Biomedical subjects

Anna Fidziańska

Publications and source records attributed to Anna Fidziańska.

12 recordsLinked to original sources

PubMed2006

Rimmed vacuoles with beta-amyloid and tau protein deposits in the muscle of children with hereditary myopathy.

We investigated whether beta-amyloid and tau protein are involved in the formation of inclusion body myositis (IBM)-like inclusions found in children with rimmed vacuoles and congenitally affected muscles. We immunostained muscle biopsy specimens from four children and one 18-year-old boy with congenital myopathy containing rimmed vacuoles and IBM-like inclusions with antibodies against beta-amyloid, tau protein and ubiquitin. Focal accumulations of both beta-amyloid and phosphorylated tau coexisted with tubulofilamentous structures in all cases. Our studies demonstrate for the first time that the full morphological phenotype of IBM including beta-amyloid and tau protein deposits may also develop in children, and that congenital, probably genetic, muscle defects may lead to abnormal protein aggregation in IBM-like inclusions.

Adolescent↗

PubMed2006

Dilated cardiomyopathy caused by LMNA mutations. Clinical and morphological studies.

BACKGROUND: Dilated cardiomyopathy (DCM) is familial in about 20-35% of patients. The most frequently encountered mutations associated with DCM are found in LMNA. AIM: To define the frequency of LMNA mutations in a series of consecutive DCM patients and to evaluate the phenotype of mutation carriers. METHODS: We screened the 12 exons of LMNA in a series of 61 Polish patients with DCM diagnosed angiographically, as well as in two DCM families. RESULTS: Two mutations were detected in 5 mutation carriers (D192G in one proband and Y481Stop in one proband and 3 of his offspring), which represents 3.3% (2/61) of the DCM patients. These mutations were absent from 100 controls. The D192G mutation was found in a 26-year-old patient with mild DCM and heart failure leading to death within two years after onset of symptoms. Mild conduction disease was also present. Ultrastructural analysis of the endomyocardial biopsy showed a striking alteration of nuclear morphology. This finding can explain nuclear fragility and is in agreement with the pathophysiological mechanical hypothesis of LMNA mutations. All four Y481Stop mutation-carriers were affected. Three phenotypes were found: in the proband, cardiac dysrhythmia and pacemaker requirement preceded DCM leading to heart transplantation; the proband's 13-year old daughter had conduction disease (2nd degree A-V block) with subtle skeletal muscle involvement documented by immunofluorescence study; ventricular arrhythmia was detected in the proband's son at the age of 11 and in the proband's daughter at the age of 18. Serum creatine kinase was normal in all mutation carriers.

Adolescent↗

PubMed2006

Progression of morphological changes within CNS in a transgenic rat model of familial amyotrophic lateral sclerosis.

UNLABELLED: An analysis of the dynamics of histological and immunocytochemical changes in the CNS of a transgenic rat model of fALS in various periods of life was performed. Material was obtained from animals on the 60th day of age (4), 93rd day of age (3) and 120th presymptomatic day and from 3 animals in paretic stage of the disease. Formalin-fixed and paraffin-embedded slices were stained with HE and Klüver-Barrera method. Immunoreactions to GFAP, S-100, ferritin, neurofilament, ubiquitin, synaptophysin and tau protein were also performed. Within the brain tissues patchy neuronal loss and dark or ischaemic neurons were dispersed in cortical layers, CA1, CA3 and CA4 hippocampal areas and structures of the hemispheres and brain stem. In the spinal cord, numerous alpha motoneurons were dark or ischaemic. Vacuoles or small pale spots were visible in their cytoplasm. Microspongiosis surrounded some motoneurons, particularly cells subjected to neuronophagy. Neuronophagy, sporadically observed at the age of 60th day, was more extensive on the 93rd day of age, and at the age of 120 days already involved all interneurons of the anterior and posterior horns. In the immune reaction to neurofilament numerous fibres, often thick, fragmented or rosary-like, were observed. They were located within subcortical white matter, external and internal capsules, anterior horns of the spinal cord. Changes became more intensive with age. Astrocytic reactivity was weak in animals on the 60th and 93rd day of life. Non-numerous cells were immunoreactive to GFAP and S-100, although an increase of astrocytic nuclei was observed. On the 120th day of age and in symptomatic stage astrocytic hypertrophy and proliferation were intensive. But from the 60th day of age ubiquitin and tau protein immunopositive material was accumulated in the perinuclear area of astroglial cytoplasm. Immunoreaction of nerve cells to these proteins was negative. CONCLUSIONS: 1) In the subclinical stage of the disease the pathological process within the CNS takes place already on the 60th day of age and its intensity increases with age. 2) Morphological changes are not limited to motor neuronal cells. Various structures of the CNS are damaged. 3) Weak astroglial reaction probably depends on pathological accumulation of ubiquitin and tau protein in cytoplasm. 4) Astroglial cells are probably also a "target" for pathogenic factors in the rat model of fALS.

Age Factors↗

PubMed2006

Ultrastructural changes in lumbar spinal cord in transgenic SOD1G93A rats.

The purpose of this study was to determine structural changes which trigger the onset and progression of amyotrophic lateral sclerosis in rats expressing a human SOD1 transgene with mutation G93A. Lumbar spinal cord of affected rats in early and late presymptomatic (PM, 60 and 93 days of age) and symptomatic (S, 120 days of age) stage of the disease were analyzed ultrastructurally. At 60 days the structure of lumbar spinal cord as well as alpha motoneurons type S and F appeared normal; however, careful examination revealed that approximately 15% of axons were filled with mitochondria that were abnormal in number, size and morphology. Grossly swollen mitochondria with disrupted cristae were a prominent feature in all large axons at 93 days of age. At this time swelling and dilated mitochondria were observed also in type S motoneurons, while type F had small, well preserved mitochondria. At symptomatic stage the alpha motoneurons showed moderate neuronal loss, mainly of the S type. The most interesting finding at this stage was the occurrence of motoneurons with morphological signs of apoptotic-like degeneration. Such apoptotic-like motoneurons were characterized by nuclear and cytoplasmic condensation, chromatin compaction and formation of uniformly dense, dark structures. Numerous axons with very dark, compact interior as well as apoptotic bodies were irregularly scattered throughout the neuropil. Our ultrastructural study indicates that dying motoneurons in transgenic mutant SOD1G93A rats exhibit reminiscent apoptotic morphology which is preceded by significant mitochondrial abnormalities mainly in proximal axons and S motoneurons. Different reaction of slow and fast motoneurons to degenerating factors requires further analysis.

Animals↗

PubMed2005

A novel desmin R355P mutation causes cardiac and skeletal myopathy.

A novel desmin R355P mutation has been identified in a patient with familial cardiac and skeletal myopathy. Two types of desmin storage were observed in the skeletal muscles. The spheroid-like bodies dominated in type 2 fibres while extensive accumulation of granulofilamentous material was found in type 1 fibres and in cardiomyocytes. A novel missense mutation R355P in the rod domain located in the C-terminal part of the 2B subunit is the eighth missense mutation, which changes the original aminoacid into proline. Proline is known to disrupt the alpha-helix and distort a unique stutter sequence that is critically important for proper filament assembly.

Adult↗

PubMed2004

Coexistence of X-linked recessive Emery-Dreifuss muscular dystrophy with inclusion body myositis-like morphology.

We reported three cases (two familial and one sporadic) of X-linked Emery-Dreifuss muscular dystrophy (EDMD), genetically documented. Two patients demonstrated a typical inclusion body myositis (IBM)-like morphology. The third patient had only minor changes. Patients had elbow and ankle contractures, progressive wasting of humeroperoneal muscles and cardiac failure (pacemaker implantation in all). There was a mutation within the Xq28 gene and complete absence of emerin in the nuclear membrane. Mononuclear cell infiltrations, rimmed vacuoles, amyloid deposits, as well as cytoplasmic and nuclear tubulofilamentous muscle inclusions were most unusual findings. Coexistence of IBM-like morphology and X-linked recessive EDMD might indicate that pathological features of IBM are nonspecific and may be present in other neuromuscular disorders.

Adult↗

PubMed2003

Architectural abnormalities in muscle nuclei. Ultrastructural differences between X-linked and autosomal dominant forms of EDMD.

OBJECTIVES: The aim of our study was to compare the ultrastructure of myonuclei in both forms of Emery-Dreifuss dystrophy (EDMD)-X-linked and dominantly autosomally transmitted. The muscle biopsies were taken from rectus femoris in four X-linked EDMD cases and three ADEDMD cases. METHODS: The biopsies were evaluated using immunocytochemical staining to establish emerin or A/C lamins deficiency. The muscle ultrastructure, especially that of nuclei, was analysed to find out whether there are differences between the two forms of EDMD. RESULTS: In both forms of EDMD, there was an aberrant nuclear architecture. In the X-linked form, the breakdown of fragile nuclear membrane and presence of nucleoplasm extrusion were a distinct feature. In the AD from, there was chromatin reorganization and loss of nucleoplasm volume.

Adult↗

PubMed2002

"Cap disease"--a failure in the correct muscle fibre formation.

Four unrelated patients are reported with muscle hypotonia, weakness, skeletal dysmorphism and respiratory insufficiency since childhood. Muscle tissues were found to contain a number of muscle fibres with abnormal structure. Peripherally located structures such as a cap lacking in ATP-ase and fast myosin activity, rich in desmin, tropomyosin and alpha-actinin consisted of abnormally arranged myofibrils. The position of the peripherally situated myofibrils, as well as their abnormal sarcomere pattern, seems to point to an error in fusion and muscle protein synthesis. Whether our cases of congenital myopathy with cap structures are of hereditary origin or of a sporadic type remains unknown, so far. It seems that the result of our study, as well as data presented in the literature, allows us to divede cap disease into two forms: fatal and nonfatal. The morphological changes in the muscle fibres are identical in all the presented cases but the number of muscle fibres with cap structures is much higher in the fatal form.

Adolescent↗

PubMed2002

Motoneuron death in normal and spinal muscular atrophy-affected human fetuses.

The onset and sequence of motoneuron death in the lumbar part of spinal cord of seven control and five affected fetuses carrying deletion of exon 7 in the SMN gene were studied by light and electron microscopy. Naturally occurring motoneuron death in control fetuses was detected between 8 and 13 weeks of gestation. In affected fetuses motoneuron death was prolonged and also observed at 16 and 20 weeks of gestation. In addition, motoneurons in the affected fetuses displayed nuclear abnormalities as early as 16 weeks of gestation and the changes progressed as the affected fetuses developed and can be considered first signs of motoneuron degeneration.

Apoptosis↗

PubMed2002

Phenomenon of Schwann cell apoptosis in a case of congenital hypomyelinating neuropathy with basal lamina onion bulb formation.

We analyzed a sural nerve biopsy of a child with congenital hypomyelinating neuropathy. A lack of normally myelinated fibres, abnormal architecture of premyelin fibres and basal lamina onion bulbs were identified. The most prominent pathological finding was the appearance of significant death of Schwann cells with apoptotic morphology. This new finding may suggest that abnormal premyelin fibres are susceptible to death and that their disappearance is responsible for empty basal lamina onion bulb formation.

Apoptosis↗

PubMed2002

Suicide muscle cell programme-apoptosis. Ultrastructural study.

To establish the ultrastructural criteria of suicide muscle cell programme-apoptosis we investigated the muscle biopsies of acute fatal spinal muscular atrophy (SMA) infants with gene survival motor neurone (SMN) exon 7 deletion. The muscle cell apoptosis was characterised by precisely sequential morphology of both cell nucleus and sarcoplasm. The most characteristic feature was the aggregation of nuclear chromatin initially into peripherally located ring and later into uniformly dense, dark masses. Accompanying features included sarcoplasmic condensation cell shrinking and fragmentation into multiple bodies. The coexistence of muscle cells at different stages of apoptosis in the same tissue section was the most prominent and specific feature of suicide muscle cell programme. The appearance of an identical sequence of ultrastructural changes in muscle as observed in other tissues suggests that a unique mechanism is involved in genetically programmed cell death.

Apoptosis↗

PubMed2002

Is the normal content of sulfhydryl groups attributable to sparing from dystrophic pathology in dystrophin-deficient muscles?

Deficiency of dystrophin in skeletal muscles is supposed to be responsible for all the symptoms associated with Duchenne dystrophy (DMD) and Becker dystrophy (BMD). The dystrophin-deficient mdx mice, however, are clinically almost asymptomatic. Hence, other factor(s) might be responsible for the muscle pathology in DMD and BDM. As sulfhydryl groups are involved in maintaining the structure of membranes and the protein-phospholipid interactions, total, protein-bound and free sulfhydryl groups (-SH) in DMD, BMD, limb-girdle dystrophy (LGMD) and the mdx mice muscles have been determined. A significant decrease of total and protein-bound -SH groups content and an increased proportion of free -SH groups in DMD and BMD was found. In LGMD the changes of total and protein-bound -SH groups content were less expressed. In the mdx mice muscles the content of -SH groups was generally normal, only a higher than normal proportion of free-SH groups content in old and senile animals, especially in their diaphragm, was present. To test the sarcolemmal integrity, albumin/creatine kinase (CK) influx/efflux was determined. In early stages of DMD and BMD the albumin influx was increased. In advanced stages of these diseases albumin influx was not observed. In LGMD albumin penetration was present only in a few fibres. CK efflux in vitro was increased both in early and advanced DMD cases. In BMD and LGMD CK efflux was increased only in early stages of the diseases. In mdx mice an increased influx/efflux of albumin/CK was stated in adult animals. The changes persisted in the mdx hind limb muscles up to the senile age of the animals. In the mdx diaphragm of senile animals albumin did not penetrate the muscle cell and no increase of CK efflux was observed. It is suggested that changes in the distribution of -SH groups take part in the molecular disorganisation of the sarcolemma in course dystrophinopathies. Normal content of the sulfhydryl groups is supposed to be attributable to sparing from dystrophic pathology in dystrophin-deficient mdx mice muscles.

Adolescent↗