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Biomedical subjects

R Medori

Publications and source records attributed to R Medori.

At least 37 records · Page 2Linked to original sources
PubMed1992

Fatal familial insomnia: a second kindred with mutation of prion protein gene at codon 178.

Fatal familial insomnia (FFI), a condition characterized by inability to sleep, dysautonomia, motor disturbances, and selective thalamic atrophy is a prion disease linked to a GAC----AAC mutation at codon 178 of the prion gene. These data were obtained from one kindred. We now report a second kindred affected by FFI and carrying the same mutation. The finding of the same disease phenotype and genotype in a second family further validates FFI as a distinct disease entity and a phenotype of the GAC----AAC mutation at codon 178 of the prion gene.

Base Sequence↗
PubMed1992

Production of single-stranded DNA for sequencing: an alternative approach.

We describe a simple procedure for the direct sequencing of single-stranded, PCR-amplified, target regions of human genomic DNA. At variance with previously reported procedures, purification of the desired double-stranded DNA was introduced. This additional step allowed the single-stranded amplification and sequencing of the target gene. This step is required for direct sequencing of some amplified regions of human genomic DNA. However, no individual technique seems suitable to generate and sequence all single-stranded DNA.

Base Sequence↗
PubMed1991

Becker muscular dystrophy or spinal muscular atrophy?--Dystrophin studies resolve conflicting results of electromyography and muscle biopsy.

We studied a 29-year-old man with slowly progressive proximal leg weakness, calf hypertrophy, and high serum levels of creatine kinase activity. Clinically, it was not possible to identify his as a sporadic instance of Becker muscular dystrophy (BMD) or one of spinal muscular atrophy. The problem arose because electromyography and elevated creatine kinase suggested a myopathy whereas changes in the muscle biopsy resembled a neurogenic disorder. The diagnosis of BMD was made by DNA analysis which detected a deletion at Xp21 and by immunoelectrophoresis and immunohistochemical tests that identified an abnormal form of gene product, dystrophin. These studies were important for genetic counselling, identifying an X-linked disease instead of one that is autosomal recessive.

Adult↗
PubMed1991

Dystrophin deficiency in young girls with sporadic myopathy and normal karyotype.

We studied dystrophin in three young girls with a sporadic myopathy of early onset, manifested by mild to severe limb weakness, calf hypertrophy, high serum creatine kinase, normal karyotype, and morphologic features in muscle consistent with muscular dystrophy. DNA analysis did not reveal a deletion of the dystrophin gene. Immunohistochemical studies of dystrophin in muscle biopsies showed a mosaic of fibers with and without dystrophin, and immunoblot analysis showed partial dystrophin deficiency in all three patients, more severe in the patient with the highest proportion of dystrophin-deficient fibers. These observations suggest that the patients are Duchenne muscular dystrophy carriers. The data also support the concept that uneven lyonization in muscle is responsible for the clinical myopathy in these patients. We suggest that any girl with sporadic proximal limb weakness should be evaluated as a possible Duchenne carrier by dystrophin studies.

Child↗
PubMed1990

Partial dystrophin deficiency in monozygous twin carriers of the Duchenne gene discordant for clinical myopathy.

We studied monozygous twin women, age 63. One, asymptomatic, had a serum creatine kinase (CK) level of 191 units (normal, 1 to 50); her son died of typical Duchenne muscular dystrophy (DMD) at age 18. Her twin sister had symptomatic limb weakness from about age 40. Her serum CK was 495 units. EMG and muscle biopsy were compatible with myopathy. In the asymptomatic twin, the peripheral blood lymphocyte karyotype was 46,XX. In the affected twin, 18% of cells were 45,X, and the others 46,XX, without X/autosome translocation. DNA analysis did not reveal a deletion at the DMD locus. Immunologic studies of dystrophin showed a partial deficiency of the protein that was more severe in the symptomatic twin. The clinical discordance and the different severity of dystrophin deficiency may have resulted from the effects of lyonization.

Creatine Kinase↗
PubMed1989

The thalamus participates in the regulation of the sleep-waking cycle. A clinico-pathological study in fatal familial thalamic degeneration.

Loss of slow-wave sleep (SWS) and abnormal REM sleep behaviour were associated with a lack of vegetative and endocrine circadian rhythms in a patient with fatal familial thalamic degeneration. Physiological EEG patterns of SWS (spindles, K complexes, delta activity) were absent. EEG fast rhythms could not be induced by barbiturate or benzodiazepine administration. RO 15-1788, a benzodiazepine antagonist, induced arousal and awakened the patient from coma. Pathological findings were severe neuronal loss restricted to the anterior and dorso-medial thalamic nuclei. The clinical and electrophysiological data, together with the pathological correlates, emphasize the role played by the thalamus in the regulation of the sleep-waking and other circadian cycles.

Circadian Rhythm↗
PubMed1989

Two dissimilar brothers with Becker's dystrophy have an identical genetic defect.

Becker's muscular dystrophy is phenotypically heterogeneous, but the clinical expression is usually similar in patients within the same family. We report here 2 brothers affected with Becker's muscular dystrophy in whom the disease followed completely different courses. The disease started in both patients before their teens. However, the oldest sibling died at 37, following many years of severe disability, whereas the other sibling, now 26, has normal muscle strength. In addition, since the age of 13, the younger brother has had epilepsy and has been treated with phenytoin combined with other antiepileptic drugs. Analysis of the DNA from each of the 2 brothers revealed a similar deletion at the 5' end of the dystrophin gene. The different clinical courses despite the similar mutational event suggest that intrinsic muscle factors due to modified genes or environmental phenomena such as prolonged treatment with phenytoin or other antiepileptic agents may have influenced the clinical course.

Adult↗
PubMed1989

Genetic abnormalities in Duchenne and Becker dystrophies: clinical correlations.

Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD) are two allelic forms of an X-linked muscle disorder exhibiting phenotypic heterogeneity. We studied 49 individuals clinically diagnosed as having classic DMD, female DMD, mild DMD "outliers," and BMD. The patients' DNA was analyzed and alterations detected were correlated with particular phenotypes. We found that 14 of 32 classic DMD patients have an internal deletion in the same, relatively small, region of the gene; therefore this region may undergo deletions at a higher rate than the remainder of the gene. We could detect no alterations in the DNA in the remaining 18 patients. Selected patients from both groups failed to show muscle dystrophin. Seven of 11 patients with a mild DMD or BMD phenotype showed deletions at the 5' end of the gene. The other 4 patients failed to show deletions. Three of the patients with both a mild phenotype and a deletion at the 5' end had normal or low amounts of a dystrophin of smaller molecular weight. Patients with classic DMD who had a detectable deletion had a milder clinical course than those without. Contrary to a previous report, no patient in the population of clinically precisely defined DMD boys showed a deletion at the 5' end; thus, the outlier and BMD patients may be genetically different from boys with classic DMD. This correlation may be of diagnostic and prognostic significance.

Adolescent↗
PubMed1988

Characterization of dystrophin in muscle-biopsy specimens from patients with Duchenne's or Becker's muscular dystrophy.

A deficiency of the protein dystrophin has recently been shown to be the probable cause of Duchenne's muscular dystrophy. We sought to determine the relation between the clinical phenotype and the status of dystrophin in muscle-biopsy specimens from 103 patients with various neuromuscular disorders. We found very low levels (less than 3 percent of normal levels) or no dystrophin in the severe Duchenne phenotype (35 of 38 patients), low concentrations of dystrophin in the intermediate (outlier) phenotype (4 of 7), and dystrophin of abnormal molecular weight in the mild Becker phenotype (12 of 18). Normal levels of dystrophin of normal molecular weight were found in nearly all the patients (38 of 40) with 20 other neuromuscular disorders we studied. These data show the clinical consequences of both quantitative alterations (in Duchenne's and intermediate dystrophy) in a single protein. The biochemical assay for dystrophin should prove helpful in delineating myopathies that overlap clinically with Duchenne's and Becker's dystrophies, and it shows promise as an accurate diagnostic tool.

Adolescent↗
PubMed1988

Changes in axon size and slow axonal transport are related in experimental diabetic neuropathy.

In the sciatic system of rats with streptozocin (SZ)-induced diabetes, delay of axonal transport of neurofilament (NF) proteins, tubulin, and other proteins is associated with a change in axonal caliber, which increases by 40% in lumbar motor roots and decreases by 36% in tibial nerves. Since in large myelinated axons caliber is a function of the number of NF, which, in turn, is regulated by axonal transport, we studied the correlation of the number of NF and microtubules (MT) with axonal cross-sectional area in the sciatic system of SZ-treated rats to investigate whether the changes in caliber could be attributed to the impairment of transport. Despite the changes in cross-sectional area, diabetic axons in both proximal motor roots and distal tibial nerves maintained the ratios of number of NF and MT to cross-sectional area found in controls. Our findings suggest that, in rats with SZ-induced diabetes, the proximal and distal alterations of axonal caliber are an adjustment to the change in number of NF and/or MT that results from the impairment of the slow axonal transport.

Animals↗
PubMed1988

MELAS syndrome: characteristic migrainous and epileptic features and maternal transmission.

Severe prolonged migrainous symptoms and prolonged partial status epilepticus are characteristic features of the MELAS syndrome (mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes). Maternal transmission previously found in myoclonus epilepsy and ragged-red fibers (MERRF), another mitochondrial disease, is suggested in this disorder as well.

Adolescent↗
PubMed1988

Experimental diabetic neuropathy: similar changes of slow axonal transport and axonal size in different animal models.

Analysis of slow axonal transport in sciatic and primary visual systems of BB rats with spontaneous diabetes of 2.5-3.5 months duration revealed a delay in transport of the neurofilament (NF) subunits, tubulin, actin, and the 60, 52, and 30 kDa polypeptides in both systems. The polypeptides examined were not affected uniformly. Rather, the transport of the 60, 52, and 30 kDa polypeptides and the rapidly moving component of tubulin, all constituents of the slow component b (SCb) of axonal transport, appeared to be more severely delayed than the transport of polypeptide constituents of the slow component a (SCa), such as NF and the slow-moving tubulin. Transport was not impaired in diabetic BB rats maintained normoglycemic with optimal doses of insulin. A 52 kDa polypeptide constituent of SCb was identified as neuron-specific enolase, and the 30 and 60 kDa polypeptides are likely to be aldolase and pyruvate kinase; all 3 are glycolytic enzymes. Morphometric analysis revealed that the cross-sectional area of sciatic axons was increased proximally at the level of the motor roots and decreased distally at the level of the tibial nerve. The changes in slow transport and caliber observed in central and peripheral axonal systems of diabetic BB rats are virtually identical to those previously described in rats with streptozotocin-induced diabetes, another model of insulin-dependent diabetes. In both models, the alterations of axonal caliber are likely to be secondary to the impairment of axonal transport.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1986

Structural basis of gamma-diketone neurotoxicity: non-neurotoxicity of 3,3-dimethyl-2,5-hexanedione, a gamma-diketone incapable of pyrrole formation.

The chronic exposure to gamma-diketones results in the formation of giant neurofilament (NF)-containing axonal enlargements, followed by axonal degeneration in peripheral axons. Based on the specific ability of gamma-diketones to react with primary amino groups to form pyrroles, and the observation of such reaction with NF protein in vitro and with other proteins in vivo, it has been proposed that pyrrole formation at primary amino groups of NF protein is responsible for the neurotoxicity of gamma-diketones. We have tested this hypothesis through an investigation of the neurotoxicity in rats of 3,3-dimethyl-2,5-hexanedione (3,3-DMHD), a gamma-diketone which is incapable of forming pyrroles. 3,3-DMHD was found to produce only a slight alteration of axonal caliber and no clinical neurotoxicity after up to 12 weeks of administration, at a dose over 20 times that for which its isomer 3,4-dimethyl-2,5-hexanedione (3,4-DMHD) produced massive focal NF-containing axonal enlargements and complete paralysis in 4 weeks. These results support the view that the pyrrole-forming capability of gamma-diketones is the initial molecular event in the pathogenesis of gamma-diketone neurotoxicity.

Animals↗