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Biomedical subjects

M Wender

Publications and source records attributed to M Wender.

At least 19 recordsLinked to original sources
PubMed2000

[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↗
PubMed1999

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↗
PubMed1999

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↗
PubMed1999

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↗
PubMed1998

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↗
PubMed1998

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↗
PubMed1998

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↗
PubMed1998

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↗
PubMed1997

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↗
PubMed1996

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↗
PubMed1996

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↗
PubMed1995

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↗
PubMed1994

Myelin-oligodendroglia complex in rats subjected to experimental cardiac arrest.

In an experimental model of clinical death induced in rats using the method of Korpachev et al. (1982) the myelinoligodendroglia complex was evaluated using the morphometric method of investigation. The results documented acute oedema of oligodendroglia nuclei in the early period, and degenerative changes later on. The studies of myelinated fibers seem to testify some differences in sensitivity according to the axon and myelin diameter on the influence of ischemia. The later changes of myelinated nervous fibers in the postresuscitation syndrome seem to be the secondary effect of autoimmune dependent neuronal destruction, whereas the alterations of oligodendroglia only partially contribute to the myelin lesion.

Animals↗
PubMed1994

The effect of large-dose prednisone therapy on IgG subclasses in multiple sclerosis.

The effect of large-dose prednisone therapy (3960 mg over 56 days) on IgG subclasses in the cerebrospinal fluid and sera, as well as on their intrathecal synthesis, was studied in 15 patients with clinically definite multiple sclerosis. The concentration of IgG subclasses was measured using ELISA with monoclonal antibodies against human IgG subclasses, secondary biotinylated antibody and avidin-biotin-peroxidase complex. There was a decrease of IgG1, IgG3 and IgG4 in the CSF of MS patients after the treatment, but the differences did not reach statistical significance. The IgG index was decreased about 34% (p < 0.01) after the therapy. This was mainly due to diminished synthesis of IgG1 and IgG3. The significance of IgG subclasses in the pathogenesis of MS is discussed.

Adult↗
PubMed1994

Reduced expression of erythrocyte complement receptor (C3bR) in MS.

The study was carried out in patients with MS (n-121) and in control group (n-519). On the basis of haemagglutination intensity and results of radioimmunoassay three phenotypes of complement receptor were classified: high HH, medium HL, and low LL. Considerable differences were observed in the distribution of these phenotypes between controls and MS in whom the low phenotype was more frequent. Family studies suggest that reduced expression of the complement receptor on the erythrocytes depends in MS on the disease process in the first place, and not on genetic factors.

Erythrocytes↗
PubMed1994

Free sterols in senile human brain.

Autopsy material of 18 patients, who died between 66-86 years of age and of 4 ones, who died between 20 and 38 years of age was investigated. The white matter of frontal lobe, corpus callosum and cerebellum was studied using histological and biochemical methods. According to the results of neuropathological studies, the material of aged patients was divided into two subgroups: patients with vascular changes only and brains with senile atrophy of Alzheimer type. Chemical changes in all aging brain regions studied included higher proportion of desmosterol and differences in the pattern of cholesterol isomers. These findings are interpreted as suggesting some chemical transformations of cellular membranes in the cerebral white matter of the aging. The above mentioned changes were almost identical despite presence of the signs of Alzheimer's type senile atrophy, therefore it is not possible to explain their significance in developing of dementia process.

Adult↗
PubMed1994

Myelin lipids and proteins in experimental global ischemia.

The experiments were performed on white rats, in which clinical death was induced according to the method described by Korpatchev et al. (1982). After cardiac arrest and cessation of respiratory function lasting 5 minutes resuscitatory action was performed. The lipids and proteins of the cerebral myelin fraction were studied in animals sacrificed 1, 9 and 14 days after global ischemia. The obtained results lead to the following conclusions: 1. Myelin lipids in postreanimation syndrome are characterized by a marked increase in cholesteryl esters and a mild one of lysophosphatidylcholine content. 2. Myelin lipids in the predemyelinating period demonstrate a general pattern of reaction, notwithstanding to the character of the primary noxious agent. 3. After global ischemia a great fall of small basic protein in the myelin fraction and subsequently of SBP to LBP ratio occurred. 4. Various noxious agents affect different proteins of the myelin membranes and the resulting changes seem to be characteristic for various pathological processes.

Animals↗