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2. PKCδ deficiency inhibits fetal development and is associated with heart elastic fiber hyperplasia and lung inflammation in adult PKCδ knockout mice

Author

Niino, Yuko S., primary, Kawashima, Ikuo, additional, Iguchi, Yoshinobu, additional, Kanda, Hiroaki, additional, Ogura, Kiyoshi, additional, Mita-Yoshida, Kaoru, additional, Ono, Tomio, additional, Yamazaki, Maya, additional, Sakimura, Kenji, additional, Yogosawa, Satomi, additional, Yoshida, Kiyotsugu, additional, Shioda, Seiji, additional, and Gotoh, Takaya, additional

Published
2021
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5. Use of a modified [alpha]-N-acetylgalactosaminidase in the development of enzyme replacement therapy for Fabry disease

Author

Tajima, Youichi, Kawashima, Ikuo, Tsukimura, Takahiro, Sugawara, Kanako, Kuroda, Mayuko, Suzuki, Toshihiro, Togawa, Tadayasu, Chiba, Yasunori, Jigami, Yoshifumi, Ohno, Kazuki, Fukushige, Tomoko, Kanekura, Takuro, Itoh, Kohji, Ohashi, Toya, and Sakuraba, Hitoshi

Subjects
Fabry's disease -- Genetic aspects, Fabry's disease -- Care and treatment, Hamsters -- Physiological aspects, Hamsters -- Genetic aspects, Enzymes -- Health aspects, Enzymes -- Research, Biological sciences
Abstract

The article explains the developments, properties and applications of a modified [alpha]-N-acetylgalactosaminidase (NAGA) produced in Chinese hamster ovary cells. The produced compound is shown to be extremely useful in the development of the enzyme replacement theory (ERT) that can be employed as a treatment of the Fabry disease.

Published
2009

15. Production of recombinant [beta]-hexosaminidase A, a potential enzyme for replacement therapy for Tay-Sachs and Sandhoff diseases, in the methylotrophic yeast Ogataea minuta

Author

Akeboshi, Hiromi, Chiba, Yasunori, Kasahara, Yoshiko, Takashiba, Minako, Tsuji, Daisuke, Itoh, Kohji, Jigami, Yoshifumi, Sakuraba, Hitoshi, Takaoka, Yuki, Ohsawa, Mai, Tajima, Youichi, and Kawashima, Ikuo

Subjects
Yeast fungi -- Genetic aspects, Yeast fungi -- Physiological aspects, Mammals -- Genetic aspects, Mammals -- Physiological aspects, Biological sciences
Abstract

Recombinant [beta]-hexosaminidase A (HexA) was produced in the methylotrophic yeast Ogataea minuta to prepare a large amount of HexA for treatment based enzyme replacement therapy (ERT). The problem of antigenicity due to differences in N-glycan structures between mammalian and yeast glycoproteins was resolved by using [alpha]-1,6-mannosyltransferase deficient yeast as the host.

Published
2007

17. 高感度酵素抗体法を用いたRett症候群および他の神経疾患における髄液ガングリオシド分析

Author

NOVO, Maria de Lourdes P., SANAI, Yutaka, KAWASHIMA, Ikuo, SUZUKI, Yoshiyuki, ROSEMBERG, Sergio, MORITA, Mariko, OSAWA, Makiko, and FUKUYAMA, Yukio

Abstract

年齢2～10歳のRett症候群患者12名と,同年齢の髄液検査が必要であった他疾患患者19名,および正常対照例7名において,脳脊髄液中の5つの主要なガングリオシドGM1, GD1a, GD1b, GT1bおよびGQ1bを感度の高い酵素抗体法で測定した.我々は,この方法を用いて標準曲線を作成し,これらを測定できた.本法は,高感度な検査法であることを証明した.対象症例における脳脊髄液中の総ガングリオシド量は,脳脊髄液1ml当たり,正常対照例で100～900ng,神経疾患患者で25ngから最大5,000ngの値をとっていた.Rett症候群を含め,どの神経疾患でも特別なパターンは認められなかった.過去にRett症候群においては,あるガングリオシドが大脳および小脳で低下しているという所見の報告があったが,この所見と関連する結果は髄液では得られなかった.また,我々が,髄液における5つの主要なガングリオシドの値をRett症候群患者と正常および疾患対照例と比較した所では,そのデータからRett症候群を予測させるような低下パターンを見出すことはできなかった.但し,12例中5例でGD1aが, 4例でGT1bおよびGQ1bの合計値が正常対照例の下限値よりも低下していた.Rett症候群の独歩可能な患児と不可能な患児における髄液ガングリオシド値の比較検討では差がなく,また異った臨床ステージの患者間の比較検討でも差がなかった.しかしながら,髄膜炎の急性期,熱性けいれんの直後,またRett症候群のけいれんの多い児2名を含み,てんかん患児の一部で髄液中のガングリオシド,主として,GD1b,GT1b値が上昇していた., The cerebrospinal fluid (CSF) gangliosides GM1, GDla, GDlb, GTlb and GQlb were measured using a highly sensitive enzyme-immunostaining technique, in 12 patients with Rett syndrome (RS) ranging in age from 2y to 10y, in age-matched patients with various neurologic diseases (n=19) and in normal control subjects (n=7). The method used proved to be highly sensitive; a standard curve was established and we were able to obtain reliable assay results. Total CSF gangliosides varied widely among normal controls (100～900 ng/ml CSF) as well as in those with neurologic diseases (25 to 5,000 ng/ml CSF). No specific ganglioside pattern was found in any of the disease groups, including RS. Although previous reports have shown reductions in the levels of gangliosides in the RS brain, we found no evidence of a predictable and constant pattern of reduced levels of any of the five major CSF gangliotetraose series gangliosides in this syndrome; however, the amount of GDla was reduced in five of the 12 RS patients, and the amount of GQ1b+GT1b was reduced in four as compared with the minimum value obtained in the control group. Analysis of CSF ganglioside levels in RS patients revealed no differences between ambulant and non-ambulant patients, nor were there any differences among patients in different clinical stages. There was, however, a positive correlation between CSF ganglioside levels, mainly the b-pathway gangliosides, and the presence and frequency of seizures in some patients, including the one with febrile convulsion, those in the acute stage of meningitis, two of the RS patients and some of those with epileptic syndromes.

Published
1996

21. Use of a Modified α-N-Acetylgalactosaminidase in the Development of Enzyme Replacement Therapy for Fabry Disease

Author

Tajima, Youichi, primary, Kawashima, Ikuo, additional, Tsukimura, Takahiro, additional, Sugawara, Kanako, additional, Kuroda, Mayuko, additional, Suzuki, Toshihiro, additional, Togawa, Tadayasu, additional, Chiba, Yasunori, additional, Jigami, Yoshifumi, additional, Ohno, Kazuki, additional, Fukushige, Tomoko, additional, Kanekura, Takuro, additional, Itoh, Kohji, additional, Ohashi, Toya, additional, and Sakuraba, Hitoshi, additional

Published
2009
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23. Production of Recombinant β-Hexosaminidase A, a Potential Enzyme for Replacement Therapy for Tay-Sachs and Sandhoff Diseases, in the Methylotrophic Yeast Ogataea minuta

Author

Akeboshi, Hiromi, primary, Chiba, Yasunori, additional, Kasahara, Yoshiko, additional, Takashiba, Minako, additional, Takaoka, Yuki, additional, Ohsawa, Mai, additional, Tajima, Youichi, additional, Kawashima, Ikuo, additional, Tsuji, Daisuke, additional, Itoh, Kohji, additional, Sakuraba, Hitoshi, additional, and Jigami, Yoshifumi, additional

Published
2007
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24. Comparison of the effects of agalsidase alfa and agalsidase beta on cultured human Fabry fibroblasts and Fabry mice

Author

Sakuraba, Hitoshi, primary, Murata-Ohsawa, Mai, additional, Kawashima, Ikuo, additional, Tajima, Youichi, additional, Kotani, Masaharu, additional, Ohshima, Toshio, additional, Chiba, Yasunori, additional, Takashiba, Minako, additional, Jigami, Yoshifumi, additional, Fukushige, Tomoko, additional, Kanzaki, Tamotsu, additional, and Itoh, Kohji, additional

Published
2005
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27. Changes in Composition of Newly Synthesized Sphingolipids of HeLa Cells During the Cell Cycle. Suppression of Sphingomyelin and Higher-Glycosphingolipid Synthesis and Accumulation of Ceramide and Glucosylceramide in Mitotic Cells

Author

Yokoyama, Kazuaki, primary, Suzuki, Minoru, additional, Kawashima, Ikuo, additional, Karasawa, Ken, additional, Nojima, Shoshichi, additional, Enomoto, Takemi, additional, Tai, Tadashi, additional, Suzuki, Akemi, additional, and Setaka, Morio, additional

Published
1997
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34. Delineation of the epitope recognized by an antibody specific for N‐glycolylneuraminic acid–containing gangliosides.

Author

Moreno, Ernesto, Lanne, Boel, Vázquez, Ana María, Kawashima, Ikuo, Tai, Tadashi, Fernández, Luis Enrique, Karlsson, Karl‐Anders, Ångström, Jonas, and Pérez, Rolando

Abstract

P3 is a mouse monoclonal antibody (mAb) that binds to several NeuGc‐containing gangliosides. It also reacts with antigens expressed in human breast tumors (Vázquez et al. (1995) Hybridoma, 14, 551–556). In this work, the binding specificity of P3 has been characterized in more detail using a panel of glycolipids that included several disialylated gangliosides and several chemical derivatives of NeuGc‐GM3. The carboxyl group and the nitrogen function of sialic acid were found to play important roles in the antibody binding, whereas the glycerol tail appears to be nonrelevant. Molecular modeling was used to analyze the binding data, including the finding that P3 selectively recognizes the internal NeuGc in GD3. For this purpose, conformational studies of GD3 were performed using molecular dynamics. It was concluded that sialic acid binds the P3 antibody through its upper face (the one on which the carboxyl group is exposed) and the C4‐C5 side of the sugar ring, whereas none or very little contact between the galactose residue and the protein is evident. Conformational analysis of GD3 revealed that, despite the large flexibility of the NeuGcα8NeuGc linkage, the P3 binding epitope on the external sialic acid is not well exposed for any of the possible conformations this linkage can adopt, whereas the internal sialic acid presents the epitope in a proper way for several of these conformations. As a final result, a coherent picture of the epitope that fits the wide binding data was obtained. [ABSTRACT FROM PUBLISHER]

Published
1998
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35. Carbohydrate-Carbohydrate Binding of Ganglioside to Integrin α5Modulates α5β1Function*

Author

Wang, Xiaoqi, Sun, Ping, Al-Qamari, Abbas, Tai, Tadashi, Kawashima, Ikuo, and Paller, Amy S.

Abstract

Gangliosides GT1b and GD3, components of keratinocyte membranes, inhibit keratinocyte adhesion to fibronectin. Although ganglioside sialylation is known to be important, the mechanism of inhibition is unknown. Using purified insect recombinant α5and β1proteins and α5β1integrin from lysed keratinocyte-derived SCC12 cells, we have shown that GT1b and GD3 inhibit the binding of α5β1to fibronectin. Co-immunoprecipitation of GT1b and α5β1from SCC12 cells and direct binding of GT1b and GD3 to affinity-purified α5β1from SCC12 cells and insect recombinant α5β1, particularly the α5subunit, further suggest interaction between ganglioside and α5β1. The carbohydrate moieties of integrin appear to be critical since gangliosides are unable to bind deglycosylated forms of α5β1from SCC12 and insect cells or poorly glycosylated recombinant α5β1from Escherichia colicells. The GT1b-α5β1interaction is inhibited by concanavalin A, suggesting that GT1b binds to mannose structures in α5β1. The preferential binding of GT1b to high mannose rather than reduced mannose ovalbumin further implicates the binding of GT1b to mannose structures. These data provide evidence that highly sialylated gangliosides regulate α5β1-mediated adhesion of epithelial cells to fibronectin through carbohydrate-carbohydrate interactions between GT1b and the α5subunit of α5β1integrin.

Published
2001
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