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Biomedical subjects

L Kappos

Publications and source records attributed to L Kappos.

At least 109 records · Page 6Linked to original sources
PubMed1993

Treatment of multiple sclerosis with 15 +/- deoxyspergualin. Design of a controlled study with close MRI-monitoring.

The rationale and design of a prospective randomized double blind study of 15 +/- Deoxyspergualin in the treatment of Multiple Sclerosis are presented. The study was started in autumn 1992 and will include more than 200 patients who will be randomized either to DSG low dose or DSG high dose or placebo. Average number of contrast enhancing lesions in monthly cranial MRIs during the first six months of treatment and change in EDSS at the end of the two-year study period will be the main efficacy parameters.

Adolescent↗
PubMed1993

Protein kinases expressed in aggregating brain cell cultures during myelination.

Serum-free aggregating rat brain cell cultures provide sufficient cell surface and paracrine interactions between neurons and glial cells for compact myelination. We are interested in the part played in these signalling pathways by protein kinases and have used a PCR cDNA cloning approach to catalogue the protein kinase genes expressed by these cultures. 8 transmembrane protein kinases were identified: IGF1-R, trk B, bFGF-R, c-met, Tyro2, Tyro1, Tyro4 and a novel eck-related gene. The first 4 are receptors for ligands with known trophic functions. Tyro2 is a novel gene related to the EGF-R. The latter 3 belong to the eck gene family of more than 8 highly related putative receptors for, as yet, unknown ligands. 8 cDNAs for intracellular protein kinases were also isolated including 3 novel genes. Ongoing studies are investigating whether these proteins contribute to myelination and/or could be used as therapeutic targets in demyelinating diseases.

Animals↗
PubMed1992

Expression of the B cell-associated tyrosine kinase gene Lyn in primary neuroblastoma tumours and its modulation during the differentiation of neuroblastoma cell lines.

The src-related intracellular protein tyrosine kinase Lyn is a signal transducing molecule for surface immunoglobulin M and is expressed predominantly in hemopoietic cells. We report here the expression of the lyn gene in human neuroblastoma. In surgical tumour samples lyn transcripts were found preferentially at early stages whereas they were barely detectable in highly malignant tumours. In a cloned human neuroblastoma cell line, Be(2)C, lyn mRNA levels increased during neuronal differentiation induced by retinoic acid. Lyn mRNA levels were undetectable and did not respond to retinoic acid in a glial-type neuroblastoma clone, SH-EP. Retinoic acid-induced glial differentiation was associated with a reduction of lyn transcripts in a clonal I-type neuroblastoma cell line, SH-IN, which shares properties of both neuronal- and glial-type clones. Like pp60c-src Lyn may be involved in a signalling pathway of neuroblasts committed to neuronal differentiation.

Amino Acid Sequence↗
PubMed1991

[Facial myokymia caused by pontine lesions and central fever in multiple sclerosis--case report].

We report on a 35-year old patient with multiple sclerosis (MS) with clinically and electrophysiologically typical facial myokymia, appearing during an acute bout of the disease. Magnetic resonance imaging (MRI) disclosed two new pontine lesions. During a follow-up period of eight months facial myokymia subsided, but five months later central fever with good therapeutic response to carbamazepine developed. In this report we discuss the potential mechanisms of myokymia and central temperature dysregulation in MS.

Adult↗
PubMed1991

Magnetic resonance imaging in monitoring the treatment of multiple sclerosis: concerted action guidelines.

Serial gadolinium enhanced MRI of the brain detects much clinically silent disease activity in early relapsing-remitting and secondary progressive multiple sclerosis (MS), and thus has an important role in monitoring the effects of therapy. Based on the proceedings of a recent Commission of the European Communities (CEC) workshop and a review of the literature, guidelines are presented for using MRI to monitor treatment trials in MS. The guidelines consider: A) MRI system and techniques; B) patient selection; C) trial design; D) analysis of results. Priorities for future research are also indicated.

Brain↗
PubMed1990

Search for retroviral sequences in peripheral blood mononuclear cells and brain tissue of multiple sclerosis patients.

DNAs from peripheral blood mononuclear cells (PBMCs) of 21 patients with multiple sclerosis (MS), 1 patient with tropical spastic paraparesis (TSP) as well as DNAs from brain and spinal cord of 5 MS cases and 3 controls were examined for human T-cell lymphotropic virus (HTLV)-related sequences by polymerase chain reaction. The primers used were derived from the HTLV-I gag, env and tax genes. Amplified products were separated on agarose gels, blotted onto nylon membranes and hybridized to specific radiolabelled oligonucleotides. The sensitivity of amplification and hybridization was one copy of target DNA in 10(5) cellular genomes. None of the specimens was positive for HTLV-I sequences except the TSP probe. These negative data are all the more significant because brain material from MS patients was used in these studies. Our studies thus fail to support speculations that HTLV-I is involved in the aetiology of multiple sclerosis.

Adult↗
PubMed1990

A 10-year matched-pairs study comparing azathioprine and no immunosuppression in multiple sclerosis.

In a retrospective matched-pairs study the efficacy of azathioprine treatment was compared with no treatment over a period of at least 10 years. Of 277 patients with clinically definite multiple sclerosis seen during the years 1973 and 1974, 42 pairs were selected by similarity in disability score, sex, age and disease duration. Only 3 patients were lost to follow-up, and in 2 cases the initial diagnosis could not be confirmed. At the end of the 10-year period the number of wheelchair-bound, bedridden or deceased patients was double in the untreated as compared with the azathioprine-treated group but the number of non- or only minimally handicapped patients was similar in each group. The mean disability score was significantly lower in the treated group. Although caution is warranted as in every retrospective study because of insufficiently controlled confounding variables, these results support a positive but weak long-term effect of azathioprine.

Adult↗
PubMed1990

Myelin autoreactivity in multiple sclerosis: recognition of myelin basic protein in the context of HLA-DR2 products by T lymphocytes of multiple-sclerosis patients and healthy donors.

A panel of 20 human myelin basic protein (hMBP)-specific T-lymphocyte lines was generated from the peripheral blood of eight multiple sclerosis (MS) patients and two healthy donors, most of them expressing the HLA-DR2 haplotype, which is associated with an increased susceptibility to MS. Using HLA-DR gene-transfected mouse L-cell lines as antigen-presenting cells, we established that of the 20 hMBP-specific T-lymphocyte lines, 7 were restricted by the DR2a gene products of the DR2Dw2 haplotype. Four T-cell lines recognized hMBP in the context of the DR2b products of the DR2Dw2 haplotype. DR2b-restricted T-cell responses were demonstrable only in T-cell lines derived from MS patients. The hMBP epitopes presented by the DR2a heterodimer were mapped to peptides covering amino acid residues 1-44, 76-91, 131-145, or 139-153 and to a region spanning the thrombin-cleaved bond at Arg130-Ala131. DR2b-restricted T-cell lines recognized epitopes within amino acids 80-99 and 148-162. Peptide 139-153 was also presented in the context of HLA-DR1 molecules. Our data show that (i) in MS patients both the DR2a and DR2b products of the DR2Dw2 haplotype function as restriction elements for the myelin autoantigen hMBP, (ii) the DR2a molecule presents at least five different epitopes to hMBP-specific T lymphocytes, and (iii) anti-hMBP T-cell lines derived from individual donors can differ in their antigen fine specificity as well as in their HLA restriction.

Adult↗