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Analysis of Ag-presenting cells in the conjunctiva during the development of experimental immune-mediated blepharoconjunctivitis.

https://arctichealth.org/en/permalink/ahliterature50604
Source
Curr Eye Res. 2004 Oct-Nov;29(4-5):277-86
Publication Type
Article
Author
Akemi Ozaki
Atsuki Fukushima
Waka Ishida
Olga Zinchuk
Kazuyo Fukata
Yoshihiro Hayashi
Hideaki Enzan
Masaru Takata
Hideo Yagita
Hisayuki Ueno
Author Affiliation
Department of Ophthalmology, Kochi Medical School, Kohasu, Oko-cho, Nankoku City 783-8505, Japan.
Source
Curr Eye Res. 2004 Oct-Nov;29(4-5):277-86
Language
English
Publication Type
Article
Keywords
Animals
Antigen-Presenting Cells - immunology
Antigens, CD - metabolism
Antigens, CD86
Blepharitis - immunology
Blotting, Western
Cell Count
Conjunctiva - immunology
Conjunctivitis, Allergic - immunology
Extracellular Signal-Regulated MAP Kinases - metabolism
Flow Cytometry
Histocompatibility Antigens Class II - metabolism
Immunoenzyme Techniques
Immunophenotyping
Lymphocyte Activation
Macrophages - immunology
Male
Membrane Glycoproteins - metabolism
Microscopy, Confocal
Models, Theoretical
Ovalbumin - immunology
Phosphorylation
Rats
Rats, Inbred BN
T-Lymphocytes - immunology
Abstract
PURPOSE: The aim of this study was to investigate the phenotypes of antigen (Ag) presenting cells (APCs) in the conjunctiva during the development of experimental immune-mediated blepharoconjunctivitis (EC), which serves as a model for investigation of severe types of human allergic conjunctivitis. METHODS: Brown Norway rats treated by ovalbumin (OVA) were used in this study. To confirm the restriction of MHC class II by OVA-specific T cells, monoclonal Abs against MHC class II were added to the conventional proliferation assay. To evaluate the MHC class II expression in the conjunctiva during the development of EC, an immunohistochemical analysis, either as the single or double staining, was performed. Conjunctival fibroblast cell lines were established from naive rats and the MHC class II expression was evaluated by flow cytometric analysis. To examine the roles of costimulatory molecules, OVA-specific T cells were stimulated with anti-TcR Ab and anti-CD28 Ab and then subjected for Western blotting to evaluate the ERK phosphorylation. Finally, in vivo expression of B7 molecules was examined immunohistochemically. RESULTS: OVA-specific T cells recognized OVA in the context of MHC class II. MHC class II was expressed in conjunctival macrophages but not in fibroblasts. EC induction was accompanied by abundant infiltration of macrophages positive for MHC class II. MHC class II was also expressed in conjunctival epithelial cells by EC induction. Stimulation from CD28 was necessary for ERK phosphorylation. B7-2, but not B7-1, was expressed in the conjunctiva. CONCLUSION: Conjunctival macrophages may represent a major source of APCs for the induction of EC in the conjunctiva.
PubMed ID
15590473 View in PubMed
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[Anders Jahre Prize for young researchers 1993. Syndecan--a regulator of growth factor activities between cells and cell matrix interface]

https://arctichealth.org/en/permalink/ahliterature23845
Source
Nord Med. 1994;109(3):72-3
Publication Type
Article
Date
1994
Author
M. Jalkanen
Author Affiliation
Bioteknikcentrum, Abo Universitet och Abo Akademi.
Source
Nord Med. 1994;109(3):72-3
Date
1994
Language
Swedish
Publication Type
Article
Keywords
Awards and Prizes
Cell Division
Cell Transformation, Neoplastic
English Abstract
Extracellular Matrix Proteins - metabolism
Fibroblast Growth Factor 1 - metabolism
Heparitin Sulfate - metabolism
Membrane Glycoproteins - metabolism
Molecular Biology
Proteoglycans - metabolism
Signal Transduction
Sweden
Abstract
Syndecans are a four member family of cell surface proteoglycans, which via their heparan sulfate chains can bind both extracellular matrix molecules and heparin-binding growth factors. In signal transduction they cooperate with tyrosine kinase receptors and thus can participate in the regulation of cell growth and behaviour. Besides the fact that their developmental expression follows morphogenetic rather than histological boundaries, also changes in their expression take place during development of diseases. Among these, the loss of syndecan expression during malignant transformation suggests that syndecans could play a role in restricting tumor growth and metastasis.
PubMed ID
7511221 View in PubMed
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The ATF6-Met[67]Val substitution is associated with increased plasma cholesterol levels.

https://arctichealth.org/en/permalink/ahliterature149216
Source
Arterioscler Thromb Vasc Biol. 2009 Sep;29(9):1322-7
Publication Type
Article
Date
Sep-2009
Author
Steven J R Meex
Daphna Weissglas-Volkov
Carla J H van der Kallen
Donna J Thuerauf
Marleen M J van Greevenbroek
Casper G Schalkwijk
Coen D A Stehouwer
Edith J M Feskens
Lonneke Heldens
Torik A Ayoubi
Marten H Hofker
Bradly G Wouters
Robert Vlietinck
Janet S Sinsheimer
Marja-Riitta Taskinen
Johanna Kuusisto
Markku Laakso
Tjerk W A de Bruin
Päivi Pajukanta
Christopher C Glembotski
Author Affiliation
Department of Internal Medicine and Cardiovascular Research Institute Maastricht, Wageningen University, The Netherlands. steven.meex@intmed.unimaas.nl
Source
Arterioscler Thromb Vasc Biol. 2009 Sep;29(9):1322-7
Date
Sep-2009
Language
English
Publication Type
Article
Keywords
Activating Transcription Factor 6 - blood - genetics
Amino Acid Substitution
Apolipoproteins B - blood
Cardiovascular Diseases - blood - genetics
Cholesterol - blood
Cohort Studies
Finland
Genetic Predisposition to Disease
Hela Cells
Heat-Shock Proteins - genetics - metabolism
Humans
Hyperlipidemia, Familial Combined - blood - genetics
Membrane Glycoproteins - metabolism
Methionine
Netherlands
Polymorphism, Single Nucleotide
Promoter Regions, Genetic
Risk assessment
Transfection
Up-Regulation
Valine
Abstract
Activating transcription factor 6 (ATF6) is a sensor of the endoplasmic reticulum stress response and regulates expression of several key lipogenic genes. We used a 2-stage design to investigate whether ATF6 polymorphisms are associated with lipids in subjects at increased risk for cardiovascular disease (CVD).
In stage 1, 13 tag-SNPs were tested for association in Dutch samples ascertained for familial combined hyperlipidemia (FCHL) or increased risk for CVD (CVR). In stage 2, we further investigated the SNP with the strongest association from stage 1, a Methionine/Valine substitution at amino-acid 67, in Finnish FCHL families and in subjects with CVR from METSIM, a Finnish population-based cohort. The combined analysis of both stages reached region-wide significance (P=9 x 10(-4)), but this association was not seen in the entire METSIM cohort. Our functional analysis demonstrated that Valine at position 67 augments ATF6 protein and its targets Grp78 and Grp94 as well as increases luciferase expression through Grp78 promoter.
A common nonsynonymous variant in ATF6 increases ATF6 protein levels and is associated with cholesterol levels in subjects at increased risk for CVD, but this association was not seen in a population-based cohort. Further replication is needed to confirm the role of this variant in lipids.
Notes
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PubMed ID
19667116 View in PubMed
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Biglycan deficiency interferes with ovariectomy-induced bone loss.

https://arctichealth.org/en/permalink/ahliterature52066
Source
J Bone Miner Res. 2003 Dec;18(12):2152-8
Publication Type
Article
Date
Dec-2003
Author
Karina L Nielsen
Matthew R Allen
Susan A Bloomfield
Thomas L Andersen
Xiao-Dong Chen
Hans S Poulsen
Marian F Young
Anne-Marie Heegaard
Author Affiliation
Nordic Bioscience A/S, Herlev, Denmark. kln@nordicbioscience.com
Source
J Bone Miner Res. 2003 Dec;18(12):2152-8
Date
Dec-2003
Language
English
Publication Type
Article
Keywords
Animals
Bone Density
Carrier Proteins - metabolism
Female
Glycoproteins - metabolism
Male
Membrane Glycoproteins - metabolism
Mice
Mice, Inbred C57BL
Mice, Knockout
Models, Animal
Osteoclasts - physiology
Osteoporosis - prevention & control
Ovariectomy
Proteoglycans - deficiency
Receptors, Cytoplasmic and Nuclear - metabolism
Receptors, Tumor Necrosis Factor
Research Support, Non-U.S. Gov't
Abstract
Biglycan is a matrix proteoglycan with a possible role in bone turnover. In a 4-week study with sham-operated or OVX biglycan-deficient or wildtype mice, we show that biglycan-deficient mice are resistant to OVX-induced trabecular bone loss and that there is a gender difference in the response to biglycan deficiency. INTRODUCTION: Biglycan (bgn) is a small extracellular matrix proteoglycan enriched in skeletal tissues, and biglycan-deficient male mice have decreased trabecular bone mass and bone strength. The purpose of this study was to investigate the bone phenotype of the biglycan-deficient female mice and to investigate the effect of estrogen depletion by ovariectomy (OVX). MATERIALS AND METHODS: OVX or sham operations were performed on 21-week-old mice that were divided into four groups: wt sham (n = 7), wt OVX (n = 9), bgn-deficient sham (n = 10) and bgn-deficient OVX (n = 10). The mice were killed 4 weeks after surgery. Bone mass and bone turnover were analyzed by peripheral quantitative computed tomography (pQCT), biochemical markers, and histomorphometry. RESULTS AND CONCLUSIONS: In contrast to the male mice, there were only few effects of bgn deficiency on bone metabolism in female mice, showing a clear gender difference. However, when stressed by OVX, the female bgn knockout (KO) mice were resistant to the OVX-induced trabecular bone loss. The wt mice showed a decrease in trabecular bone mineral density by pQCT measurements, a decrease in trabecular bone volume (BV/TV), and an increase in mineral apposition rate. In contrast, no significant changes were detected in bgn KO mice after OVX. In addition, analysis of the bone resorption marker deoxypyridinoline showed no significant increase in the bgn KO OVX mice compared with bgn KO sham mice. Measurements of serum osteoprotegerin (OPG) and RANKL revealed increased levels of OPG and decreased levels of RANKL in the bgn KO mice compared with wt mice. In conclusion, the bgn deficiency protects against increased trabecular bone turnover and bone loss in response to estrogen depletion, supporting the concept that bgn has dual roles in bone, where it may modulate both formation and resorption ultimately influencing the bone turnover process.
PubMed ID
14672350 View in PubMed
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Breast cancer biological subtypes and protein expression predict for the preferential distant metastasis sites: a nationwide cohort study.

https://arctichealth.org/en/permalink/ahliterature131332
Source
Breast Cancer Res. 2011;13(5):R87
Publication Type
Article
Date
2011
Author
Harri Sihto
Johan Lundin
Mikael Lundin
Tiina Lehtimäki
Ari Ristimäki
Kaija Holli
Liisa Sailas
Vesa Kataja
Taina Turpeenniemi-Hujanen
Jorma Isola
Päivi Heikkilä
Heikki Joensuu
Author Affiliation
Laboratory of Molecular Oncology, University of Helsinki, Biomedicum Helsinki, Haartmaninkatu 8, 00290, Helsinki, Finland. harri.sihto@helsinki.fi
Source
Breast Cancer Res. 2011;13(5):R87
Date
2011
Language
English
Publication Type
Article
Keywords
Antigens, CD - metabolism
Bone Neoplasms - metabolism - secondary
Brain Neoplasms - metabolism - secondary
Breast Neoplasms - metabolism - pathology
Cadherins - metabolism
Cohort Studies
Cyclooxygenase 2 - metabolism
Female
Finland
Follow-Up Studies
Glycoproteins - metabolism
Humans
Intermediate Filament Proteins - metabolism
Keratin-5 - metabolism
Liver Neoplasms - metabolism - secondary
Lung Neoplasms - metabolism - secondary
Nerve Tissue Proteins - metabolism
Nestin
Peptides - metabolism
Proteins - analysis - metabolism
Receptor, Epidermal Growth Factor - metabolism
Receptor, erbB-2 - metabolism
Receptors, Estrogen - metabolism
Receptors, Progesterone - metabolism
Skin Neoplasms - metabolism - secondary
Transcription Factors - metabolism
Abstract
Some molecular subtypes of breast cancer have preferential sites of distant relapse. The protein expression pattern of the primary tumor may influence the first distant metastasis site.
We identified from the files of the Finnish Cancer Registry patients diagnosed with breast cancer in five geographical regions Finland in 1991-1992, reviewed the hospital case records, and collected primary tumor tissue. Out of the 2,032 cases identified, 234 developed distant metastases after a median follow-up time of 2.7 years and had the first metastatic site documented (a total of 321 sites). Primary tumor microarray (TMA) cores were analyzed for 17 proteins using immunohistochemistry and for erbB2 using chromogenic in situ hybridization, and their associations with the first metastasis site were examined. The cancers were classified into luminal A, luminal B, HER2+ enriched, basal-like or non-expressor subtypes.
A total of 3,886 TMA cores were analyzed. Luminal A cancers had a propensity to give rise first to bone metastases, HER2-enriched cancers to liver and lung metastases, and basal type cancers to liver and brain metastases. Primary tumors that gave first rise to bone metastases expressed frequently estrogen receptor (ER) and SNAI1 (SNAIL) and rarely COX2 and HER2, tumors with first metastases in the liver expressed infrequently SNAI1, those with lung metastases expressed frequently the epidermal growth factor receptor (EGFR), cytokeratin-5 (CK5) and HER2, and infrequently progesterone receptor (PgR), tumors with early skin metastases expressed infrequently E-cadherin, and breast tumors with first metastases in the brain expressed nestin, prominin-1 and CK5 and infrequently ER and PgR.
Breast tumor biological subtypes have a tendency to give rise to first distant metastases at certain body sites. Several primary tumor proteins were associated with homing of breast cancer cells.
Notes
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PubMed ID
21914172 View in PubMed
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CD80(B7.1) and CD86(B7.2) do not have distinct roles in setting the Th1/Th2 balance in autoimmunity in rats.

https://arctichealth.org/en/permalink/ahliterature57471
Source
Scand J Immunol. 2001 Nov;54(5):486-94
Publication Type
Article
Date
Nov-2001
Author
I A MacPhee
D R Turner
H. Yagita
D B Oliveira
Author Affiliation
Department of Renal Medicine, St. George's Hospital Medical School, Cranmer Terrace, London SW17 0RE, UK. imacphee@sghms.ac.uk
Source
Scand J Immunol. 2001 Nov;54(5):486-94
Date
Nov-2001
Language
English
Publication Type
Article
Keywords
Animals
Antibodies, Monoclonal - pharmacology
Antigens, CD - metabolism
Antigens, CD80 - metabolism
Antigens, CD86
Autoimmunity - drug effects
Encephalomyelitis, Autoimmune, Experimental - immunology
Female
Immunoglobulin E - biosynthesis
Lymphocyte Activation
Male
Membrane Glycoproteins - metabolism
Mercuric Chloride - toxicity
Rats
Rats, Inbred BN
Rats, Inbred Lew
Th1 Cells - immunology
Th2 Cells - immunology
Vasculitis - immunology
Weight Loss - immunology
Abstract
Some data suggest that the interaction between CD28 and CD80 (B7.1) stimulates Th1-responses and that CD28 and CD86 (B7.2) stimulates Th2-responses, however this is controversial. We addressed this issue by using mercuric chloride (HgCl2)-induced autoimmunity in Brown Norway (BN) rats as a highly polarized Th2 model and experimental autoimmune encephalomyelitis (EAE) in Lewis rats as a highly polarized Th1 model. Monoclonal antibodies (MoAbs) to CD80 and CD86, given singly, had little effect in either model, however when given together they almost completely suppressed the HgCl2-induced autoimmunity: the peak immunoglobulin (Ig)E concentration was 3.25 microg/ml in treated animals versus 2770 microg/ml in controls (P
PubMed ID
11696200 View in PubMed
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CDw150 associates with src-homology 2-containing inositol phosphatase and modulates CD95-mediated apoptosis.

https://arctichealth.org/en/permalink/ahliterature51619
Source
J Immunol. 1999 May 15;162(10):5719-27
Publication Type
Article
Date
May-15-1999
Author
S V Mikhalap
L M Shlapatska
A G Berdova
C L Law
E A Clark
S P Sidorenko
Author Affiliation
Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology, Academy of Science of Ukraine, Kiev, Ukraine.
Source
J Immunol. 1999 May 15;162(10):5719-27
Date
May-15-1999
Language
English
Publication Type
Article
Keywords
Antigens, CD45 - metabolism
Antigens, CD95 - metabolism
Apoptosis
B-Lymphocytes - metabolism
Carrier Proteins - metabolism
Glycoproteins - metabolism
Immunoglobulins - metabolism
Intracellular Signaling Peptides and Proteins
Lymphoproliferative Disorders - immunology
Phosphoric Monoester Hydrolases - metabolism
Protein Binding
Protein-Serine-Threonine Kinases
Protein-Tyrosine Kinase - metabolism
Proto-Oncogene Proteins - metabolism
Proto-Oncogene Proteins c-akt
Receptor Aggregation
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Research Support, U.S. Gov't, P.H.S.
Signal Transduction
src Homology Domains
Abstract
CDw150, a receptor up-regulated on activated T or B lymphocytes, has a key role in regulating B cell proliferation. Patients with X-linked lymphoproliferative disease have mutations in a gene encoding a protein, DSHP/SAP, which interacts with CDw150 and is expressed in B cells. Here we show that CDw150 on B cells associates with two tyrosine-phosphorylated proteins, 59 kDa and 145 kDa in size. The 59-kDa protein was identified as the Src-family kinase Fgr. The 145-kDa protein is the inositol polyphosphate 5'-phosphatase, SH2-containing inositol phosphatase (SHIP). Both Fgr and SHIP interact with phosphorylated tyrosines in CDw150's cytoplasmic tail. Ligation of CDw150 induces the rapid dephosphorylation of both SHIP and CDw150 as well as the association of Lyn and Fgr with SHIP. CD95/Fas-mediated apoptosis is enhanced by signaling via CDw150, and CDw150 ligation can override CD40-induced rescue of CD95-mediated cell death. The ability of CDw150 to regulate cell death does not correlate with serine phosphorylation of the Akt kinase, but does correlate with SHIP tyrosine dephosphorylation. Thus, the CDw150 receptor may function to regulate the fate of activated B cells via SHIP as well as via the DSHP/SAP protein defective in X-linked lymphoproliferative disease patients.
PubMed ID
10229804 View in PubMed
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Critical role of photoreceptor apoptosis in functional damage after retinal detachment.

https://arctichealth.org/en/permalink/ahliterature50744
Source
Curr Eye Res. 2002 Mar;24(3):161-72
Publication Type
Article
Date
Mar-2002
Author
Toshio Hisatomi
Taiji Sakamoto
Yoshinobu Goto
Ichiro Yamanaka
Yuji Oshima
Yasuaki Hata
Tatsuro Ishibashi
Hajime Inomata
Santos A Susin
Guido Kroemer
Author Affiliation
Department of Ophthalmology, Graduate School of Medical Sciences, Kyushu University, Higashi-ku, Fukuoka, Japan.
Source
Curr Eye Res. 2002 Mar;24(3):161-72
Date
Mar-2002
Language
English
Publication Type
Article
Keywords
Animals
Antigens, CD95 - metabolism
Apoptosis - physiology
Apoptosis Inducing Factor
Caspases - antagonists & inhibitors
Cell Count
Cytochrome c Group - metabolism
Electroretinography
Enzyme Inhibitors - pharmacology
Flavoproteins - metabolism
Growth Substances - pharmacology
Membrane Glycoproteins - metabolism
Membrane Proteins - metabolism
Nerve Growth Factor - pharmacology
Photoreceptors - metabolism - pathology - physiopathology
Rats
Rats, Inbred BN
Research Support, Non-U.S. Gov't
Retina - metabolism - pathology
Retinal Detachment - pathology - physiopathology
Abstract
PURPOSE: Although apoptosis is assumed to play a pivotal role in retinal function loss, its mechanism and real influence on retinal function are still unclear. To investigate the relation between retinal function and apoptosis, we studied photoreceptor apoptosis in experimental retinal detachment (RD). METHODS: We induced RD by subretinal injection of sodium hyaluronate in Brown Norway rats. Apoptotic photoreceptors were detected by TdT-dUTP Terminal Nick-End Labeling (TUNEL). To evaluate the function of the detached retina, electroretinograms (ERGs) were taken on day 1, 3 with corneal electrodes and full-field stimulation. RESULTS: Apoptotic DNA fragmentation appeared 12 hours after RD, was most prominent on day 3, and decreased thereafter. The ERGs showed that the amplitudes of dark-adapted a-waves and light adapted 2 Hz b-waves decreased immediately after RD and continued to decrease over time. The administration of Fas/Fc chimera recombinant protein or a caspase inhibitor, Z-VAD.fmk, failed to prevent either photoreceptor apoptosis or retinal functional damage. In contrast, brain derived neurotrophic factor (BDNF) and basic fibroblast growth factor (bFGF) significantly impeded both apoptosis and dysfunction. The ERGs recognized the functional changes sensitively, and these ERG changes correlated well to the amount of photoreceptor apoptosis. Immunohistochemical study showed that apoptosis-inducing factor (AIF), a novel caspase-independent apoptotic factor, was relocalized from mitochondria to the nucleus in this process. CONCLUSIONS: The present results showed that apoptosis was a key phenomenon in the retinal dysfunction in RD and that this process was transmitted mainly by mitochondria-dependent pathways rather than Fas/Fas-L or downstream caspase dependent pathways.
PubMed ID
12221523 View in PubMed
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30 records – page 1 of 3.