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Biomedical subjects

F Zipp

Publications and source records attributed to F Zipp.

45 records · Page 3Linked to original sources
PubMed1996

[Influence of genetic factors on multiple sclerosis].

Epidemiological studies have provided evidence for a genetic contribution to the susceptibility of multiple sclerosis (MS). One in six patients has at least one affected family member. The concordance rate is approximately 25% in monozygotic twins, and 3% in siblings, however the prevalence in adopted siblings is similar to the general population (0.1%) MS is thought to be a T cell-mediated autoimmune disease and therefore genes controlling the immune response have been studied intensively as potential susceptibility factors. The best documented association was found for genes of the human-leukocyte antigen complex. Other possible susceptibility genes may reside in the regions of the T cell receptors and the tumour necrosis factors. So far it is clear, that MS is a multifactorial disease in which several genes must be involved. Population genetics and molecular biology will help to characterise further these susceptibility factors.

Autoimmune Diseases↗
PubMed1995

Genetic control of multiple sclerosis: increased production of lymphotoxin and tumor necrosis factor-alpha by HLA-DR2+ T cells.

Lymphotoxin (LT) and tumor necrosis factor-alpha (TNF-alpha) play an important role in the pathogenesis of multiple sclerosis (MS). MS is associated with the HLA-DR2, Dw2, DQ6 HLA class II haplotype. Because both LT and TNF-alpha are encoded in the HLA region, the HLA association of MS may be related to the production of these cytokines. To test this hypothesis, we investigated the production of LT, TNF-alpha, and interferon-gamma (IFN-gamma) by CD4+ T-cell lines (TCLs) specific for myelin basic protein (MBP) or tetanus toxoid (TT) isolated from MS patients and normal controls. After stimulation with specific antigen but not mitogen, TCLs from HLA-DR2+ donors produced significantly more LT and TNF-alpha than TCLs from DR2- donors. In contrast, HLA-DR2+ and DR2- TCLs did not differ in the production of IFN-gamma, a cytokine also produced by T cells but not encoded in the HLA region. Increased secretion of LT and TNF-alpha was unrelated to the specificity (MBP vs TT), MHC restriction (HLA-DR2 vs other DR molecules), or source (MS vs normal) of the TCLs. There was no significant association of the cytokine production with individual LT or TNF-alpha alleles, indicating that the increased production of these cytokines may be linked to other polymorphic genes in this region. The results suggest that the association of MS with HLA-DR2 implies a genetically determined propensity of T cells to produce increased amounts of LT and TNF-alpha.

Animals↗
PubMed1995

Lamotrigine in Parkinson's disease--a double blind study.

Antiglutamatergic acting substances are considered to be useful tools for the treatment of hypokinesia in animal models for Parkinson's disease (PD). Moreover, most known antiglutamatergic compounds act postsynaptically and are either toxic or weak with regard to their clinical potency. The antiepileptic drug "Lamotrigine (LTG)" inhibits presynaptic glutamate release and may therefore provide a novel approach for PD therapy. Encouraging results from a pilot project led us to establish a placebo controlled trial including 20 patients with PD. The substance was generally well tolerated. There was a significant difference in the investigator's overall assessment of efficacy (6/10 vs. 2/10 improvement; p < 0.05) and a tendency for LTG to exhibit a beneficial effect in some registration parameters, but no significant differences in motor response were found between the two groups. We failed to confirm that LTG mediates a strong antiparkinsonian effect in this small study, but to clearly demonstrate slight or moderate beneficial effects larger groups are required.

Adult↗
PubMed1995

The role of autoimmune T lymphocytes in the pathogenesis of multiple sclerosis.

Autoimmune T cells play a key role as regulators and effectors of autoimmune disease. In multiple sclerosis (MS), activated T cells specific for myelin components or other locally expressed autoantigens enter the CNS and recognize their antigen(s) on local antigen-presenting cells. After local stimulation, the T cells produce a plethora of cytokines and inflammatory mediators that have profound effects on the local cellular environment, induce and recruit additional inflammatory cells, and contribute to myelin damage. An increasingly detailed knowledge of these processes will greatly facilitate the development of new immunotherapies. This article focuses on the role of T cells in MS. We provide a brief overview of the principles of T-cell immunology, discuss the experimental techniques available for studying T cells, address the role of T cells in the pathogenesis of MS, and highlight modern concepts for immunotherapy.

Amino Acid Sequence↗
PubMed1993

Lamotrigine--antiparkinsonian activity by blockade of glutamate release?

Recent experiments provide evidence that the NMDA-antagonist MK-801 has a locomotor-stimulating effect in monoamine-depleted rodents. These findings are based upon a hypothetical pathway-circuit including the basal ganglia as a model reflecting hypo- and hyperkinetic movement disorders. We have treated 5 patients suffering from Parkinson's disease with the antiepileptic drug "lamotrigine" which does not appear to be an NMDA-antagonist but acts functionally as a glutamate antagonist by inhibition of presynaptic glutamate release.

Aged↗
PubMed1993

[Isolated unilateral hypoglossal nerve paralysis in carotid dissection].

A 41-year-old man presented with a unilateral atrophy and paresis of his tongue which were not explained by any pathological finding in the brainstem or at the base of the skull. The diagnosis of right internal carotid artery dissection was suggested by magnetic resonance imaging and ultrasound examination and confirmed by arterial angiography. During anticoagulant therapy clinical recovery and angiographical improvement occurred.

Adult↗
PubMed1989

Entorhinal fibers form synaptic contacts on parvalbumin-immunoreactive neurons in the rat fascia dentata.

The entorhinal cortex gives rise to a dense projection to the outer two-thirds of the dentate molecular layer. The main target neurons are the granule cells. This study demonstrates that entorhinal fibers labeled by anterograde degeneration also terminate on parvalbumin-containing non-granule cells in the rat fascia dentata. Since the calcium-binding protein parvalbumin was recently found coexistent with gamma-aminobutyric acid in inhibitory hippocampal neurons, the described connection provides evidence for a role of entorhinal fibers in feed-forward inhibition of the granule cells.

Animals↗