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Biomedical subjects

E Byrne

Publications and source records attributed to E Byrne.

At least 73 records · Page 4Linked to original sources
PubMed1993

Phenotypic expression of mtDNA heteroplasmy in the skeletal muscle of patients with oculomyopathy: defect in mitochondrial protein synthesis.

The biochemical consequences of mtDNA heteroplasmy, observed in patients with a range of diseases associated with the mitochondrial respiratory enzymes deficiency is of particular interest, as they might provide information with regard to the regulatory interactions which govern the expression of the human mitochondrial genome. Three patients with chronic progressive external ophthalmoplegia (CPEO) were investigated to study the consequences of mtDNA heteroplasmy on mitochondrial protein synthesis. All 3 patients exhibited partially deleted mtDNA species (varying in size from 10.5 to 14 kb) in their skeletal muscle, which co-existed with the normal 16.5 kb mtDNA. The examination of mitochondrial translation products following the incorporation of [35S]methionine by isolated mitochondria, showed grossly abnormal patterns of mitochondrial translation products, suggesting a major disturbance in the regulation of mitochondrial protein synthesis.

Adult↗
PubMed1993

Significance of mitochondrial DNA deletions in myotonic dystrophy.

Mitochondrial DNA (mtDNA) deletions have been noted in small quantities in a handful of atypical cases of myotonic dystrophy and there are clinical and pathological parallels between this autosomal dominant disease and certain mitochondrial myopathies where such deletions are well recognised. We studied 20 individuals from typical pedigrees of myotonic dystrophy (of whom 19 were clinically affected) with Southern blot analysis, and 2 of the affected individuals with PCR analysis of mtDNA, but were unable to demonstrate the previously noted deletions in any quantity by either method. We conclude that especially in view of known naturally occurring large scale and minor length variants in mtDNA, these previous findings are of dubious relevance to the disease.

Adolescent↗
PubMed1993

Mitochondrial encephalomyopathy: variable clinical expression within a single kindred.

The clinical manifestations of mitochondrial encephalomyopathy are described in four generations of a single kindred. The age of onset of major neurological disturbance varied from 3-70 years. In some patients, deafness was the only manifestation; in others, recurrent bouts of status epilepticus associated with focal neurological deficits and headache, caused severe disability or death. Examples of all three adult forms of mitochondrial encephalomyopathy: MELAS, MERFF and Kearns Sayre syndrome, were represented within the kindred. Associated features included deafness, short stature, non-insulin-dependent diabetes mellitus, migraine, peptic ulceration and severe constipation. The nt 3243 A-G MELAS mutation was detected in two members of the kindred. This study highlights the diversity of clinical expression of a mitochondrial mutation within a single kindred.

Adolescent↗
PubMed1993

Apparent hydrocephalus and chronic multiple sclerosis: a report of two cases.

Generalised ventricular dilatation with or without cerebral atrophy is common in longstanding multiple sclerosis. This has been widely assumed to be due to periventricular white matter atrophy rather than true communicating hydrocephalus although it can be difficult to distinguish between these on radiological grounds. Here we report 2 chronic MS patients who had progressive dementia, gait disturbance and urinary incontinence and in whom neuroimaging, and in one case CSF infusion studies, suggested hydrocephalus. Both significantly improved following shunting procedures. We suggest that further study is required to investigate whether a significant proportion of patients with chronic MS and dilated ventricles have shunt-responsive hydrocephalus.

Cerebrospinal Fluid Shunts↗
PubMed1993

Motor nerve biopsy: feasibility and safety.

Motor nerve biopsy was attempted on 19 occasions in 18 patients. Nerve tissue was obtained in 16. The nerves biopsied included those to the anconeus (4 times), palmaris longus (6), flexor sublimus (1), triceps (2), extensor carpi radialis (1), quadriceps (1) and gastrocnemius (1). Attempts to biopsy the radial nerve, the nerve to plantaris and the left common peroneal nerves failed in 2 patients. The lengths of nerve obtained varied from 1 to 3 cm, and from 1-5 fasciculi were present in the specimens. Sufficient material for both electron microscopy and teasing was present in 11. No patient experienced increased weakness, but one had transient paraesthesiae in the distal forearm following biopsy of the nerve to the palmaris longus. We conclude that motor nerve biopsy as described is both feasible and safe. The nerve to the palmaris longus, where that muscle was present, provided the optimum specimen for pathological studies.

Adult↗
PubMed1993

Aseptic meningoencephalitis in primary Sjögren's syndrome. Response to plasmapheresis and absence of CNS vasculitis at autopsy.

It has been suggested that cerebral vasculitis is the pathogenetic mechanism of the central nervous system manifestations of primary Sjögren's syndrome. We present a fatal case of aseptic meningoencephalitis in an 18-year-old woman with primary Sjögren's syndrome in whom there was no evidence of cerebral vasculitis at autopsy. On two occasions her condition improved markedly following plasmapheresis.

Adolescent↗
PubMed1992

Helper virus induced T cell lymphoma in nonhuman primates after retroviral mediated gene transfer.

Moloney Murine Leukemia Virus (MoMuLV) causes T cell neoplasms in rodents but is not known to be a pathogen in primates. The core protein and enzyme genes of the MoMuLV genome together with an amphotropic envelope gene are utilized to engineer the cell lines that generate retroviral vectors for use in current human gene therapy applications. We developed a producer clone that generates a very high concentration of retroviral vector particles to optimize conditions for gene insertion into pluripotent hematopoietic stem cells. This producer cell line also generates a much lower concentration of replication-competent virus that arose through recombination. Stem cells from rhesus monkeys were purified by immunoselection with an anti-CD34 antibody, incubated in vitro for 80-86 h in the presence of retroviral vector particles with accompanying replication-competent virus and used to reconstitute recipients whose bone marrow had been ablated by total body irradiation. The retroviral vector genome was detected in circulating cells of five of eight transplant recipients of CD34+ cells and in the circulating cells of two recipients of infected, unfractionated bone marrow mononuclear cells. Three recipients of CD34+ cells had a productive infection with replication-competent virus. Six or seven mo after transplantation, each of these animals developed a rapidly progressive T cell neoplasm involving the thymus, lymph nodes, liver, spleen, and bone marrow. Lymphoma cells contained 10-50 copies of the replication-competent virus, but lacked the retroviral vector genome. We conclude that replication-competent viruses arising from producer cells making retroviral vectors can be pathogenic in primates, which underscores the importance of carefully screening retroviral producer clones used in human trials to exclude contamination with replication-competent virus.

Animals↗
PubMed1992

RSI revisited.

Explore the source record for details and available documents.

Cumulative Trauma Disorders↗
PubMed1992

Tissue segregation of a heteroplasmic mtDNA mutation in MERRF (myoclonic epilepsy with ragged red fibers) encephalomyopathy.

The distribution of the causal 8344A-->G mtDNA mutation has been examined in six tissues of a patient with myoclonic epilepsy with ragged red fibers (MERRF), to study the developmental genetics of this type of mitochondrial disorder, and to determine the pathophysiological importance of the mtDNA heteroplasmy generally observed in such patients. Heteroplasmy of the mtDNA was observed in all six tissues (cerebellum, cerebrum, pancreas, liver, muscle, and heart) suggesting that, whereas the mtDNA mutation is relatively new, the mutated population must have existed before the formation of the three primary embryonic layers. The tissue distribution reveals significant variations in the ratio between the mutated and the normal mtDNA species, indicating the randomness of mtDNA segregation during developmental cell division and differentiation events. The result suggests the existence of tissue-specific nuclear factor(s) that determines the expression of the 8344A-->G mutation in various tissues; in MERRF syndrome, expression is mainly in the central nervous system.

Adult↗
PubMed1992

Respiratory chain failure in adult muscle fibres: relationship with ageing and possible implications for the neuronal pool.

A histochemical analysis of mitochondrial enzyme activity was carried out in 103 human diaphragmatic skeletal muscles from 49 subjects of different ages, obtained either at the time of abdominal surgery or at necropsy. Evidence of respiratory failure (cytochrome oxidase negativity) was seen in occasional fibres from the fourth decade on with an approximate 10-fold increase between the fourth and ninth decade (0.16% to 2.85%). A similar incidence of mitochondrial failure in CNS neurones to that documented in skeletal muscle could easily account for attrition of 25% of neurones over a 50-year period as reported in the literature. Possible theoretical relationships between morphological markers of mitochondrial failure and cell attrition are explored. While the projections from muscle to neurone are somewhat speculative, it is clear that if a similar extent of mitochondrial pathology exists in the brain to that documented in skeletal muscle, this could easily account for neuronal loss in the ageing brain.

Adolescent↗
PubMed1992

Breastmilk oversupply despite retained placental fragment.

In clients experiencing oversupply, lactation consultants should question more closely the frequency of milk ejection reflexes and whether the mother is experiencing them only during breastfeeding or frequently, even while not nursing. If the mother is still experiencing vaginal bleeding, even if she is producing large quantities of milk, she should be encouraged to talk with her health care provider about having a sonogram in order to rule out the possibility of a retained placental fragment.

Adult↗
PubMed1992

Polyneuropathy, organomegaly, endocrinopathy, M-protein and skin change (POEMS) syndrome with IgG kappa paraproteinemia.

The POEMS syndrome is an infrequently reported multisystem disorder which presents usually as an obscure polyneuropathy, with almost all cases reported in Japan. A 64 yr old caucasian man presented with a 12 mth history of a severe sensorimotor neuropathy in association with dermato-endocrine features. Detection of a monoclonal IgG kappa paraprotein and mixed osteosclerotic/lytic bone lesions consistent with a plasma cell dyscrasia led to diagnosis of the POEMS syndrome. Unique ultrastructural features were present on sural nerve biopsy in addition to the unusual association with monoclonal kappa-light chain. This case illustrates that the POEMS syndrome may also occur in caucasian subjects.

Humans↗
PubMed1992

New concepts in respiratory chain diseases.

Recent advances in mitochondrial cytopathies are reviewed. Particular emphasis is given to diseases related to mitochondrial DNA mutations, a field now encompassing myopathic and encephalopathic syndromes, some more common degenerative disorders, and certain aspects of the aging process. Diseases caused by defective oxidative energy generation now have an important place in human pathology.

Base Sequence↗