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Biomedical subjects

B Scarth

Publications and source records attributed to B Scarth.

8 recordsLinked to original sources

A rapid monoclonal antibody blood theophylline assay; lack of cross-reactivity with enprofylline.

We evaluated a rapid monoclonal antibody theophylline assay for two reasons: (a) to determine its specificity with respect to the possible confounding influence of a structurally related xanthine, enprofylline, and (b) to assess its accuracy relative to high-performance liquid chromatography (HPLC). Blood samples were taken from 233 patients who had been randomized in double-blind fashion to receive either oral theophylline (n = 117) or enprofylline (n = 116) for the treatment of chronic reversible obstructive airways disease. Monoclonal antibody assays (MAAs) were performed in 10 clinical sites by 10 trained paramedical technicians. Three patients, who actually received enprofylline but not theophylline, had MAA theophylline values of > or = 3.2 micrograms/ml, giving a specificity of 97%. HPLC determination of simultaneous blood samples confirmed that theophylline levels were in fact < 3.2 micrograms/ml and that theophylline was not being taken surreptitiously. Good correlation was observed between MAA and HPLC in patients taking theophylline (y = 1.07 x + 0.36; r = 0.93; standard error of the estimate (SEE) = 1.93). However, there was wide variability from technician to technician such that r values for individual sites ranged from 0.67 to 0.99. Based on the overall correlation, the prediction of an individual HPLC value from an individual MAA value had broad 95% confidence limits: when the MAA value was 10 micrograms/ml, the predicted HPLC value was 9.19 +/- 3.32; when MAA = 15 micrograms/ml; HPLC = 13.19 +/- 3.33; and when MAA = 20 micrograms/ml; HPLC = 17.19 +/- 3.36.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Effect of protease inhibitors on skeletal muscle lysosomal enzyme activity and resting membrane potential.

Inhibition of lysosomal enzyme activity by protease inhibitors in denervated muscle was studied in vitro by incubating muscle homogenates with increasing concentrations of inhibitor and determining acid protease activity. Pepstatin was the most potent inhibitor of protease activity, followed in order of inhibitor potency by chloroquine, aprotinin, and leupeptin. The in vivo uptake of chloroquine or leupeptin by denervated muscle was greater than that of innervated muscle, and repeated administration of the drug led to a decrease in muscle N-acetylglucosaminidase activity. Repeated administration of chloroquine had no effect on resting membrane potential of muscle fibers in the soleus or extensor digitorum longus measured in vivo. Chloroquine attenuated the marked decrease in the resting membrane potential of the extensor 2.5 days after denervation, but had no effect on that of the denervated soleus. Possible involvement of proteases in lowering the membrane potential of denervated muscle is discussed.

Acetylglucosaminidase↗

Neurotoxicity of Adriamycin and misonidazole in the mouse.

The neurotoxicity of the anticancer drug adriamycin was investigated in the peripheral nerve of the mouse. Injection of adriamycin into the sciatic nerve resulted in biochemical and morphologic signs of severe axonal degeneration. The biochemical evidence was based on marked increases in lysosomal enzyme activity. Acid protease and N-acetylglucosaminidase remained elevated for more than 70 days after injecting the drug. In contrast, local injection of the radiation-sensitizing drug misonidazole into the peripheral nerve failed to increase lysosomal enzyme activity.

Animals↗

Peripheral nerve autografts increase soleus muscle hydrolase activity.

A peripheral nerve autograft placed on the surface of a normally innervated muscle has been shown to induce acetylcholine hypersensitivity and myofibrillar degeneration. Using a similar preparation, we determined the acid protease, alkaline protease, and N-acetylglucosaminidase activity in rat soleus muscle and the effect of protease inhibitors on these enzymes. Three days after nerve transplant, the muscle showed a significant increase in all three enzymes assayed. The protease inhibitors leupeptin and pepstatin totally prevented the nerve-induced increase in hydrolase activity. Our data suggest that muscle degeneration is secondary to an inflammatory response induced by the nerve.

Acetylglucosaminidase↗

Neurotoxin-induced hydrolase activity in peripheral nerve.

The effect of neurotoxins which block axonal transport or impulse transmission was examined on sciatic nerve hydrolase activity. Subepineural injection of batrachotoxin (BTX) or colchicine resulted in a 4-9 fold increase in acid protease and N-acetylglucosaminidase activity with a smaller increase in acid phosphatase activity. The enzyme remained elevated for up to 48 days. Similar injections of tetrodotoxin (TTX) led to a relatively small increase in the activity of these enzymes which returned to normal values within two days. The prolonged increase in hydrolase activity produced by BTX and colchicine suggests that blockade of axonal transport may be mediated by nerve necrosis.

Acetylglucosaminidase↗