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  • 1
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    Immunotherapeutic approaches to Alzheimer's disease (2003)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2003-11-01
    Description: Although neurodegenerative diseases such as Alzheimer's disease are not classically considered mediated by inflammation or the immune system, in some instances the immune system may play an important role in the degenerative process. Furthermore, it has become clear that the immune system itself may have beneficial effects in nervous system diseases considered neurodegenerative. Immunotherapeutic approaches designed to induce a humoral immune response have recently been developed for the treatment of Alzheimer's disease. These studies have led to human trials that resulted in both beneficial and adverse effects. In animal models, it has also been shown that immunotherapy designed to induce a cellular immune response may be of benefit in central nervous system injury, although T cells may have either a beneficial or detrimental effect depending on the type of T cell response induced. These areas provide a new avenue for exploring immune system-based therapy of neurodegenerative diseases and will be discussed here with a primary focus on Alzheimer's disease. We will also discuss how these approaches affect microglia activation, which plays a key role in therapy of such diseases.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Monsonego, Alon -- Weiner, Howard L -- New York, N.Y. -- Science. 2003 Oct 31;302(5646):834-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA. amonsonego@rics.bwh.harvard.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/14593170" target="_blank"〉PubMed〈/a〉
    Keywords: Alzheimer Disease/*therapy ; Alzheimer Vaccines/adverse effects/*therapeutic use ; Amyloid beta-Peptides/*immunology/metabolism ; Animals ; Antibody Formation ; Antigen-Presenting Cells/immunology ; Central Nervous System/immunology ; Clinical Trials as Topic ; Humans ; Immunity, Innate ; Immunity, Mucosal ; Immunization ; *Immunotherapy/adverse effects ; Lymphocyte Activation ; Microglia/immunology ; Nitric Oxide/metabolism ; T-Lymphocytes/immunology
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
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  • 2
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    Control of T(reg) and T(H)17 cell differentiation by the aryl hydrocarbon receptor (2008)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2008-03-26
    Description: Regulatory T cells (T(reg)) expressing the transcription factor Foxp3 control the autoreactive components of the immune system. The development of T(reg) cells is reciprocally related to that of pro-inflammatory T cells producing interleukin-17 (T(H)17). Although T(reg) cell dysfunction and/or T(H)17 cell dysregulation are thought to contribute to the development of autoimmune disorders, little is known about the physiological pathways that control the generation of these cell lineages. Here we report the identification of the ligand-activated transcription factor aryl hydrocarbon receptor (AHR) as a regulator of T(reg) and T(H)17 cell differentiation in mice. AHR activation by its ligand 2,3,7,8-tetrachlorodibenzo-p-dioxin induced functional T(reg) cells that suppressed experimental autoimmune encephalomyelitis. On the other hand, AHR activation by 6-formylindolo[3,2-b]carbazole interfered with T(reg) cell development, boosted T(H)17 cell differentiation and increased the severity of experimental autoimmune encephalomyelitis in mice. Thus, AHR regulates both T(reg) and T(H)17 cell differentiation in a ligand-specific fashion, constituting a unique target for therapeutic immunomodulation.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Quintana, Francisco J -- Basso, Alexandre S -- Iglesias, Antonio H -- Korn, Thomas -- Farez, Mauricio F -- Bettelli, Estelle -- Caccamo, Mario -- Oukka, Mohamed -- Weiner, Howard L -- AI435801/AI/NIAID NIH HHS/ -- NS38037/NS/NINDS NIH HHS/ -- P01 NS038037/NS/NINDS NIH HHS/ -- R01 AI073542/AI/NIAID NIH HHS/ -- R01 AI073542-01/AI/NIAID NIH HHS/ -- R01 AI073542-02/AI/NIAID NIH HHS/ -- R01 NS059996/NS/NINDS NIH HHS/ -- R01AI073542-01/AI/NIAID NIH HHS/ -- England -- Nature. 2008 May 1;453(7191):65-71. doi: 10.1038/nature06880. Epub 2008 Mar 23.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, Massachusetts 02115, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18362915" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Carbazoles/metabolism/pharmacology ; *Cell Differentiation ; Encephalomyelitis, Autoimmune, Experimental/chemically induced/immunology ; Forkhead Transcription Factors/genetics/metabolism ; Humans ; Indoles/metabolism/pharmacology ; Interleukin-17/*metabolism ; Ligands ; Mice ; Mice, Inbred C57BL ; Receptors, Aryl Hydrocarbon/genetics/*metabolism ; T-Lymphocytes, Helper-Inducer/*cytology/drug effects/*metabolism ; T-Lymphocytes, Regulatory/*cytology/drug effects/*metabolism ; Tetrachlorodibenzodioxin/metabolism/pharmacology ; Transforming Growth Factor beta1/immunology/metabolism
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
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  • 3
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    Shared human T cell receptor V beta usage to immunodominant regions of myelin basic protein (1990)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 1990-05-25
    Description: Multiple sclerosis (MS) may be an autoimmune disease mediated by T cells specific for a myelin protein. Investigations have demonstrated myelin basic protein (MBP)-reactive T cells that were activated in vivo in MS patients, suggesting that MBP may be a target antigen in MS. The variable (V) region of the T cell receptor (TCR) beta chain was examined among 83 T cell lines from both MS patients and healthy subjects that were reactive with the immunodominant region of human MBP (residues 84 to 102) or with a second immunodominant region of MBP (143 to 168). V beta 17 and to a lesser extent V beta 12 were frequently used in recognition of MBP(84-102) among different individuals. In contrast, V beta 17 was very infrequent among lines reactive with MBP (143-168). These data demonstrate shared TCR V beta gene usage for the recognition of immunodominant regions of the human autoantigen MBP. Such TCR structures may be used as targets for specific immunotherapy in MS.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wucherpfennig, K W -- Ota, K -- Endo, N -- Seidman, J G -- Rosenzweig, A -- Weiner, H L -- Hafler, D A -- 1 K11 HL 02228-01/HL/NHLBI NIH HHS/ -- NS 00981/NS/NINDS NIH HHS/ -- R01 NS 24247/NS/NINDS NIH HHS/ -- New York, N.Y. -- Science. 1990 May 25;248(4958):1016-9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/1693015" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Base Sequence ; Blotting, Southern ; Epitopes ; Gene Rearrangement, beta-Chain T-Cell Antigen Receptor ; Humans ; Molecular Sequence Data ; Multiple Sclerosis/immunology ; Myelin Basic Protein/*immunology ; Polymerase Chain Reaction ; Receptors, Antigen, T-Cell/*genetics ; Receptors, Antigen, T-Cell, alpha-beta ; T-Lymphocytes/*physiology
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
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  • 4
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    Regulatory T cell clones induced by oral tolerance: suppression of autoimmune encephalomyelitis (1994)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 1994-08-26
    Description: Experimental autoimmune encephalomyelitis (EAE) is a cell-mediated autoimmune disease that serves as an animal model for multiple sclerosis. Oral administration of myelin basic protein (MBP) suppresses EAE by inducing peripheral tolerance. T cell clones were isolated from the mesenteric lymph nodes of SJL mice that had been orally tolerized to MBP. These clones were CD4+ and were structurally identical to T helper cell type 1 (TH1) encephalitogenic CD4+ clones in T cell receptor usage, major histocompatibility complex restriction, and epitope recognition. However, they produced transforming growth factor-beta with various amounts of interleukin-4 and interleukin-10 and suppressed EAE induced with either MBP or proteolipid protein. Thus, mucosally derived TH2-like clones induced by oral antigen can actively regulate immune responses in vivo and may represent a different subset of T cells.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Chen, Y -- Kuchroo, V K -- Inobe, J -- Hafler, D A -- Weiner, H L -- AR/A143220/AR/NIAMS NIH HHS/ -- NS29352/NS/NINDS NIH HHS/ -- NS30843/NS/NINDS NIH HHS/ -- New York, N.Y. -- Science. 1994 Aug 26;265(5176):1237-40.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/7520605" target="_blank"〉PubMed〈/a〉
    Keywords: Administration, Oral ; Amino Acid Sequence ; Animals ; CD4-Positive T-Lymphocytes/*immunology ; Clone Cells ; Encephalomyelitis, Autoimmune, Experimental/*immunology ; Epitopes/immunology ; *Immune Tolerance ; Interleukin-10/biosynthesis ; Interleukin-4/biosynthesis ; Lymph Nodes/immunology ; Major Histocompatibility Complex ; Mesentery/immunology ; Mice ; Molecular Sequence Data ; Myelin Basic Protein/administration & dosage/*immunology ; Myelin Proteins/immunology ; Myelin Proteolipid Protein ; Receptors, Antigen, T-Cell/immunology ; Transforming Growth Factor beta/biosynthesis
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
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  • 5
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    Effects of oral administration of type II collagen on rheumatoid arthritis (1993)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 1993-09-24
    Description: Rheumatoid arthritis is an inflammatory synovial disease thought to involve T cells reacting to an antigen within the joint. Type II collagen is the major protein in articular cartilage and is a potential autoantigen in this disease. Oral tolerization to autoantigens suppresses animal models of T cell-mediated autoimmune disease, including two models of rheumatoid arthritis. In this randomized, double-blind trial involving 60 patients with severe, active rheumatoid arthritis, a decrease in the number of swollen joints and tender joints occurred in subjects fed chicken type II collagen for 3 months but not in those that received a placebo. Four patients in the collagen group had complete remission of the disease. No side effects were evident. These data demonstrate clinical efficacy of an oral tolerization approach for rheumatoid arthritis.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Trentham, D E -- Dynesius-Trentham, R A -- Orav, E J -- Combitchi, D -- Lorenzo, C -- Sewell, K L -- Hafler, D A -- Weiner, H L -- AG00294/AG/NIA NIH HHS/ -- MO1 RR01032/RR/NCRR NIH HHS/ -- New York, N.Y. -- Science. 1993 Sep 24;261(5129):1727-30.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Medicine, Beth Israel Hospital, Boston, MA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8378772" target="_blank"〉PubMed〈/a〉
    Keywords: Administration, Oral ; Adult ; Aged ; Arthritis, Rheumatoid/*drug therapy/immunology ; Autoimmune Diseases/*drug therapy/immunology ; Collagen/*administration & dosage/adverse effects/therapeutic use ; Double-Blind Method ; Female ; Humans ; Immune Tolerance ; Male ; Middle Aged ; Placebo Effect ; T-Lymphocytes/immunology
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 6
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    Double-blind pilot trial of oral tolerization with myelin antigens in multiple sclerosis (1993)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 1993-02-26
    Description: Multiple sclerosis (MS) is thought to be an autoimmune disease mediated by T lymphocytes that recognize myelin components of the central nervous system. In a 1-year double-blind study, 30 individuals with relapsing-remitting MS received daily capsules of bovine myelin or a control protein to determine the effect of oral tolerization to myelin antigens on the disease. Six of 15 individuals in the myelin-treated group had at least one major exacerbation; 12 or 15 had an attack in the control group. T cells reactive with myelin basic protein were reduced in the myelin-treated group. No toxicity or side effects were noted. Although conclusions about efficacy cannot be drawn from these data, they open an area of investigation for MS and other autoimmune diseases.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Weiner, H L -- Mackin, G A -- Matsui, M -- Orav, E J -- Khoury, S J -- Dawson, D M -- Hafler, D A -- NS23132/NS/NINDS NIH HHS/ -- NS24247/NS/NINDS NIH HHS/ -- New York, N.Y. -- Science. 1993 Feb 26;259(5099):1321-4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/7680493" target="_blank"〉PubMed〈/a〉
    Keywords: Adult ; Antigens, Differentiation, T-Lymphocyte/analysis ; Autoantigens/*administration & dosage ; Double-Blind Method ; Female ; HLA-DR2 Antigen/genetics ; Haplotypes ; Humans ; Immune Tolerance ; Male ; Multiple Sclerosis/genetics/*therapy ; Myelin Basic Protein/immunology ; Myelin Sheath/immunology ; Pilot Projects ; T-Lymphocytes/immunology
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 7
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    Immunology. How does the immune system tolerate food? (2016)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2016-02-26
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kuhn, Chantal -- Weiner, Howard L -- New York, N.Y. -- Science. 2016 Feb 19;351(6275):810-1. doi: 10.1126/science.aaf2167. Epub 2016 Feb 18.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA. ; Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA. hweiner@rics.bwh.harvard.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26912876" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Dietary Proteins/*immunology ; Dyspepsia/*immunology ; Gastrointestinal Microbiome/*immunology ; Intestine, Small/*immunology/*microbiology ; T-Lymphocytes, Regulatory/*immunology
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 8
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    Viral receptors on isolated murine and human ependymal cells (1982)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 1982-01-22
    Description: Viruses that infect ependyma cause ependymitis in humans and hydrocephalus in experimental animals. We report that reovirus type 1 (which induces hydrocephalus in mice) binds to the surface of isolated human and murine ciliated ependymal cells. With the use of recombinant viral clones, the binding property was mapped to the type 1 viral hemagglutinin, which also determines in vivo the affinity of reovirus type 1 for ependyma. Mumps virus, measles virus, parainfluenza type 3, and herpes simplex virus type 1 bind to murine ependyma cells, whereas reovirus type 3, herpes simplex virus type 2, and poliovirus type 2 do not.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Tardieu, M -- Weiner, H L -- 1K07-NS00237/NS/NINDS NIH HHS/ -- NSAI-16998/NS/NINDS NIH HHS/ -- New York, N.Y. -- Science. 1982 Jan 22;215(4531):419-21.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/6276976" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cells, Cultured ; Ependyma/*metabolism/microbiology ; Hemagglutinins, Viral/metabolism ; Humans ; Hydrocephalus/microbiology ; Measles virus/metabolism ; Mice ; Mumps virus/metabolism ; Parainfluenza Virus 3, Human/metabolism ; Receptors, Virus/*metabolism ; Reoviridae/*metabolism ; Simplexvirus/metabolism
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
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  • 9
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    Tissue distribution and developmental expression of the messenger RNA encoding angiogenin (1987)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 1987-07-17
    Description: New blood vessel growth occurs during normal fetal development and in diseases such as cancer and diabetes. The polypeptide angiogenin induces new blood vessel growth in two biological assays and may play a role in the vascular development of the fetus and in the neovascularization that accompanies diseases and wound healing. A complementary DNA probe for human angiogenin was used to examine the tissue distribution of angiogenin messenger RNA (mRNA) in the developing rat and in selected transformed cell lines. Angiogenin mRNA was detected predominantly in adult liver but was also detectable at low levels in other tissues. The expression of the angiogenin gene in rat liver was found to be developmentally regulated; mRNA levels were low in the developing fetus, increased in the neonate, and maximal in the adult. The amount of angiogenin mRNA in human HT-29 colon carcinoma and SK-HEP hepatoma cells was not greater than that in normal rat liver. These results demonstrate that angiogenin is predominantly expressed in adult liver, that the pattern of angiogenin gene expression is not temporally related to vascular development in the rat, and that the transformed cells studied do not contain more angiogenin mRNA than does normal liver. If angiogenin activity is controlled at the transcriptional level, the results of this study suggest that the primary function of angiogenin in vivo may be in processes other than the regulation of vascular growth.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Weiner, H L -- Weiner, L H -- Swain, J L -- HL26831/HL/NHLBI NIH HHS/ -- New York, N.Y. -- Science. 1987 Jul 17;237(4812):280-2.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2440105" target="_blank"〉PubMed〈/a〉
    Keywords: Age Factors ; Animals ; Cell Line ; Gene Expression Regulation ; Humans ; Liver/physiology ; Neoplasm Proteins/*genetics ; Neovascularization, Pathologic ; RNA, Messenger/genetics ; Rats ; *Ribonuclease, Pancreatic ; Tissue Distribution
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 10
    Electronic Resource
    Electronic Resource
    Oral Tolerance: Immunologic Mechanisms and Treatment of Animal and Human Organ-Specific Autoimmune Diseases by Oral Administration of Autoantigens (1994)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Immunology 12 (1994), S. 809-837 
    Details
    ISSN: 0732-0582
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1146/annurev.iy.12.040194.004113
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