Antibodies to GMl ganglioside inhibit morphine analgesia

It has been shown that the injection of antiganglioside serum into the periacqueductal gray matter of rats blocks morphine induced analgesia. This result is due to the action of antibodies to GMl ganglioside since the specific removal of these antibodies from the antiserum with pure GMl ganglioside eliminates the blocking activity. Specificity for GMl ganglioside was further shown by the blocking activity of choleragenoid, which binds specifically to GMl sites. Antibodies to other brain constituents, namely S-100 protein and myelin, did not block the morphine analgesia.     

Differential Cell- and Immuno-Biological Properties of Murine B16-F1 and F10 Melanomas: Oncogene c-fos Expression,Sensitivity to LAK Cells and/or IL-2, and Components of Gangliosides

Differential cell- and immuno-biological properties of two murine melanoma B16 variants, B16-F1 and F10, were investigated. Studies focused on the expression of proto-oncogene c-fos, sensitivities to LAK cells and/or IL-2, and modulation of the expression of ganglioside components after treatment with IL-2. Proto-oncogene c-fos was found to be highly expressed in F10 lines by an in situ hybridization technique and also in F10 lung metastatic nests by immunofluorescent staining with anti-c-fos antibody. F1 melanomas were more sensitive to local injection of IL-2. F10 melanomas hardly responded to IL-2 treatment, but successive injections of a combination of LAK cells and IL-2 did cause prolongation of survival rates, even of F10 melanoma-burdened mice. A major component of gangliosides of both F1 and F10 melanomas was GM₃. Production of GM₃ in F10 melanomas treated with IL-2 for 4 days increased, and, if the treatment was continued for 7 days, minor components of gangliosides, such as GM₂, GM₁, and GD_1a, appeared only in F1 melanomas, while the increase of production of GM₃ disappeared in both melanomas. These experimental results may provide clues for additional mechanisms which allow these two murine melanoma variants to show different implantation and metastasis rates.     

Lipid composition of the cerebral gray and white matter in a case with Fukuyama type congenital muscular dystrophy

When compared with an age-matched normal control and a Duchenne muscular dystrophy (DMD) case, the patient with FCMD had an unusual ganglioside pattern in the cerebral gray matter. The total level of lipid-bound sialic acid in the cerebral gray matter was also slightly decreased. However, other lipid compositions of the cerebral gray and white matter were normal compared with those in the control case.     

Dopaminergic dysfunction in neonatal hypothyroidism: differential effects of GM1 ganglioside

The effects of daily treatment with GM₁ ganglioside (30 mg/kg s.c.) from birth to day 30, on striatal pre- and postsynaptic markers of the dopaminergic system in euthyroid- and 32 day-old hypothyroid rats were studied. The purpose was to assess whether GM₁ could prevent the extensive, hypothyroidism-provoked impairment of dopaminergic neurotransmission. Neonatal administration of GM₁ well counteracted the hypothyroidism-related deficits in striatal synaptosomal uptake of [³H]dopamine and in membrane binding of [³H]tyramine, a putative marker for the vesicular carrier of dopamine. In the hypothyroid striatum, the decrease of concentrations of DOPAC and HVA, the loss of [³H]SCH-23,390-labelled D₁-receptors and the decrease of basal- or dopamine-stimulated, Di-mediated activity of adenylate cyclase were not prevented by gm₁. Although somatic and neurobehavioural aberrations of hypothyroids were not at all or only partially ameliorated, a slight improvement of the thyroid status was suggested by less decreased levels of serum thyroxine (T₄) after treatment with GM₁ The ganglioside-driven selective recovery of the transport and storage process of [³H]dopamine might result either from a chronically-exerted stimulation by GM₁ on the NA/K- and Mg-ATPase activities, thus reflecting on the ATPase-dependent neuronal and vesicular transport processes of dopamine or from a GM₁-promoted maturation of the otherwise retarded functionality of dopaminergic nerve endings in the neonatal hypothyroid striatum.     

Antisera to different glycolipids induce myelin alterations in mouse spinal cord tissue cultures

To study the demyelinative effects of antibodies to glycolipids, well-myelinated cultures of mouse spinal cord tissue were exposed to antisera against galactocerebroside and two gangliosides (GM₁ and GM₄), as well as to anti-white matter antiserum. The demyelinative process was evaluated by morphologic and biochemical techniques. Cultures exposed to anti-white matter and anti-galactocerebroside antisera showed the most marked changes. These consisted of a decrease in the number of oligodendroglial cells and dissolution and phagocytosis of myelin. Concomitantly, the activity of 2′,3′-cyclic nucleotide-3′-phosphohydrolase (CNPase) was decreased by 60–70%. This occured within 24 h of exposure to a relatively low concentration of serum (10%). Cultures exposed to anit-GM₁ and anti-GM₄ antisera showed similar changes but to a lasser degree. The CNPase activity was decreased about 30% within 48 h of exposure to a 25% concentration of these antisera. This diminution represents about a 20% loss of myelin, an observation corroborated by electron microscopy where myelin but not oligodendroglial cell was observed. Therefore, in addition to anti-galactocerebroside activity, which was previously found to be the major antibody responsible for the demyelinating activity induced by anti-whole CNS tissue antiserum, these data suggest that antibodies to gangliosides like GM₁ and GM₄ might also play a role in immune-mediated demyelination, including perhaps, the human demyelinating diseases.     

Anti-gal-C antibody in autoimmune neuropathies subsequent to mycoplasma infection

Four of 82 patients with Guillain-Barré syndrome (GBS) and 1 of 12 with multifocal motor neuropathy (MMN), who previously had had Mycoplasma pneumoniae infections, had serum antibody to galactocerebroside (Gal-C). Two patients with GBS without mycoplasma infection also had anti-Gal-C antibody, whereas none of the normal or the disease controls had it. As Gal-C is a major glycolipid antigen in myelin, anti-Gal-C antibody may function in the pathogenesis of autoimmune demyelinative neuropathies. Mycoplasma pneumoniae appears to be an important preceding infectious agent in autoimmune neuropathies with anti-Gal-C antibody. © 1995 John Wiley & Sons, Inc.     

Alteration of Human Melanoma Gangliosides by IFN-γ, IL-2, and IL-4

In lesions of malignant melanoma, melanoma cells are exposed to various cytokines produced by inflammatory reactions. As a result, transformation of melanoma cells is expected to occur. We studied alterations in human melanoma cell line ganglioside composition after exposing melanoma cell lines to interferon (IFN)-γ, interleukin (IL)-2, and IL-4 by biochemical methods. IFN-γ increases the ratio of a-series gangliosides and the ratio of GM3/GD3. This suggests an alteration of immunoreactivity, a decrease in ganglioside sialyltransferase II activity, and an decrease in the malignant character of these cells. The alteration of the ganglioside profile varied among cytokines and cell lines. The progression of malignant melanoma may be influenced by reciprocal interactions between the melanoma cells and the host immune system.     

Topology and patch-clamp analysis of the sodium channel in relationship to the anti-lipid a antibody in campylobacteriosis

An infecting strain VLA2/18 of Campylobacter jejuni was obtained from an individual with campylobacteriosis and used to prepare chicken sera by experimental infection to investigate the role of serum anti-ganglioside antibodies in Guillain-Barré syndrome. Both sera of the patient and chicken contained anti-ganglioside antibodies and anti-Lipid A (anti-Kdo2-Lipid A) antibodies directed against the lipid A portion of the bacterial lipooligosaccharide. The anti-Kdo2-Lipid A activities inhibited voltage-gated Na (Nav) channel of NSC-34 cells in culture. We hypothesized that anti-Kdo2-Lipid A antibody acts on the functional inhibition of Nav1.4. To test this possibility, a rabbit peptide antibody (anti-Nav1.4 pAb) against a 19-mer peptide (KELKDNHILNHVGLTDGPR) on the alpha subunit of Nav1.4 was produced. Anti-Nav1.4 pAb was cross-reactive to Kdo2-Lipid A. Anti-Kdo2-lipid A antibody activity in the chicken serum was tested for the Na(+) current inhibition in NSC-34 cells in combination with mu-Conotoxin and tetrodotoxin. Contrary to our expectations, the anti-Kdo2-Lipid A antibody activity was extended to Nav channels other than Nav1.4. By overlapping structural analysis, it was found that there might be multiple peptide epitopes containing certain dipeptides showing a structural similarity with v-Lipid A. Thus, our study suggests the possibility that there are multiple epitopic peptides on the extracellular domains of Nav1.1 to 1.9, and some of them may represent target sites for anti-Kdo2-Lipid A antibody, to induce neurophysiological changes in GBS by disrupting the normal function of the Nav channels.     

单唾液酸四己糖神经节苷脂联合奥沙利铂对HCT116细胞增殖和周期的影响

目的研究外源性单唾液酸四己糖神经节苷脂(GM1)联合奥沙利铂对HCT116细胞增殖和细胞周期的影响。方法进行人结肠癌肿瘤细胞株HCT116细胞培养,HCT116细胞在20μmol/L奥沙利铂与不同浓度GM1(5~300μmol/L)联合干预,孵育12、24、48 h后通过CCK-8法检测药物对于HCT116细胞增殖活性的影响。倒置显微镜观察药物作用后细胞形态学变化。流式细胞术检测GM1联合奥沙利铂对于HCT116细胞细胞周期分布及凋亡的影响。结果奥沙利铂导致HCT116细胞增殖活性显著降低,该作用呈现显著时间依赖性,并且不受GM1药物作用的影响(P>0.05)。细胞形态学观察,奥沙利铂作用24 h后,HCT116细胞生长出现显著抑制,联合使用GM1对奥沙利铂引起的HCT116细胞的生长抑制亦无明显影响。流式细胞术检测,奥沙利铂作用24 h后,HCT116细胞周期G0/G1期和S期细胞减少,G2/M期细胞增多,细胞凋亡增多(P<0.05),联合使用GM1对于奥沙利铂引起的HCT116细胞细胞周期和凋亡的改变无明显影响(P>0.05)。结论GM1在体外不降低奥沙利铂对HCT116细胞增殖的抑制作用,不影响奥沙利铂引起的细胞周期和凋亡的变化。     

神经节苷脂联合康复干预治疗高危儿脑损伤的临床研究

目的 探讨神经节苷脂联合康复干预对高危儿脑损伤临床治疗效果.方法 采用多组对照比较法,将160例高危儿脑损伤病例,按入院先后顺序分为对照组（A组）、康复干预组（B组）、神经节苷脂组（C组）、神经节苷脂联合康复干预组（D组）,每组40例.4组均给予神经内科基础护理,A组不作其他处理;B组再给予康复干预治疗;C组再服用神经节苷脂20 mg/d,连服10 d;D组再给予B、C两组的联合治疗.对各组的临床疗效进行比较分析,并探讨年龄对治疗效果的影响.结果 A、B、C、D组总有效率分别为5%、47.5%、50%、90%,D组与其余3组比较均有显著差异（P＜0.05）,B、C组间无显著差异（P＞0.05）,但显著高于A组（P＜0.05）.患儿年龄与治疗有效率具有负相关性,年龄越小,治疗有效率越高.结论 神经节苷脂联合康复干预对高危儿脑损伤治疗效果明显,具有很好的临床应用前景.