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)

Eight patients representing five different, probably hereditary neurological syndromes with oligophrenia and hypogonadism as the common features have been examined clinically and endocrinologically. Two sisters suffered from polyneuropathy, one male from ataxia, one male from spastic tetraplegia, two sisters and a brother from myopathy and one male patient from epilepsy and polyneuropathy. The latter patient was diagnosed as having an acute intermittent porphyria. All the patients had degenerative neurological disorders. The karyotypes were normal. The patients all had signs of hypogonadism. Four male patients had marked testicular atrophy but otherwise normal external genitalia. The testosterone levels in the blood were normal or slightly decreased. Three of the females had their menarche at a normal age but a very early menopause. The fourth female has never menstruated. The four females had normal breasts and body hair. All patients had high basal luteinizing hormone (LH) and follicle-stimulating hormone levels and the response to i.v. LH-releasing hormone was exaggerated. The prolactin values were normal. None of the examined patients had any signs of thyroid or adrenal insufficiency and the sella turcica was normal. A possible etiology to their hypergonadotropic hypogonadism is discussed.
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PMID:Hypergonadotropic hypogonadism in oligophrenia. 68 19

Miniature swine were fed brominated sesame oil at dietary levels of 0, 5, 25, 50 or 500 mg/kg of body weight for 17 weeks and brominated soybean oil at levels of 0, 5, 50 or 500 mg/kg of body weight for 28 weeks. Growth rate and food intake were decreased only at the high dose level in the brominated sesame oil study. In both studies, signs of lethargy and ataxia occurred in pigs fed the highest dose, and were probably due to a dose-related increase in serum bromine concentrations. Marked elevations in lactic dehydrogenase (LDH), serum glutamic-oxalacetic transaminase (SGOT) and serum glutamicpyruvic transaminase (SGPT) values were seen at the highest dose level with both substances and these enzyme activities were increased at the 50 mg/kg dose level in the brominated sesame oil study. Histopathologic lesions were confined to animals given the highest dose level of either oil. Marked fatty degeneration of the hepatic plate cells and renal tubular epithelial cells were seen in both studies. In the brominated sesame oil study, neutral fat was moderately increased in the myocardium of the pigs fed 500 mg/kg. However, marked diffuse accumulation of LDH, marked diffuse fatty degeneration and focal degeneration, and/or necrosis of individual or small groups of cardiac muscle fibers were seen in the group fed brominated soybean oil at 500 mg/kg. A moderate to marked testicular atrophy was also observed in this group. A dose-related accumulation of total and hexane-soluble bromine was observed in all tissues examined in both studies; the highest concentrations occurred in adipose tissue of the pigs given the highest dose level. Kidneys, livers, hearts and thyroids of these groups also contained large amounts of bromine. In pigs given the 50 mg/kg dose level, total and hexane-soluble bromine concentrations were higher in the brominated sesame oil study than in the longer brominated soybean oil study and may be responsible for the elevations in LDH, SGPT and SGOT activities in this group.
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PMID:The toxicity of brominated sesame oil and brominated soybean oil in miniature swine. 94 71

VP 16-213 (etoposide, abbr. to VP), an oncostatic drug, was administered orally to Crj : CD (Sprague-Dawley) rats of both sexes at dose levels of 1, 3, 10 and 30 mg/kg/day for six months with the object of examining its chronic toxicity and the reversibility of toxic effects. The summarized results obtained are as follows: VP 30 mg/kg suppressed body weight increase and feed intake, and brought transient diarrhea, anemia and depilation. Some animals receiving this dose died showing systemic debility, emaciation and ataxia. VP 3 mg/kg and higher predominantly decreased red blood cell count as well as white blood cell count accompanied with lowered lymphocyte fraction. VP 30 mg/kg lowered total serum protein content and elevated A/G ratio in males, and lowered serum alkaline phosphatase activity in females. VP 10 and 30 mg/kg predominantly induced thymic atrophy, testicular atrophy with suppression of spermatogenesis and tubular atrophy, a decrease in epididymal weight, and splenic erythropoiesis. Above-described changes excluding the findings on testis and epididymis in VP 30 mg/kg group were shown to be generally reversible. Based on these results, the non-effect dose level of VP under the present experimental condition was estimated to be 1 mg/kg/day against rats of both sexes.
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PMID:[Toxicity studies of VP 16-213 (III)--Oral six-month chronic toxicity in rats]. 376

VP 16-213 (etoposide, abbr. to VP), an oncostatic drug, was administered intravenously to Crj : CD (Sprague-Dawley) rats of both sexes at dose levels of 0.15, 0.50, 1.5 and 4.5 mg/kg/day for one month with the object of examining its subacute toxicity and the reversibility of toxic effects. For the purpose of comparison, vincristine (abbr. to VCR) was administered in the same manner at dose levels of 0.04 and 0.08 mg/kg/day. The summarized results obtained are as follows: VP 0.50 mg/kg and higher suppressed body weight increase and food intake dose-responsively. VP 4.5 mg/kg brought depilation and anemia, and some of male animals receiving this dose died showing systemic debility, emaciation and ataxia. VP 0.50 mg/kg and higher decreased white blood cell count accompanied with lowered lymphocyte fraction, and 1.5 and 4.5 mg/kg predominantly decreased red blood cell count. VP 1.5 and 4.5 mg/kg lowered total serum protein content and serum alkaline phosphatase activity, and elevated A/G ratio. VP 0.50 mg/kg and higher predominantly decreased testicular weight, and 1.5 and 4.5 mg/kg predominantly brought thymic atrophy, hypoplasia of bone marrow and testicular atrophy with suppression of spermatogenesis and tubular atrophy. VP 4.5 mg/kg induced atrophy of germinal centers and hemosiderosis in spleen, and epididymal atrophy with decrease of sperms in number and appearance of giant cells. Above-described changes excluding the findings on testis and epididymis were generally reversible. Most of the findings for a reference drug, VCR, were similar to those for VP, and their severities brought by VP 1.5 and 4.5 mg/kg were comparable to those by VCR 0.04 and 0.08 mg/kg, respectively. Based on these results, the non-effect dose level of VP under the present experimental condition was estimated to be 0.15 mg/kg/day against rats of both sexes.
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PMID:[Toxicity studies of VP 16-213 (IV)--Intravenous one-month subacute toxicity in rats]. 376 1

Dimethylethoxysilane (DMES), a volatile liquid, is used by NASA to waterproof the heat-protective silica tiles and blankets on the Space Shuttle. Acute, 2-wk, and 13-wk inhalation exposures to DMES vapor were conducted in male and female Fischer 344 rats. In the acute study, rats were exposed to 4000, 2000, 1000, 500, or 0 (control) ppm DMES for 4 h and observed for 14 days. There were no deaths. Narcosis and ataxia were observed in rats of the two highest concentrations only. These signs disappeared within 1 h following exposure. There were no DMES-related gross or microscopic tissue lesions in rats of all exposure groups. In the 2-wk study, rats were exposed for 6 h/day, 5 days/wk to 3000, 1000, 300, 100, or 0 ppm DMES. During exposure, narcosis was observed in rats of the 3000 and 1000 ppm groups. There was a mild decrease in body weight gain in rats of the 3000 ppm group. A decrease in platelet count, an increase in bile acids, and reduced weights of the thymus, testis, and liver were observed in rats of the 3000 ppm group. Microscopically, hypospermatogenesis and spermatid giant cells were observed in the seminiferous tubules of the testes of rats exposed to 3000 ppm DMES. In the 13-wk study, rats were exposed 6 h/day, 5 days/wk to 2000, 600, 160, 40, or 0 ppm DMES. During exposure, rats of the 2000 ppm group exhibited mild narcosis and loss of startle reflex. Recovery from these central nervous system signs was rapid. Body weights were mildly decreased for rats of the 2000 ppm group. There were no exposure-related effects in hematology, serum chemistry, or urinalysis. Female rats of the 2000 ppm group had delayed estrous cycles (6 days compared to 5 days in control rats). Noteworthy organ weight changes in rats of the 2000 ppm group included decreases in thymus, liver, and testicular weights; however, pathologic lesions were observed in the testes only. Sperm motility, epididymal sperm count, and testicular spermatid count were dramatically reduced. Microscopic lesions included degeneration of the seminiferous tubular cells, pyknosis or absence of germ cells, and hypospermia in the epididymis. Rats of the 600 ppm group had a slight decrease in thymic weight and a transient decrease in body weight. Results of the acute, 2-wk, and 13-wk inhalation studies indicate DMES concentrations of 1000 ppm and higher produce narcosis that rapidly disappears following exposure. Repeated exposure of rats to DMES at either 3000 ppm for 2 wk or 2000 ppm for 13 wk caused testicular atrophy and hypospermia in male rats. Female rats exposed to 2000 ppm for 13 wk had delayed estrous cycles. Toxicological effects in rats of the 600 ppm group were minimal and equivocal. The 160 ppm concentration was a no-observable-effect level (NOEL) for 13 wk of exposure to DMES.
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PMID:Acute, 2-week, and 13-week inhalation toxicity studies on dimethylethoxysilane vapor in Fischer 344 rats. 1153 68

Refsum disease is caused by a deficiency of phytanoyl-CoA hydroxylase (PHYH), the first enzyme of the peroxisomal alpha-oxidation system, resulting in the accumulation of the branched-chain fatty acid phytanic acid. The main clinical symptoms are polyneuropathy, cerebellar ataxia, and retinitis pigmentosa. To study the pathogenesis of Refsum disease, we generated and characterized a Phyh knockout mouse. We studied the pathological effects of phytanic acid accumulation in Phyh(-/-) mice fed a diet supplemented with phytol, the precursor of phytanic acid. Phytanic acid accumulation caused a reduction in body weight, hepatic steatosis, and testicular atrophy with loss of spermatogonia. Phenotype assessment using the SHIRPA protocol and subsequent automated gait analysis using the CatWalk system revealed unsteady gait with strongly reduced paw print area for both fore- and hindpaws and reduced base of support for the hindpaws. Histochemical analyses in the CNS showed astrocytosis and up-regulation of calcium-binding proteins. In addition, a loss of Purkinje cells in the cerebellum was observed. No demyelination was present in the CNS. Motor nerve conduction velocity measurements revealed a peripheral neuropathy. Our results show that, in the mouse, high phytanic acid levels cause a peripheral neuropathy and ataxia with loss of Purkinje cells. These findings provide important insights in the pathophysiology of Refsum disease.
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PMID:Ataxia with loss of Purkinje cells in a mouse model for Refsum disease. 1900 1