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Article ; Online: The fungal pattern recognition receptor, Dectin-1, and the associated cluster of C-type lectin-like receptors.

Huysamen, Cristal / Brown, Gordon D

2008 Volume 290, Issue 2, Page(s) 121–128

Abstract: The mammalian natural killer gene complex (NKC) contains several families of type II transmembrane C-type lectin-like receptors (CLRs) that are best known for their involvement in the detection of virally infected or transformed cells, through the ... ...

Abstract	The mammalian natural killer gene complex (NKC) contains several families of type II transmembrane C-type lectin-like receptors (CLRs) that are best known for their involvement in the detection of virally infected or transformed cells, through the recognition of endogenous (or self) proteinacious ligands. However, certain CLR families within the NKC, particularly those expressed by myeloid cells, recognize structurally diverse ligands and perform a variety of other immune and homoeostatic functions. One such family is the 'Dectin-1 cluster' of CLRs, which includes MICL, CLEC-2, CLEC12B, CLEC9A, CLEC-1, Dectin-1 and LOX-1. Here, we review each of these CLRs, exploring our current understanding of their ligands and functions and highlighting where they have provided new insights into the underlying mechanisms of immunity and homeostasis.
MeSH term(s)	Animals ; Fungi/immunology ; Humans ; Lectins, C-Type/immunology ; Membrane Proteins/immunology ; Mycoses/immunology ; Mycoses/microbiology ; Nerve Tissue Proteins/immunology ; Receptors, Mitogen/immunology ; Receptors, Pattern Recognition/immunology
Chemical Substances	Lectins, C-Type ; Membrane Proteins ; Nerve Tissue Proteins ; Receptors, Mitogen ; Receptors, Pattern Recognition ; dectin 1
Language	English
Publishing date	2008-01-11
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	752343-9
ISSN	1574-6968 ; 0378-1097
ISSN (online)	1574-6968
ISSN	0378-1097
DOI	10.1111/j.1574-6968.2008.01418.x
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Article: The fungal pattern recognition receptor, Dectin-1, and the associated cluster of C-type lectin-like receptors

Huysamen, Cristal / Brown, Gordon D

FEMS microbiology letters. 2009 Jan., v. 290, no. 2

2009

Abstract	The mammalian natural killer gene complex (NKC) contains several families of type II transmembrane C-type lectin-like receptors (CLRs) that are best known for their involvement in the detection of virally infected or transformed cells, through the recognition of endogenous (or self) proteinacious ligands. However, certain CLR families within the NKC, particularly those expressed by myeloid cells, recognize structurally diverse ligands and perform a variety of other immune and homoeostatic functions. One such family is the 'Dectin-1 cluster' of CLRs, which includes MICL, CLEC-2, CLEC12B, CLEC9A, CLEC-1, Dectin-1 and LOX-1. Here, we review each of these CLRs, exploring our current understanding of their ligands and functions and highlighting where they have provided new insights into the underlying mechanisms of immunity and homeostasis.
Keywords	homeostasis
Language	English
Dates of publication	2009-01
Size	p. 121-128.
Publisher	Blackwell Publishing Ltd
Publishing place	Oxford, UK
Document type	Article
ZDB-ID	752343-9
ISSN	1574-6968 ; 0378-1097
ISSN (online)	1574-6968
ISSN	0378-1097
DOI	10.1111/j.1574-6968.2008.01418.x
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Article: CLEC9A is a novel activation C-type lectin-like receptor expressed on BDCA3+ dendritic cells and a subset of monocytes.

Huysamen, Cristal / Willment, Janet A / Dennehy, Kevin M / Brown, Gordon D

The Journal of biological chemistry

2008 Volume 283, Issue 24, Page(s) 16693–16701

Abstract: We describe here the first characterization of CLEC9A, a group V C-type lectin-like receptor located in the "Dectin-1 cluster" of related receptors, which are encoded within the natural killer (NK)-gene complex. Expression of human CLEC9A is highly ... ...

Abstract	We describe here the first characterization of CLEC9A, a group V C-type lectin-like receptor located in the "Dectin-1 cluster" of related receptors, which are encoded within the natural killer (NK)-gene complex. Expression of human CLEC9A is highly restricted in peripheral blood, being detected only on BDCA3(+) dendritic cells and on a small subset of CD14(+)CD16(-) monocytes. CLEC9A is expressed at the cell surface as a glycosylated dimer and can mediate endocytosis, but not phagocytosis. CLEC9A possesses a cytoplasmic immunoreceptor tyrosine-based activation-like motif that can recruit Syk kinase, and we demonstrate, using receptor chimeras, that this receptor can induce proinflammatory cytokine production. These data indicate that CLEC9A functions as an activation receptor.
MeSH term(s)	Amino Acid Motifs ; Amino Acid Sequence ; Animals ; Base Sequence ; Dendritic Cells/cytology ; Endocytosis ; Humans ; Intracellular Signaling Peptides and Proteins/metabolism ; Lectins, C-Type ; Lipopolysaccharide Receptors/biosynthesis ; Mice ; Models, Biological ; Molecular Sequence Data ; Monocytes/cytology ; Protein-Tyrosine Kinases/metabolism ; Receptors, IgG/biosynthesis ; Receptors, Mitogen/chemistry ; Receptors, Mitogen/metabolism ; Receptors, Mitogen/physiology ; Syk Kinase
Chemical Substances	CLEC9a protein, human ; Intracellular Signaling Peptides and Proteins ; Lectins, C-Type ; Lipopolysaccharide Receptors ; Receptors, IgG ; Receptors, Mitogen ; Protein-Tyrosine Kinases (EC 2.7.10.1) ; SYK protein, human (EC 2.7.10.2) ; Syk Kinase (EC 2.7.10.2) ; Syk protein, mouse (EC 2.7.10.2)
Language	English
Publishing date	2008-04-11
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2997-x
ISSN	1083-351X ; 0021-9258
ISSN (online)	1083-351X
ISSN	0021-9258
DOI	10.1074/jbc.M709923200
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Article ; Online: Assessing the DNA methylation status of single cells with the comet assay.

Wentzel, Johannes F / Gouws, Chrisna / Huysamen, Cristal / Dyk, Etresia van / Koekemoer, Gerhard / Pretorius, Pieter J

Analytical biochemistry

2010 Volume 400, Issue 2, Page(s) 190–194

Abstract: The comet assay (single cell gel electrophoresis) is a cost-effective, sensitive, and simple technique that is traditionally used for analyzing and quantifying DNA damage in individual cells. The aim of this study was to determine whether the comet assay ...

Abstract	The comet assay (single cell gel electrophoresis) is a cost-effective, sensitive, and simple technique that is traditionally used for analyzing and quantifying DNA damage in individual cells. The aim of this study was to determine whether the comet assay could be modified to detect changes in the levels of DNA methylation in single cells. We used the difference in methylation sensitivity of the isoschizomeric restriction endonucleases HpaII and MspI to demonstrate the feasibility of the comet assay to measure the global DNA methylation level of individual cells. The results were verified with the well-established cytosine extension assay. We were able to show variations in DNA methylation after treatment of cultured cells with 5-azacytidine and succinylacetone, an accumulating metabolite in human tyrosinemia type I.
MeSH term(s)	Azacitidine/chemistry ; Azacitidine/pharmacology ; Comet Assay/methods ; Cytosine/metabolism ; DNA Methylation ; DNA-Cytosine Methylases/metabolism ; Deoxyribonuclease HpaII/metabolism ; Hep G2 Cells ; Heptanoates/chemistry ; Heptanoates/pharmacology ; Humans ; Tyrosinemias/metabolism
Chemical Substances	Heptanoates ; succinylacetone (51568-18-4) ; Cytosine (8J337D1HZY) ; DNA modification methylase HpaII (EC 2.1.1.-) ; DNA-Cytosine Methylases (EC 2.1.1.-) ; Deoxyribonuclease HpaII (EC 3.1.21.-) ; Azacitidine (M801H13NRU)
Language	English
Publishing date	2010-05-15
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1110-1
ISSN	1096-0309 ; 0003-2697
ISSN (online)	1096-0309
ISSN	0003-2697
DOI	10.1016/j.ab.2010.02.008
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Article: CLEC9A Is a Novel Activation C-type Lectin-like Receptor Expressed on BDCA3⁺ Dendritic Cells and a Subset of Monocytes

Huysamen, Cristal / Willment, Janet A / Dennehy, Kevin M / Brown, Gordon D

Journal of biological chemistry. 2008 June 13, v. 283, no. 24

2008

Abstract	We describe here the first characterization of CLEC9A, a group V C-type lectin-like receptor located in the "Dectin-1 cluster" of related receptors, which are encoded within the natural killer (NK)-gene complex. Expression of human CLEC9A is highly restricted in peripheral blood, being detected only on BDCA3⁺ dendritic cells and on a small subset of CD14⁺CD16⁻ monocytes. CLEC9A is expressed at the cell surface as a glycosylated dimer and can mediate endocytosis, but not phagocytosis. CLEC9A possesses a cytoplasmic immunoreceptor tyrosine-based activation-like motif that can recruit Syk kinase, and we demonstrate, using receptor chimeras, that this receptor can induce proinflammatory cytokine production. These data indicate that CLEC9A functions as an activation receptor.
Language	English
Dates of publication	2008-0613
Size	p. 16693-16701.
Publishing place	American Society for Biochemistry and Molecular Biology
Document type	Article
ZDB-ID	2997-x
ISSN	1083-351X ; 0021-9258
ISSN (online)	1083-351X
ISSN	0021-9258
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Article: Characterisation of murine MICL (CLEC12A) and evidence for an endogenous ligand.

Pyz, Elwira / Huysamen, Cristal / Marshall, Andrew S J / Gordon, Siamon / Taylor, Philip R / Brown, Gordon D

European journal of immunology

2008 Volume 38, Issue 4, Page(s) 1157–1163

Abstract: Inhibitory receptors are required for the control of cellular activation and they play essential roles in regulating homeostasis and immunity. We previously identified a human inhibitory C-type lectin-like receptor, MICL (CLEC12A), a heavily glycosylated ...

Abstract	Inhibitory receptors are required for the control of cellular activation and they play essential roles in regulating homeostasis and immunity. We previously identified a human inhibitory C-type lectin-like receptor, MICL (CLEC12A), a heavily glycosylated monomer predominantly expressed on myeloid cells. Here we characterise the murine homolog of MICL (mMICL), and demonstrate that the receptor is structurally and functionally similar to the human orthologue (hMICL), although there are some notable differences. mMICL is expressed as a dimer and is not heavily glycosylated; however, like hMICL, the receptor can recruit inhibitory phosphatases upon activation, and is down-regulated on leukocytes following stimulation with selected TLR agonists. Using novel monoclonal antibodies, we demonstrate that, like the human receptor, mMICL is predominantly expressed by myeloid cells. However, mMICL is also expressed by B cells and CD8+ T cells in peripheral blood, and NK cells in the bone marrow. Finally, we show that mMICL recognises an endogenous ligand in a variety of murine tissues, suggesting that the receptor plays a role in homeostasis.
MeSH term(s)	Amino Acid Sequence ; Animals ; Humans ; Lectins, C-Type/chemistry ; Lectins, C-Type/genetics ; Lectins, C-Type/metabolism ; Ligands ; Mice ; Molecular Sequence Data ; Rats ; Receptors, Mitogen/chemistry ; Receptors, Mitogen/genetics ; Receptors, Mitogen/metabolism ; Sequence Alignment ; Sequence Homology, Amino Acid
Chemical Substances	CLEC12A protein, mouse ; Lectins, C-Type ; Ligands ; Receptors, Mitogen
Language	English
Publishing date	2008-03-19
Publishing country	Germany
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	120108-6
ISSN	1521-4141 ; 0014-2980
ISSN (online)	1521-4141
ISSN	0014-2980
DOI	10.1002/eji.200738057
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Article: Characterisation of murine MICL (CLEC12A) and evidence for an endogenous ligand

Pyż, Elwira / Huysamen, Cristal / Marshall, Andrew S.J / Gordon, Siamon / Taylor, Philip R / Brown, Gordon D

European journal of immunology. 2008 Apr., v. 38, no. 4

2008

Abstract	Inhibitory receptors are required for the control of cellular activation and they play essential roles in regulating homeostasis and immunity. We previously identified a human inhibitory C-type lectin-like receptor, MICL (CLEC12A), a heavily glycosylated monomer predominantly expressed on myeloid cells. Here we characterise the murine homolog of MICL (mMICL), and demonstrate that the receptor is structurally and functionally similar to the human orthologue (hMICL), although there are some notable differences. mMICL is expressed as a dimer and is not heavily glycosylated; however, like hMICL, the receptor can recruit inhibitory phosphatases upon activation, and is down-regulated on leukocytes following stimulation with selected TLR agonists. Using novel monoclonal antibodies, we demonstrate that, like the human receptor, mMICL is predominantly expressed by myeloid cells. However, mMICL is also expressed by B cells and CD8⁺ T cells in peripheral blood, and NK cells in the bone marrow. Finally, we show that mMICL recognises an endogenous ligand in a variety of murine tissues, suggesting that the receptor plays a role in homeostasis.
Language	English
Dates of publication	2008-04
Size	p. 1157-1163.
Publishing place	Wiley-VCH Verlag
Document type	Article
ZDB-ID	120108-6
ISSN	1521-4141 ; 0014-2980
ISSN (online)	1521-4141
ISSN	0014-2980
DOI	10.1002/eji.200738057
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Article ; Online: In vitro antioxidant, antimutagenic and genoprotective activity of Rosa roxburghii fruit extract.

van der Westhuizen, Francois H / van Rensburg, Catharina S Janse / Rautenbach, George S / Marnewick, Jeanine L / Loots, Du Toit / Huysamen, Cristal / Louw, Roan / Pretorius, Pieter J / Erasmus, Elardus

Phytotherapy research : PTR

2008 Volume 22, Issue 3, Page(s) 376–383

Abstract: The antioxidant properties of the fruit of the Rosa roxburghii (RR) plant have been associated with several putative health promoting effects. The possible cytotoxic, mutagenic/antimutagenic and genotoxic effects of RR fruit extract were investigated. ... ...

Abstract	The antioxidant properties of the fruit of the Rosa roxburghii (RR) plant have been associated with several putative health promoting effects. The possible cytotoxic, mutagenic/antimutagenic and genotoxic effects of RR fruit extract were investigated. The effect on antioxidant status and protection against induced oxidative stress were also investigated using primary rat hepatocytes. A RR fruit extract containing 45 g/L total ascorbic acid and 65 g/L total polyphenols was used in this study. Dilutions up to 0.08% (v/v) increased significantly the antioxidant status in primary rat hepatocytes. The glutathione redox state was decreased with RR treatment but was increased in Chang liver cells and MT-2 lymphoblast. No cyto- or genotoxicity were observed at levels of up to 5% (v/v) of the fruit extract. In addition, a significant protection against t-BHP induced oxidative stress was observed in primary rat hepatocytes. The Ames test revealed no mutagenic activity using the Salmonella typhimurium strains TA98, TA100 and TA102. A significant antimutagenic effect of the extract was observed against the metabolic activated mutagens 2-acetylaminofluorene and aflatoxin B1 and to a lesser extent against methyl methanesulfonate. It is concluded that these results support the associated health promoting potential of Rosa Roxburghii fruit and in particular against oxidative stress.
MeSH term(s)	Animals ; Antimutagenic Agents/pharmacology ; Antioxidants/pharmacology ; Carcinogens/pharmacology ; Cells, Cultured ; Comet Assay ; DNA Damage/drug effects ; Fruit/chemistry ; Glutathione/analysis ; Glutathione/drug effects ; Hepatocytes/cytology ; Hepatocytes/drug effects ; Male ; Oxidation-Reduction/drug effects ; Oxidative Stress/drug effects ; Plant Extracts/pharmacology ; Plant Extracts/toxicity ; Rats ; Rats, Sprague-Dawley ; Rosa/chemistry ; Salmonella typhimurium/drug effects ; tert-Butylhydroperoxide/pharmacology
Chemical Substances	Antimutagenic Agents ; Antioxidants ; Carcinogens ; Plant Extracts ; tert-Butylhydroperoxide (955VYL842B) ; Glutathione (GAN16C9B8O)
Language	English
Publishing date	2008-03
Publishing country	England
Document type	Journal Article
ZDB-ID	639136-9
ISSN	1099-1573 ; 0951-418X
ISSN (online)	1099-1573
ISSN	0951-418X
DOI	10.1002/ptr.2330
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Zs.B 3092: Show issues

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Article: In vitro antioxidant, antimutagenic and genoprotective activity of Rosa roxburghii fruit extract

van der Westhuizen, Francois H / van Rensburg, Catharina S. Janse / Rautenbach, George S / Marnewick, Jeanine L / Loots, Du Toit / Huysamen, Cristal / Louw, Roan / Pretorius, Pieter J / Erasmus, Elardus

Phytotherapy research. 2008 Mar., v. 22, no. 3

2008

Abstract	The antioxidant properties of the fruit of the Rosa roxburghii (RR) plant have been associated with several putative health promoting effects. The possible cytotoxic, mutagenic/antimutagenic and genotoxic effects of RR fruit extract were investigated. The effect on antioxidant status and protection against induced oxidative stress were also investigated using primary rat hepatocytes. A RR fruit extract containing 45 g/L total ascorbic acid and 65 g/L total polyphenols was used in this study. Dilutions up to 0.08% (v/v) increased significantly the antioxidant status in primary rat hepatocytes. The glutathione redox state was decreased with RR treatment but was increased in Chang liver cells and MT-2 lymphoblast. No cyto- or genotoxicity were observed at levels of up to 5% (v/v) of the fruit extract. In addition, a significant protection against t-BHP induced oxidative stress was observed in primary rat hepatocytes. The Ames test revealed no mutagenic activity using the Salmonella typhimurium strains TA98, TA100 and TA102. A significant antimutagenic effect of the extract was observed against the metabolic activated mutagens 2-acetylaminofluorene and aflatoxin B1 and to a lesser extent against methyl methanesulfonate. It is concluded that these results support the associated health promoting potential of Rosa Roxburghii fruit and in particular against oxidative stress. Copyright © 2007 John Wiley & Sons, Ltd.
Keywords	Ames test ; Rosa ; Salmonella typhimurium ; aflatoxin B1 ; antimutagenic activity ; antioxidant activity ; antioxidants ; ascorbic acid ; cytotoxicity ; fruit extracts ; fruits ; genotoxicity ; hepatocytes ; methyl methanesulfonate ; mutagenicity ; oxidative stress ; polyphenols ; rats
Language	English
Dates of publication	2008-03
Size	p. 376-383.
Publishing place	John Wiley & Sons, Ltd.
Document type	Article
ZDB-ID	639136-9
ISSN	1099-1573 ; 0951-418X
ISSN (online)	1099-1573
ISSN	0951-418X
DOI	10.1002/ptr.2330
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Article ; Online: Human dectin-1 deficiency and mucocutaneous fungal infections.

Ferwerda, Bart / Ferwerda, Gerben / Plantinga, Theo S / Willment, Janet A / van Spriel, Annemiek B / Venselaar, Hanka / Elbers, Clara C / Johnson, Melissa D / Cambi, Alessandra / Huysamen, Cristal / Jacobs, Liesbeth / Jansen, Trees / Verheijen, Karlijn / Masthoff, Laury / Morré, Servaas A / Vriend, Gert / Williams, David L / Perfect, John R / Joosten, Leo A B /

Wijmenga, Cisca / van der Meer, Jos W M / Adema, Gosse J / Kullberg, Bart Jan / Brown, Gordon D / Netea, Mihai G

The New England journal of medicine

2011 Volume 361, Issue 18, Page(s) 1760–1767

Abstract: Mucocutaneous fungal infections are typically found in patients who have no known immune defects. We describe a family in which four women who were affected by either recurrent vulvovaginal candidiasis or onychomycosis had the early-stop-codon mutation ... ...

Abstract	Mucocutaneous fungal infections are typically found in patients who have no known immune defects. We describe a family in which four women who were affected by either recurrent vulvovaginal candidiasis or onychomycosis had the early-stop-codon mutation Tyr238X in the beta-glucan receptor dectin-1. The mutated form of dectin-1 was poorly expressed, did not mediate beta-glucan binding, and led to defective production of cytokines (interleukin-17, tumor necrosis factor, and interleukin-6) after stimulation with beta-glucan or Candida albicans. In contrast, fungal phagocytosis and fungal killing were normal in the patients, explaining why dectin-1 deficiency was not associated with invasive fungal infections and highlighting the specific role of dectin-1 in human mucosal antifungal defense.
MeSH term(s)	Animals ; Candida albicans/immunology ; Candidiasis/genetics ; Candidiasis/immunology ; Candidiasis, Chronic Mucocutaneous/genetics ; Candidiasis, Vulvovaginal/genetics ; Codon, Nonsense ; Cytokines/biosynthesis ; Female ; Genetic Predisposition to Disease ; Humans ; Lectins, C-Type ; Male ; Mammals/genetics ; Membrane Proteins/deficiency ; Membrane Proteins/genetics ; Membrane Proteins/immunology ; Nerve Tissue Proteins/deficiency ; Nerve Tissue Proteins/genetics ; Nerve Tissue Proteins/immunology ; Onychomycosis/genetics ; Pedigree
Chemical Substances	Codon, Nonsense ; Cytokines ; Lectins, C-Type ; Membrane Proteins ; Nerve Tissue Proteins ; dectin 1
Language	English
Publishing date	2011-09-06
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	207154-x
ISSN	1533-4406 ; 0028-4793
ISSN (online)	1533-4406
ISSN	0028-4793
DOI	10.1056/NEJMoa0901053
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