Kooperativer Bibliotheksverbund

Berlin Brandenburg

X
and
and

Your email was sent successfully. Check your inbox.

An error occurred while sending the email. Please try again.

Proceed reservation?

Export
Filter
Type of Medium
Language
Year
Person/Organisation
Topic
Source
Journal
  • 1
    Article
    Article
    Pathogenetic mechanisms of amyloid A amyloidosis (2013)
    Details
    Language: English
    In: Proceedings of the National Academy of Sciences of the United States of America, 01 October 2013, Vol.110(40), pp.16115-20
    Description: Systemic amyloid A (AA) amyloidosis is a serious complication of chronic inflammation. Serum AA protein (SAA), an acute phase plasma protein, is deposited extracellularly as insoluble amyloid fibrils that damage tissue structure and function. Clinical AA amyloidosis is typically preceded by many years of active inflammation before presenting, most commonly with renal involvement. Using dose-dependent, doxycycline-inducible transgenic expression of SAA in mice, we show that AA amyloid deposition can occur independently of inflammation and that the time before amyloid deposition is determined by the circulating SAA concentration. High level SAA expression induced amyloidosis in all mice after a short, slightly variable delay. SAA was rapidly incorporated into amyloid, acutely reducing circulating SAA concentrations by up to 90%. Prolonged modest SAA overexpression occasionally produced amyloidosis after long delays and primed most mice for explosive amyloidosis when SAA production subsequently increased. Endogenous priming and bulk amyloid deposition are thus separable events, each sensitive to plasma SAA concentration. Amyloid deposits slowly regressed with restoration of normal SAA production after doxycycline withdrawal. Reinduction of SAA overproduction revealed that, following amyloid regression, all mice were primed, especially for rapid glomerular amyloid deposition leading to renal failure, closely resembling the rapid onset of renal failure in clinical AA amyloidosis following acute exacerbation of inflammation. Clinical AA amyloidosis rarely involves the heart, but amyloidotic SAA transgenic mice consistently had minor cardiac amyloid deposits, enabling us to extend to the heart the demonstrable efficacy of our unique antibody therapy for elimination of visceral amyloid.
    Keywords: 3rs ; Disease Model ; Amyloid -- Metabolism ; Amyloidosis -- Physiopathology ; Inflammation -- Complications ; Serum Amyloid A Protein -- Metabolism
    ISSN: 00278424
    E-ISSN: 1091-6490
    DOI: 10.1073/pnas.1306621110
    URL: View this record in MEDLINE/PubMed
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Article
    Open Access Request
  • 2
    Article
    Article
    Antibodies to human serum amyloid P component eliminate visceral amyloid deposits (2010)
    Details
    Language: English
    In: Nature, 04 November 2010, Vol.468(7320), pp.93-7
    Description: Accumulation of amyloid fibrils in the viscera and connective tissues causes systemic amyloidosis, which is responsible for about one in a thousand deaths in developed countries. Localized amyloid can also have serious consequences; for example, cerebral amyloid angiopathy is an important cause of haemorrhagic stroke. The clinical presentations of amyloidosis are extremely diverse and the diagnosis is rarely made before significant organ damage is present. There is therefore a major unmet need for therapy that safely promotes the clearance of established amyloid deposits. Over 20 different amyloid fibril proteins are responsible for different forms of clinically significant amyloidosis and treatments that substantially reduce the abundance of the respective amyloid fibril precursor proteins can arrest amyloid accumulation. Unfortunately, control of fibril-protein production is not possible in some forms of amyloidosis and in others it is often slow and hazardous. There is no therapy that directly targets amyloid deposits for enhanced clearance. However, all amyloid deposits contain the normal, non-fibrillar plasma glycoprotein, serum amyloid P component (SAP). Here we show that administration of anti-human-SAP antibodies to mice with amyloid deposits containing human SAP triggers a potent, complement-dependent, macrophage-derived giant cell reaction that swiftly removes massive visceral amyloid deposits without adverse effects. Anti-SAP-antibody treatment is clinically feasible because circulating human SAP can be depleted in patients by the bis-d-proline compound CPHPC, thereby enabling injected anti-SAP antibodies to reach residual SAP in the amyloid deposits. The unprecedented capacity of this novel combined therapy to eliminate amyloid deposits should be applicable to all forms of systemic and local amyloidosis.
    Keywords: Amyloid -- Drug Effects ; Amyloidosis -- Prevention & Control ; Antibodies -- Immunology ; Serum Amyloid P-Component -- Antagonists & Inhibitors
    ISSN: 00280836
    E-ISSN: 1476-4687
    DOI: 10.1038/nature09494
    URL: View this record in MEDLINE/PubMed
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Article
    Open Access Request
  • 3
    Article
    Article
    Hereditary Systemic Amyloidosis Due to Asp76Asn Variant β 2 -Microglobulin (2012)
    Details
    In: The New England Journal of Medicine, 2012, Vol.366(24), pp.2276-2283
    Description: We describe a kindred with slowly progressive gastrointestinal symptoms and autonomic neuropathy caused by autosomal dominant, hereditary systemic amyloidosis. The amyloid consists of Asp76Asn variant β 2 -microglobulin. Unlike patients with dialysis-related amyloidosis caused by sustained high plasma concentrations of wild-type β 2 -microglobulin, the affected members of this kindred had normal renal function and normal circulating β 2 -microglobulin values. The Asp76Asn β 2 -microglobulin variant was thermodynamically unstable and remarkably fibrillogenic in vitro under physiological conditions. Previous studies of β 2 -microglobulin aggregation have not shown such amyloidogenicity for single-residue substitutions. Comprehensive biophysical characterization of the β 2 -microglobulin variant, including its 1.40-Å, three-dimensional structure, should allow further elucidation of fibrillogenesis and protein misfolding. A kindred with familial amyloidosis was found to have bowel and autonomic dysfunction and the sicca syndrome from an aspartate-to-asparagine alteration at amino acid 76 of β2-microglobulin. Unexpectedly, this alteration promoted fibrillogenesis and tissue deposition. Summary We describe a kindred with slowly progressive gastrointestinal symptoms and autonomic neuropathy caused by autosomal dominant, hereditary systemic amyloidosis. The amyloid consists of Asp76Asn variant β2-microglobulin. Unlike patients with dialysis-related amyloidosis caused by sustained high plasma concentrations of wild-type β2-microglobulin, the affected members of this kindred had normal renal function and normal circulating β2-microglobulin values. The Asp76Asn β2-microglobulin variant was thermodynamically unstable and remarkably fibrillogenic in vitro under physiological conditions. Previous studies of β2-microglobulin aggregation have not shown such amyloidogenicity for single-residue substitutions. Comprehensive biophysical characterization of the β . . .
    Keywords: Amyloidosis, Familial -- Genetics ; Beta 2-Microglobulin -- Genetics;
    ISSN: 0028-4793
    E-ISSN: 1533-4406
    DOI: 10.1056/NEJMoa1201356
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Article
    Open Access Request
  • 4
    Article
    Article
    Trapping of palindromic ligands within native transthyretin prevents amyloid formation.(MEDICAL SCIENCES)(Author abstract)(Report) (2010)
    Details
    Language: English
    In: Proceedings of the National Academy of Sciences of the United States, Nov 23, 2010, Vol.107(47), p.20483(6)
    Description: Transthyretin (TTR) amyloidosis is a fatal disease for which new therapeutic approaches are urgently needed. We have designed two palindromic ligands, 2,2'-(4,4'-(heptane-1,7-diylbis(oxy))bis (3,5-dichloro-4,1-phenylene)) bis(azanediyl)dibenzoic acid (mds84) and 2,2'-(4,4'-(undecane-1,11-diylbis(oxy))bis(3,5-dichloro-4,1-phenylene)) bis(azanediyl)dibenzoic acid (4ajm15), that are rapidly bound by native wild-type TTR in whole serum and even more avidly by amyloidogenic TTR variants. One to one stoichiometry, demonstrable in solution and by MS, was confirmed by X-ray crystallographic analysis showing simultaneous occupation of both T4 binding sites in each tetrameric TrR molecule by the pair of ligand head groups. Ligand binding by native TTR was irreversible under physiological conditions, and it stabilized the tetrameric assembly and inhibited amyloidogenic aggregation more potently than other known ligands. These superstabilizers are orally bioavailable and exhibit low inhibitory activity against cyclooxygenase (COX). They offer a promising platform for development of drugs to treat and prevent TTR amyloidosis. crystallography | mass spectrometry | protein structure | stabilization doi/ 10.1073/pnas.1008255107
    Keywords: Amyloidosis -- Research ; Base Sequence -- Research ; Ligands (Biochemistry) -- Research
    ISSN: 0027-8424
    Source: Cengage Learning, Inc.
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Article
  • 5
    Article
    Article
    Trapping of palindromic ligands within native transthyretin prevents amyloid formation (2010)
    Details
    Language: English
    In: Proceedings of the National Academy of Sciences of the United States of America, 23 November 2010, Vol.107(47), pp.20483-8
    Description: Transthyretin (TTR) amyloidosis is a fatal disease for which new therapeutic approaches are urgently needed. We have designed two palindromic ligands, 2,2'-(4,4'-(heptane-1,7-diylbis(oxy))bis(3,5-dichloro-4,1-phenylene)) bis(azanediyl)dibenzoic acid (mds84) and 2,2'-(4,4'-(undecane-1,11-diylbis(oxy))bis(3,5-dichloro-4,1-phenylene)) bis(azanediyl)dibenzoic acid (4ajm15), that are rapidly bound by native wild-type TTR in whole serum and even more avidly by amyloidogenic TTR variants. One to one stoichiometry, demonstrable in solution and by MS, was confirmed by X-ray crystallographic analysis showing simultaneous occupation of both T4 binding sites in each tetrameric TTR molecule by the pair of ligand head groups. Ligand binding by native TTR was irreversible under physiological conditions, and it stabilized the tetrameric assembly and inhibited amyloidogenic aggregation more potently than other known ligands. These superstabilizers are orally bioavailable and exhibit low inhibitory activity against cyclooxygenase (COX). They offer a promising platform for development of drugs to treat and prevent TTR amyloidosis.
    Keywords: Ligands ; Amyloid -- Biosynthesis ; Amyloidosis -- Metabolism ; Fenamates -- Metabolism ; Prealbumin -- Metabolism
    ISSN: 00278424
    E-ISSN: 1091-6490
    DOI: 10.1073/pnas.1008255107
    URL: View this record in MEDLINE/PubMed
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Article
    Open Access Request
  • 6
    Article
    Article
    Isolation and characterization of pharmaceutical grade human pentraxins, serum amyloid P component and C‐reactive protein, for clinical use (2012)
    Details
    Language: English
    In: Journal of Immunological Methods, 31 October 2012, Vol.384(1-2), pp.92-102
    Description: The human pentraxin proteins, serum amyloid P component (SAP) and C‐reactive protein (CRP) are important in routine clinical diagnosis, SAP for systemic amyloidosis and CRP for monitoring the non‐specific acute phase response. They are also targets for novel therapies currently in development but their roles in health and disease are controversial. Thus, both for clinical use and to rigorously elucidate their functions, structurally and functionally intact, pharmaceutical grade preparations of the natural, authentic proteins are required. We report here the production from normal human donor plasma and the characterization of the first such preparations. Importantly, we demonstrate that, contrary to reports using recombinant proteins and less well characterized preparations, neither CRP nor SAP stimulate the release by human peripheral blood mononuclear cells of any TNFα, IL‐6 or IL‐8, nor does SAP cause release of IL‐1β or IL‐10. Furthermore neither of our preparations was pro‐inflammatory in mice .
    Keywords: C‐Reactive Protein ; Cytokine ; Good Manufacturing Practice ; Mononuclear Cells ; Pharmaceutical ; Serum Amyloid P Component ; Medicine ; Biology
    ISSN: 0022-1759
    E-ISSN: 1872-7905
    DOI: 10.1016/j.jim.2012.07.013
    URL: View record in ScienceDirect (Access to full text may be restricted)
    URL: View full text in ScienceDirect
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Article
    Open Access Request
  • 7
    Article
    Article
    Trapping of palindromic ligands within native transthyretin prevents amyloid formation (2015)
    Details
    Language: English
    In: 2015
    Keywords: Blood Serum ; Ligands ; Amyloidosis ; Drugs ; Binding Sites ; X-Ray Diffraction ; Stoichiometry ; Prostaglandin Synthase ; Amyloid ; Prealbumin
    Source: AGRIS (Food and Agriculture Organization of the United Nations)
    URL: View full text (authentication may be required)
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Article
  • 8
    Article
    Article
    Antibodies to human serum amyloid P component eliminate visceral amyloid deposits (2010)
    Details
    In: Nature, 2010, Vol.468(7320), p.93
    ISSN: 0028-0836
    E-ISSN: 1476-4687
    DOI: 10.1038/nature09494
    Source: Nature Publishing Group
    URL: View this record in Nature
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Article
    Open Access Request
  • 9
    Article
    Article
    Structural and functional characterization of three human immunoglobulin κ light chains with different pathological implications (1996)
    Details
    Language: English
    In: BBA - Molecular Basis of Disease, 1996, Vol.1317(3), pp.161-167
    Description: The structural properties of three immunoglobulins light chains: κ SCI, responsible for light chain deposition disease (Bellotti, V., Stoppini, M., Merlini, G., Zapponi, M.C., Meloni, M.L., Banfi, G. and Ferri, G. (1991) Biochim. Biophys. Acta 1097, 177–182), k INC responsible for light chain amyloidosis (Ferri, G., Stoppini, M., Iadarola, P., Bellotti, V. and Merlini, G. (1989) Biochim. Biophys. Acta 995, 103–108) and the non-pathogenic κ MOS were analyzed by fluorescence spectroscopy and circular dichroism. Comparative evaluation of the data shows that SCI and MOS have similar stability under different conditions, while the amyloid k INC behaves as a very unstable protein. As calculated from the GdnHCl curves, the midpoint of unfolding transition was 1.35 M for SCI, 1.20 M for MOS and 0.1 M for INC. Analysis of CD spectra evidences that the three proteins conserve their conformation in the range of pH 4–8. Change in temperature at pH 4.0 produces the premature transition of INC ( T m 40°C) with respect to SCI and MOS ( T m 50°C). At this pH both the pathological SCI and INC light chains aggregate at a temperature of 20°C lower than the normal counterpart. The specific kidney deposition of κ SCI has been evidenced after injection of the 125 I labelled light chain into mice. No deposition was detectable in the case of INC and MOS.
    Keywords: Light Chain ; Light Chain Deposition Disease ; Amyloidosis ; Unfolding ; Biology ; Chemistry
    ISSN: 0925-4439
    E-ISSN: 1879-260X
    DOI: 10.1016/S0925-4439(96)00049-X
    URL: View record in ScienceDirect (Access to full text may be restricted)
    URL: View full text in ScienceDirect
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Article
    Open Access Request
  • 10
    Article
    Article
    Structural basis of ligand specificity in the human pentraxins, C-reactive protein and serum amyloid P component (2011)
    Details
    Language: English
    In: Journal of molecular recognition : JMR, 2011, Vol.24(2), pp.371-7
    Description: The normal physiological roles of the phylogenetically conserved human plasma proteins C-reactive protein (CRP) and serum amyloid P component (SAP) are not known. Novel drugs targeting their ligand specificities are in clinical development as both proteins have significant pathophysiological effects, SAP in promoting amyloidosis and CRP in exacerbating ischemic injury. Both proteins bind to phosphoethanolamine and we show here that, under physiological conditions, phosphoethanolamine is bound with higher affinity by human SAP than by human CRP. An explanation is provided by X-ray crystal structures that show SAP residue Tyr74 allowing additional hydrophobic protein-ligand interactions compared with the equivalent Thr76 of CRP. Docking simulations show many more low energy positions for phosphoethanolamine bound by CRP than by SAP and are consistent with the crystallographic and functional binding results. These fundamental observations on structure-activity relationships will aid the design of improved pentraxin targeting drugs.
    Keywords: C-Reactive Protein -- Chemistry ; Serum Amyloid P-Component -- Chemistry
    E-ISSN: 1099-1352
    DOI: 10.1002/jmr.1090
    URL: View this record in MEDLINE/PubMed
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Article
    Open Access Request
Nothing or not found what you are looking for? Please check your search query or use the Interlibrary Loan Search.
Close ⊗
This website uses cookies and the analysis tool Matomo. Further information can be found on the KOBV privacy pages