Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0040822 (tremor)
 18,428 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Purkinje cell toxicity is one of the characteristic features of the Gordon phenomenon, a syndrome manifested by ataxia, muscular rigidity, paralysis, and tremor that may lead to death (Gordon, 1933). Two members of the RNase superfamily found in humans, EDN (eosinophil-derived neurotoxin) and ECP (eosinophil cationic protein), cause the Gordon phenomenon when injected intraventricularly into guinea pigs or rabbits. We have found that another member of the RNase superfamily, an antitumor protein called onconase, isolated from Rana pipiens oocytes and early embryos, will also cause the Gordon phenomenon when injected into the cerebrospinal fluid of guinea pigs at a dose similar to that of EDN (LD50, 3-4 micrograms). Neurologic abnormalities of onconase-treated animals were indistinguishable from those of EDN-treated animals, and histology showed dramatic Purkinje cell loss in the brains of onconase-treated animals. The neurotoxic activity of onconase correlates with ribonuclease activity. Onconase modified by iodoacetic acid to eliminate 70% and 98% of the ribonuclease activity of the native enzyme displays a similar decrease in ability to cause the Gordon phenomenon. In contrast, the homologous bovine pancreatic RNase A injected intraventricularly at a dose 5000 times greater than the LD50 dose of EDN or onconase is not toxic and does not cause the Gordon phenomenon. A comparison of the RNase activities of EDN, onconase, and bovine pancreatic RNase A using three pancreatic RNA substrates demonstrates that onconase is orders of magnitude less active enzymatically than EDN and RNase A. Thus, another member of the RNase superfamily in addition to EDN and ECP can cause the Gordon phenomenon.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Toxicity of an antitumor ribonuclease to Purkinje neurons. 830 53

A pilot study in 14 patients with mild asthma was performed to study the anti-inflammatory efficacy of theophylline (CAS 58-55-9). At the start, during and at the end of a 3 months' treatment with oral sustained release theophylline and during 1 week thereafter, the influence on airway hyperreactivity and ECP (eosinophil cationic protein) serum levels was investigated. Airway responsiveness was expressed as the cumulative provocative dose of methacholine necessary to decrease FEV1 by 20% (PD20-FEV1). Data of 8 patients were suitable for evaluation. At a mean predose serum concentration of 6.5 mg/l, theophylline increased the mean PD20-FEV1 for methacholine from 151 micrograms (at start) to 332 micrograms (at the end of medication), and reduced the mean ECP serum concentration from 34.6 to 24.5 micrograms/l. Up to 1 week after theophylline treatment, the improvement of airway hyperreactivity compared to the baseline was maintained, whereas ECP-serum levels tended to increase. Thus, theophylline markedly attenuated airway hyperreactivity in patients with bronchial asthma at "subtherapeutic" serum theophylline concentrations as well as ECP serum concentrations, suggesting the anti-inflammatory efficacy of theophylline. These observations may have therapeutic implications in the treatment of patients with mild asthma. A slight improvement of lung function and dyspnoea, and a reduction of additional beta 2-bronchodilator use was also observed. Two patients only complained of slight nausea, tremor and restlessness.
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PMID:[The anti-inflammatory action of an oral sustained-release theophylline preparation. Results of a clinical pilot study with low dosages]. 967 55