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Biomedical subjects

G T Wang

Publications and source records attributed to G T Wang.

At least 55 records · Page 3Linked to original sources

Efficacy of Cydectin moxidectin 1% injectable against experimental infections of Dictyocaulus viviparus and Bunostomum phlebotomum superimposed on natural gastrointestinal infections in calves.

Twenty male Holstein calves averaging 105 kg in weight and naturally infected with gastrointestinal nematodes and small numbers of lungworm and hookworm, were given experimental infections with the two latter species to provide adult and larval stages for anthelmintic evaluation. Following random allotment, one group of 10 calves was injected subcutaneously with moxidectin at a dosage of 0.2 mg kg-1 of body weight. A second group of 10 was injected subcutaneously with unmedicated blank vehicle at a dosage of 1 ml per 50 kg of body weight. Fecal samples were examined before treatment and at 7 and 13 days after treatment. The 20 calves were necropsied for worm recovery at 13 and 14 days after treatment. All calves were positive for lungworm and hookworm on the treatment date. Treatment was 100% effective in elimination of hookworm eggs and lungworm larvae and 99.9% in reducing total egg counts at both 7 and 13 days after treatment. Moxidectin was 100% effective (P less than 0.01) in eliminating the following 11 species of nematodes. Dictyocaulus viviparus mature and immature adults (E5), Bunostomum phlebotomum adults and L4, Ostertagia ostertagi adults and early L4, Ostertagia lyrata adult males, Haemonchus placei adults. Trichostrongylus axei adults, Cooperia spp., including Cooperia punctata, Cooperia spatulata, and Cooperia pectinata adults, Oesophagostomum radiatum adults and Trichuris discolor adults. No adverse reactions to moxidectin treatment were observed.

Animals↗

Characterization of recombinant human renin: kinetics, pH-stability, and peptidomimetic inhibitor binding.

The kinetic behavior and pH-stability of recombinant human renin was analyzed using a new fluorogenic substrate based on the normal P6-P3' renin cleavage sequence in human angiotensinogen. The design of this fluorogenic substrate makes possible, for the first time, direct monitoring of the kinetics of proteolytic conversion of prorenin to renin. The pH-stability profile for renin, measured with the substrate at 25 degrees C, indicated a broad plateau of stability between pH 6.0 and 10.0. Analysis of the pH-activity profile of renin for the substrate indicated a minimum Km (approximately 1.8 microM) at pH approximately 7.4 and a maximum Vm between pH 7.4 and 8.0. The thermodynamics of the binding of a novel, soluble, peptidomimetic inhibitor to renin indicated it is possible to retain the tight-binding characteristics and enthalpy contributions to binding of larger peptide-derived inhibitors, while reducing inhibitor size and entropic contributions to binding. A novel derivative of the fluorogenic substrate, containing a 3-methyl histidine substitution at the P2 site, was used to test the recent hypothesis that renin functions by virtue of substrate-directed catalysis.

Amino Acid Sequence↗

Novel fluorogenic substrates for assaying retroviral proteases by resonance energy transfer.

The 11-kD protease (PR) encoded by the human immunodeficiency virus 1 (HIV-1) is essential for the correct processing of viral polyproteins and the maturation of infectious virus, and is therefore a target for the design of selective acquired immunodeficiency syndrome (AIDS) therapeutics. To facilitate the identification of novel inhibitors of HIV-1 PR, as well as to permit detailed studies on the enzymology and inhibition of this enzyme, a continuous assay for its activity was developed that was based on intramolecular fluorescence resonance energy transfer (RET). The assay used the quenched fluorogenic substrate 4-(4-dimethylaminophenylazo)benzoic acid (DABCYL)--Ser Gln Asn Tyr Pro Ile Val Gln--5-[(2-aminoethyl)amino]naphthalene-1 sulfonic acid (EDANS), whose peptide sequence is derived from a natural processing site for HIV-1 PR. Incubation of recombinant HIV-1 PR with the fluorogenic substrate resulted in specific cleavage at the Tyr-Pro bond and a time-dependent increase in fluorescence intensity that was linearly related to the extent of substrate hydrolysis. An internally quenched fluorogenic substrate was also designed that was selectively cleaved by the related PR from avian myeloblastosis virus (AMV). The fluorescence quantum yields of the HIV-1 PR and AMV PR substrates in the RET assay increased by 40.0- and 34.4-fold, respectively, per mole of substrate cleaved. Because of its simplicity, rapidity, and precision in the determination of reaction rates required for kinetic analysis, this method offers many advantages over the commonly used high-performance liquid chromatography- or electrophoresis-based assays for peptide substrate hydrolysis by retroviral PRs.

Amino Acid Sequence↗

[Treatment of operated late gastric carcinoma with prescription of strengthening the patient's resistance and dispelling the invading evil in combination with chemotherapy: follow-up study of 158 patients and experimental study in animals].

158 cases of late gastric carcinoma (11 males and 47 females, age 30-70 years) were treated postoperatively with TCM prescriptions of strengthening the patient's resistance and dispelling the invading evil in combination with chemotherapy. The main ingredients were Radix Codonopsis Pilosulae, Radix Astragali seu Hedysari, Rhizoma Atractylodes, Herba Solani Hyrati, Herba Oldenlandiae and Herba Salviae. The prescription was individualized by adding or subtracting some herbs according to TCM syndrome diagnosis at the time of patient's visit. The decoction was given daily for a long time, three to four years or even longer. It was given alone or together with regimes of chemotherapy at random. The average survival rates at 3 and 5 years were 41.07% and 30.36% respectively. Seven patients have lived for more than 11 years. 10 years survival rate was 12.5%. The combination of Chinese medicine with chemotherapy was better than chemotherapy regime alone (single 5-Fu or CCNU+5-Fu, MMF). Immunological studies of the survivors revealed an enhancement of both humoral and cellular immunity especially the function of peripheral NK cells. The decoction had been given to mice bearing Ehrlich ascites tumor. The amount of ascitic fluid was reduced and its cancer cell count decreased besides a significant increase in over-all survival rate of the animals. It suggested that the above prescription might have an inhibitory or even killing effect on tumor cells. T cell immunity of the treated mice was also improved as seen among patients.

Adult↗

Anthelmintic efficacy, safety, and residue evaluation of levamisole gel formulation in cattle.

Anthelmintic efficacy, safety, and residue studies were conducted in beef calves using a levamisole gel formulation. The effectiveness of levamisole gel and tablet formulations was studied in 30 calves with experimental infection of Ostertagia ostertagi. Removal of 33- to 34-day-old O ostertagi was 99.6% and 97.7%, for the gel and tablet formulation, respectively, when administered orally to supply 8 mg of levamisole HCl equivalent/kg of body weight. A comparative blood concentration study was also used to demonstrate bioequivalence of the levamisole gel to the tablet formulation. In a cross-over-designed test, 5 cattle/treatment group were dosed orally with levamisole 11.5% gel or levamisole tablets at the dosage rate of 8 mg of levamisole HCl/kg. Blood levamisole values were similar with the levamisole gel and tablet formulations. In a safety study, 3 groups of 6 calves each were given levamisole gel orally to provide 8, 24, or 40 mg of levamisole HCl/kg. A 4th group served as controls. Adverse clinical signs were not observed in cattle treated with the recommended dosage level of 8 mg/kg. Transient salivation was noticed in 1 placebo control calf, 2 calves given 24 mg/kg, and 4 calves given 40 mg/kg. Edible tissues from cattle given a single oral dose of levamisole gel (8 mg/kg) were analyzed for drug residues 2 hours and 2, 3, 5, and 7 days after treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Cleavage of fluorogenic substrates for APP-processing proteases by human brain extracts. Ca(2+)-substrate interaction is responsible for Ca2+ stimulation of the neural protease activity.

The proteases that cleave amyloid precursor protein (APP) leading to generation of amyloid A beta peptide are potential targets for therapeutical intervention of Alzheimer disease. We have been pursuing the identification and characterization of these proteases using as probes the fluorogenic substrates encompassing the cleavage sites of APP that we described recently (Wang, G. T., Krafft, G. A. [1992] Bioorg. Med. Chem. Lett. 2, 1665). This article describes results of experiments designed to examine the effect of Ca(2+) on the cleavage of these substrates by human brain extracts. Fluorogenic substrates encompassing either the N-terminal amyloidogenic cleavage site or the secretory cleavage site were synthesized in five formats with various peripheral residues. Incubation with extracts from normal brain tissue revealed that more negatively charged amyloidogenic substrates were less reactive and exhibited larger rate enhancement in the presence of Ca(2+). The results imply that Ca(2+) stimulation of substrate cleavage by brain proteases occurs primarily as a result of Ca(2+)-substrate interactions, and caution against interpretations that invoke the involvement of Ca(2+)-stimulated proteases in A beta formation.

Alzheimer Disease↗