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

A degenerative skeletal muscle disease with vascular, neurologic, and renal lesions and a probable familial distribution was identified in 4-20-month-old purebred Gelbvieh cattle. Thirteen affected animals were confirmed from 6 separate beef herds, with a mortality rate of 100%. Clinical signs in affected animals consisted of ataxia, weakness, and terminal recumbency. Gross and histologic muscle lesions were indicative of nutritional myopathy of ruminants, with a lack of myocardial lesions in most cases and only rare myocardial changes in a few animals. Acute to chronic lesions in most large skeletal muscle groups consisted of degeneration, necrosis, regeneration, fibrosis, and atrophy. Fibrinoid necrosis of arterioles was a common feature in multiple tissues. Lesions in the spinal cord white matter and peripheral nerves consisted of degeneration of the dorsal columns and axons, respectively. Changes in the kidneys consisted of chronic interstitial nephritis with fibrosis, hyaline droplet change and tubular epithelial vacuolar change and were most severe in the older calves. Intracytoplasmic myoglobin and iron were demonstrated within the hyaline droplets in degenerate renal cortical tubular epithelial cells. Vitamin E levels were deficient in most (6/7) of the animals tested. Investigation of the pedigree of affected animals revealed a common ancestry for all but 1 of the animals whose parentage could be traced. This investigation suggests that a hereditary metabolic defect, possibly involving antioxidant metabolism, could be responsible for this condition. Renal disease, possibly secondary to myoglobinuria, may be unique to this bovine condition.
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PMID:A familial degenerative neuromuscular disease of Gelbvieh cattle. 1193 35

Polyglutamine diseases, such as Huntington disease (HD) and spinocerebellar ataxia 1 and 3, are autosomal dominant neurodegenerative disorders. They are caused by CAG trinucleotide repeat expansions that are translated into abnormally long polyglutamine tracts. One of the pathological hallmarks in polyglutamine diseases is the formation of intranuclear inclusions of polyglutamine-containing proteins in the brain. Although causal relationships between polyglutamine aggregation and cellular toxicity are much debated, inhibition of the polyglutamine-mediated protein aggregation may provide treatment options for polyglutamine diseases. However, the extreme insolubility of expanded polyglutamines makes it difficult to prepare polyglutamine-containing proteins on a large scale and to search for aggregation inhibitors by in vitro high-throughput screening. To overcome this we developed a novel in vitro model system for polyglutamine diseases using myoglobin as a host protein. We searched for small molecules that inhibit polyglutamine-mediated aggregation by in vitro screening with a mutant myoglobin containing a 35 polyglutamine repeat. The screening assay revealed that disaccharides have a potential to inhibit polyglutamine-induced protein aggregation and to increase survival in a cellular model of HD. Oral administration of trehalose, the most effective disaccharide in vitro, decreased polyglutamine aggregates in the cerebrum and liver, improved motor dysfunction and extended life span in a transgenic mouse model of HD. In vitro experiments suggest that the beneficial effects of trehalose result from its ability to bind and stabilize polyglutamine-containing proteins. The lack of toxicity and high solubility, coupled with its efficacy upon oral administration, make trehalose promising as a therapeutic drug or lead compound for the treatment of polyglutamine diseases. The stabilization of aggregation-prone proteins with small molecules is an attractive strategy because it can block the initial stage of the disease cascade. In addition, this therapeutic approach could be applied not only to polyglutamine diseases but also to a wide variety of misfolding-induced diseases.
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PMID:A novel therapeutic strategy for polyglutamine diseases by stabilizing aggregation-prone proteins with small molecules. 1575 3

A case of Legionella pneumophila pneumonia with rhabdomyolysis-induced acute tubulointerstitial nephritis (ATIN) and prolonged renal dysfunction is presented. The patient was a 54-year-old man, admitted with high-grade fever, ataxia and muscle dysfunction; chest roentgenogram showed multilobular infiltrations. L pneumophila was detected in his sputum and urine, by PCR and by culture, and L pneumophila pneumonia was diagnosed. Despite antimicrobial treatment, he developed renal failure and rhabdomyolysis. Renal biopsy showed the presence of myoglobin casts that occluded the distal tubuli and tubulointerstitial nephritis, leading to the diagnosis of rhabdomyolysis-induced ATIN. Renal function subsequently normalised, and he was discharged. This is believed to be the first pathological evidence of involvement of rhabdomyolysis in legionellosis-associated ATIN.
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PMID:Pathological evidence of rhabdomyolysis-induced acute tubulointerstitial nephritis accompanying Legionella pneumophila pneumonia. 1855 70