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Toshio Ariga - One of the best experts on this subject based on the ideXlab platform.
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Anti-Sulfoglucuronosyl Paragloboside Antibody: A Potential Serologic Marker of Amyotrophic Lateral Sclerosis.
ASN neuro, 2016Co-Authors: Seigo Usuki, Brandy Quarles, Michael H. Rivner, Toshio ArigaAbstract:Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by progressive degeneration of upper and lower motor neurons. Although the etiology of ALS is obscure, genetic studi...
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Anti-Sulfoglucuronosyl Paragloboside Antibody
SAGE Publishing, 2016Co-Authors: Seigo Usuki, Brandy Quarles, Michael H. Rivner, Toshio ArigaAbstract:Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by progressive degeneration of upper and lower motor neurons. Although the etiology of ALS is obscure, genetic studies of familiar ALS suggest a multifactorial etiology for this condition. Similarly, there probably are multiple causes for sporadic ALS. Autoimmune-mediated motor neuron dysfunction is one proposed etiology for sporadic ALS. In the present study, anti-glycolipid antibodies including GM1, GD1b, GD3, and sulfoglucuronosyl Paragloboside (SGPG) were investigated in the sera of a large number of patient samples, including 113 ALS patients and 50 healthy controls, by means of enzyme-linked immunosorbent assay with affinity parametric complex criterion evaluation and thin-layer chromatography immunooverlay (immuno-TLC). Anti-SGPG antibodies were found in the sera of 13.3% ALS patients (15 out of 113). The highest titer reached 1:1600. The presence of anti-SGPG antibodies in the serum samples was also confirmed by immuno-TLC. Importantly, a multiple logistic regression analysis showed that the presence of anti-SGPG antibody was positively correlated with age ( p
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as a Target of Monoclonal IgM in Demyelinative Neuropathy
2013Co-Authors: Endothelial Cells, Toshio Ariga, Sulfoglucuronosyl Paragloboside, Takashi K, Hiide Yoshino, Masanaga YamawakiAbstract:Abstract. Since a number of anti-glycosphingolipid (GSL) antibody activities have been demonstrated in patients with various neurological disorders, the presence of common antigens between brain microvascular endothelial cells (BMECs) and the nervous tissues presents a potential mechanism for the penetration of macromolecules from the circulation to the nervous system parenchyma. We first investigated GSL composition of cultured bovine BMECs. Bovine BMECs express GM3(NeuAc) and GM3(NeuGc) as the major gangliosides, and GM1, GDla, GDlb, GTlb, as well as sialyl Paragloboside and sialyl lactosaminylParagloboside as the minor species. Sulfoglucuronosyl Paragloboside was also found to be a component of the BMEC acidic GSL fraction, but its concentratio
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Glycosphingolipid antigens in neural tumor cell lines and anti-glycosphingolipid antibodies in sera of patients with neural tumors.
Neuro-Signals, 2008Co-Authors: Toshio Ariga, Seigo Usuki, Keiji Suetake, Makoto Nakane, Masaru Kubota, Ikuo KawashimaAbstract:To characterize biomarkers in neural tumors, we analyzed the acidic lipid fractions of 13 neural tumor cell lines using enzyme-linked immunoabsorbent assay (ELISA) and high-performance thin-layer chromatography (HPTLC) immunostaining. Sulfated glucuronosyl glycosphingolipids (SGGLs) are cell surface molecules that are endowed with the Human Natural Killer-1 (HNK-1) carbohydrate epitope. These glycosphingolipids (GSLs) were expressed in all cell lines with concentrations ranging from 210 to 330 ng per 2 x 10(6) cells. Sulfoglucuronosyl Paragloboside (SGPG) was the prominent species with lesser amounts of sulfoglucuronosyl lactosaminyl Paragloboside (SGLPG) in these tumor cell lines as assessed by quantitative HPTLC immunostaining. Among the gangliosides surveyed, GD3 and 9-O-acetylated GD3 (OAc-GD3) were expressed in all tumor cell lines. In contrast, fucosyl-GM1 was not found to restrict to small cell lung carcinoma cells. In addition, we have analyzed serum antibody titers against SGPG, GD3, and OAc-GD3 in patients with neural tumors by ELISA and HPTLC immunostaining. All sera had high titers of antibodies of the IgM isotype against SGPG (titers over 1:3,200), especially in tumors such as meningiomas, germinomas, orbital tumors, glioblastomas, medulloblastomas, and subependymomas. Serum in a patient with subependymomas also had a high anti-SGGL antibody titer of the IgG and IgA types (titers over 12,800). The titer of anti-GD3 antibody was also elevated in patients with subependymomas and medulloblastomas; the latter cases also had a high titer of antibody against OAc-GD3. Our data indicate that certain GSL antigens, especially SGGLs, GD3, and OAc-GD3, are expressed in neural tumor cells and may be considered as tumor-associated antigens that represent important biomarkers for neural tumors. Furthermore, antibody titers in sera of patients with these tumors may be of diagnostic value for monitoring the presence of tumor cells and tumor progression.
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Glycosphingolipid composition of primary cultured human brain microvascular endothelial cells.
Journal of neuroscience research, 2004Co-Authors: Takashi Kanda, Masanaga Yamawaki, Toshio Ariga, Hisako Kubodera, Hong Lian Jin, Kiyoshi Owada, Takeshi Kasama, Hidehiro MizusawaAbstract:Glycosphingolipid (GSL) antigens have been considered to be involved in the pathogenesis of autoimmune neurologic disorders including multiple sclerosis. To establish the GSL pattern specific for endothelial cells forming blood-brain barrier (BBB), we established a method to yield sufficient quantities of highly purified human brain microvascular endothelial cells (HBMECs) and compared their GSL composition to that of human umbilical cord vein endothelial cells (HUVECs), as the representative of endothelial cells not forming BBB. The major gangliosides were GM3 and sialyl Paragloboside (LM1), and the major neutral GSLs were lactosylceramide (LacCer), globotriaosylceramide (Gb3), and globoside (Gb4). Trace amounts of GM1, GD1a, GD1b, GT1b, and sulfoglucuronosyl Paragloboside (SGPG) could be detected by the high performance thin layer chromatography-overlay method. SGPG was detected only at a nonconfluent state in an amount almost 1/30 that of in nonconfluent HUVECs. Conversely, GM3 and LM1 increased significantly after confluency. The amount of Gb3 in HBMECs was almost as twice that in HUVECs. The significance of these differences in GSL content between HBMECs and HUVECs and between confluent and nonconfluent states is obscure. It might be related, however, to the defense mechanism at the BBB and to the susceptibility of the central nervous system in some disorders that target cell surface GSL, such as hemolytic uremic syndrome.
Masanaga Yamawaki - One of the best experts on this subject based on the ideXlab platform.
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as a Target of Monoclonal IgM in Demyelinative Neuropathy
2013Co-Authors: Endothelial Cells, Toshio Ariga, Sulfoglucuronosyl Paragloboside, Takashi K, Hiide Yoshino, Masanaga YamawakiAbstract:Abstract. Since a number of anti-glycosphingolipid (GSL) antibody activities have been demonstrated in patients with various neurological disorders, the presence of common antigens between brain microvascular endothelial cells (BMECs) and the nervous tissues presents a potential mechanism for the penetration of macromolecules from the circulation to the nervous system parenchyma. We first investigated GSL composition of cultured bovine BMECs. Bovine BMECs express GM3(NeuAc) and GM3(NeuGc) as the major gangliosides, and GM1, GDla, GDlb, GTlb, as well as sialyl Paragloboside and sialyl lactosaminylParagloboside as the minor species. Sulfoglucuronosyl Paragloboside was also found to be a component of the BMEC acidic GSL fraction, but its concentratio
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Glycosphingolipid composition of primary cultured human brain microvascular endothelial cells.
Journal of neuroscience research, 2004Co-Authors: Takashi Kanda, Masanaga Yamawaki, Toshio Ariga, Hisako Kubodera, Hong Lian Jin, Kiyoshi Owada, Takeshi Kasama, Hidehiro MizusawaAbstract:Glycosphingolipid (GSL) antigens have been considered to be involved in the pathogenesis of autoimmune neurologic disorders including multiple sclerosis. To establish the GSL pattern specific for endothelial cells forming blood-brain barrier (BBB), we established a method to yield sufficient quantities of highly purified human brain microvascular endothelial cells (HBMECs) and compared their GSL composition to that of human umbilical cord vein endothelial cells (HUVECs), as the representative of endothelial cells not forming BBB. The major gangliosides were GM3 and sialyl Paragloboside (LM1), and the major neutral GSLs were lactosylceramide (LacCer), globotriaosylceramide (Gb3), and globoside (Gb4). Trace amounts of GM1, GD1a, GD1b, GT1b, and sulfoglucuronosyl Paragloboside (SGPG) could be detected by the high performance thin layer chromatography-overlay method. SGPG was detected only at a nonconfluent state in an amount almost 1/30 that of in nonconfluent HUVECs. Conversely, GM3 and LM1 increased significantly after confluency. The amount of Gb3 in HBMECs was almost as twice that in HUVECs. The significance of these differences in GSL content between HBMECs and HUVECs and between confluent and nonconfluent states is obscure. It might be related, however, to the defense mechanism at the BBB and to the susceptibility of the central nervous system in some disorders that target cell surface GSL, such as hemolytic uremic syndrome.
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Sulfoglucuronosyl glycolipids as putative antigens for autoimmune inner ear disease
Journal of Neuroimmunology, 1998Co-Authors: Masanaga Yamawaki, A Tokuda, Aristides Sismanis, J S Yu, Toshio Ariga, Robert K. YuAbstract:Abstract Autoimmune inner ear disease is diagnosed based on clinical history of fluctuating but progressive sensorineural hearing loss (SNHL) with or without vestibular symptoms occurring over weeks to months. An initial response to steroids or immunosuppressive drugs usually reverses the hearing loss. In search of specific diagnostic and therapeutic markers for autoimmune inner ear diseases, we investigated serum anti-glycolipid antibody activities in these patients by two different methods, HPTLC-immunoblotting and ELISA. We found that 37 out of 74 patients of clinically diagnosed autoimmune inner ear disease (30 of sensorineural hearing loss (SNHL) (group I), 14 of vestibular symptoms only (group II), 30 of Menieres symptoms (with both hearing loss and vestibular symptoms) (group III)) showed positive anti-sulfoglucuronosyl lactosaminyl Paragloboside (SGLPG) antibody titers ( p
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Generation and characterization of anti‐sulfoglucuronosyl Paragloboside monoclonal antibody NGR50 and its immunoreactivity with peripheral nerve
Journal of neuroscience research, 1996Co-Authors: Masanaga Yamawaki, Toshio Ariga, Tadashi Tai, John W. Bigbee, Ikuo Kawashima, H. Ozawa, Takashi KandaAbstract:Sulfoglucuronosyl Paragloboside (SGPG) is a member of the sulfated glucuronic acid-containing glycolipid (SGGL) family found primarily in peripheral nerves. These glycolipids contain the HNK-1 carbohydrate epitope and are recognized by monoclonal IgM from patients with chronic demyelinating neuropathy and paraproteinemia. Recent studies indicate that SGGLs may serve as ligands for selectins, amphoterin, and laminin, suggesting that these glycolipids may play an important role in cellular adhesion. To elucidate the biological function of these glycolipids, we produced a murine monoclonal antibody (mAb) and studied its antigenic specificity. Using an enzyme-linked immunosorbent assay (ELISA), we found that the mAb designated as NGR50 belonged to the IgG2a subclass, and that the minimal titer (2 SD above the mean optical density value of control) of this mAb was 1:640, with 20 ng of purified SGPG as the antigen. Thin-layer chromatography (TLC) immunoblotting revealed that this mAb reacted specifically with SGPG and sulfoglucuronosyl lactosaminyl Paragloboside (SGLPG), which is a structural analogue of the former, but not with other glycolipids. Desulfated derivates of SGPG and SGLPG did not react with mAb NGR50. Western blot analysis showed crossreactivity with human myelin-associated glycoprotein (MAG), but not with rat MAG or rat glycoprotein P0. Unlike anti-HNK-1 monoclonal antibody, however, NGR50 reacted only weakly with several proteins in the 20-30-kD regions, including human P0, suggesting that mAb50 has a different fine specificity as an anti-HNK-1 antibody. Immunocytochemical study of rat sciatic nerve using mAb NGR50 revealed positive staining at the outer surface of the myelin sheath and Schwann cells, as well as in the intervening connective tissues. Faint staining was also visible at the axolemmal-myelin interface; however, compact myelin was not stained.
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generation and characterization of anti sulfoglucuronosyl Paragloboside monoclonal antibody ngr50 and its immunoreactivity with peripheral nerve
Journal of Neuroscience Research, 1996Co-Authors: Masanaga Yamawaki, Toshio Ariga, Tadashi Tai, John W. Bigbee, Ikuo Kawashima, H. Ozawa, Takashi KandaAbstract:Sulfoglucuronosyl Paragloboside (SGPG) is a member of the sulfated glucuronic acid-containing glycolipid (SGGL) family found primarily in peripheral nerves. These glycolipids contain the HNK-1 carbohydrate epitope and are recognized by monoclonal IgM from patients with chronic demyelinating neuropathy and paraproteinemia. Recent studies indicate that SGGLs may serve as ligands for selectins, amphoterin, and laminin, suggesting that these glycolipids may play an important role in cellular adhesion. To elucidate the biological function of these glycolipids, we produced a murine monoclonal antibody (mAb) and studied its antigenic specificity. Using an enzyme-linked immunosorbent assay (ELISA), we found that the mAb designated as NGR50 belonged to the IgG2a subclass, and that the minimal titer (2 SD above the mean optical density value of control) of this mAb was 1:640, with 20 ng of purified SGPG as the antigen. Thin-layer chromatography (TLC) immunoblotting revealed that this mAb reacted specifically with SGPG and sulfoglucuronosyl lactosaminyl Paragloboside (SGLPG), which is a structural analogue of the former, but not with other glycolipids. Desulfated derivates of SGPG and SGLPG did not react with mAb NGR50. Western blot analysis showed crossreactivity with human myelin-associated glycoprotein (MAG), but not with rat MAG or rat glycoprotein P0. Unlike anti-HNK-1 monoclonal antibody, however, NGR50 reacted only weakly with several proteins in the 20-30-kD regions, including human P0, suggesting that mAb50 has a different fine specificity as an anti-HNK-1 antibody. Immunocytochemical study of rat sciatic nerve using mAb NGR50 revealed positive staining at the outer surface of the myelin sheath and Schwann cells, as well as in the intervening connective tissues. Faint staining was also visible at the axolemmal-myelin interface; however, compact myelin was not stained.
Takashi Kanda - One of the best experts on this subject based on the ideXlab platform.
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Glycosphingolipid composition of primary cultured human brain microvascular endothelial cells.
Journal of neuroscience research, 2004Co-Authors: Takashi Kanda, Masanaga Yamawaki, Toshio Ariga, Hisako Kubodera, Hong Lian Jin, Kiyoshi Owada, Takeshi Kasama, Hidehiro MizusawaAbstract:Glycosphingolipid (GSL) antigens have been considered to be involved in the pathogenesis of autoimmune neurologic disorders including multiple sclerosis. To establish the GSL pattern specific for endothelial cells forming blood-brain barrier (BBB), we established a method to yield sufficient quantities of highly purified human brain microvascular endothelial cells (HBMECs) and compared their GSL composition to that of human umbilical cord vein endothelial cells (HUVECs), as the representative of endothelial cells not forming BBB. The major gangliosides were GM3 and sialyl Paragloboside (LM1), and the major neutral GSLs were lactosylceramide (LacCer), globotriaosylceramide (Gb3), and globoside (Gb4). Trace amounts of GM1, GD1a, GD1b, GT1b, and sulfoglucuronosyl Paragloboside (SGPG) could be detected by the high performance thin layer chromatography-overlay method. SGPG was detected only at a nonconfluent state in an amount almost 1/30 that of in nonconfluent HUVECs. Conversely, GM3 and LM1 increased significantly after confluency. The amount of Gb3 in HBMECs was almost as twice that in HUVECs. The significance of these differences in GSL content between HBMECs and HUVECs and between confluent and nonconfluent states is obscure. It might be related, however, to the defense mechanism at the BBB and to the susceptibility of the central nervous system in some disorders that target cell surface GSL, such as hemolytic uremic syndrome.
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Generation and characterization of anti‐sulfoglucuronosyl Paragloboside monoclonal antibody NGR50 and its immunoreactivity with peripheral nerve
Journal of neuroscience research, 1996Co-Authors: Masanaga Yamawaki, Toshio Ariga, Tadashi Tai, John W. Bigbee, Ikuo Kawashima, H. Ozawa, Takashi KandaAbstract:Sulfoglucuronosyl Paragloboside (SGPG) is a member of the sulfated glucuronic acid-containing glycolipid (SGGL) family found primarily in peripheral nerves. These glycolipids contain the HNK-1 carbohydrate epitope and are recognized by monoclonal IgM from patients with chronic demyelinating neuropathy and paraproteinemia. Recent studies indicate that SGGLs may serve as ligands for selectins, amphoterin, and laminin, suggesting that these glycolipids may play an important role in cellular adhesion. To elucidate the biological function of these glycolipids, we produced a murine monoclonal antibody (mAb) and studied its antigenic specificity. Using an enzyme-linked immunosorbent assay (ELISA), we found that the mAb designated as NGR50 belonged to the IgG2a subclass, and that the minimal titer (2 SD above the mean optical density value of control) of this mAb was 1:640, with 20 ng of purified SGPG as the antigen. Thin-layer chromatography (TLC) immunoblotting revealed that this mAb reacted specifically with SGPG and sulfoglucuronosyl lactosaminyl Paragloboside (SGLPG), which is a structural analogue of the former, but not with other glycolipids. Desulfated derivates of SGPG and SGLPG did not react with mAb NGR50. Western blot analysis showed crossreactivity with human myelin-associated glycoprotein (MAG), but not with rat MAG or rat glycoprotein P0. Unlike anti-HNK-1 monoclonal antibody, however, NGR50 reacted only weakly with several proteins in the 20-30-kD regions, including human P0, suggesting that mAb50 has a different fine specificity as an anti-HNK-1 antibody. Immunocytochemical study of rat sciatic nerve using mAb NGR50 revealed positive staining at the outer surface of the myelin sheath and Schwann cells, as well as in the intervening connective tissues. Faint staining was also visible at the axolemmal-myelin interface; however, compact myelin was not stained.
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generation and characterization of anti sulfoglucuronosyl Paragloboside monoclonal antibody ngr50 and its immunoreactivity with peripheral nerve
Journal of Neuroscience Research, 1996Co-Authors: Masanaga Yamawaki, Toshio Ariga, Tadashi Tai, John W. Bigbee, Ikuo Kawashima, H. Ozawa, Takashi KandaAbstract:Sulfoglucuronosyl Paragloboside (SGPG) is a member of the sulfated glucuronic acid-containing glycolipid (SGGL) family found primarily in peripheral nerves. These glycolipids contain the HNK-1 carbohydrate epitope and are recognized by monoclonal IgM from patients with chronic demyelinating neuropathy and paraproteinemia. Recent studies indicate that SGGLs may serve as ligands for selectins, amphoterin, and laminin, suggesting that these glycolipids may play an important role in cellular adhesion. To elucidate the biological function of these glycolipids, we produced a murine monoclonal antibody (mAb) and studied its antigenic specificity. Using an enzyme-linked immunosorbent assay (ELISA), we found that the mAb designated as NGR50 belonged to the IgG2a subclass, and that the minimal titer (2 SD above the mean optical density value of control) of this mAb was 1:640, with 20 ng of purified SGPG as the antigen. Thin-layer chromatography (TLC) immunoblotting revealed that this mAb reacted specifically with SGPG and sulfoglucuronosyl lactosaminyl Paragloboside (SGLPG), which is a structural analogue of the former, but not with other glycolipids. Desulfated derivates of SGPG and SGLPG did not react with mAb NGR50. Western blot analysis showed crossreactivity with human myelin-associated glycoprotein (MAG), but not with rat MAG or rat glycoprotein P0. Unlike anti-HNK-1 monoclonal antibody, however, NGR50 reacted only weakly with several proteins in the 20-30-kD regions, including human P0, suggesting that mAb50 has a different fine specificity as an anti-HNK-1 antibody. Immunocytochemical study of rat sciatic nerve using mAb NGR50 revealed positive staining at the outer surface of the myelin sheath and Schwann cells, as well as in the intervening connective tissues. Faint staining was also visible at the axolemmal-myelin interface; however, compact myelin was not stained.
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Interleukin 1 beta up-regulates the expression of sulfoglucuronosyl Paragloboside, a ligand for L-selectin, in brain microvascular endothelial cells
Proceedings of the National Academy of Sciences of the United States of America, 1995Co-Authors: Takashi Kanda, Masanaga Yamawaki, Toshio ArigaAbstract:Treatment of cultured bovine brain microvascular endothelial cells (BMECs) with interleukin 1 beta (IL-1 beta), an inflammatory cytokine, was shown to induce the accumulation of sulfoglucuronosyl Paragloboside (SGPG), a glycolipid bearing the HNK-1 epitope. This resulted in the attachment of a greater number of human lymphocytes to the treated than to the untreated BMEC monolayers. Attachment of human lymphocytes to the IL-1 beta-activated BMEC cells could be blocked either by incubation of the human lymphocytes with an anti-L-selectin antibody or by application of an anti-SGPG antibody to the BMECs. These results suggest that SGPG may act as an important ligand for L-selectin for the regulation of the attachment of activated lymphocytes and their subsequent invasion into the nervous system parenchyma in inflammatory disorders of the central and peripheral nervous systems.
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Glycosphingolipid antigens in cultured bovine brain microvascular endothelial cells: sulfoglucuronosyl Paragloboside as a target of monoclonal IgM in demyelinative neuropathy [corrected].
The Journal of cell biology, 1994Co-Authors: Takashi Kanda, Hiide Yoshino, Toshio Ariga, Masanaga YamawakiAbstract:Since a number of anti-glycosphingolipid (GSL) antibody activities have been demonstrated in patients with various neurological disorders, the presence of common antigens between brain microvascular endothelial cells (BMECs) and the nervous tissues presents a potential mechanism for the penetration of macromolecules from the circulation to the nervous system parenchyma. We first investigated GSL composition of cultured bovine BMECs. Bovine BMECs express GM3(NeuAc) and GM3(NeuGc) as the major gangliosides, and GM1, GD1a, GD1b, GT1b, as well as sialyl Paragloboside and sialyl lactosaminylParagloboside as the minor species. Sulfoglucuronosyl Paragloboside was also found to be a component of the BMEC acidic GSL fraction, but its concentration was lower in older cultures. On the other hand, the amounts of neutral GSLs were extremely low, consisting primarily of glucosylceramide. In addition, we analyzed the effect of anti-SGPG IgM antibody obtained from a patient of demyelinative polyneuropathy with macroglobulinemia against cultured BMECs. Permeability studies utilizing cocultured BMEC monolayers and rat astrocytes revealed that the antibody facilitated the leakage of [carboxy-14C]-inulin and 125I-labeled human IgM through BMEC monolayers. A direct cytotoxicity of this antibody against BMECs was also shown by a leakage study using [51Cr]-incorporated BMECs. This cytotoxicity depended on the concentration of the IgM antibody, and was almost completely blocked by preincubation with the pure antigen, sulfoglucuronosyl Paragloboside. Our present study strongly supports the concept that immunological insults against BMECs induce the destruction or malfunction of the blood-nerve barrier, resulting in the penetration of the immunoglobulin molecule to attach peripheral nerve parenchyma.
Halina Miller-podraza - One of the best experts on this subject based on the ideXlab platform.
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Influenza Viruses Display High-Affinity Binding to Human Polyglycosylceramides Represented on a Solid-Phase Assay Surface
Virology, 1996Co-Authors: Mikhail Matrosovich, Halina Miller-podraza, Susann Teneberg, James S. Robertson, Karl-anders KarlssonAbstract:Polyglycosylceramides (PGCs), complex glycolipids containing up to 50 or more sugar residues, are recognized as the minor components of the cell-surface membranes, but a knowledge on their tissue distribution, structure, and function is limited. In this study, the binding of influenza viruses to preparations of PGCs was investigated using a TLC overlay assay and a microwell adsorption assay. The ability of PGCs to bind influenza virus was dependent on the source from which they were derived. Preparations of PGCs from human erythrocytes were found to support binding of A and B influenza virus strains at a much lower concentration than sialyl-6-Paragloboside and to be somewhat better receptors for these viruses compared to the sialylglycoprotein fetuin. A high virus-binding activity of PGCs suggests that these species could potentially serve as biologically important cell-surface receptors for influenza viruses.
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Unexpected carbohydrate cross-binding by Escherichia coli heat-labile enterotoxin. Recognition of human and rabbit target cell glycoconjugates in comparison with cholera toxin
Bioorganic and Medicinal Chemistry, 1996Co-Authors: Karl-anders Karlsson, Jörgen Bergström, Timothy Raymond Hirst, Susann Teneberg, Anders Kjellberg, Jonas Ångström, Halina Miller-podrazaAbstract:The bacterial protein enterotoxins, cholera toxin (CT) of Vibrio cholerae and heat-labile toxin (LT) of Escherichia coli, induce diarrhea by enhancing the secretory activity of the small intestine of man and rabbit (animal model). This physiological effect is mediated by toxin binding to a glycolipid receptor, the ganglioside GM1, Galβ3GalNAcβ4(NeuAcα3)Galβ4Glcβ1Cer. However, LT, but not CT, was recently shown by us to bind also to Paragloboside, Galβ4GlcNAcβ3Galβ4Glcβ1Cer, identified in the target cells. By molecular modeling of this tetrasaccharide in the known binding site of LT, the saccharide-peptide interaction was shown to be limited to the terminal disaccharide (N-acetyllactosamine). This sequence is expressed in many glycoconjugates, and we have therefore assayed glycolipids and glycoproteins prepared from the target tissues. In addition to Paragloboside, receptor activity for LT was detected in glycoproteins of human origin and in polyglycosylceramides of rabbit. However, CT bound only to GM1. Two variants of LT with slightly different sequences, human (hLT) and porcine (pLT), were identical in their binding to target glycoproteins and polyglycosylceramides, but different regarding Paragloboside, which was positive for pLT but negative for hLT. This difference is discussed on basis of modeling, taking in view the difference at position 13, with Arg in pLT and His in hLT. Although N-acetyllactosamine is differently recognized in form of Paragloboside by the two toxin variants, we speculate that this sequence in human glycoproteins and rabbit polyglycosylceramides is the basis for the common binding. Much work remains, however, to clear up this unexpected sophistication in target recognition.
Karl-anders Karlsson - One of the best experts on this subject based on the ideXlab platform.
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Influenza Viruses Display High-Affinity Binding to Human Polyglycosylceramides Represented on a Solid-Phase Assay Surface
Virology, 1996Co-Authors: Mikhail Matrosovich, Halina Miller-podraza, Susann Teneberg, James S. Robertson, Karl-anders KarlssonAbstract:Polyglycosylceramides (PGCs), complex glycolipids containing up to 50 or more sugar residues, are recognized as the minor components of the cell-surface membranes, but a knowledge on their tissue distribution, structure, and function is limited. In this study, the binding of influenza viruses to preparations of PGCs was investigated using a TLC overlay assay and a microwell adsorption assay. The ability of PGCs to bind influenza virus was dependent on the source from which they were derived. Preparations of PGCs from human erythrocytes were found to support binding of A and B influenza virus strains at a much lower concentration than sialyl-6-Paragloboside and to be somewhat better receptors for these viruses compared to the sialylglycoprotein fetuin. A high virus-binding activity of PGCs suggests that these species could potentially serve as biologically important cell-surface receptors for influenza viruses.
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Unexpected carbohydrate cross-binding by Escherichia coli heat-labile enterotoxin. Recognition of human and rabbit target cell glycoconjugates in comparison with cholera toxin
Bioorganic and Medicinal Chemistry, 1996Co-Authors: Karl-anders Karlsson, Jörgen Bergström, Timothy Raymond Hirst, Susann Teneberg, Anders Kjellberg, Jonas Ångström, Halina Miller-podrazaAbstract:The bacterial protein enterotoxins, cholera toxin (CT) of Vibrio cholerae and heat-labile toxin (LT) of Escherichia coli, induce diarrhea by enhancing the secretory activity of the small intestine of man and rabbit (animal model). This physiological effect is mediated by toxin binding to a glycolipid receptor, the ganglioside GM1, Galβ3GalNAcβ4(NeuAcα3)Galβ4Glcβ1Cer. However, LT, but not CT, was recently shown by us to bind also to Paragloboside, Galβ4GlcNAcβ3Galβ4Glcβ1Cer, identified in the target cells. By molecular modeling of this tetrasaccharide in the known binding site of LT, the saccharide-peptide interaction was shown to be limited to the terminal disaccharide (N-acetyllactosamine). This sequence is expressed in many glycoconjugates, and we have therefore assayed glycolipids and glycoproteins prepared from the target tissues. In addition to Paragloboside, receptor activity for LT was detected in glycoproteins of human origin and in polyglycosylceramides of rabbit. However, CT bound only to GM1. Two variants of LT with slightly different sequences, human (hLT) and porcine (pLT), were identical in their binding to target glycoproteins and polyglycosylceramides, but different regarding Paragloboside, which was positive for pLT but negative for hLT. This difference is discussed on basis of modeling, taking in view the difference at position 13, with Arg in pLT and His in hLT. Although N-acetyllactosamine is differently recognized in form of Paragloboside by the two toxin variants, we speculate that this sequence in human glycoproteins and rabbit polyglycosylceramides is the basis for the common binding. Much work remains, however, to clear up this unexpected sophistication in target recognition.
