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Biomedical subjects

H Somer

Publications and source records attributed to H Somer.

At least 37 records · Page 2Linked to original sources
PubMed1997

Absence of calpain 3 in a form of limb-girdle muscular dystrophy (LGMD2A).

Antibodies that recognise the muscle-specific calpain 3 (CANP3) were used in a 'blind' study to label blots of skeletal muscle from 12 control subjects and from 12 patients with various muscle diseases. Calpain 3 was clearly detected in all control muscle samples analysed, even though some of the muscle had been at room temperature for over an hour before being dissected and snap-frozen. Calpain 3 was also detected in the muscle biopsies from non-LGMD2A patients, but was absent in samples from 3 patients with LGMD2A. These results show that (i) calpain 3 protein can be detected in whole extracts of human muscle, and (ii) that antibodies can be used to differentiate patients with LGMD2A from those with other muscle diseases. This represents an invaluable diagnostic aid since the limb-girdle dystrophies are very difficult to separate on clinical grounds alone. One possible function that was considered for calpain 3 was the post-translational cleavage of the 97 kDa dystroglycan precursor polypeptide into the mature alpha- and beta-dystroglycan proteins. The beta-dystroglycan band was the correct size on blots of LGMD2A muscle, indicating that calpain 3 is probably not involved in the post-translational processing of dystroglycan.

Animals↗
PubMed1997

Muscle-eye-brain disease: a neuropathological study.

A combination of congenital central nervous, ocular and muscular abnormalities is characteristic of muscle-eye-brain disease (MEB), of Fukuyama congenital muscular dystrophy (FCMD), and of Walker-Warburg syndrome (WWS). The nosological relationship of these inherited malformative disorders is still unestablished, although the genetic locus for FCMD has been excluded in MEB. We present the first postmortem neuropathological study of MEB based on 2 male patients. Apart from sharply limited occipital agyric areas, their brains showed coarse gyri with an abnormally nodular surface ("cobblestone cortex"). Both the cerebral and cerebellar cortices showed a total disorganization without horizontal lamination. The haphazardly oriented cortical neurons formed irregular clusters or islands, separated by gliovascular strands extending from the pia. The ocular abnormalities included a pronounced glial preretinal membrane. Although MEB shares the cobblestone cortex-type malformation with FCMD and WWS, the cerebral and ocular manifestations are less severe than in WWS. Furthermore, a consistently weak staining for laminin alpha2 chain (merosin) was found in muscle biopsy specimens from 4 MEB patients, while normal immunoreactivity was observed for the laminin beta2 chain, reported to be severely deficient in WWS. These findings support nosological independence of MEB.

Adult↗
PubMed1997

Autosomal dominant progressive external ophthalmoplegia with multiple deletions of mtDNA: clinical, biochemical, and molecular genetic features of the 10q-linked disease.

Autosomal dominant progressive external ophthalmoplegia (adPEO) is a mitochondrial disease characterized by accumulation of multiple large deletions of mtDNA in patients' tissues. We previously showed that the disease is genetically heterogeneous by assigning two nuclear loci predisposing to mtDNA deletions: one on chromosome 10q 23.3-24.3 in a Finnish family and one on 3p 14.1-21.2 in three Italian families. To reveal any locus-specific disease features, we report here the clinical, biochemical, and molecular genetic characteristics of the 10q-linked disease in the single family reported to date. All seven patients and four asymptomatic subjects had ragged-red fibers and multiple deletions of mtDNA in their muscle. Ptosis and external ophthalmoplegia were the major clinical findings, and depression or avoidant personality traits were frequently, but not consistently, present in the subjects carrying mutant mtDNA. In six of the subjects with mutant mtDNA, the activities of the respiratory chain complexes I or IV, or both, were below or within the low normal range. Two autopsy studies revealed the characteristic distribution of mutant mtDNA in these patients: highest proportion of mutant mtDNA is found in different parts of the brain, followed by the skeletal and ocular muscle, and the heart.

Adult↗
PubMed1996

Osteoporosis-pseudoglioma syndrome, a disorder affecting skeletal strength and vision, is assigned to chromosome region 11q12-13.

Osteoporosis-pseudoglioma syndrome (OPS) is an autosomal recessive disorder characterized by severe juvenile-onset osteoporosis and congenital or juvenile-onset blindness. The pathogenic mechanism is not known. Clinical, biochemical, and microscopic analyses suggest that OPS may be a disorder of matrix homeostasis rather than a disorder of matrix structure. Consequently, identification of the OPS gene and its protein product could provide insights regarding common osteoporotic conditions, such as postmenopausal and senile osteoporosis. As a first step toward determining the cause of OPS, we utilized a combination of traditional linkage analysis and homozygosity mapping to assign the OPS locus to chromosome region 11q12-13. Mapping was accomplished by analyzing 16 DNA samples (seven affected individuals) from three different consanguineous kindreds. Studies in 10 additional families narrowed the candidate region, supported locus homogeneity, and did not detect founder effects. The OPS locus maps to a 13-cM interval between D11S1298 and D11S971 and most likely lies in a 3-cM region between GSTP1 and D11S1296. At present, no strong candidate genes colocalize with OPS.

Alleles↗
PubMed1995

Myosin heavy-chain fragments and cardiac troponins in the serum in rhabdomyolysis. Diagnostic specificity of new biochemical markers.

BACKGROUND: Myosin is the major structural protein in muscle. Antibodies to beta-type heavy meromyosin react with cardiac and slow-twitch skeletal muscle. Cardiac TnT and TnI were developed as tissue-specific indicators. OBJECTIVES: To study myosin heavy-chain fragments as a delayed marker of previous rhabdomyolysis. To examine the cardiac specificity of cardiac troponin T (TnT) and cardiac troponin I (TnI) in patients with severe skeletal muscle damage. DESIGN AND METHODS: Serum myosin heavy-chain fragments, TnT, and TnI were studied up to 12 days after diagnosis in relationship to the serum creatine kinase level in 20 patients with rhabdomyolysis. The mean peak serum creatine kinase activity was 91,300 U/L. Myosin heavy-chain fragments were measured by an immunoradiometric assay, TnT by a one-step immunoenzymometric assay, and TnI by an immunoenzymometric assay. RESULTS: Values for serum myosin heavy-chain fragments were greater than the upper limit of normal in all patients. The peak value (70 times the upper normal limit, on average) was usually achieved 4 to 7 days after the diagnosis of rhabdomyolysis, and it was increased up to 12 days. The peak level of TnT was increased in 95% of the patients, and it correlated strongly with the peak activity of serum creatine kinase. The highest TnI value was above the detection limit of myocardial infarction in 30% of the patients. Half of these patients were the only patients with ischemic changes observed on an electrocardiogram performed on admission to the hospital. CONCLUSIONS: The measurement of myosin heavy-chain fragments was useful in the diagnosis of previous rhabdomyolysis up to 12 days. The role of TnT was negligible as an indicator of cardiac muscle damage in patients with severe rhabdomyolysis. Cardiac TnI is a more tissue-specific marker for myocardial damage even with concurrent rhabdomyolysis.

Adult↗
PubMed1995

An autosomal locus predisposing to deletions of mitochondrial DNA.

The molecular mechanisms by which the nuclear genome regulates the biosynthesis of mitochondrial DNA (mtDNA) are only beginning to be unravelled. A naturally occurring in vivo model for a defect in this cross-talk of two physically separate genomes is a human disease, an autosomal dominant progressive external ophthalmoplegia, in which multiple deletions of mtDNA accumulate in the patients' tissues. The assignment of this disease locus to 10q 23.3-24.3 is the first direct evidence for involvement of both nuclear and mitochondrial genomes in a single disorder.

Base Sequence↗
PubMed1994

Antimyosin scintigraphy in patients with acquired and hereditary muscular disorders.

Scintigraphy with indium-111 labelled antimyosin has an established role in the evaluation of cardiac muscle damage. This antibody has been shown to cross-react with myosin in skeletal muscle. We therefore studied the usefulness of this method for the detection of skeletal muscle lesions in rhabdomyolysis, myositis and hereditary muscular dystrophies. All nine patients with rhabdomyolysis had focal uptake of antimyosin antibody which correlated with the clinical findings of soft tissue damage. However, a number of symptomless lesions were also detected by immunoscintigraphy. In rhabdomyolysis the target to non-target uptake ratios varied from 1.3 to 7.6. Diffuse uptake of antibody in skeletal muscle was observed in all three patients with polymyositis-dermatomyositis and in 12 out of 13 patients with muscular dystrophies. In myositis the intensity of antibody accumulation correlated reasonably well with the magnitude of oedema detected by magnetic resonance imaging (MRI). Most patients with Becker type or non-X-chromosomal muscular dystrophies showed slight or moderate uptake of antibody, mainly in the lower extremities. In these patients more antibody accumulated in the calves than in the thighs, whereas the findings on MRI were more prominent in the thighs than in the calves, presumably because of the better preserved muscle bulk in the calves. We conclude that antimyosin scintigraphy can be used for the detection of muscle lesions not only in acquired muscle diseases but also in hereditary muscular disorders, and that immunoscintigraphy provides information on muscle disease activity not obtainable with MRI.

Adult↗
PubMed1994

MRI of the brain in muscle-eye-brain (MEB) disease.

Muscle-eye-brain (MEB) disease belongs to the spectrum of rare congenital syndromes with migration disorders of the brain and muscular dystrophy, along with the Walker-Warburg syndrome and Fukuyama congenital muscular dystrophy. Their features overlap, and differential diagnosis presents some difficulties. We examined the brain of 10 patients with MEB using high-field MRI and found a uniform pattern consisting of a pachygyria-type cortical migration disorder, septal and corpus callosum defects and severe hypoplasia of the pons in 7 of them.

Adolescent↗
PubMed1993

Progressive unilateral hypertrophic myopathy: a case study.

A 12-year-old girl had progressive unilateral muscle hypertrophy limited to the sole, tibialis anterior, and biceps femoris muscles. The affected muscles showed complex repetitive discharges by electromyography, necrosis and variation of fiber size upon histopathological examination, and increased metabolic activity in biochemical studies. The findings suggest a myopathic origin, but the actual cause remains unknown.

Child↗
PubMed1993

The DM mutation; diagnostic applications in the Finnish population.

A pair of marker loci, D19S63 and D19S51, which are tightly linked to the myotonic dystrophy (DM) locus, were used to evaluate diagnostic applicability in the Finnish population. Results were then compared to direct detection of the mutation. The D19S63 locus revealed a linkage disequilibrium, since in 16 DM families as many as 75% of DM chromosomes carried the same allele 3 for D19S63, and 25% carried allele 1. However, when the data for D19S51 and D19S63 were considered together as a haplotype, the statistical significance of this linkage disequilibrium was considerably reduced. As expected, the best method for reliable evaluation of the carrier risk was direct analysis of the mutation. Thirteen particularly difficult cases were resolved and in 46% of them the decision could be made only by direct visualization of the mutation. However, in a few cases where the size of the CTG-repeat expansion was close to the normal size range, linked markers proved to be useful to determine the affected chromosomes. Present findings indicate that analysis of the D19S63 locus coupled to direct demonstration of the mutation provides the basis for DNA diagnostics of DM in the Finnish population.

Alleles↗
PubMed1992

Inherited idiopathic dilated cardiomyopathy with multiple deletions of mitochondrial DNA.

Idiopathic dilated cardiomyopathy (DCM) is often familial, but the pathogenetic mechanisms of DCM are unknown. We report a woman and her son who both died of DCM. The son's cardiac and skeletal muscles showed a high proportion of mitochondrial DNA (mtDNA) with multiple large deletions by Southern-blot hybridisation and polymerase chain reaction analyses. Amplification of the mother's cardiac mtDNA from 20-year-old paraffin-embedded sections showed that she also had deletions of mtDNA. These data suggest that a subgroup of inherited DCMs is associated with mtDNA mutations.

Adolescent↗
PubMed1992

Terminal deletion of chromosome 4p (4p16.3) shows a breakpoint between loci linked to Huntington disease.

A 15-year-old boy with a terminal deletion of the short arm of chromosome 4 is described. The patient has a mild clinical phenotype that is incompatible with Wolf-Hirschhorn syndrome. Careful neurological examination including CT scan did not show any signs of Huntington disease. The chromosomal breakpoint was analyzed by means of polymorphic DNA probes localized close to the tentative Huntington (HD) locus. The breakage has occurred between D4S43 and D4S90 loci and thus deletes part of the chromosomal candidate regions for the HD locus.

Abnormalities, Multiple↗
PubMed1992

Beta-adrenergic system in myotonic dystrophy.

Myotonic dystrophy (DM) is considered an inherited membrane disorder, but the basic defect is unknown. We studied plasma catecholamines as well as lymphocyte and muscle beta-adrenergic receptor densities and functioning in 19 DM patients and 15 control subjects. Plasma adrenaline and noradrenaline concentrations were not significantly different between DM patients and controls. In isolated lymphocytes basal cAMP production was 157 +/- 26 pmol/mg protein/10 min in DM patients and 91 +/- 12 pmol/mg protein/10 min in controls (n.s.), whereas isoproterenol-stimulated cAMP production was significantly higher in DM patients (285 +/- 42 pmol/mg protein) compared with control subjects (168 +/- 21 pmol/mg protein, P less than 0.05). Lymphocyte beta-adrenoceptor densities were similar among DM patients (50 +/- 3 fmol/mg protein) and controls (47 +/- 5 fmol/mg protein). beta-Adrenoceptor densities were also similar in muscle biopsy specimens (12.9 +/- 1 in DM and 13.1 +/- fmol/mg protein in controls). The correlation between lymphocyte and skeletal muscle receptor densities was r = 0.35 in DM patients and r = 0.22 in controls. The results do not support the hypothesis of adrenergic dysfunction in DM despite its membrane involvement.

Adolescent↗