Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0004134 (ataxia)
 15,886 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Tremors, mental changes, opsoclonus, muscle weakness, gait ataxia, incoordination, and slurred speech developed in several employees in a Virginia chemical plant during the summer of 1974. Epidemiologic and clinical studies suggested that the chlorinated insecticide chlordecone (Kepone) was responsible. Severity of symptoms seemed directly related to dose and duration of exposure. Five sural nerve and six muscle biopsy specimens were examined by light microscopy and electronmicroscopy. The sural nerves were also evaluated by computerized morphometry, which showed considerable decrease in the number of unmyelinated fibers and lesser abnormalities of myelinated fibers. Compared with the nerves of the control subjects, those of patients may have had an increase in Reich and Elzholz bodies, and a modest increase in endoneurial collagen. There were occasional "collagen pockets," stacks of Schwann cell cytoplasmic membranes, redundant Schwann cell cytoplasmic folds, and fewer unmyelinated axons. The skeletal muscles contained increased amounts of lipofuscin and lipidlike droplets in subsarcolemmal areas and within intermyofibrillary spaces; the significance of this is unknown. Fiber size variability, type I predominance, and type grouping were present in three cases. All results strongly suggest that chlordecone is a neurotoxic agent predominantly affecting Schwann cells and unmyelinated fibers of peripheral nerves.
 ...
PMID:Chlordecone intoxication in man. II. Ultrastructure of peripheral nerves and skeletal muscle. 7 56

Chlordecone (0.1 to 10 mg) or corn oil vehicle was injected into Japanese quail eggs on day 1 of incubation. Higher doses (0.5-10 mg per egg) produced tremor and ataxia at hatching and dose-related decreases in hatchability and survivability. Doses lower than 0.25 mg per egg had no effects. Gonad weights were not affected at 12 weeks of age. A second study examined the effect of injecting 0.5 mg of chlordecone into the egg on day 1, 3, 7 or 14 of incubation. Chlordecone-induced tremor was present at hatching regardless of the day of injection. Significant decreases in hatchability and increases in embryonic mortality were seen when chlordecone was injected on day 1 of incubation. Survivability to 5 weeks of age was decreased in birds receiving chlordecone on day 1 or 3 of incubation. At 75 to 84 days of age, egg production was decreased only in birds injected on day 1 of incubation. The offspring from these studies were mated and the hatchability and reproductive capability of these birds was studied at 75 to 84 days of age and found to be not significantly affected. In a third study, birds exposed to 0.5 mg of chlordecone or vehicle on day 1 of incubation were trained as adults in a food reinforced operant task. Exposure to chlordecone affected performance during the first 3 of 15 days of a match-to-sample task. The baseline response rate of these animals on a food reinforced random interval 60 sec schedule was then determined. During the last two weeks of asymptotic performance, chlordecone-exposed birds had a significantly lower rate of responding than controls. These data indicate that in ovo exposure to chlordecone can have significant long-term effects on conditioned behavior and egg production, particularly if exposure occurs on day 1 of incubation.
 ...
PMID:Direct administration of chlordecone into Japanese quail eggs has persistent effects on conditioned behavior of adults. 243 60

Occupational exposures to neurotoxic chemicals have produced large outbreaks of illness in chemical and pesticide workers worldwide. Outbreaks of occupational neurologic disease in the United States have included (1) the Kepone episode in Hopewell, Virginia, in which 76 workers at a pesticide plant producing the chlorinated hydrocarbon insecticide, Kepone, developed a previously unrecognized syndrome of nervousness, tremor, ataxia, weight loss, opsoclonus, pleuritic and joint pain, and oligospermia; (2) an outbreak of 104 cases of autonomic neuropathy in polyurethane foam workers in Marblehead, Massachusetts, manifest principally by urinary bladder dysfunction, which followed exposure to a new catalyst, dimethylaminopropionitrile (DMAPN); and (3) an outbreak of acute mixed motor and sensory neuropathy in 48 plastic fabric workers in Columbus, Ohio, exposed to the solvent methyl butyl ketone (MBK). These outbreaks underscore the vulnerability of chemical workers to neurotoxins. In addition, occurrence of these large, easily detectable epidemics suggests that many more smaller clusters and single cases of neurologic disease of undetermined origin, particularly in younger adults, may be caused by exposure to occupational or to other toxic chemicals. Detection of the etiology of chemically induced neurologic illness requires a high index of suspicion and careful ascertainment of occupational history.
 ...
PMID:Clinical epidemiology of occupational neurotoxic disease. 616 Apr 6