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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.

We studied antibody responses after immunization with ganglio-series gangliosides against 10 strains of inbred mice, including Balb/c, C57BL/6, A/J, C3H/HeN, C3H/HeJ, CBA/N, AKR/N, NZB/N, DBA/2 and nu/nu Balb/c. Twelve gangliosides having NeuAc as their sialic acid moiety (GM4, GM3, GM2, GM1, GD3, O-Ac-GD3, GD2, GD1a, GD1b, GT1a, GT1b and GQ1b), four gangliosides having NeuGc (GM3, GM2, GM1 and GD3) and four asialo-gangliosides (GA4, GA3, GA2 and GA1) were injected intravenously adsorbed to Salmonella minnesota. The antibody titers of the mice sera were determined by an enzyme-linked immunosorbent assay and an immune adherence assay. Antibody responses were found to depend not only on the ganglioside used as an immunogen but also on the mouse strain. Gangliosides having a trisaccharide sequence (NeuAc alpha 2----8NeuAc alpha 2----3Gal-) such as GD3, GD2, GD1b, GT1a and GQ1b, in particular O-Ac-GD3, induced high-titer antibody responses, whereas those having a disaccharide sequence (NeuAc alpha 2----3Gal-) such as GM4, GM3, GM2, GM1, GD1a and GT1b induced low-titer antibody responses. On the other hand, gangliosides with NeuGc developed minimum titers. In contrast, asialogangliosides induced much higher responses than the corresponding gangliosides. The differences in ceramide portions of these gangliosides did not appear to be involved in inducing antibody responses. Mice could be divided into three groups according to the magnitude of their antibody responses: Group 1, those that produce the highest antibody responses (C3H/HeN and A/J); Group 2, those that demonstrate moderate antibody titers (Balb/c, C57BL/6, DBA/2 and nu/nu Balb/c); and Group 3, those that make minimum responses (AKR/N, C3H/HeJ, CBA/N and NZB/N). The pattern of reactivity to the various gangliosides was similar in all the strains tested.