Irena Niebrój-Dobosz

Matrix metalloproteinases and their tissue inhibitors in serum and cerebrospinal fluid of patients with amyotrophic lateral sclerosis

Background and purpose:  Matrix metalloproteinases (MMPs) are implicated in the pathogenesis of motor neuron degeneration in amyotrophic lateral sclerosis (ALS). We investigated the expression of MMPs and tissue inhibitors of matrix metalloproteinases (TIMPs) in serum and cerebrospinal fluid (CSF) correlating the results with age, disease duration and the clinical course.

Anti-neural antibodies in serum and cerebrospinal fluid of amyotrophic lateral sclerosis (ALS) patients

Objectives ‐ An autoimmune basis has been implicated in the pathogenesis of amyotrophic lateral sclerosis (ALS). This hypothesis is supported by the presence of antibodies that interact with motoneuron antigens in serum of these patients. Against autoimmunity are the discrepances in the frequency of the antibodies appearance and also failure of immunosuppression. The aim of our study was to evaluate the titer of antibodies against GM1‐gangliosides, AGM1‐gangliosides and anti‐sulfatides in paired serum and cerebrospinal fluid samples in the ALS patients. Material and methods ‐ Serum of 103 and CSF of 79 patients with ALS was examined. The “disease controls” consisted of 22 cases of other motor neuron diseases and 50 healthy, age‐matched normals. CSF was drawn at the same time from 79 ALS patients, 6 cases of the “disease controls” and 50 normals. To study the titer of antibodies against GM1‐gangliosides, AGM1‐gangliosides and sulfatides the ELISA technique has been applied. Results ‐ An increased titer against GM1‐gangliosides, AGM1‐gangliosides and sulfatides in ALS appeared in serum in 18%, 32% and 11%, resp., in the “disease controls” the increased antibodies titer appeared in single cases. In CSF the appropriate values in ALS were 20%, 15%, 8%, resp. In the “disease controls” a high antibodies titer was a rare finding. Conclusions ‐ It is concluded that in some ALS cases and also in some patients with other motor neuron diseases an autoimmune mechanism may contribute to motor neuron injury.

Erythrocyte ghosts (Na++K+) ATPase activity in duchenne's dystrophy and myotonia

SummaryIn Duchenne muscular dystrophy the activity of (Na++K+) ATPase in erythrocyte ghosts is reduced and its reaction to ouabain is paradoxical both in low sodium and high sodium systems. No such changes were seen in a case of Becker dystrophy, in limb-girdle dystrophy, and in neurogenic atrophy of muscles. In myotonic dystrophy and congenital myotonia the activity of ATPase and its inhibition by ouabain were depressed.ZusammenfassungDie Aktivität der Na+ und der K+ aktivierbaren ATP-ase der Erythrocyten ist in Fällen von Duchennescher Muskeldystrophie vermindert. Ihre Reaktion auf Ouabain ist sowohl in einem System mit niedrigen wie in einem System mit hohem Natriumgehalt in paradoxer Weise verändert, indem sie aktiviert wird, während sie in Fällen von Beckerscher Dystrophie und von Dystrophie vom Rumpfgürtel-Typus sowie in neurogenen Muskelatrophien gehemmt wird. Bei der myotonischen Dystrophie und der kongenitalen Myotonie ist die Aktivität der ATP-ase vermindert und weniger gehemmt.

Serum IgM anti-GM1 ganglioside antibodies in lower motor neuron syndromes

Lower motor neuron syndromes (LMNS) are heterogenous conditions, which include patients with progressive lower motor neuron disease (LMND) and cases with the clinical phenotype of motor neuropathy (MN). The aim of this study was to estimate the IgM anti‐GM1 ganglioside antibodies titer and the ratio of the light chains in order to define the presence of autoimmunity process in particular cases with LMNS. Twenty‐eight patients were diagnosed with LMND and 15 patients were diagnosed with MN (10 patients with multifocal motor neuropathy with conduction block, five patients with MN without conduction block). Total of 103 patients with classical amyotrophic lateral sclerosis (ALS) and 50 healthy, age‐matched persons were also tested. The IgM anti‐GM1 ganglioside titer and the ratio of lambda/kappa light chains in serum were determined using the ELISA technique. High titer of IgM anti‐GM1 antibodies were detected in serum of 46% LMND patients, 80% of MN patients, and 18% of the classical ALS cases. An elevated ratio of lambda/kappa light chains appeared in 18% of LMND patients, and in 67% of the MN cases. The lambda/kappa light chains ratio was normal in all ALS patients. The presence of elevated titer of IgM anti‐GM1 ganglioside antibodies and the changed ratio of the light chains supports the presence of autoimmune process in LMNS and may provide clues for their management.

Correlative biochemical and morphological studies of myelination in human ontogenesis

SummaryBiochemical, light and electron microscopic observations in six human fetuses between the 16th and 34th weeks of gestation and five infants, 1 day to 3 years old, are presented. The results indicate that myelination of the human spinal cord started before the 16th week of gestation, as a considerable amount of myelin is isolated at this time biochemically, and occasionally axons with loose myelin coils are observed in the electron microscope. It is also stressed that morphological studies are insufficient to evaluate the completion time of the myelination process, as it can be shown biochemically that qualitative myelin maturation takes a long time.

Tenascin-C in human cardiac pathology

Tenascin-C (TN-C), a hexameric extracellular matrix glycoprotein, is a pleiotropic regulator of a variety of cell functions associated with embryogenesis, wound healing, cell proliferation, differentiation, motility, and nerve regeneration. Due to its role in remodeling processes, TN-C is involved with many pathologic states including cardiac and vascular diseases as well as inflammation and cancer. Assessment of circulating TN-C may help with identification of heart disease, especially in conjunction other cardiac biomarkers. It may be considered a specific biomarker useful in detecting cardiac pathology, especially in early disease stages and subsequent monitoring of cardiologic therapy. This review will highlight the biochemistry and usefulness of TN-C in clinical laboratory diagnostics to date.

Progeria caused by a rare LMNA mutation p.S143F associated with mild myopathy and atrial fibrillation

We present a 6-year-old girl with premature aging associated with mild myopathy, displaying muscle weakness, joint contractures and hyporeflexia. Genetic analysis revealed rare heterozygous point mutation in lamin A/C gene, g.428C>T. Cardiological evaluation showed atrial fibrillation, but we did not find signs of coronary heart disease, which is life-threatening cardiovascular complication in progeria. Electron microscopy of the muscle revealed abnormalities in nuclear architecture, i.e. blebbing, thick lamina and peripheral distribution of heterochromatin. As some diagnostic criteria characteristic for classic progeria are not fulfilled, this case could be regarded as atypical progeria associated with myopathy and atrial fibrillation. To our knowledge, this is the second case of such association described in the literature.

Immunoblot analysis of sarcoplasmic calcium binding proteins in Duchenne muscular dystrophy

The Western blotting technique was used to detect parvalbumin and S-100 protein in muscles from 10 Duchenne muscular dystrophy (DD) patients, 13 patients with other muscle diseases and 5 age-matched healthy subjects. DD muscles were found to contain decreased amounts of parvalbumin and the S-100 protein. The parvalbumin level did not relate to the age of the patients and the stage of the disease. The S-100 protein decreased progressively with the age of the patients. In a very advanced DD case the S-100 protein was present in trace amounts. In other primary myopathies, including Becker dystrophy, and neurogenic muscular atrophy both parvalbumin and S-100 protein levels were similar to that observed in healthy subjects. The decrease in the amount of both calcium binding proteins may contribute to the elevation of free intracellular Ca2+ level in the sarcoplasm of dystrophic muscle and would result in abnormalities in processes regulated by these proteins. The mechanism(s) responsible for the decrease of parvalbumin and S-100 protein in DD muscles are discussed.

Myofibrillar protein pattern in experimental myotonia in rats.

Experimental myotonia was induced in rats by long-term administration of 20,25-diazacholesterol. Electrophysiological, morphological and biochemical investigations were carried out on m. soleus, m. extensor digitorum longus and m. gastrocnemius. The effect of 20,25-diazacholesterol administration on myofibrillar proteins was studied and a significant rise in the concentration of a protein presumed to be alpha-actinin was demonstrated in m. gastrocnemius. A change of the same character, not statistically significant, was observed in the m. extensor digitorum longus.

Osteopontin – a fibrosis-related marker – in dilated cardiomyopathy in patients with Emery-Dreifuss muscular dystrophy

Abstract Background: As osteopontin (OPN) may be assumed to have diagnostic/prognostic value in heart diseases, it is worth assessing whether it is also involved in the pathogenesis and can be applied in the diagnosis of the dilated cardiomyopathy (DCM) in Emery-Dreifuss muscular dystrophy (EDMD). Methods: Serum levels of osteopontin were quantified by means of sandwich immunoassay in 25 EDMD patients (10 laminopathies AD-EDMD and 15 emerinopathies – X-EDMD), eight carriers of X-EDMD, nine disease controls (patients with dystrophinopathy) and 20 age-matched healthy controls. Results: The levels of circulating OPN were elevated in all AD-EDMD and X-linked EDMD patients, as well as in X-EDMD carriers and patients suffering progressive muscular dystrophy. There was no correlation between the osteopontin level and different cardiac parameters, including left-ventricular end-diastolic diameter, left atrial diameter, the left ventricular ejection fraction and the CK-MB level. There was a slight negative correlation with the ages of the patients. Conclusions: The presented results indicate that assessments of circulating OPN levels may help to identify EDMD patients at risk of dilated cardiomyopathy and might be therefore included among the set of biomarkers referred to with a view to appropriate early cardiologic diagnosis and therapy being commenced with in time.