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Biomedical subjects

A J Steck

Publications and source records attributed to A J Steck.

At least 19 recordsLinked to original sources
PubMed1992

[Autoimmune paraneoplastic neurological syndromes].

Paraneoplastic neurological syndromes are well established causes of neurological dysfunction in cancer patients. Recently an auto-immune origin has been found for the Lambert-Eaton myasthenic syndrome, the subacute sensory neuronopathy of Denny-Brown, the paraneoplastic cerebellar degeneration, the paraneoplastic opsoclonus-myoclonus as well as a few other minor syndromes. Indeed patients suffering from these diseases have been found to produce antibodies directed against the central nervous system. These antibodies can be detected as much as a year before the cancer is found and they are therefore interesting for neurological and oncologic diagnosis.

Autoimmune Diseases↗
PubMed1992

Comparison of the N-linked oligosaccharide structures of the two major human myelin glycoproteins MAG and P0: assessment and relative occurrence of oligosaccharide structures by serial lectin affinity chromatography of 14C-glycopeptides.

The N-linked oligosaccharide structures of human myelin-associated glycoprotein (MAG) and P0 have been characterized by serial lectin affinity chromatography (SLAC) of 14C-glycopeptides. 14C-Glycopeptides were prepared from purified MAG derivative and P0 by extensive proteolytic digestion and N-14C-acetylation. Assuming that all the 14C-glycopeptides were radiolabelled to the same specific radioactivity, the relative occurrence of the oligosaccharide structures was correlated to the amount of incorporated radioactivity. Sixteen and 15 fractions were generated by SLAC of MAG and P0 14C-glycopeptides, respectively. Despite this tremendous structural heterogeneity, the oligosaccharide "fingerprints" of MAG and P0 obtained by SLAC displayed similarities: (a) of the three types of N-linked oligosaccharides, the complex type accounted for 80.4% and 94.9% of MAG and P0 radioactivity, respectively; (b) biantennary complex oligosaccharides were the major structures present on MAG and P0; (c) approximately 60% of MAG and P0 oligosaccharides possessed a bisecting N-acetylglucosamine residue; and (d) large amounts of oligosaccharides with an alpha(1-6)fucose residue were found in both MAG and P0 and, noticeably, approximately 25% of the tri- and/or tetraantennary and approximately 90% of the bisected biantennary oligosaccharides of both glycoproteins contained alpha(1-6)fucose residues in the core. This study demonstrates that MAG and P0, both belonging to the immunoglobulin superfamily, display structural similarities in their N-linked oligosaccharide contents.

Carbon Radioisotopes↗
PubMed1992

Comparison of the N-linked oligosaccharide structures of the two major human myelin glycoproteins MAG and P0: assessment of the structures bearing the epitope for HNK-1 and human monoclonal immunoglobulin M found in demyelinating neuropathy.

The epitope for HNK-1 and patient's monoclonal autoantibodies in demyelinating polyneuropathy associated with immunoglobulin M gammopathy is borne by different types of N-linked oligosaccharide structures in human P0 and myelin-associated glycoprotein (MAG). Fourteen glycopeptide fractions bearing different oligosaccharide structures were obtained from either MAG or P0 glycopeptides by serial lectin affinity chromatography on concanavalin A-Sepharose, Phaseolus vulgaris erythrophytohemagglutinin-agarose, Pisum sativum agglutinin-agarose, and Phaseolus vulgaris leucophytohemagglutinin-agarose. As shown by dot-TLC plate immunostaining, the same MAG and P0 glycopeptide fractions were recognized by HNK-1 and patient's immunoglobulin M, confirming that these antibodies display similar specificities. The antigenic carbohydrate was present in glycopeptide fractions that either interact with Pisum sativum agglutinin-agarose or were bound by Aleuria aurantia agglutinin-digoxigenin, indicating that these structures contained alpha(1-6)fucose residues. This study demonstrates that the L2/HNK-1 epitope is borne mainly or even exclusively by N-linked oligosaccharide structures alpha(1-6)fucosylated in the core.

Antibodies, Monoclonal↗
PubMed1992

Carbohydrate moieties of myelin-associated glycoprotein, major glycoprotein of the peripheral nervous system myelin and other myelin glycoproteins potentially involved in cell adhesion.

The myelin-associated glycoprotein (MAG) and the major glycoprotein of the peripheral nervous system myelin (P0) are two members of the family of cell adhesion molecules (CAMs). A role in cell adhesion of the carbohydrate moiety of these molecules has been attributed to the presence of N-glycans bearing the HNK-1 carbohydrate epitope. On the other hand, it has been suggested that these glycoproteins could be ligands of an endogenous mannose-binding lectin present in myelin, the cerebellar soluble lectin (CSL). In order to further document the heterogeneity of the glycans of these two CAMs, we have used several probes: an anti-carbohydrate antibody of the HNK-1 type, called Elec-39, the plant lectin concanavalin A (ConA), and the endogenous lectin CSL involved in myelin compaction. This study shows that CSL binds to a small proportion of the polypeptide chains of MAG found in adult CNS of rats and man and the polypeptide chains of P0 molecules from adult human and rat sciatic nerve. For MAG from adult rat brain, the binding of CSL is restricted to glycans of polypeptide chains which could be separated from the others according to their solubility properties. These MAG molecular entities react also with the Elec-39 antibody and with ConA. These results confirm that P0 and MAG are heterogeneous in their carbohydrate moieties.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Inflammatory neuropathy: pathogenesis and clinical features.

The nature of the underlying mechanisms in inflammatory and immune-mediated neuropathies continues to represent an intensive area of research. Different auto-antibodies that are thought to cause specific neuropathic syndromes have been described. The involvement of T cells, cytokines, complement and class II molecules in the pathogenesis of these syndromes has also been studied. There is also intensive investigation into the area of immunotherapy, in particular in the use of intravenous immunoglobulin (Ig).

Autoantibodies↗
PubMed1991

Anti-myelin-associated glycoprotein antibodies in patients with a monoclonal IgM gammopathy and polyneuropathy, and a simplified method for the preparation of glycolipid antigens.

The two sulfated glucuronic acid containing glycolipids, sulfate-3-glucuronyl paragloboside (SGPG) and sulfate-3-glucuronyl lactosaminyl paragloboside (SGLPG), were prepared by ion exchange chromatography of lipid extracts from bovine cauda equina. Thin layer chromatography (TLC) immunostaining and an enzyme-linked immunosorbent assay (ELISA) were used to show that the SGPG/SGLPG fraction was free of crossreactive antigenic components such as gangliosides. The results obtained by ELISA demonstrate that sera of all patients were validated IgM monoclonal anti-myelin-associated glycoprotein (MAG) demyelinating neuropathy display high titer antibodies with high affinity type titration curves. These antibodies were absent from the sera of 16 patients with other neurological diseases and ten normal controls. ELISA with SGPG/SGLPG as an antigen appears to be a valuable and highly specific immunodiagnostic test for determining anti-MAG antibody titers in the sera of patients. The amount (approximately 0.4 mg) of SGPG/SGLPG partially purified from 10 g of fresh tissue is sufficient for the preparation of approximately 100 96-well plates for ELISA procedures.

Chromatography, Ion Exchange↗
PubMed1991

[Efficacy and tolerance of cyclosporin A in the treatment of multiple sclerosis].

The use and tolerance of cyclosporine A (Cy A) and azathioprine (AZA) are compared as long-term immunosuppression treatment for multiple sclerosis. 38 patients with multiple sclerosis were randomized and received either Cy A (5 mg/kg/d) or AZA (2 mg/kg/d) during 24 months. These patients were assessed clinically and with different biological parameters. The Cy A blood level was controlled, and Cy A was well tolerated without side effects forcing to stop the treatment. However, its benefits were limited when the different clinical scores are compared.

Adult↗
PubMed1991

Borrelia rhombencephalomyelopathy.

Three patients, in whom the diagnosis of Borrelia burgdorferi infection was unknown for several years, developed a biphasic involvement of the central nervous system: an acute brain-stem dysfunction was followed up, in two patients, by a progressive, disabling myelitis and, in one patient, by further relapsing-remitting episodes of severe multifocal rhombencephalitis. The most consistent cerebrospinal fluid abnormalities in the analysis of sequential specimens were elevated total IgM levels that normalized after penicillin therapy. The neuropathologic findings in one patient showed microgliosis and meningovascular involvement of the central nervous system, resulting in two ischemic infarcts in the myelencephalon. Few spirochetes were localized in the leptomeninges and around subependymal vessels of the fourth ventricle. The vascular element consisted of an obliterative inflammatory vasculopathy in the medullary parenchyma. This study (1) provides pathologic evidence that a vascular disease induced by B burgdorferi is a pathogenetic mechanism for cerebrovascular diseases, and (2) emphasizes the similarities between neuroborreliosis and neurosyphilis.

Adult↗
PubMed1991

Predictive value of anti-GM1 ganglioside antibodies in neuromuscular diseases: a study of 180 sera.

The incidence of anti-GM1 antibodies in the serum of 104 patients with neurological diseases, 35 patients with non-neurological diseases (NND) and 41 normal controls was determined by enzyme-linked immunosorbent assay (ELISA). Anti-GM1 antibodies were found in 90% of patients presenting with a motor neuropathy (all except one had multifocal conduction blocks). A large proportion (60%) of these patients displayed high antibody titer ranging from 101 to 788. A low incidence of anti-GM1 antibodies was found in the other groups of patients, i.e. 21% of amyotrophic lateral sclerosis (ALS), 26% of other neurological diseases (OND) and 23% of NND. High antibody titers ranging from 106 to 260 were found in two (5%) ALS patients, one (2%) OND patient (myasthenia gravis), and one (3%) NND patient (Waldenström's disease). This study shows that high titers of anti-GM1 antibodies are found in a large proportion of patients with motor neuropathy with multifocal conduction blocks. This argues for a possible autoimmune origin of this neuropathy. We suggest that anti-GM1 antibody determination should be included systematically in the evaluation of all patients with motor neuron diseases and predominantly motor neuropathies.

Adult↗
PubMed1991

Serum antibodies to GM1 and GM3-gangliosides in systemic lupus erythematosus with chronic inflammatory demyelinating polyradiculoneuropathy.

Acute symmetric demyelinating polyneuropathy of the Guillain-Barré type is known in systemic lupus erythematosus (SLE). Chronic idiopathic demyelinating polyneuropathy (CIDP) has been reported rarely with SLE. A case is reported of CIDP accompanying SLE with autoantibodies against GM1- and GM3-gangliosides. There was no historical evidence to suggest SLE, and CIDP was the first manifestation of SLE. The 38-year-old patient had elevated CSF-protein, slow nerve conduction velocities, sural nerve biopsy revealed mixed axon loss with demyelination and CIDP white matter lesions were observed in magnetic resonance imaging, the GM1- and GM3-autoantibodies may play a role in the pathogenesis of CIDP in SLE.

Adult↗
PubMed1991

[Lambert-Eaton myasthenic syndrome. Physiopathological aspects and therapeutic modalities].

A 68-year old man experienced a progressive proximal tetraparesis with anhidrosis and a single episode of horizontal diplopia before presenting exertional dyspnea; pulmonary investigations revealed a small cell carcinoma of the lung. Clinical and electrophysiological investigations with abnormal SFEMG, repetitive stimulations and autonomic assessment pointed to a pre-synaptic neuromuscular dysfunction compatible with a Lambert-Eaton syndrome. Antibodies to acetylcholine receptors and calcium channels were negative. Thoracic radiotherapy combined with chemotherapy produced marked improvement: repeated electrophysiological evaluations showed a strong correlation between median nerve CMAP amplitude and clinical course. This case prompted us to discuss current concepts of pre-synaptic dysfunction, and paraneoplastic syndrome, and to review therapeutic strategies, in the light of recent studies of Lambert-Eaton syndrome.

Aged↗
PubMed1990

The epitope(s) recognized by HNK-1 antibody and IgM paraprotein in neuropathy is present on several N-linked oligosaccharide structures on human P0 and myelin-associated glycoprotein.

The mouse monoclonal antibody HNK-1 and the human monoclonal IgM antibody present in patients with polyneuropathy both recognize carbohydrate epitope(s) on human myelin-associated glycoprotein and P0. In the present study, the oligosaccharide structures that bear the antibody epitope(s) were investigated. The extracellular derivative of myelin-associated glycoprotein (dMAG) was purified by immunoaffinity chromatography. P0 was electroeluted from gel slices. Western blot analysis of whole glycoproteins demonstrated that the epitopes for HNK-1 and the human monoclonal IgM antibody were different. The glycopeptides obtained by proteolysis of purified dMAG and P0 were separated and characterized by affinity chromatography on concanavalin A-Sepharose. Both dMAG and P0 displayed heterogeneity in their oligosaccharide structures, i.e., they both contained mainly tri- and tetraantennary oligosaccharides (approximately 80%), although biantennary (10%) and high-mannose and/or hybrid (10%) oligosaccharides were present. The human monoclonal IgM antibody epitope was present on all types of isolated oligosaccharide structures from either dMAG and P0. The HNK-1 epitope was present on all types of oligosaccharide structures of dMAG, whereas it was present only on tri- and tetraantennary structures of P0.

Antibodies, Monoclonal↗
PubMed1990

Cyclosporine versus azathioprine in the treatment of multiple sclerosis: 12-month clinical and immunological evaluation.

The aim of this trial was to compare the efficacy and tolerance of cyclosporine A (CYA) and azathioprine (AZA) as long-term immunosuppressive treatment for patients with multiple sclerosis. 31 randomly assigned patients completed a 12-month treatment with either CYA (5 mg/kg/day) or AZA (2 mg/kg/day). Evaluation included serial quantitative clinical assessments and circulating T cell markers. The CYA treatment group improved in only one of three scoring systems (p less than 0.05), while no difference was observed in the AZA group. CYA and AZA did not influence CD4+/CD8+ ratio of circulating T cells but affected HNK-1+ cells. The overall frequency of abnormal laboratory values were comparable in both groups. We conclude that CYA given in a low dose is relatively well tolerated but its benefits appear to be of limited value.

Adult↗