Task force on minimum standards for health care of people with multiple sclerosis: June 1999.
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Delivery of Health Care↗
Biomedical subjects
M Wender
Publications and source records attributed to M Wender.
Biological markers to confirm diagnosis and monitor the therapy in multiple sclerosis patients.
In patients suspected of multiple sclerosis (MS), even in the case of MRI positive changes, cerebrospinal fluid (CSF) analysis is of great practical value. Until now, however, only IgG index, restricted oligoclonal IgG bands and the examination of IgG subclasses have been of practical value. The determination of other immunological markers is too expensive to be introduced into laboratory diagnostic standards in MS. However, the clinical trials should be monitored by a large set of markers of MS activity, including the estimation of anti MBP antibodies, presence of MBP material in the CSF and concentration of sVCAM-1, ICAM-1, PECAM-1 in CSF and serum.
Biomarkers↗
The effect of short-term treatment with interferon beta 1a on acute experimental allergic encephalomyelitis.
The clinical and histological picture and immunocytochemical expression of some cytokines on infiltrates in the central nervous system of Lewis rats were studied in adult rats in the course of short-term therapy of acute experimental allergic encephalomyelitis with interferon beta 1a (IFN beta 1a). There was established the beneficial effect of the short-term treatment of EAE with IFN beta 1a, applied at the early onset of the experimental disease. The effect of IFN beta 1a on EAE seems likely to be associated with the inhibition of proinflammatory cytokines and stimulation of anti-inflammatory ones.
Acute Disease↗
[Actual clinical and immunological problems of neurosyphilis and neurotuberculosis].
In the past neurosyphilis and tuberculosis of the nervous system were the basic clinical problems in neurology. The decrease of the incidence rate has changed the situation. However, in the last few years, especially in connection with HIV infection, the incidence has even started to increase. In Poland the epidemiological situation is not alarming, but there exists some concern connected with the epidemic of syphilis and tuberculosis in countries near the Polish eastern border. In the laboratory diagnosis of syphilis the highest specificity and sensitivity has the TPHA test. In the therapy till now the best results are obtained with megadoses of penicillin. Early diagnosis of tuberculous meningitis, what is the decisive factor for positive results of the treatment can be obtained by PCR technique for detection of DNA genome of mycobacterium. In the treatment the method of choice is the concomitant use of four antimycobacterial drugs. However, there exists the serious problem of often observed drug resistance of mycobacterium.
Enzyme-Linked Immunosorbent Assay↗
Limited pattern of TCR delta chain gene rearrangement on the RNA level in multiple sclerosis.
Susceptibility to multiple sclerosis (MS) is most likely affected by a number of genes, including HLA and T-cell receptor (TCR) genes. T cells expressing gamma/delta receptors seem to contribute to autoagression in MS, as evidenced by their localization in the MS plaques in the brain. The aim of this study was to analyse the TCRdelta chain gene rearrangement at the RNA (cDNA) level and compare to the DNA pattern rearrangement. TCRdelta gene rearrangement was analysed in MS patients and healthy individuals with the use of primers specific for Vdelta1-6 and Jdelta1 genes (at the DNA level) and specific for Vdelta1-6 and Cdelta1 genes (at the cDNA level). The size of PCR products was analysed on agarose gel and by ALF-Express (Pharmacia). Additionally, the lymphocyte surface immunophenotype was studied with specific monoclonal antibodies. At the DNA level a restricted pattern of Vdelta3-Jdelta1 and Vdelta5-Jdelta1 was found only in MS patients. Contrary to DNA, mono-, oligoclonal RNA (cDNA) rearrangements were limited to Vdelta1-Cdelta1, Vdelta2-Cdelta1 and Vdelta3-Cdelta1 only in MS patients as well. Surface immunophenotype analysis revealed in MS a much higher frequency of activated gamma/delta T lymphocytes, i.e. expressing HLA-DR and CD25. An elevated level of CD56 positive cells in MS was recorded. Mono-oligoclonal pattern of TCRdelta gene rearrangement at the RNA level, along with increase in activated gamma/delta T cells, strongly argue for a significant role of gamma/delta T lymphocytes in the pathogenesis of MS.
Journal Article↗
[New look on pathology of multiple sclerosis?].
Recent studies made using immunohistochemistry, three dimensional imaging in confocal microscopy and magnetic resonance spectroscopy testified that, not only demyelination, but also axonal damage occur already in early phase of multiple sclerosis. There exists the direct correlation between axonal changes and chronic disability of the patients. The results indicate the need for intensive treatment of multiple sclerosis as early as definite diagnosis is made.
Brain↗
Increased serum levels of soluble PECAM-1 in multiple sclerosis patients with brain gadolinium-enhancing lesions.
Platelet endothelial cell adhesion molecule, PECAM-1 (CD31) is a 130-kDa glycoprotein, member of the immunoglobulin superfamily, which is involved in transendothelial migration of leukocytes. It is expressed on endothelial cells, lymphocytes, monocytes, neutrophils, basophils and platelets. We present data showing that soluble PECAM-1 is significantly increased in sera of multiple sclerosis patients with active, gadolinium enhancing lesions. Since we have found increased levels of sPECAM-1 in sera of patients with active MRI lesions, but not in those of patients without enhancing lesions, the molecule may be regarded as marker of MS activity. Soluble PECAM-1 may be involved in immunomodulatory mechanism leading to inhibition of migration of leukocytes in MS.
Adult↗
A Polish pedigree with Alzheimer's disease determined by a novel mutation in exon 12 of the presenilin 1 gene: clinical and molecular characterization.
The presenilin 1 (PS-1) gene, recently identified on chromosome 14q24.3, is a major gene involved into the autosomal dominant forms of early onset Alzheimer's disease (EOAD). Mutations of the PS-1 gene are responsible for the majority of familial EOAD. We found a novel mutation in a Polish family with EOAD from the Poznań region. The mutation at codon 424 in exon 12 of the PS-1 gene leads to an amino acid substitution Leu-Arg in a transmembrane domain VIII of the presenilin 1 molecule. The change is predicted to have a drastic effect on the protein function because it is associated with a very early age of onset (a range of 30-35 years) and a quick progression (about a 4-5 years duration) of the disease.
Adult↗
Diversity of V delta-J delta gene rearrangement in peripheral blood lymphocytes and intrathecal IgG synthesis in multiple sclerosis.
The object of the study is a comparison of intrathecal IgG synthesis and gamma/delta TCR genes rearrangement in multiple sclerosis. The subgroup of 13 cases with intrathecal IgG synthesis and positive oligoclonal bands was compared with 8 cases with IgG index below 0.75 and with undetectable oligoclonal bands. TCR gene rearrangement was studied in peripheral blood lymphocytes by PCR analysis. In majority of cases of the first group the V delta-J delta junctional repertoire was restricted as evidenced by oligoclonal rearrangement. Monoclonal pattern of rearrangement was also established in some cases concerning V delta 1-J delta 1 and V delta 5-J delta 1. In all cases with one exception, demonstrating IgG index < 0.75 and with negative oligoclonal bands in CSF the oligo- or polyclonal pattern of V delta-J delta gene rearrangement was noticed. It is therefore suggested that subset T and B lymphocytes may undergo clonal expansion in MS as evidenced by restricted pattern of V delta-J delta rearrangement and intrathecal oligoclonal IgG synthesis, respectively. Oligoclonal expansion at certain B and T cells may occur due to stimulation by an antigen related to MS pathogen.
Antibodies, Monoclonal↗
Atypical case of sporadic Creutzfeldt-Jakob disease (CJD) in a young adult.
The great concern exists that new variant of CJD (nvCJD) developed as a result of exposure to bovine spongiform encephalopathy (BSE)-infected meat products. Therefore, all cases of CJD in the young, as the one of ours are the matter of interest. The 21-year-old female developed a rapid progression of pyramidal, extrapyramidal and cerebellar signs, visual loss and psychiatric symptoms, leading to death in 16 weeks. The microscopic features were: a neuronal loss accentuated in cerebral cortex with extensive astroglia proliferation and spongiform changes. Immunohistochemical staining, revealed the presence of "synaptic" deposits of PrP in the cerebral cortex and in the cerebellum. No florid amyloid plaques were present. The case was diagnosed as a sporadic CJD, with some features of Heidenhein variant (visual symptoms) and corticostriatocerebellar category. The pathological findings excluded a nv CJD which is linked with BSE.
Adult↗
Gamma/delta T cell receptor genes rearrangement in the blood and brain of multiple sclerosis patients. A preliminary study.
The characterization of TCR gamma/delta gene diversity in peripheral blood lymphocytes and in cerebral white matter of MS patients was performed. In overwhelming majority of MS cases the V delta-J delta junctional repertoire was restricted as evidenced by oligoclonal rearrangements concerning V delta 1-J delta 1, V delta 2-J delta 1, V delta 3-J delta 1, V delta 5-J delta 1. The obtained results indicate, that the restricted pattern of TCR gene rearrangement may suggest oligoclonal expansion of certain clones of gamma/delta T cells that may be involved in recognition of putative autoantigen, significant in the etiopathogenesis of MS. The very striking positive correlation between monoclonal pattern of V delta-J delta rearrangement in peripheral blood and cerebral white matter of MS patients indicate that the gamma/delta T lymphocytes play significant role in MS pathogenesis.
Adult↗
Screening for presenilin-1 gene mutations by PCR-SSCP analysis in patients with early-onset Alzheimer's disease.
The majority of early-onset familial Alzheimer's disease (EOAD) has been associated with mutations in a novel gene on chromosome 14 which has been termed presenilin-1 gene. We screened for mutations within the presenilin-1 gene in twenty patients with EOAD using a PCR-SSCP analysis. We found three aberrant (mutant?) band patterns for exons 4 and 7 in three unrelated patients.
Adult↗
Apolipoprotein E genotypes in sporadic early and late-onset Alzheimer's disease.
Recent data have demonstrated that presence of apolipoprotein E (APOE) epsilon *4 allele is a major risk factor of Alzheimer's disease (AD). We determined the APOE genotypes in 64 patients with sporadic probable AD and 43 non-demented aged controls selected from Poznań region and the western part of Poland using the polymerase chain reaction (PCR) followed by the restriction fragment length polymorphism (RFLP) analysis. We confirmed a strong correlation of the APOE epsilon *4 allele with sporadic late-onset AD. In contrast to many previous reports we did not found an association between the APOE epsilon *4 allele and sporadic early-onset AD.
Adult↗
Free sterols in the rat white matter following experimental global ischemia.
The pattern of free sterols occurring in the cerebral white matter was studied in an experimental model of global ischemia that was induced in rats by means of the method described by KORPACHEV et al. (1982). Sterol isolation, separation and identification was accomplished by suitable extraction procedures followed by gas-chromatography-mass spectrometry of the purified sterol extracts. It has been shown that the percentage of lanosterol happened to decrease sharply following the ischemic state and other sterols, typically occurring in maturating brains and absent in the control brain specimens from adult rats, such as 4,4-dimethylcholesterol, 4,4-dimethylcholest-5,8,24-triene-3 beta-ol and 4,4,14-trimethylcholest-5,8-diene-3 beta-ol happened to appear. The appearance of these forms of free sterols in the postischemic brain is interpreted as a biochemical exponent of regeneration processes occurring in the white matter membranes following the injury suffered during the experimental heart arrest.
Animals↗
Association between the PI*M3 allele of alpha 1-antitrypsin and Alzheimer's disease? A preliminary report.
The deposition of beta A4-amyloid in senile plaques in the brain and small cerebral vessels is one of the pathological hallmarks of Alzheimer's disease (AD). Serine protease inhibitors (serpins) such as alpha 1-antitrypsin and alpha 1-antichymotrypsin have been found to be associated with beta-amyloid deposits; interest in their role in the pathogenesis of AD has therefore recently increased. We have analyzed alpha 1-antitrypsin phenotypes in a sample of 29 Polish patients with probable Alzheimer's disease. We have found an increased frequency of the PI*M3 allele (0.1897) in patients in comparison with the general population control (0.0563).
Adult↗
Cholesterol synthesis in the rat brain in course of late development as determined by 3-hydroxy-3-methylglutaryl CoA reductase activity.
The activity of 3-hydroxy-3-methylglutaryl-CoA reductase (E.C. 1.1.1.88), the key regulatory enzyme in the process of cholesterol biosynthesis was evaluated in different development stages of rat brain. The obtained results have shown an almost twofold increase of HMG-CoA reductase activity in one year old rats compared to the reference 4 months old animals. The activity of the cerebral HMG-CoA reductase in two years old animals dropped to the level observed in the reference group. The enhancement of activity of the regulatory enzyme for cholesterol biosynthesis occurs in parallel with an appearance of quantitatively minor, other than cholesterol, free sterol normally absent in the brains of young animals.
Animals↗
IgG subclasses in neurological disorders.
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Adult↗
Transformation of sterols pattern in course of late development of rat brain.
Free sterol content was determined in the late period of development of the rat brain using the method of gas chromatography-mass spectrometry. The results obtained have shown that the free sterol pattern is very unstable in course of late period of ontogenic development. In contrast to young adult rats, in which apart from cholesterol only trimethylcholestenon and trace amounts of desmosterol were visible, in the brain of 1 and 2 years old rats some new sterols are appearing. There are cholestadien, cholest-5-en-3-on, 4 methyl-cholesten, cholest-5-en-3-ethoxy and 4,4,14-trimethyl-5-alpha-cholest-24-en-3-en. There are also qualitative differences in the structure of some sterols (various isomers) between both groups of late development. These changes, indicating some transformation of cellular membranes seem to be the result of biologically programmed late ontogenic development.
Aging↗