Deficient repair of alkylation damage of DNA in Alzheimer's disease and amyotrophic lateral sclerosis cells.
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Alkylating Agents↗
Biomedical subjects
R Tandan
Publications and source records attributed to R Tandan.
Childhood giant axonal neuropathy. Case report and review of the literature.
Giant axonal neuropathy (GAN) is a rare autosomal recessive childhood disorder characterized by a peripheral neuropathy and features of central nervous system involvement. Typically seen are distal axonal swellings filled with 8-10 nm in diameter neurofilaments in central and peripheral axons, and intermediate filament collections in several other cell types. Many neurotoxins produce a morphologically similar neuropathy in humans and experimental animals. Defective nerve fiber energy metabolism has been postulated as a cause in these toxic neuropathies. It is possible that GAN represents an inborn error of metabolism of enzyme-linked sulfhydryl containing proteins, resulting in impaired production of energy necessary for the normal organization of intermediate filaments.
Axons↗
Deficient DNA repair in amyotrophic lateral sclerosis cells.
We studied survival and DNA repair capacity in cultured sporadic ALS and control skin fibroblasts after treatment with DNA damaging agents producing different types of lesions. Mean survival in ALS and control fibroblasts was similar after exposure to ultraviolet (UV) light, x-rays and mitomycin C (MMC). Both mean survival and mean unscheduled (repair) DNA synthesis (UDS) were significantly reduced in ALS fibroblasts following treatment with the alkylating agent methyl methane sulfonate (MMS). These data suggest that ALS cells are relatively deficient in the repair of alkylation damage, possibly of apurinic/apyrimidinic sites, and that they are not unduly sensitive to DNA damage produced by UV light, x-rays and MMC. Normal survival and UDS seen in some patients' cells after MMS treatment indicate a spectrum of repair efficiency, and suggest heterogeneity of the biochemical defect in ALS.
Adult↗
Serial evaluation of neuromuscular function in management of chronic inflammatory demyelinating polyneuropathy. A case report.
In this case report, we describe the serial evaluation of neuromuscular function of a woman with chronic inflammatory demyelinating polyneuropathy and document the return of limb strength and hand function after plasmapheresis and immunosuppressive therapy. The assessment of muscle strength and functional abilities by physical therapists can provide timely, objective, and quantitative information that is important to the medical management of patients with neurologic disease.
Activities of Daily Living↗
Clinical subtypes, DNA repair efficiency, and therapeutic trials in the post-polio syndromes.
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Alzheimer Disease↗
Amyotrophic lateral sclerosis: Part 1. Clinical features, pathology, and ethical issues in management.
Amyotrophic lateral sclerosis (ALS) is a progressive degenerative disease of the motor system in adults that occurs in sporadic, familial, and Western Pacific forms. Involvement of non-motor pathways has been increasingly recognized, both clinically and pathologically. Although the usual course is relentlessly progressive with death in half the cases within three years from onset, it can sometimes be protracted. Degeneration and loss of large motor neurons in the cerebral cortex, brainstem, and cervical and lumbar spinal cord are characteristic. Marked reduction in the number of large myelinated fibers is notable in the cervical and lumbar ventral roots. Peripheral nerves show reduced numbers of large myelinated fibers, acute axonal degeneration at all levels, and distal axonal atrophy. Motor end-plates reveal small or absent nerve terminals. Subclinical non-motor system involvement includes neuronal loss in Clarke's nucleus and dorsal root ganglia, degeneration of non-motor tracts in the spinal cord, loss of receptors in the dorsal horns of the spinal cord, and myelinated fiber loss with segmental demyelination in sensory and mixed nerves. The serious implications of the diagnosis of ALS make it mandatory to exclude similar potentially treatable disorders. Management should be multidisciplinary, and discussions with the patient and family members should be frank and frequent. Discussions about ventilatory support should take place early in the disease so that death from respiratory failure can be prevented, when that is desired, and conversely to obviate the discontent and anger that accompany involuntary life on a ventilator.
Amyotrophic Lateral Sclerosis↗
Amyotrophic lateral sclerosis: Part 2. Etiopathogenesis.
The pathogenesis of the motor neuronal degeneration in amyotrophic lateral sclerosis (ALS) is unclear, though several possible etiological factors are currently being investigated. A unifying hypothesis will have to explain the diverse geographical occurrence, clinical features, and selective vulnerability and relative resistance of different neuronal populations in the disease. It is possible that different biochemical defects underlie this diversity, or alternatively that the many factors incriminated in the etiology may act upon an underlying genetic-biochemical abnormality to trigger premature neuronal death. Viruses, metals, endogenous toxins, immune dysfunction, endocrine abnormalities, impaired DNA repair, altered axonal transport, and trauma have all been etiologically linked with ALS, but convincing research evidence of a causative role for any of these factors is yet to be demonstrated.
Aged↗
Plasma exchange in chronic inflammatory demyelinating polyradiculoneuropathy.
Eleven consecutive patients with progressive chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) underwent plasma exchange. Eight patients were previously unresponsive to prednisone, two were started on prednisone with plasma exchange, and one did not receive corticosteroids. Electrodiagnostic studies revealed evidence of an acquired demyelinating polyradiculoneuropathy with varying degrees of axonal degeneration. Neurologic impairment was monitored using conventional functional status index. Five patients demonstrated substantial clinical improvement, beginning 2 days to 3 weeks after initiating plasma exchange. Two additional patients improved following a second course of plasma exchange, and four patients demonstrated minimal or no change. Comparison of responding and nonresponding patients showed no differences related to the presence or absence of antecedent illness, duration of disease, duration of maximum weakness, or severity of impairment prior to plasma exchange. Responders had significantly prolonged F-response and motor distal latencies compared to nonresponders. Results in this unselected, consecutive patient trial suggest a temporal relationship between plasma exchange and clinical improvement in some patients with progressive CIDP.
Adolescent↗
Myelomalacia and hypoglycorrhachia in malignant atrophic papulosis.
A 25-year-old man with the skin lesions of malignant atrophic papulosis had clinical and electrodiagnostic evidence of a multifocal asymmetric myelomalacia or polyradiculopathy in association with elevated CSF protein and hypoglycorrhachia. Autopsy findings included widespread infarctions and necrosis of brain, brainstem, and spinal cord. The combined clinical and laboratory findings were similar to those seen in systemic lupus erythematosus, sarcoidosis, or meningeal carcinomatosis. Thus, malignant atrophic papulosis should be added to the differential diagnosis of either polyradiculopathy or myelomalacia.
Adult↗