33 results match your criteria deposition agrin

Neuronal MT1-MMP mediates ECM clearance and Lrp4 cleavage for agrin deposition and signaling in presynaptic development.

J Cell Sci 2020 08 5;133(15). Epub 2020 Aug 5.

School of Biomedical Sciences, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong

Agrin is a crucial factor that induces postsynaptic differentiation at neuromuscular junctions (NMJs), but how secreted agrin is locally deposited in the context of extracellular matrix (ECM) environment and its function in presynaptic differentiation remain largely unclear. Here, we report that the proteolytic activity of neuronal membrane-type 1 matrix metalloproteinase (MT1-MMP; also known as MMP14) facilitates agrin deposition and signaling during presynaptic development at NMJs. Firstly, agrin deposition along axons exhibits a time-dependent increase in cultured neurons that requires MMP-mediated focal ECM degradation. Read More

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MASP-2 Is a Heparin-Binding Protease; Identification of Blocking Oligosaccharides.

Front Immunol 2020 28;11:732. Epub 2020 Apr 28.

Department of Nephrology, University Medical Center Groningen, Groningen, Netherlands.

It is well-known that heparin and other glycosaminoglycans (GAGs) inhibit complement activation. It is however not known whether fractionation and/or modification of GAGs might deliver pathway-specific inhibition of the complement system. Therefore, we evaluated a library of GAGs and their derivatives for their functional pathway specific complement inhibition, including the MASP-specific C4 deposition assay. Read More

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Plasma vitronectin is reduced in patients with myasthenia gravis: Diagnostic and pathophysiological potential.

J Circ Biomark 2019 Jan-Dec;8:1849454419875912. Epub 2019 Sep 11.

Department of Biomedical Sciences, University of Sassari, Viale San Pietro, Sassari, Italy.

Myasthenia gravis (MG) is an autoimmune disease leading to varying degrees of skeletal muscle weakness. It is caused by specific antibodies directed against definite components in the postsynaptic membrane at the neuromuscular junction (NMJ), such as the acetylcholine receptor (AChR) and the muscle-specific kinase (MUSK) receptor. In clinical practice, MG patients may be classified into three main subgroups based on the occurrence of serum autoantibodies directed against AChR or MUSK receptor or antibody-negative. Read More

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September 2019

Distinctive peri-luminal presence of agrin in murine and human carotid atherosclerotic plaques.

Histol Histopathol 2018 Jul 6;33(7):717-726. Epub 2018 Feb 6.

Department of Experimental Medical Science, Lund University, Lund, Sweden.

The clinical consequences of arterial atherosclerotic lesions depend, apart from their size, on their composition of cellular and extracellular components. While an intact endothelium at the interface of atherosclerotic plaques towards the blood can prevent its erosion, underlying smooth muscle cells within the plaque can reduce the risk of plaque ruptures, due to the deposition of stabilizing extracellular matrix. Basement membranes underlay and support the function of endothelial cells, and embed smooth muscle cells in the media, the source of most smooth muscle cells within atherosclerotic plaques. Read More

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Synthesis and deposition of basement membrane proteins by primary brain capillary endothelial cells in a murine model of the blood-brain barrier.

J Neurochem 2017 03 8;140(5):741-754. Epub 2016 Sep 8.

Laboratory of Neurobiology, Department of Health Science and Technology, Aalborg University, Aalborg, Denmark.

The brain vascular basement membrane is important for both blood-brain barrier (BBB) development, stability, and barrier integrity and the contribution hereto from brain capillary endothelial cells (BCECs), pericytes, and astrocytes of the BBB is probably significant. The aim of this study was to analyse four different in vitro models of the murine BBB for expression and possible secretion of major basement membrane proteins from murine BCECs (mBCECs). mBCECs, pericytes and glial cells (mainly astrocytes and microglia) were prepared from brains of C57BL/6 mice. Read More

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The protective role of fucosylated chondroitin sulfate, a distinct glycosaminoglycan, in a murine model of streptozotocin-induced diabetic nephropathy.

PLoS One 2014 5;9(9):e106929. Epub 2014 Sep 5.

Serviço e Disciplina de Nefrologia, Departamento de Clínica Médica and Hospital Universitário Clementino Fraga Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.

Background: Heparanase-1 activation, albuminuria, and a decrease in glomerular heparan sulfate (HS) have been described in diabetic nephropathy (DN). Glycosaminoglycan (GAG)-based drugs have been shown to have renoprotective effects in this setting, although recent trials have questioned their clinical effectiveness. Here, we describe the effects of fucosylated chondroitin sulfate (FCS), a novel GAG extracted from a marine echinoderm, in experimentally induced DN compared to a widely used GAG, enoxaparin (ENX). Read More

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February 2016

The heparan sulfate proteoglycan agrin contributes to barrier properties of mouse brain endothelial cells by stabilizing adherens junctions.

Cell Tissue Res 2014 Nov 9;358(2):465-79. Epub 2014 Aug 9.

Theodor Kocher Institute, University of Bern, Freiestrasse 1, 3012, Bern, Switzerland.

Barrier characteristics of brain endothelial cells forming the blood-brain barrier (BBB) are tightly regulated by cellular and acellular components of the neurovascular unit. During embryogenesis, the accumulation of the heparan sulfate proteoglycan agrin in the basement membranes ensheathing brain vessels correlates with BBB maturation. In contrast, loss of agrin deposition in the vasculature of brain tumors is accompanied by the loss of endothelial junctional proteins. Read More

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November 2014

Extracellular matrix alterations in late-onset Fuchs' corneal dystrophy.

Invest Ophthalmol Vis Sci 2014 May 15;55(6):3700-8. Epub 2014 May 15.

Department of Ophthalmology, Friedrich-Alexander University Erlangen-Nuremberg, Erlangen, Germany.

Purpose: To characterize the alterations of extracellular matrix proteins in Descemet's membranes (DM) of patients with late-onset Fuchs' corneal dystrophy (FCD) and to differentiate them from nonspecific alterations in pseudophakic bullous keratopathy (PBK).

Methods: Human DM-endothelial cell complexes were obtained from patients with late-onset FCD (n = 40), PBK (n = 6), and control eyes (n = 5). Gene expression profiles of endothelial cells were compared using a commercial real-time PCR array and quantitative real-time PCR assays for confirmation of differentially expressed genes. Read More

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Ultrastructural alterations of human cortical capillary basement membrane in human brain oedema.

Folia Neuropathol 2014 ;52(1):10-21

Prof. Orlando José Castejón, MD, Biological Research Institute, Faculty of Medicine, Zulia University, Maracaibo, Venezuela, fax: 58-261-7831611, e-mail:

The capillary basement membranes are examined in severe traumatic brain injuries, vascular malformation, congenital hydrocephalus and brain tumours. They exhibit homogeneous and nodular thickening, vacuolization, rarefaction, reduplication, and deposition of collagen fibers. Their average thickness varied according to the aetiology and severity of brain oedema. Read More

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Nephronectin binds to heparan sulfate proteoglycans via its MAM domain.

Matrix Biol 2013 Apr 26;32(3-4):188-95. Epub 2013 Jan 26.

Laboratory of Extracellular Matrix Biochemistry, Institute for Protein Research, Osaka University, 3-2 Yamadaoka, Suita, Osaka 565-0871, Japan.

Nephronectin is a basement membrane protein comprising five N-terminal epidermal growth factor (EGF)-like repeats, a central linker segment containing an Arg-Gly-Asp (RGD) motif and a C-terminal meprin-A5 protein-receptor protein tyrosine phosphatase μ (MAM) domain. Nephronectin has been shown to interact with α8β1 integrin through the central linker segment, but its interactions with other molecules remain to be elucidated. Here, we examined the binding of nephronectin to a panel of glycosaminoglycan (GAG) chains. Read More

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Changes in brain β-amyloid deposition and aquaporin 4 levels in response to altered agrin expression in mice.

J Neuropathol Exp Neurol 2011 Dec;70(12):1124-37

Jackson Laboratory, Bar Harbor, Maine 04609, USA.

Conditions that compromise the blood-brain barrier (BBB) have been increasingly implicated in the pathogenesis of Alzheimer disease (AD). AGRIN is a heparan sulfate proteoglycan found abundantly in basement membranes of the cerebral vasculature, where it has been proposed to serve a functional role in the BBB. Furthermore, AGRIN is the major heparan sulfate proteoglycan associated with amyloid plaques in AD brains. Read More

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December 2011

Nephritogenic antibodies bind in glomeruli through interaction with exposed chromatin fragments and not with renal cross-reactive antigens.

Autoimmunity 2011 Aug 19;44(5):373-83. Epub 2011 Jan 19.

Molecular Pathology Research Group, Institute of Medical Biology, University of Tromsø, Norway.

Cross-reactivity of anti-double stranded DNA (anti-dsDNA) antibodies with glomerular antigens has been postulated as a key factor in the development of lupus nephritis. Because no direct proof has been presented on anti-dsDNA antibodies binding in vivo to glomerular structures, we have analysed the binding of potentially nephritogenic anti-dsDNA antibodies to α-actinin and laminin. By enzyme-linked immunosorbent assay and surface plasmon resonance (SPR) analyses, we demonstrate that monoclonal antibodies (mAbs) bind both double-stranded DNA and α-actinin at high affinity. Read More

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Limited expression of heparan sulphate proteoglycans associated with Aβ deposits in the APPswe/PS1dE9 mouse model for Alzheimer's disease.

Neuropathol Appl Neurobiol 2010 Oct;36(6):478-86

Radboud University Nijmegen Medical Centre, Department of Neurology, Department of Laboratory Medicine, Donders Institute for Brain, Cognition and Behaviour, Radboud University, Nijmegen, the Netherlands.

Aims: Alzheimer's disease (AD) is characterized by deposition of the amyloid beta (Aβ) peptide in brain parenchyma and vasculature. Several proteins co-deposit with Aβ, including heparan sulphate proteoglycans (HSPG). HSPG have been suggested to contribute to Aβ aggregation and deposition, and may influence plaque formation and persistence by stimulating Aβ fibrillization and by protecting Aβ against degradation. Read More

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October 2010

Agrin and CD34 immunohistochemistry for the discrimination of benign versus malignant hepatocellular lesions.

Am J Surg Pathol 2009 Jun;33(6):874-85

1st Department of Pathology and Experimental Cancer Research, Semmelweis University, Budapest, Hungary.

Agrin is a recently identified proteoglycan component of vascular and bile duct basement membranes in the liver. The selective deposition of agrin in hepatocellular carcinoma (HCC) microvessels versus sinusoidal walls prompted us to investigate the utility of agrin immunohistochemistry (IHC) in detecting malignant hepatocellular lesions. We focused on the differential diagnostic problems often presented by hepatocellular adenomas (HCAs) and dysplastic nodules. Read More

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[Selective deposition of agrin in the microvasculature of hepatocellular carcinoma: aspects in pathogenesis and differential diagnosis].

Péter Tátrai

Magy Onkol 2008 Dec;52(4):379-83

Semmelweis Egyetem, Patológiai Tudományok Doktori Iskola 1091, Budapest.

Hepatocellular carcinoma (HCC) accounts for 90% of primary liver cancers and is the fifth most common malignancy worldwide. HCC typically develops in the cirrhotic liver. Our preliminary results indicated that agrin, a heparan sulfate proteoglycan (HSPG) detected by us for the first time in the liver, accumulates in the basement membranes (BMs) of the cirrhotic liver and HCC. Read More

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December 2008

Muscle-wide secretion of a miniaturized form of neural agrin rescues focal neuromuscular innervation in agrin mutant mice.

Proc Natl Acad Sci U S A 2008 Aug 6;105(32):11406-11. Epub 2008 Aug 6.

Biozentrum and Institute of Physiology, Department of Biomedicine, University of Basel, Klingelbergstrasse 70, 4056 Basel, Switzerland.

Agrin and its receptor MuSK are required for the formation of the postsynaptic apparatus at the neuromuscular junction (NMJ). In the current model the local deposition of agrin by the nerve and the resulting local activation of MuSK are responsible for creating and maintaining the postsynaptic apparatus including clusters of acetylcholine receptors (AChRs). Concomitantly, the release of acetylcholine (ACh) and the resulting depolarization disperses those postsynaptic structures that are not apposed by the nerve and thus not stabilized by agrin-MuSK signaling. Read More

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Inherited diseases of the glomerular basement membrane.

Nat Clin Pract Nephrol 2008 Jan;4(1):24-37

Institut National de la Santé et de la Recherche Médicale, INSERM U574, Hôpital Necker-Enfants Malades, Paris F75015, France.

The glomerular basement membrane (GBM) is a specialized form of basement membrane that has a major role in the maintenance of the glomerular filtration barrier. Like all basement membranes, it contains four main components: type IV collagen, laminin, nidogen, and heparan sulfate proteoglycans. Different isoforms of these large molecules are produced. Read More

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January 2008

C. elegans agrin is expressed in pharynx, IL1 neurons and distal tip cells and does not genetically interact with genes involved in synaptogenesis or muscle function.

PLoS One 2007 Aug 15;2(8):e731. Epub 2007 Aug 15.

Friedrich Miescher Institute for Biomedical Research, Novartis Research Foundation, Basel, Switzerland.

Agrin is a basement membrane protein crucial for development and maintenance of the neuromuscular junction in vertebrates. The C. elegans genome harbors a putative agrin gene agr-1. Read More

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Agrin is highly expressed by chondrocytes and is required for normal growth.

Histochem Cell Biol 2007 Apr 21;127(4):363-74. Epub 2006 Dec 21.

Department of Orthopedics, Division for Biochemistry of Joint and Connective Tissue Diseases, University of Ulm, RKU, Oberer Eselsberg 45, 89081, Ulm, Germany.

Agrin is a heparan sulfate proteoglycan that is best known for its crucial involvement in the organization and maintenance of postsynaptic structures at the neuromuscular junction. Consistent with this role, mice deficient of agrin die at birth due to respiratory failure. Here we examined the early postnatal development of agrin-deficient mice in which perinatal death was prevented by transgenic expression of neural agrin in motor neurons. Read More

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[Transfection of agrin gene on the recovery of muscle function after free neurovascular muscle transfer].

Zhonghua Zheng Xing Wai Ke Za Zhi 2006 Sep;22(5):378-82

Changzheng Hospital, Second Military Medical University of PLA, Shanghai 200003, China.

Objective: To investigate the effects of transfection of agrin gene on the recovery of muscle function after a free neurovascular muscle transfer.

Methods: The electrical gene transfection was performed when the gracilis muscle of the SD rat was completed free neurovascular transfer. The experimental group was treated with pCS2+ -agrin, the group with plasmid pCS2+ as the negative control and the group with normal saline as the frank control. Read More

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September 2006

Molecular chaperons, amyloid and preamyloid lesions in the BRI2 gene-related dementias: a morphological study.

Neuropathol Appl Neurobiol 2006 Oct;32(5):492-504

Queen Square Brain Bank, Department of Molecular Neuroscience, Institute of Neurology, University College London, London, UK.

Molecular chaperons or amyloid-associated proteins (AAPs) are deposited in vascular and parenchymal amyloid lesions in Alzheimer's disease (AD) and other amyloidoses. AAPs, such as apolipoprotein E (ApoE) or apolipoprotein J (ApoJ) have been strongly implicated in the pathogenesis of AD in vitro and in vivo. Furthermore the possession of the ApoE in4 allele is a well-studied risk factor for AD. Read More

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October 2006

Reduced perlecan expression and accumulation in human carotid atherosclerotic lesions.

Atherosclerosis 2007 Feb 18;190(2):264-70. Epub 2006 Apr 18.

Department of Molecular Medicine and Surgery, Karolinska Institutet, Karolinska University Hospital, SE-171 76 Stockholm, Sweden.

Heparan sulfate in the extracellular matrix of the artery wall has been proposed to possess anti-atherogenic properties by interfering with lipoprotein retention, suppression of inflammation, and inhibition of smooth muscle cell growth. Previously, the amount of heparan sulfate in atherosclerotic lesions from humans and animals has been shown to be reduced but the identity or identities of the heparan sulfate molecules being down regulated in this disease are not known. In this study, atherosclerotic lesions were retrieved from 44 patients undergoing surgery for symptomatic carotid stenosis. Read More

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February 2007

An extracellular pathway for dystroglycan function in acetylcholine receptor aggregation and laminin deposition in skeletal myotubes.

J Biol Chem 2006 May 10;281(19):13365-13373. Epub 2006 Mar 10.

Department of Biology, McGill University, Montréal General Hospital Research Institute, Montréal, Québec H3G 1A4, Canada; Center for Research in Neuroscience, McGill University, Montréal General Hospital Research Institute, Montréal, Québec H3G 1A4, Canada. Electronic address:

The dystroglycan (DG) complex is involved in agrin-induced acetylcholine receptor clustering downstream of muscle-specific kinase where it regulates the stability of acetylcholine receptor aggregates as well as assembly of the synaptic basement membrane. We have previously proposed that this entails coordinate extracellular and intracellular interactions of its two subunits, alpha- and beta-DG. To assess the contribution of the extracellular and intracellular portions of DG, we have used adenoviruses to express full-length and deletion mutants of beta-DG in myotubes derived from wild-type embryonic stem cells or from cells null for DG. Read More

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Kinetics of glycosaminoglycan deposition in splenic AA amyloidosis induced in mink.

Scand J Immunol 2004 Dec;60(6):600-8

Department of Rheumatology/Institute of Immunology, Rikshospitalet, University of Oslo, Oslo, Finland.

The kinetics of splenic glycosaminoglycan (GAG) expression in mink has been investigated during the course of AA amyloid induction, i.e. at 3 to 6 weeks of lipopolysaccharide (LPS) treatment. Read More

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December 2004

A synthetic heparanase inhibitor reduces proteinuria in passive Heymann nephritis.

J Am Soc Nephrol 2004 Nov;15(11):2882-92

Austin Research Institute, Department of Nephrology, University of Melbourne, Australia.

The beta-D-endoglycosidase heparanase has been proposed to be important in the pathogenesis of proteinuria by acting to selectively degrade the negatively charged side chains of heparan sulfate proteoglycans (HSPG) within the glomerular basement membrane (GBM). A loss of the negatively charged HSPG may result in alteration of the permselective properties of the GBM, loss of glomerular epithelial and endothelial cell anchor points, and liberation of growth factors. This study examined the effect of PI-88, a sulfated oligosaccharide heparanase inhibitor, on renal function, glomerular ultrastructure, and proteinuria. Read More

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November 2004

Differential effects of neurotrophins and schwann cell-derived signals on neuronal survival/growth and synaptogenesis.

J Neurosci 2003 Jun;23(12):5050-60

Department of Biology, Hong Kong University of Science and Technology, Kowloon, Hong Kong.

Recent studies have shown that the survival of mammalian motoneurons in vitro is promoted by neurotrophins (NTs) and cAMP. There is also evidence that neurotrophins enhance transmitter release. We thus investigated whether these agents also promote synaptogenesis. Read More

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Heparan sulfate proteoglycan expression in cerebrovascular amyloid beta deposits in Alzheimer's disease and hereditary cerebral hemorrhage with amyloidosis (Dutch) brains.

Acta Neuropathol 2001 Dec;102(6):604-14

Department of Pathology, University Medical Center, P.O. Box 9101, 6500 HB Nijmegen, The Netherlands.

Cerebrovascular deposition of amyloid beta protein (A beta) is a characteristic lesion of Alzheimer's disease (AD) and hereditary cerebral hemorrhage with amyloidosis of the Dutch type (HCHWA-D). Besides A beta, several other proteins and proteoglycans accumulate in cerebral amyloid angiopathy (CAA). We have now analyzed the expression of the heparan sulfate proteoglycan (HSPG) subtypes agrin, perlecan, glypican-1, syndecans 1-3 and HS glycosaminoglycan (GAG) side chains in CAA in brains of patients with AD and HCHWA-D. Read More

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December 2001

Glomerular extracellular matrix and growth factors in diffuse mesangial sclerosis.

Pediatr Nephrol 2001 May;16(5):429-38

INSERM U423, Tour Lavoisier, Hôpital Necker-Enfants Malades, Université René Descartes, 149, rue de Sèvres, 75743 Paris, France.

Unlabelled: Diffuse mesangial sclerosis, isolated (IDMS) or observed in the context of Denys-Drash syndrome (DDS) due to WT1 mutation, is characterized by early onset nephrotic syndrome progressing to renal failure. A striking morphological feature is the rapid development of glomerulosclerosis.

The Aims Of Our Study Were: (1) to analyze the glomerular distribution of extracellular matrix (ECM) antigens at the early stage of DMS, (2) to determine the composition of the ECM accumulated within the mesangial areas and leading to glomerular sclerosis, and (3) to analyze the expression of growth factors, transforming growth factor-beta 1 (TGF beta 1) and platelet-derived growth factor A (PDGFA). Read More

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Abnormal synapse formation in agrin-depleted hippocampal neurons.

A Ferreira

J Cell Sci 1999 Dec;112 ( Pt 24):4729-38

Department of Cell and Molecular Biology and Institute for Neuroscience, Northwestern University, Chicago IL 60611, USA.

Agrin, a 200 kDa extracellular matrix protein, participates in the maturation of the postsynaptic target at the neuromuscular junction. Although agrin has also been detected in central neurons, little is known about its role in the formation of their synapses. In the present study, the pattern of expression, localization and function of agrin in developing hippocampal neurons were analyzed. Read More

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December 1999

Reduction in glomerular heparan sulfate correlates with complement deposition and albuminuria in active Heymann nephritis.

J Am Soc Nephrol 1999 Aug;10(8):1689-99

Division of Nephrology, University Hospital, St. Radboud, Nijmegen, The Netherlands.

In a time-study of active Heymann nephritis, the expression of agrin, the main heparan sulfate proteoglycan in the glomerular basement membrane, was analyzed in relation to deposition of IgG and complement in the glomerular capillary wall and the development of albuminuria. Binding of IgG autoantibodies to the glomerular capillary wall could be detected from 2 wk onward, followed by activation of complement after 6 wk. Progressive albuminuria developed from 6 wk onward to a level of 274+/-68 mg/18 h at week 12. Read More

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