other less conserved residues. Long (58-59 amino acids) SAK-II peptides display both enzymatic and K(+) channel inhibitory activities. Medium size (42-43 amino acid) SAK-III peptides are gating modifiers which interact either with cardiac HERG or Kv3 channels by altering their voltage-dependent properties. SAK-III toxins bind to the S3C region in the outer vestibule of Kv channels. Sea anemones have proven to be a rich source of pharmacological tools, and some of the SAK toxins are now useful drugs for the diagnosis and treatment of autoimmune diseases. PMID:19184586

Diochot, Sylvie; Lazdunski, Michel

2009-01-01

375

Emotional Lability in Children and Adolescents with Attention Deficit/Hyperactivity Disorder (ADHD): Clinical Correlates and Familial Prevalence  

ERIC Educational Resources Information Center

|Background: The goal of this study was to investigate the occurrence, severity and clinical correlates of emotional lability (EL) in children with attention deficit/hyperactivity disorder (ADHD), and to examine factors contributing to EL and familiality of EL in youth with ADHD. Methods: One thousand, one hundred and eighty-six children with ADHD…

Sobanski, Esther; Banaschewski, Tobias; Asherson, Philip; Buitelaar, Jan; Chen, Wai; Franke, Barbara; Holtmann, Martin; Krumm, Bertram; Sergeant, Joseph; Sonuga-Barke, Edmund; Stringaris, Argyris; Taylor, Eric; Anney, Richard; Ebstein, Richard P.; Gill, Michael; Miranda, Ana; Mulas, Fernando; Oades, Robert D.; Roeyers, Herbert; Rothenberger, Aribert; Steinhausen, Hans-Christoph; Faraone, Stephen V.

2010-01-01

376

Evidence for the involvement of a labile protein in stimulation of adrenal steroidogenesis under conditions not inhibitory to protein synthesis  

SciTech Connect

Evidence is presented to support the hypothesis that synthesis of a labile protein is required for stimulation of steroidogenesis in rat adrenocortical cells. Amino acids L-canavanine and L-S-aminoethylcysteine, at concentrations as high as 5 mM, each inhibited steroidogenesis to a much greater extent than they inhibited protein synthesis. S-Aminoethylcysteine caused a 50% decrease in the stimulated rate of corticosterone production under conditions where incorporation of (35S)methionine into protein was unchanged. Both amino acids block stimulation of steroid synthesis at a step subsequent to the formation of cAMP and before the synthesis of progesterone. The onset of this effect, after the addition of the amino acids, on corticosterone production is quite rapid. These results provide support, that is not dependent on inhibition of protein synthesis, for the hypothesis that a labile protein mediates stimulation of steroidogenesis. Reversal of canavanine and S-aminoethylcysteine inhibition of steroidogenesis by arginine and lysine, respectively, suggests that the inhibitors are functioning as amino acid analogs. S-Aminoethylcysteine inhibits the incorporation of (3H)lysine into protein as well as inhibits steroidogenesis; further, (3H)S-aminoethylcysteine is incorporated into protein that is nonstimulatory. These results suggest that lysine residues play an essential role in the function of the labile protein or that the labile protein contains a large number of lysine residues.

Krueger, R.J.; Orme-Johnson, N.R.

1988-05-01

377

ReCLIP (Reversible Cross-Link Immuno-Precipitation): An Efficient Method for Interrogation of Labile Protein Complexes  

PubMed Central

The difficulty of maintaining intact protein complexes while minimizing non-specific background remains a significant limitation in proteomic studies. Labile interactions, such as the interaction between p120-catenin and the E-cadherin complex, are particularly challenging. Using the cadherin complex as a model-system, we have developed a procedure for efficient recovery of otherwise labile protein-protein interactions. We have named the procedure “ReCLIP” (Reversible Cross-Link Immuno-Precipitation) to reflect the primary elements of the method. Using cell-permeable, thiol-cleavable crosslinkers, normally labile interactions (i.e. p120 and E-cadherin) are stabilized in situ prior to isolation. After immunoprecipitation, crosslinked binding partners are selectively released and all other components of the procedure (i.e. beads, antibody, and p120 itself) are discarded. The end result is extremely efficient recovery with exceptionally low background. ReCLIP therefore appears to provide an excellent alternative to currently available affinity-purification approaches, particularly for studies of labile complexes.

Smith, Andrew L.; Friedman, David B.; Yu, Huapeng; Carnahan, Robert H.; Reynolds, Albert B.

2011-01-01

378

Exploring the Relationship Between Wetland Methane Emissions and Net Ecosystem Productivity Using Experimental Shading and Labile Carbon Additions  

Microsoft Academic Search

Methane (CH4) emissions from wetlands are positively correlated with net ecosystem productivity (NEP); however the relative importance of proposed controlling mechanisms remains poorly understood. The carbon supply hypothesis suggests that recent photosynthesis contributes labile carbon substrate to methanogenic habitats, resulting in higher CH4 emissions with increases in NEP. Plant gas transport is also hypothesized to be important for conducting gases

S. Owens; J. C. von Fischer

2007-01-01

379

On the Labile Memory Buffer in the Attentional Blink: Masking the T2 Representation by Onset Transients Mediates the AB  

ERIC Educational Resources Information Center

|Report of a second target (T2) is impaired when presented within 500 ms of the first (T1). This attentional blink (AB) is known to cause a delay in T2 processing during which T2 must be stored in a labile memory buffer. We explored the buffer's characteristics using different types of masks after T2. These characteristics were inferred by…

Jannati, Ali; Spalek, Thomas M.; Di Lollo, Vincent

2011-01-01

380

Effects of phosphate buffer capacity on critical levels and relationships between soil tests and labile phosphate in wheat growing soils  

Microsoft Academic Search

Thirty-nine soils from northern New South Wales were used to examine the effects of phosphate buffer capacity on (i) the extraction of labile phosphate by four soil tests, (ii) the relationships between the four soil tests, and (iii) the critical level of each soil test required for near-maximum yield of wheat under field conditions. The results confirmed the principle, recently

I. C. R. Holford

1980-01-01

381

Estimating rates and patterns of morphological evolution from phylogenies: lessons in limb lability from Australian Lerista lizards  

PubMed Central

Squamates (lizards and snakes) offer an exciting model system for research on the evolution of body form. A new phylogenetic study in BMC Evolutionary Biology of Australian lizards shows remarkable evolutionary lability in digit numbers among closely related species, but also highlights important challenges in this area.

Wiens, John J

2009-01-01

382

Potentially Labile Soil Organic Matter in Erosional and Depositional Settings of an Undisturbed Zero-order Watershed  

Microsoft Academic Search

In eroding slopes and depositional settings, the magnitude and significance of soil erosion induced terrestrial carbon dioxide sink is closely associated with how much of the soil organic matter is available in potentially labile form, as free or occluded light fraction (fLF and oLF, respectively) and its stability. Here we use (a) density fractionation to determine the amount of light

A. A. Berhe; J. W. Harden; M. S. Torn; S. D. Burton; M. Kleber; J. Harte

2006-01-01

383

Analysis of the variation of the essential oil composition of Eucalyptus globulus Labill. from Portugal using multivariate statistical analysis  

Microsoft Academic Search

Samples of Eucalyptus globulus Labill. subsp. globulus essential oil obtained from trees of different ages, growing in maritime and inland Portuguese regions, collected in May and November periods (1991–1992), were submitted to quantitative analysis. The results obtained were interpreted using principal component analysis and cluster analysis, considering the 25 abundantly found compounds. These compounds were grouped according to their variation

Armando J. D. Silvestre; José A. S. Cavaleiro; Bernard Delmond; Claude Filliatre; Guy Bourgeois

1997-01-01

384

Immunological cross reactivity between Schistosoma mansoni and cholera toxin.  

PubMed

Intranasal administration of schistosome antigens in combination with appropriate adjuvant may be an effective route for immunization against schistosomes, since the lungs represent an important site of elimination of schistosomulae. Our previous studies have shown that in mice intranasal administration of cholera toxin (CT) before infection with Schistosoma mansoni results in an enhancement of the worm burden in comparison to nontreated infected animals. In the present study, it was shown that mice treated intranasally with CT displayed high numbers of schistosome-reactive IgM-secreting cells in the spleen as well as high levels of schistosome-reactive serum IgM antibodies, whereas no significant immunological response against two other antigens, ovalbumin (OVA) or keyhole limpet haemocyanin (KLH) was noted. Sera from mice treated intranasally with CT recognized a 22 kDA antigen on SWAP blots. This band was not demonstrable after absorption of the sera with SWAP. These findings indicate a possible cross reactivity between cholera toxin and schistosome antigens. Further analysis by Western blot revealed that a 22 kDa antigen was detected on CT blots by sera from mice and humans infected with S. mansoni. This band was not demonstrable after absorption of the mouse or the human sera with CT. The 22 kDa cross reactive antigen was heat-stable. The antibodies against the 22 kDa antigen were only found within the IgM class but not within other Ig isotypes. Our findings also indicate that the 22 kDa antigen detected by anti-S. mansoni antibodies represents the A1 fragment of the cholera toxin. PMID:9292894

Akhiani, A A; Nilsson, L A; Ouchterlony, O

1997-08-01

385

A biomimetic nanosponge that absorbs pore-forming toxins.  

PubMed

Detoxification treatments such as toxin-targeted anti-virulence therapy offer ways to cleanse the body of virulence factors that are caused by bacterial infections, venomous injuries and biological weaponry. Because existing detoxification platforms such as antisera, monoclonal antibodies, small-molecule inhibitors and molecularly imprinted polymers act by targeting the molecular structures of toxins, customized treatments are required for different diseases. Here, we show a biomimetic toxin nanosponge that functions as a toxin decoy in vivo. The nanosponge, which consists of a polymeric nanoparticle core surrounded by red blood cell membranes, absorbs membrane-damaging toxins and diverts them away from their cellular targets. In a mouse model, the nanosponges markedly reduce the toxicity of staphylococcal alpha-haemolysin (?-toxin) and thus improve the survival rate of toxin-challenged mice. This biologically inspired toxin nanosponge presents a detoxification treatment that can potentially treat a variety of injuries and diseases caused by pore-forming toxins. PMID:23584215

Hu, Che-Ming J; Fang, Ronnie H; Copp, Jonathan; Luk, Brian T; Zhang, Liangfang

2013-04-14

386

[Urological applications of botulinum toxins].  

PubMed

Botulinum toxins (BT) are one of the most powerful poisons in nature. They are responsible for human botulism and constitute a potential chemical weapon, but can also be used as a therapeutic agent. Sphincter, bladder and prostatic injections have been described in urological indications as varied as detrusor-sphincter dyssynergia and neurogenic detrusor hyperactivity, idiopathic overactive bladder symptoms, interstitial cystitis, obstructive voiding disorders related to benign prostatic hyperplasia or chronic prostatitis, and recurrent urethral stricture. This review of the literature presents the results and level of evicence in support of the use of BT in urological indications. Detrusor injections of BT-A constitute an alternative conservative treatment that is effective in the short term (6-12 months) after failure of anticholinergic agents to treat neurogenic detrusor hyperactivity (level 1b). Sphincter injections are effective in the short-term treatment of neurogenic detrusor-sphincter dyssynergia (level 1c). The efficacy observed during preliminary clinical trials of detrusor injections of BT-A for idiopathic overactive bladder symptoms or interstitial cystitis (level 4) and prostatic injections for obstruction related to BPH (level 1c) justifies the major interest raised by this new therapeutic approach. However, these preliminary results must be confirmed by comparative studies on a sufficient number of patients with long-term follow-up before considering the use of this technique in routine clinical practice. PMID:16821335

Karsenty, Gilles; Corcos, Jacques; Schurch, Brigitte

2006-06-01

387

Role of processing and intracellular transport for optimal toxicity of Shiga toxin and toxin mutants.  

PubMed

Cleavage of Shiga toxin A-fragment at a highly trypsin-sensitive site increases its enzymatic activity. To investigate the role of this cleavage site in intoxication of cells, we studied the routing, cleavage, and toxicity of mutant toxin where the trypsin-sensitive site had been eliminated. Ultrastructural analysis of toxin tagged with horseradish peroxidase demonstrated that wild-type and mutant toxins were transported from endosomes to the trans-Golgi network and further through the Golgi cisterns to the endoplasmic reticulum. Wild-type toxin was much more efficient than the mutants in provoking rapid intoxication, but after prolonged incubation time also mutants were highly toxic. The cells were able to cleave both wild-type Shiga toxin and the mutants, but the cellular location for cleavage appears to differ. Wild-type toxin was cleaved in the presence of brefeldin A, which disrupts the Golgi cisterns. This indicates that the cleavage occurs in the endosomes or in the trans-Golgi network. In contrast, the mutant Shiga-His (R248H/R251H) was not cleaved in the presence of brefeldin A, indicating that the cleavage can occur only after the toxin has left the trans-Golgi network. In vitro experiments showed that the cytosolic enzyme calpain is able to cleave Shiga-His, and results from in vivo experiments are consistent with the possibility that cleavage is carried out by calpain after the mutant A-fragment has reached the cytosol. PMID:7737376

Garred, O; Dubinina, E; Holm, P K; Olsnes, S; van Deurs, B; Kozlov, J V; Sandvig, K

1995-05-01

388

Exposure to anthrax toxin alters human leucocyte expression of anthrax toxin receptor 1.  

PubMed

Anthrax is a toxin-mediated disease, the lethal effects of which are initiated by the binding of protective antigen (PA) with one of three reported cell surface toxin receptors (ANTXR). Receptor binding has been shown to influence host susceptibility to the toxins. Despite this crucial role for ANTXR in the outcome of disease, and the reported immunomodulatory consequence of the anthrax toxins during infection, little is known about ANTXR expression on human leucocytes. We characterized the expression levels of ANTXR1 (TEM8) on human leucocytes using flow cytometry. In order to assess the effect of prior toxin exposure on ANTXR1 expression levels, leucocytes from individuals with no known exposure, those exposed to toxin through vaccination and convalescent individuals were analysed. Donors could be defined as either 'low' or 'high' expressers based on the percentage of ANTXR1-positive monocytes detected. Previous exposure to toxins appears to modulate ANTXR1 expression, exposure through active infection being associated with lower receptor expression. A significant correlation between low receptor expression and high anthrax toxin-specific interferon (IFN)-? responses was observed in previously infected individuals. We propose that there is an attenuation of ANTXR1 expression post-infection which may be a protective mechanism that has evolved to prevent reinfection. PMID:23607659

Ingram, R J; Harris, A; Ascough, S; Metan, G; Doganay, M; Ballie, L; Williamson, E D; Dyson, H; Robinson, J H; Sriskandan, S; Altmann, D M

2013-07-01

389

Human genetic variation altering anthrax toxin sensitivity  

PubMed Central

The outcome of exposure to infectious microbes or their toxins is influenced by both microbial and host genes. Some host genes encode defense mechanisms, whereas others assist pathogen functions. Genomic analyses have associated host gene mutations with altered infectious disease susceptibility, but evidence for causality is limited. Here we demonstrate that human genetic variation affecting capillary morphogenesis gene 2 (CMG2), which encodes a host membrane protein exploited by anthrax toxin as a principal receptor, dramatically alters toxin sensitivity. Lymphoblastoid cells derived from a HapMap Project cohort of 234 persons of African, European, or Asian ancestry differed in sensitivity mediated by the protective antigen (PA) moiety of anthrax toxin by more than four orders of magnitude, with 99% of the cohort showing a 250-fold range of sensitivity. We find that relative sensitivity is an inherited trait that correlates strongly with CMG2 mRNA abundance in cells of each ethnic/geographical group and in the combined population pool (P = 4 × 10?11). The extent of CMG2 expression in transfected murine macrophages and human lymphoblastoid cells affected anthrax toxin binding, internalization, and sensitivity. A CMG2 single-nucleotide polymorphism (SNP) occurring frequently in African and European populations independently altered toxin uptake, but was not statistically associated with altered sensitivity in HapMap cell populations. Our results reveal extensive human diversity in cell lethality dependent on PA-mediated toxin binding and uptake, and identify individual differences in CMG2 expression level as a determinant of this diversity. Testing of genomically characterized human cell populations may offer a broadly useful strategy for elucidating effects of genetic variation on infectious disease susceptibility.

Martchenko, Mikhail; Candille, Sophie I.; Tang, Hua; Cohen, Stanley N.

2012-01-01

390

[Use of botulinum toxin in ophthalmology].  

PubMed

Botulinum toxin A injection in essential blepharospasmus and hemifacial spasmus is an important alternative to surgical therapy. The toxin is injected into the lateral parts of the lower and upper lid in single doses of one to two nanograms under electromyographic control. The effect is visible after a few days and lasts for several months. The procedure can be repeated several times. A second important application of botulinum toxin A is strabismus. In paralytic strabismus the contracture of the antagonist of the paralyzed muscle can be weakened by local injection of botulinum toxin by means of a needle electrode under electromyographic control. Thus the contracture of the homolateral antagonist can be overcome and not seldom singular binocular vision obtained again. In cases of moderate pareses which recover spontaneously the muscle weakening effect of the toxin on the antagonist helps to restore binocular single vision. In cases of chronic paralytic strabismus the toxin injection into the antagonist facilitates the surgical intervention on the paralyzed muscle. In concomitant strabismus botulinum toxin A is above all valuable in small angle cases, in sensory strabismus, in cases of over- or undercorrection after surgery, and these especially in adults. In congenital esotropia, in commitant squints with large angles and in chronic or intermittent exotropia surgery is the preferred modality of treatment. The best results are obtained with repeated small doses. Generally a 65% reduction of the strabismus angle after two to three injections can be expected. With injections into the lids and the extraocular muscles no general systemic side effects has been observed. PMID:2191466

Huber, A

1990-04-01

391

Animal Toxins: How is Complexity Represented in Databases?  

PubMed Central

Peptide toxins synthesized by venomous animals have been extensively studied in the last decades. To be useful to the scientific community, this knowledge has been stored, annotated and made easy to retrieve by several databases. The aim of this article is to present what type of information users can access from each database. ArachnoServer and ConoServer focus on spider toxins and cone snail toxins, respectively. UniProtKB, a generalist protein knowledgebase, has an animal toxin-dedicated annotation program that includes toxins from all venomous animals. Finally, the ATDB metadatabase compiles data and annotations from other databases and provides toxin ontology.

Jungo, Florence; Estreicher, Anne; Bairoch, Amos; Bougueleret, Lydie; Xenarios, Ioannis

2010-01-01

392

Accurate prediction of scorpion toxin functional properties from primary structures.  

PubMed

Scorpion toxins are common experimental tools for studies of biochemical and pharmacological properties of ion channels. The number of functionally annotated scorpion toxins is steadily growing, but the number of identified toxin sequences is increasing at much faster pace. With an estimated 100,000 different variants, bioinformatic analysis of scorpion toxins is becoming a necessary tool for their systematic functional analysis. Here, we report a bioinformatics-driven system involving scorpion toxin structural classification, functional annotation, database technology, sequence comparison, nearest neighbour analysis, and decision rules which produces highly accurate predictions of scorpion toxin functional properties. PMID:15950506

Tan, Paul T J; Srinivasan, K N; Seah, Seng Hong; Koh, Judice L Y; Tan, Tin Wee; Ranganathan, Shoba; Brusic, Vladimir

2005-09-01

393

Inhibition of Cereulide Toxin Synthesis by Emetic Bacillus cereus via Long-Chain Polyphosphates ?  

PubMed Central

Severe intoxications caused by the Bacillus cereus emetic toxin cereulide can hardly be prevented due to the ubiquitous distribution and heat resistance of spores and the extreme thermal and chemical stability of cereulide. It would therefore be desirable to inhibit cereulide synthesis during food manufacturing processes or in prepared foods, which are stored under time-temperature abuse conditions. Toward this end, the impacts of three long-chain polyphosphate (polyP) formulations on growth and cereulide production were examined. The inhibition was dependent on the concentration and the type of the polyP blend, indicating that polyPs and not the orthophosphates were effective. Quantitative PCR (qPCR) monitoring at sublethal concentrations revealed that polyPs reduced the transcription of ces nonribosomal peptide synthetase (NRPS) genes by 3- to 4-fold along with a significantly reduced toxin production level. At lower concentrations, toxin synthesis was decreased, although the growth rate was not affected. These data indicate a differential effect on toxin synthesis independent of growth inhibition. The inhibition of toxin synthesis in food was also observed. Despite the growth of B. cereus, toxin synthesis was reduced by 70 to 100% in two model food systems (reconstituted infant food and oat milk), which were analyzed with HEp-2 cell culture assays and high-performance liquid chromatography (HPLC)/electrospray ionization-time of flight mass spectrometry (ESI-TOF-MS). Accordingly, ces promoter activity was strongly downregulated, as visualized by using a lux-based reporter strain. These data illustrate the potential of polyphosphate formulations to reduce the risk of cereulide synthesis in food and may contribute to targeted hurdle concepts.

Frenzel, Elrike; Letzel, Thomas; Scherer, Siegfried; Ehling-Schulz, Monika

2011-01-01

394

Inhibition of cereulide toxin synthesis by emetic Bacillus cereus via long-chain polyphosphates.  

PubMed

Severe intoxications caused by the Bacillus cereus emetic toxin cereulide can hardly be prevented due to the ubiquitous distribution and heat resistance of spores and the extreme thermal and chemical stability of cereulide. It would therefore be desirable to inhibit cereulide synthesis during food manufacturing processes or in prepared foods, which are stored under time-temperature abuse conditions. Toward this end, the impacts of three long-chain polyphosphate (polyP) formulations on growth and cereulide production were examined. The inhibition was dependent on the concentration and the type of the polyP blend, indicating that polyPs and not the orthophosphates were effective. Quantitative PCR (qPCR) monitoring at sublethal concentrations revealed that polyPs reduced the transcription of ces nonribosomal peptide synthetase (NRPS) genes by 3- to 4-fold along with a significantly reduced toxin production level. At lower concentrations, toxin synthesis was decreased, although the growth rate was not affected. These data indicate a differential effect on toxin synthesis independent of growth inhibition. The inhibition of toxin synthesis in food was also observed. Despite the growth of B. cereus, toxin synthesis was reduced by 70 to 100% in two model food systems (reconstituted infant food and oat milk), which were analyzed with HEp-2 cell culture assays and high-performance liquid chromatography (HPLC)/electrospray ionization-time of flight mass spectrometry (ESI-TOF-MS). Accordingly, ces promoter activity was strongly downregulated, as visualized by using a lux-based reporter strain. These data illustrate the potential of polyphosphate formulations to reduce the risk of cereulide synthesis in food and may contribute to targeted hurdle concepts. PMID:21169440

Frenzel, Elrike; Letzel, Thomas; Scherer, Siegfried; Ehling-Schulz, Monika

2010-12-17

395

Thermal degradation of paralytic shellfish poisoning toxins in scallop digestive glands  

Microsoft Academic Search

Digestive glands containing paralytic shellfish poisoning (PSP) toxins were isolated from toxic scallops. Citrate\\/phosphate buffers with the pH values ranging from 3 to 7 were added to achieve predetermined pH levels. The samples were heated at 90, 100, 110, 120 and 130°C using a computer controlled oil bath, and three tubes at each pH level were transferred into an ice

W. M Indrasena; T. A Gill

1999-01-01

396

Intracellular Survival of Leishmania major in Neutrophil Granulocytes after Uptake in the Absence of Heat-Labile Serum Factors  

Microsoft Academic Search

The role of polymorphonuclear neutrophil granulocytes (PMN) in defense against the intracellular parasite Leishmania is poorly understood. In the present study, the interaction of human PMN with Leishmania major promastigotes was investigated in vitro. In the presence of fresh human serum, about 50% of PMN phagocy- tosed the parasites within 10 min and the parasite uptake led to PMN activation,

Helmut Laufs; Kerstin Müller; Jens Fleischer; Norbert Reiling; Nicole Jahnke; Jens C. Jensenius; Werner Solbach; Tamás Laskay

2002-01-01

397

Toxin B is essential for virulence of Clostridium difficile.  

PubMed

Clostridium difficile is the leading cause of infectious diarrhoea in hospitals worldwide, because of its virulence, spore-forming ability and persistence. C. difficile-associated diseases are induced by antibiotic treatment or disruption of the normal gastrointestinal flora. Recently, morbidity and mortality resulting from C. difficile-associated diseases have increased significantly due to changes in the virulence of the causative strains and antibiotic usage patterns. Since 2002, epidemic toxinotype III NAP1/027 strains, which produce high levels of the major virulence factors, toxin A and toxin B, have emerged. These toxins have 63% amino acid sequence similarity and are members of the large clostridial glucosylating toxin family, which are monoglucosyltransferases that are pro-inflammatory, cytotoxic and enterotoxic in the human colon. Inside host cells, both toxins catalyse the transfer of glucose onto the Rho family of GTPases, leading to cell death. However, the role of these toxins in the context of a C. difficile infection is unknown. Here we describe the construction of isogenic tcdA and tcdB (encoding toxin A and B, respectively) mutants of a virulent C. difficile strain and their use in the hamster disease model to show that toxin B is a key virulence determinant. Previous studies showed that purified toxin A alone can induce most of the pathology observed after infection of hamsters with C. difficile and that toxin B is not toxic in animals unless it is co-administered with toxin A, suggesting that the toxins act synergistically. Our work provides evidence that toxin B, not toxin A, is essential for virulence. Furthermore, it is clear that the importance of these toxins in the context of infection cannot be predicted exclusively from studies using purified toxins, reinforcing the importance of using the natural infection process to dissect the role of toxins in disease. PMID:19252482

Lyras, Dena; O'Connor, Jennifer R; Howarth, Pauline M; Sambol, Susan P; Carter, Glen P; Phumoonna, Tongted; Poon, Rachael; Adams, Vicki; Vedantam, Gayatri; Johnson, Stuart; Gerding, Dale N; Rood, Julian I

2009-03-01

398

Genetic characteristics of toxigenic Clostridia and toxin gene evolution.  

PubMed

Clostridia comprise a heterogenous group of environmental bacteria containing 15 pathogenic species, which produce the most potent toxins. The origin of toxins is still enigmatic. It is hypothesized that toxins exhibiting an enzymatic activity have derived from hydrolytic enzymes, which are abundantly secreted by these bacteria, and that pore-forming toxins have evolved from an ancestor transmembrane protein. The presence of related toxin genes in distinct Clostridium species and the variability of some toxin genes support horizontal toxin gene transfer and subsequent independent evolution from strain to strain. Clostridium perfringens toxin genes involved in myonecrosis, mainly alpha toxin and perfringolysin genes, are chromosomally located, whereas toxin genes responsible for intestinal and food borne diseases are localized on plasmids except the enterotoxin gene which can be located either on the chromosome or plasmids. The distribution of these plasmids containing one or several toxin genes accounts for the diverse C. perfringens toxinotypes. Clostridium difficile strains show a high genetic variability. But in contrast to C. perfringens, toxin genes are clustered in pathogenicity locus located on chromosome. The presence of related toxin genes in distinct clostridial species like Clostridium sordellii, Clostridium novyi, and C. perfringens supports interspecies mobilization of this locus. The multiple C. difficile toxinotypes based on toxin gene variants possibly reflect strain adaptation to the intestinal environment. Botulinum toxin genes also show a high level of genetic variation. They have a diverse genetic localization including chromosome, plasmid or phage, and are spread in various Clostridium species (Clostridium botulinum groups, Clostridium argentinense, Clostridium butyricum, Clostridium baratii). Exchange of toxin genes not only include transfers between Clostridium species but also between Clostridium and other bacterial species as well as eukaryotic cells as supported by the wide distribution of related pore-forming toxins of the aerolysin family in various clostridial and non-clostridial species, animal, mushroom and plant. PMID:23707611

Popoff, Michel R; Bouvet, Philippe

2013-05-23

399

[Applications of the botulinum A toxin].  

PubMed

The botulinum A toxin inhibits the release of acethylcoline from the vesicles of presynaptic neuronal end plates. Its effect is a transient pharmacological neurectomy. The toxin is used more and more widespreadingly. It selectively inhibits certain muscles or groups of muscles. Its use is of outstanding importance in the treatment of blepharospasm, a disease possibly causing transient functional blindness. This blindness develops randomly, with undetermined duration, therefore it may even threaten the life of the patient. There is no alternative treatment. In ophthalmology, the toxin is used in the therapy of strabismus and nystagmus, as well as replacing entropion operations. Most often its use is suggested in the treatment of focal dystonies, dysphonia, tremor palatinus, dysphagia, spasm of the oesophagus sphincter muscle, nasal hypersecretion, hemifacial spasm, headaches, focal hyperhydrosis, proctalgia fugax, diabetic gastroparesis and difficulties in urination. In the past few years, the toxin has been used for esthetic reasons as well. By relaxing the muscles causing wrinkles, non-permanent result may be reached with its use. The botulinum A toxin does not have general side effects. As local side effects, haematomas and unwanted, transient paresis of the neighboring muscles can be mentioned. PMID:12785236

Zajácz, Magdolna

2003-05-01

400

Cyanobacterial toxin degrading bacteria: who are they?  

PubMed

Cyanobacteria are ubiquitous in nature and are both beneficial and detrimental to humans. Benefits include being food supplements and producing bioactive compounds, like antimicrobial and anticancer substances, while their detrimental effects are evident by toxin production, causing major ecological problems at the ecosystem level. To date, there are several ways to degrade or transform these toxins by chemical methods, while the biodegradation of these compounds is understudied. In this paper, we present a meta-analysis of the currently available 16S rRNA and mlrA (microcystinase) genes diversity of isolates known to degrade cyanobacterial toxins. The available data revealed that these bacteria belong primarily to the Proteobacteria, with several strains from the sphingomonads, and one from each of the Methylobacillus and Paucibacter genera. Other strains belonged to the genera Arthrobacter, Bacillus, and Lactobacillus. By combining the ecological knowledge on the distribution, abundance, and ecophysiology of the bacteria that cooccur with toxic cyanobacterial blooms and newly developed molecular approaches, it is possible not only to discover more strains with cyanobacterial toxin degradation abilities, but also to reveal the genes associated with the degradation of these toxins. PMID:23841072

Kormas, Konstantinos Ar; Lymperopoulou, Despoina S

2013-06-06

401

FURTHER STUDIES ON A LABILE IMMUNOGENIC PARTICULATE SUBSTANCE ISOLATED FROM MYCOBACTERIUM TUBERCULOSIS  

PubMed Central

Youmans, Anne S. (Northwestern University Medical School, Chicago, Ill.), and Guy P. Youmans. Further studies on a labile immunogenic particulate substance isolated from Mycobacterium tuberculosis. J. Bacteriol. 87:278–285. 1964.—A particulate fraction which was highly immunogenic for mice was collected by ultracentrifugation from mycobacteria disrupted in 0.25 m sucrose buffer. The active immunogenic material was present in the gelatinous pellet obtained after centrifugation at 40,000 rev/min (144,000 × g) for 3 hr. This active material could be prepared free from whole cells and cell walls. This was done either by several centrifugations at lower speeds, or by filtering the supernatant fluid from the 10,000 rev/min centrifugation through a Millipore filter (porosity 0.5 ?). No microorganisms were found on slides or in cultures made from these filtrates. The immunogenic moiety in the particulate fraction was found to be very labile. Temperatures higher than 0 to 4 C inactivated the immunogenic activity. There was an irreversible linear decrease in activity as the temperature increased. If fractions were frozen or lyophilized, the activity remained as high as the original material for 4 weeks, and then rapidly decreased. The immunogenic material also was very sensitive to the hydrogen-ion concentration; the optimal activity was found at pH 6.8 to 7.0. The activity decreased rapidly at more acid or alkaline pH values. Also, particulate fraction prepared in sucrose buffer at pH 7.3 and 7.6 was much less active than that prepared in sucrose buffer at pH 7.0. Immunogenic activity was decreased if the particulate fraction was dialyzed overnight against 0.01 m phosphate buffer or distilled water at 4 C. The detergent sodium lauryl sulfate inactivated immunogenic activity. Moreover, the use of a Waring Blendor to blend the ruptured cell mass before centrifugation decreased the activity. Finally, a markedly lower activity resulted if both the 20,000 and 40,000 rev/min centrifugations were done the day after the rupture of the cells. Some refinements in technique which are used now in the preparation of the particulate fraction are detailed.

Youmans, Anne S.; Youmans, Guy P.

1964-01-01

402

Chronic expression of H-ferritin in dopaminergic midbrain neurons results in an age-related expansion of the labile iron pool and subsequent neurodegeneration: implications for Parkinson's disease  

PubMed Central

While ferritin elevation within dopaminergic (DA) neurons of the substantia nigra (SN) is protective against neurodegeneration elicited by two toxin models of Parkinson’s disease (PD), MPTP and paraquat, in young animals, its prolonged elevation results in a selective age-related neurodegeneration. A similar age-related neurodegeneration has been reported in iron regulatory protein 2-deficient (IRP2 ?/?) mice coinciding with increased ferritin levels within degenerating neurons. This has been speculated to be due to subsequent reductions in the labile iron pool (LIP) needed for the synthesis of iron-sulfur-containing enzymes. In order to assess whether LIP reduction is responsible for age related-neurodegeneration in our ferritin transgenics, we examined LIP levels in ferritin-expressing transgenics with increasing age. While LIP levels were reduced within DA SN nerve terminals isolated from young ferritin transgenics compared to wildtype littermate controls, they were found to be increased in older transgenic animals at the age at which selective neurodegeneration is first noted. Furthermore, administration of the bioavailable iron chelator, clioquinol (CQ), to older mice was found to protect against both increased LIP and subsequent dopaminergic neurodegeneration. This suggests that age-related neurodegeneration in these mice is likely due to increased iron availability rather than its reduction. This may have important implications for PD and other related neurodegenerative conditions in which iron and ferritin have been implicated.

Kaur, Deepinder; Rajagopalan, Subramanian; Andersen, Julie K.

2009-01-01

403

Predicting the activity of Cd 2+ and Zn 2+ in soil pore water from the radio-labile metal fraction  

NASA Astrophysics Data System (ADS)

Cadmium and zinc were added at 3 and 300 mg kg -1, respectively, to 23 soils and incubated at 16°C and 80% field capacity for 818 d. Following addition of metal, changes in the radio-labile concentrations of both elements were examined on seven separate sampling occasions over 818 d. At each sample time, soil pore water was extracted using Rhizon soil solution samplers, and concentrations of Cd, Zn, dissolved organic carbon, and major cations and anions were determined. The chemical speciation program WHAM 6 was used to determine free metal ion activity, (M 2+). Similar measurements were made on a set of historically contaminated soils from old mining areas, sewage sludge disposal facilities, and industrial sources. The two data sets were combined to give a range of values for p(Cd 2+) and p(Zn 2+) that covered 5 and 4 log 10 units, respectively. A pH-dependent Freundlich model was used to predict Zn 2+ and Cd 2+ ion activity in soil pore water. Total and radio-labile metal ion concentration in the solid phase was assumed to be adsorbed on the "whole soil," humus, or free iron oxides to provide alternative model formats. The most successful models assumed that solubility was controlled by adsorption on soil humus. Inclusion of ionic strength as a model variable provided small improvements in model fit. Considering competition with Ca 2+ and between Zn 2+ and Cd 2+ produced no apparent improvement in model fit. Surprisingly, there was little difference between the use of total and labile adsorbed metal as a model determinant. However, this may have been due to a strong correlation between metal lability and pH in the data set used. Values of residual standard deviation for the parameterized models using labile metal adsorbed on humus were 0.26 and 0.28 for prediction of p(Cd 2+) and p(Zn 2+), respectively. Solubility control by pure Zn and Cd minerals was not indicated from saturation indices. However there may have been fixation of metals to non-radio-labile forms in CaCO 3 and Ca-phosphate compounds in the soils in the higher pH range. Independent validation of the Cd model was carried out using an unpublished data set that included measurements of isotopically exchangeable Cd. There was good agreement with the parameterized model.

Tye, A. M.; Young, S. D.; Crout, N. M. J.; Zhang, H.; Preston, S.; Barbosa-Jefferson, V. L.; Davison, W.; McGrath, S. P.; Paton, G. I.; Kilham, K.; Resende, L.

2003-02-01

404

Botulinum Toxin Injections: A Treatment for Muscle Spasms  

MedlinePLUS

... injections given? Botulinum toxin is mixed with saline (salt water) and injected into the muscle with a tiny needle. You may receive 5 to 10 injections. What are some side effects of botulinum toxin injections? You might have some ...

405

Detoxication of a Purified and Concentrated Diphtheria Toxin by Formalin.  

National Technical Information Service (NTIS)

Results are presented from a study of the preparation of purified and concentrated diphtheria anatoxin by detoxication of purified toxin. Acid precipitation was used to purify the toxin. Loss of activity in the supernatant fluid and the precipitate did no...

L. V. Larionova N. N. Vasilev A. A. Vorobev N. A. Kalinskaya S. V. Chevotareva

1969-01-01

406

Quantitative Electrochemiluminescence Assay for Clostridium perfringens alpha toxin.  

National Technical Information Service (NTIS)

Described is a rapid direct sandwich format electrochemiluminescence assay for identifying and assaying Clostridium perfringens alpha toxin. Biotinylated antibodies to C. perfringens alpha toxin bound to streptavidin paramagnetic beads specifically immuno...

G. A. Merrill V. R. Rivera D. D. Neal C. Young M. A. Poli

2006-01-01

407

Production of antibody against T-2 toxin.  

PubMed Central

Antibody against T-2 toxin was obtained after immunization of rabbits with bovine serum albumin-T-2 hemisuccinate conjugate. The antibody had greatest binding efficiency for T-2 toxin, less efficiency for HT-2, and least for T-2 triol. Cross-reaction of antibody with neosolaniol, T-2 tetraol, and 8-acetyl-neosolaniol was very weak. Diacetoxyscirpenol, trichodermin, vomitoxin, and verrucarin A essentially gave no cross-reaction with the antibody. The sensitivity of the binding assay for T-2 toxin detection was in the range of 1 to 20 ng per assay. Detailed methods for the preparation of the conjugate and the production of immune serum and methods for antibody determination are described.

Chu, F S; Grossman, S; Wei, R D; Mirocha, C J

1979-01-01

408

Toxin-Deficient Mutants from a Toxin-Sensitive Transformant of Cochliobolus Heterostrophus  

PubMed Central

Tox1 is the only genetic element identified which controls production of T-toxin, a linear polyketide involved in the virulence of Cochliobolus heterostrophus to its host plant, corn. Previous attempts to induce toxin-deficient (Tox(-)) mutants, using conventional mutagenesis and screening procedures, have been unsuccessful. As a strategy to enrich for Tox(-) mutants, we constructed a Tox1(+) strain that carried the corn T-urf13 gene (which confers T-toxin sensitivity) fused to a fungal mitochondrial signal sequence; the fusion was under control of the inducible Aspergillus nidulans pelA promoter which, in both A. nidulans and C. heterostrophus, is repressed by glucose and induced by polygalacturonic acid (PGA). We expected that a transformant carrying this construction would be sensitive to its own toxin when the T-urf13 gene was expressed. Indeed, the strain grew normally on medium containing glucose but was inhibited on medium containing PGA. Conidia of this strain were treated with ethylmethanesulfonate and plated on PGA medium. Among 362 survivors, 9 were defective in T-toxin production. Authenticity of each mutant was established by the presence of the transformation vector, proper mating type, and a restiction fragment length polymorphism tightly linked to the Tox1(+) locus. Progeny of each mutant crossed to a Tox1(+) tester segregated 1:1 (for wild type toxin production vs. no or reduced toxin production), indicating a single gene mutation in each case. Progeny of each mutant crossed to a Tox1(-) tester segregated 1 : 1 (for no toxin production vs. no or reduced toxin production) indicating that each mutation mapped at the Tox1 locus. Availability of Tox(-) mutants will permit mapping in the Tox1 region without interference from a known Tox1 linked translocation breakpoint.

Yang, G.; Turgeon, B. G.; Yoder, O. C.

1994-01-01

409

Vitamin losses: Retention during heat treatment and continual changes expressed by mathematical models  

Microsoft Academic Search

Processing and cooking conditions cause variable losses of vitamins. Losses vary widely according to cooking method and type of food. Degradation of vitamins depends on specific conditions during the culinary process, e.g., temperature, presence of oxygen, light, moisture, pH, and, of course, duration of heat treatment. The most labile vitamins during culinary processes are retinol (vegetable boiling, 33% retention), vitamin

Emília Lešková; Jana Kubíková; Eva Ková?iková; Martina Košická; Janka Porubská; Kristína Hol?íková

2006-01-01

410

Botulinum toxin treatment for bladder dysfunction.  

PubMed

Botulinum toxin A is available under three different protein complexes that are not interchangeable until appropriate comparative studies are undertaken. The best studied for the treatment of urinary incontinence as a result of neurogenic detrusor overactivity and overactive bladder/idiopathic detrusor overactivity is onabotulinum toxin A. This brand is only approved for the treatment of urinary incontinence as a result of neurogenic detrusor overactivity at a dose of 200?U and idiopathic detrusor overactivity at a dose of 100?U. In patients with detrusor overactivity as a result of spinal cord injury or multiple sclerosis, 200?U of onabotulinum toxin A should be injected in 30 different sites above the trigone. It was shown to be highly effective in curing or decreasing urinary symptoms of incontinence, increasing quality of life, increasing bladder capacity and decreasing maximal detrusor pressure. This effect was independent of the concomitant use of oral anticholinergic drugs. Adverse events were mild, mainly urinary tract infections and high postvoid residual requiring clean intermittent catheterization. In patients with overactive bladder/idiopathic detrusor overactivity, 100?U of onabotulinum toxin A should be injected in 20 sites above the trigone. It markedly decreases urinary incontinence and improves quality of life. Frequency and urgency episodes are also decreased. Adverse events are mild, mainly urinary tract infections and urinary retention. The latter occurred in just 5% of the patients. Candidates for onabotulinum toxin A treatment should be warned that the effect of the toxin is transient and that repeated injections will be required to maintain the effect in the long term. There is no evidence that repeated injections will have a decreased efficacy. PMID:23634720

Santos-Silva, André; da Silva, Carlos Martins; Cruz, Francisco

2013-05-02

411

ANTIGENS OF BORDETELLA PERTUSSIS II.  

PubMed Central

Banerjea, A. (Rocky Mountain Laboratory, Hamilton, Mont.) and J. Munoz. Antigens of Bordetella pertussis. II, Purification of heat-labile toxin. J. Bacteriol. 84:269–274. 1962.—A mild method of separating heat-labile toxin of Bordetella pertussis from other cellular components is described; it consists of absorbing toxin on a diethylaminoethyl cellulose column and eluting it with a gradient concentration of NaCl. Toxin preparations thus obtained consisted mainly of protein; their toxicity was destroyed by trypsin but not by ribonuclease or deoxyribonuclease.

Banerjea, A.; Munoz, J.

1962-01-01

412

Botulinum C2 toxin ADP-ribosylates actin  

Microsoft Academic Search

ADP-ribosylation of regulatory proteins is an important pathological mechanism by which various bacterial toxins affect eukary-otic cell functions. While diphtheria toxin catalyses the ADP-ribosylation of elongation factor 2, which results in inhibition of protein synthesis, cholera toxin and pertussis toxin ADP-ribosylate Ns and Ni respectively, the GTP-binding regulatory components of the adenylate cyclase system, thereby modulating the bidirectional hormonal regulation

K. Aktories; M. Bärmann; I. Ohishi; S. Tsuyama; K. H. Jakobs; E. Habermann

1986-01-01

413

Peptide Toxins in Sea Anemones: Structural and Functional Aspects  

Microsoft Academic Search

Sea anemones are a rich source of two classes of peptide toxins, sodium channel toxins and potassium channel toxins, which\\u000a have been or will be useful tools for studying the structure and function of specific ion channels. Most of the known sodium\\u000a channel toxins delay channel inactivation by binding to the receptor site 3 and most of the known potassium

Tomohiro Honma; Kazuo Shiomi

2006-01-01

414

Botulinum toxin-B and the management of hyperhidrosis  

Microsoft Academic Search

A new serotype of botulinum toxin has recently arrived in the US. Botulinum toxin type B (BTX-B), known as Myobloc in the United States and as Neurobloc in Europe, is one of seven different antigenic members of the botulinum toxin family, five of which the human nervous system is susceptible to. Like botulinum toxin type A (BTX-A), BTX-B has been

Leslie S Baumann; Monica L Halem

2004-01-01

415

Interaction between environmental factors affects the accumulation of root proteins in hydroponically grown Eucalyptus globulus (Labill.).  

PubMed

Eucalyptus globulus (Labill.) is used for pulp and paper production worldwide. In this report we studied changes in protein expression in one osmotically stressed elite clone widely used in industrial plantations in Spain. High molecular weight polyethylene glycol (PEG) was used as an osmoticum in the growing medium. Roots of rooted cuttings were sampled after 3 and 36 h of treatment. Water potential and abscissic acid content were measured in shoot and root apices to characterize the physiological states of the plants. Total soluble proteins from roots were extracted and separated using two-dimensional gel electrophoresis (2-DE). Gels were stained with Coomassie brillant blue for quantitative analysis of protein accumulation. From a total of 406 reproducible spots, 34 were found to be differentially expressed depending on treatment (osmotic versus control condition) and/or stress duration (3 h versus 36 h), and were further characterized by tandem mass spectrometry. Several proteins were reliably identified including adenosine kinase, actin, stress-related proteins as well as proteins associated to cellular processes, among which some residents of the endoplasmic reticulum. This study constitutes the first investigation of the root proteome in this important forest tree genus. PMID:20974537

Bedon, Frank; Majada, Juan; Feito, Isabel; Chaumeil, Philippe; Dupuy, Jean-William; Lomenech, Anne-Marie; Barre, Aurélien; Gion, Jean-Marc; Plomion, Christophe

2010-10-12

416

ADHD Symptom Rebound and Emotional Lability With Lisdexamfetamine Dimesylate in Children Aged 6 to 12 Years.  

PubMed

Objective: To describe symptom rebound in children with ADHD treated with lisdexamfetamine dimesylate (LDX) or placebo. Method: During a 4-week, randomized, double-blind, placebo-controlled trial of LDX, parents/caregivers completed the Conners' Parent Rating Scale-Revised: Short Form symptom rating scale throughout the day. Response, rebound, and emotional lability (EL) were assessed post hoc based on predefined criteria. Results: Most participants given LDX (n = 207) were responders throughout the day (50.7%-55.6%) versus placebo (n = 72; 11.1%-22.2%). A total of seven (3.4%) LDX participants showed rebound in the afternoon and/or evening versus seven (9.7%) with placebo. In both groups, most incidences of rebound occurred in the evening. EL (mean) was higher in LDX rebounders and nonresponders (range = 4.2-9.0) versus LDX responders (range = 1.3-1.6) and versus placebo rebounders (range = 0.7-1.9). Conclusion: ADHD symptom rebound occurred in few participants (3.3%) given LDX (accompanied by clinically significant EL). Overall, more participants given LDX versus placebo responded throughout the day. (J. of Att. Dis. 2012; XX(X) 1-XX). PMID:23407278

López, Frank A; Childress, Ann; Adeyi, Ben; Dirks, Bryan; Babcock, Thomas; Scheckner, Brian; Lasser, Robert; Shepski, John; Arnold, Valerie

2013-02-13

417

Labile Zn ions on octacalcium phosphate-derived Zn-containing hydroxyapatite surfaces  

NASA Astrophysics Data System (ADS)

We previously synthesized and characterized zinc-containing octacalcium phosphate (OCP) and its hydrolyzed Ca-deficient hydroxyapatite (HA). In the present report, we attempted to define the state of Zn in the OCP-derived Zn-calcium phosphates (CaPs) in relation to the presence of specific amino acids. Zn-containing OCPs were prepared in solutions that included Zn ions up to a concentration of 3.5 mM, and their hydrolyzates [hydrolyzed (hy)-Zn-CaP] were obtained in hot water. The materials were characterized by x-ray diffraction and scanning electron microscopy. The concentration of Ca and Zn ions at room temperature was determined by analyzing the supernatant after incubating the materials in ?-minimal essential medium (?-MEM) and HEPES buffer including cysteine, histidine, lysine, aspartic acid, and glutamic acid. Zn ions were more dissolved in ?-MEM than HEPES buffer in the absence of amino acids. The inclusion of the amino acids enhanced Zn dissolution by several hundred fold, even in HEPES buffer. Among the amino acids, both cysteine and histidine enhanced the release of Zn. The effect was particularly remarkable with cysteine even in the presence of the other amino acids tested. These results indicate that Zn ions are present as a surface labile pool, which tends to be preferentially desorbed by cysteine, a ubiquitous molecule present in serum.

Honda, Yoshitomo; Anada, Takahisa; Morimoto, Shinji; Suzuki, Osamu

2013-05-01

418

Residue Met(156) contributes to the labile enzyme conformation of coagulation factor VIIa.  

PubMed

Serine protease activation is typically controlled by proteolytic cleavage of the scissile bond, resulting in spontaneous formation of the activating Ile(16)-Asp(194) salt bridge. The initiating coagulation protease factor VIIa (VIIa) differs by remaining in a zymogen-like conformation that confers the control of catalytic activity to the obligatory cofactor and receptor tissue factor (TF). This study demonstrates that the unusual hydrophobic Met(156) residue contributes to the propensity of the VIIa protease domain to remain in a zymogen-like conformation. Mutation of Met(156) to Gln, which is found in the same position of the highly homologous factor IX, had no influence on the amidolytic and proteolytic activity of TF-bound VIIa. Furthermore, the mutation did not appreciably stabilize the labile Ile(16)-Asp(194) salt bridge in the absence of cofactor. VIIa(Gln156) had increased affinity for TF, consistent with a long range conformational effect that stabilized the cofactor binding site in the VIIa protease domain. Notably, in the absence of cofactor, amidolytic and proteolytic function of VIIa(Gln156) were enhanced 3- and 9-fold, respectively, compared with wild-type VIIa. The mutation thus selectively influenced the catalytic activity of free VIIa, identifying the Met(156) residue position as a determinant for the zymogen-like properties of free VIIa. PMID:11078728

Petrovan, R J; Ruf, W

2000-11-14

419

Lability of Neuronal Lineage Decisions Is Revealed by Acute Exposures to Ethanol  

PubMed Central

Developing neurons pass through periods of sensitivity to environmental factors, e.g., alterations induced by ethanol are defined when the exposure occurs. We tested the hypothesis that timely episodic prenatal exposure to ethanol can change the lineage of cortical neurons. This study exploited mice in which many layer V neurons expressed a Thy1-YFPh transgene and endogenously fluoresced yellow. Fetuses were exposed to ethanol or saline on gestational day (G) 14 (when layer V neurons were generated) or on G 15 or 17 (when these layer V neurons were migrating). Fetuses dosed on G 14 exhibited an increased frequency of YFP+ neurons across cortex. This contrasted with a decreased frequency following ethanol exposure on G 17. Ethanol did not affect overall density of layer V neurons or their generation. Thus, the magnitude and valence of ethanol-induced changes in YFP+ neurons are time-dependent. Cell lineage is defined at the time of origin and the window of lability for this definition continues into the early post-mitotic (migratory) period.

Miller, Michael W.; Hu, Huaiyu

2010-01-01

420

Soft antimicrobial agents: synthesis and activity of labile environmentally friendly long chain quaternary ammonium compounds.  

PubMed

A series of soft quaternary ammonium antimicrobial agents, which are analogues to currently used quaternary ammonium preservatives such as cetyl pyridinium chloride and benzalkonium chloride, were synthesized. These soft analogues consist of long alkyl chain connected to a polar headgroup via chemically labile spacer group. They are characterized by facile nonenzymatic and enzymatic degradation to form their original nontoxic building blocks. However, their chemical stability has to be adequate in order for them to have antimicrobial effects. Stability studies and antibacterial and antiviral activity measurements revealed relationship between activity, lipophilicity, and stability. Their minimum inhibitory concentration (MIC) was as low as 1 microg/mL, and their viral reduction was in some cases greater than 6.7 log. The structure-activity studies demonstrate that the bioactive compounds (i.e., MIC for Gram-positive bacteria of <10 microg/mL) have an alkyl chain length between 12 and 18 carbon atoms, with a polar headgroup preferably of a small quaternary ammonium group, and their acquired inactivation half-life must be greater than 3 h at 60 degrees C. PMID:12954069

Thorsteinsson, Thorsteinn; Másson, Már; Kristinsson, Karl G; Hjálmarsdóttir, Martha A; Hilmarsson, Hilmar; Loftsson, Thorsteinn

2003-09-11