Search PubMed⌕ Search

Biomedical subjects

M F Wu

Publications and source records attributed to M F Wu.

60 records · Page 4Linked to original sources
PubMed1984

Startle reflex inhibition in the rat: its persistence after extended repetition of the inhibitory stimulus.

Startle reflexes to intense sound bursts are inhibited by weak stimuli that briefly precede their elicitation. In three experiments the startle stimulus (a 110-dB SPL tone burst) was presented 100 ms after the final link in a train of stimuli, the length of the train varying from 1 to 1,000, its repetition rate varying from 1 per s to 10 per s, and its constituents being 40 dB or 50 dB white noise bursts of 25 ms duration. Inhibition was invariant across train length and repetition rate. In a final experiment the startle stimulus was presented a variable interval after the final link, from 40 ms to 1280 ms, with 1 or 100 noise bursts (50 dB) in the train. Inhibition developed more rapidly following the last member of the 100-stimulus train, suggestive of a "priming" or sensitization effect of stimulus repetition, but its overall strength and subsequent rate of decay were not different in the two conditions. The general persistence of inhibition following these extended series of stimuli reveals that reflex inhibition must be the outcome of a fixed and obligatory process associated with sensory input.

Acoustic Stimulation↗
PubMed1979

Ratio of rods and different cones in fishes of shallow sea.

The retinas of 4 fishes (Periophthalmus chrysopilos, Scorpaenoides marmoratus, Nemipterus bathybins, Taius tumifrons) were analysed. Rods were found to increase with depth but twin cones were not found to descrease with depth. A regional difference was also observed in the distribution of these elements in the retinas.

Animals↗
PubMedDate not supplied

Accelerated clearance of polyethylene glycol-modified proteins by anti-polyethylene glycol IgM.

Tumor therapy by the preferential activation of a prodrug at tumor cells targeted with an antibody-enzyme conjugate may allow improved treatment efficacy with reduced side effects. We examined antibody-mediated clearance of poly(ethylene glycol)-modified beta-glucuronidase (betaG-sPEG) as a method to reduce serum concentrations of enzyme and minimize systemic prodrug activation. Enzyme-linked immunosorbent assay and immunoblot analysis of two monoclonal antibodies generated by immunization of BALB/c mice with an antibody-betaG-sPEG conjugate showed that mAb 1E8 (IgG1) bound betaG and betaG-sPEG whereas mAb AGP3 (IgM) bound poly(ethylene glycol). Neither antibody affected the betaG activity. mAb 1E8 and AGP3 were modified with 36 and 208 galactose residues (1E8-36G and AGP3-208G) with retention of 72 and 48% antigen-binding activity, respectively, to target immune complexes to the asialoglycoprotein receptor on liver cells. mAb 1E8 and AGP3 cleared betaG-PEG from the circulation of mice as effectively as 1E8-36G and AGP3-208G, respectively. mAb AGP3, however, cleared betaG-sPEG more completely and rapidly than 1E8, reducing the serum concentration of betaG-sPEG by 38-fold in 8 h. AGP3 also reduced the concentration of an antibody-betaG-sPEG conjugate in blood by 280-fold in 2 h and 940-fold in 24 h. AGP3-mediated clearance did not produce obvious damage to liver, spleen, or kidney tissues. In addition, AGP3 clearance of betaG-sPEG before administration of BHAMG, a glucuronide prodrug of p-hydroxyaniline mustard, prevented toxicity associated with systemic activation of the prodrug based on mouse weight and blood cell numbers. AGP3 should be generally useful for accelerating the clearance of PEG-modified proteins as well as for improving the tumor/blood ratios of antibody-betaG-PEG conjugates for glucuronide prodrug therapy of cancer.

Aniline Mustard↗
PubMedDate not supplied

Efficient clearance of poly(ethylene glycol)-modified immunoenzyme with anti-PEG monoclonal antibody for prodrug cancer therapy.

The F(ab')(2) fragment of the anti-TAG-72 antibody, B72.3, was covalently linked to Escherichia coli-derived beta-glucuronidase that was modified with methoxypoly(ethylene glycol). The conjugate (B72.3-betaG-PEG) localized to a peak concentration in LS174T xenografts within 48 h after injection, but enzyme activity persisted in plasma such that prodrug administration had to be delayed for at least 4 days to avoid systemic prodrug activation and associated toxicity. Conjugate levels in tumors decreased to 36% of peak levels at this time. Intravenous administration of AGP3, an IgM mAb against methoxypoly(ethylene glycol), accelerated clearance of conjugate from serum and increased the tumor/blood ratio of B72. 3-betaG-PEG from 3.9 to 29.6 without significantly decreasing the accumulation of conjugate in tumors. Treatment of nude mice bearing established human colon adenocarcinoma xenografts with B72. 3-betaG-PEG followed 48 h later with AGP3 and a glucuronide prodrug of p-hydroxyaniline mustard significantly (p< or =0.0005) delayed tumor growth with minimal toxicity compared to therapy with a control conjugate or conventional chemotherapy.

Aniline Mustard↗