[International expert consensus on gene therapy for hereditary hearing loss: based on clinical trials].
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Journal Article↗
Biomedical subjects
W Yuan
Publications and source records attributed to W Yuan.
Studies on kinetic model of vitamin C two-step fermentation process.
This paper aims at analyzing the bioconversion process from L-sorbose to 2-Keto-L-gulonic acid with the aid of the growth factor assumption. Fermentation mechanism is discussed after making necessary simplifications. A model is established for this second step fermentation process. Nonlinear optimization together with Runge-Kutta method, are used to obtain model parameters. Results of computer simulation agree with experimental data to show the reliability of the kinetic model.
Ascorbic Acid↗
[Clinical and experimental study of xiao er ke cuan ling oral liquid in the treatment of infantile bronchopneumonia].
UNLABELLED: Xiao Er Ke Chuan Ling Oral Liquid (KCL) is a Chinese herbal preparation consisted of 10 herbs such as Prunus armeniacae, Scutelaria baicalensis, Lonicera japonica etc. 30 children suffering from bronchopneumonia and/or acute bronchitis were treated with KCL (treated group) and another 30 cases were treated with penicillin and aminophylline (control group). RESULTS: cure rate and effective rate in treated group was 26.6%, and 93.3% respectively. While in control group was 30% and 96.6% respectively. No significant differences were seen between them(P > 0.05). The pharmacodynamic experiment showed KCL had potent pharmacological action. The experiment on tracheal fragment of Guinea pig in vitro showed it caused moderately strong smooth muscle relaxation, through inhibition the effect of histamine and acetylcholine. Asthma induction experiment of Guinea pig in vivo showed KCL could significantly prolong the latent period of asthma and alleviate asthmatic symptom. Ammonium water cough induction experiment in mice showed it may apparently prolong cough latent period and reduce times of cough relapse and alleviate cough symptom. KCL had potent antipyretic effect on fever model induced by triple vaccine in rabbits. Bacteriostatic and antiviral experiment in vitro showed the drug had quite strong inhibitory effects for Streptococcus hemolyticus, Staphylococcus aureus, Flexners Dysentery bacillus, Diplococcus pneumoniae and Pseudomonas aeruginosa, and it could potently inhibit the respiratory syncytial virus. KCL is an effective drug in treating bronchopneumonia and acute bronchitis.
Animals↗
Phosphonate-phospholipid analogues inhibit human phospholipase A2.
A phosphonate-containing phospholipid (PL) analogue (Compound 1) designed as a transition-state inhibitor competively inhibits non-human extracellular PLA2 at a mole fraction of 0.003 in the kinetic "scooting mode" (Jain et al., Biochem 28:4135 (1989]. To further profile the activity of Compound 1, we examined its activity with purified human enzyme and in whole cell systems. Compound 1 effectively inhibited a 14 kDa human PLA2 purified from joint synovial fluid of patients with rheumatoid arthritis using 3H-AA labeled E. coli as substrate (IC50 = 1.7 microM) and a high MW PLA2 (110 kDa) isolated from the cytosol of a human monocytic cell line, U-937, which selectively hydrolyzes AA-containing PL (IC50 = 165 microM). It failed to reduce A23187-induced PGE2 or LTC4 production by human adherent monocytes or LTB4 release from human neutrophils which may be due, in part, to poor membrane partitioning.
Arthritis, Rheumatoid↗
Interfacial catalysis: the mechanism of phospholipase A2.
A chemical description of the action of phospholipase A2 (PLA2) can now be inferred with confidence from three high-resolution x-ray crystal structures. The first is the structure of the PLA2 from the venom of the Chinese cobra (Naja naja atra) in a complex with a phosphonate transition-state analogue. This enzyme is typical of a large, well-studied homologous family of PLA2S. The second is a similar complex with the evolutionarily distant bee-venom PLA2. The third structure is the uninhibited PLA2 from Chinese cobra venom. Despite the different molecular architectures of the cobra and bee-venom PLA2s, the transition-state analogue interacts in a nearly identical way with the catalytic machinery of both enzymes. The disposition of the fatty-acid side chains suggests a common access route of the substrate from its position in the lipid aggregate to its productive interaction with the active site. Comparison of the cobra-venom complex with the uninhibited enzyme indicates that optimal binding and catalysis at the lipid-water interface is due to facilitated substrate diffusion from the interfacial binding surface to the catalytic site rather than an allosteric change in the enzyme's structure. However, a second bound calcium ion changes its position upon the binding of the transition-state analogue, suggesting a mechanism for augmenting the critical electrophile.
Bee Venoms↗
Kinetic and inhibition studies of phospholipase A2 with short-chain substrates and inhibitors.
The action of the phospholipases A2 (PLA2s) from Naja naja naja, Naja naja atra, and Crotalus atrox venoms as well as the enzyme from porcine pancreas on a number of short-chain, water-soluble substrates was studied. The inhibition of these enzymes by short-chain phosphonate- and thiophosphonate-containing phospholipid analogues was also examined. The kinetic patterns observed for the action of the venom PLA2s on substrates containing phosphocholine head groups all deviated from a classical Michaelis-Menten-type behavior. With a substrate containing an anionic head group, the kinetic pattern observed was more normal. In contrast, Michaelis-Menten-type behavior was observed for the action of the porcine pancreatic PLA2 acting on all of the substrates studied. A short-chain phospholipid analogue in which the enzyme-susceptible ester was replaced with a phosphonate group was found to be a tight-binding inhibitor of the venom PLA2s with IC50 values that were some 10(4)-10(5)-fold lower than the concentration of substrate used in the assay. The degree of inhibition was found to depend dramatically on the stereochemical arrangement of substituents in the inhibitor which strongly suggests that the inhibitors are binding directly to the active site of the PLA2s. By comparison, the phosphonate analogue functioned as a poor inhibitor of the porcine pancreatic PLA2. Direct inhibitor binding studies indicated that the short-chain phosphonate inhibitor bound weakly to the venom enzymes in the absence of the short-chain substrates. Several other unusual features of the inhibition were also observed. The data are interpreted in terms of a model in which the enzyme and substrate form a lipid-protein aggregate at substrate concentrations below the critical micelle concentration (cmc). Possible reasons for the selective binding of the inhibitor to the enzyme-substrate microaggregate are discussed.
Animals↗
A new embedding method for tendon suturing.
A new embedding method in tendon suture was designed for interembedding of tendon ends to obtain interlock and strengthen antitension strength. Experiments showed that the embedding method might result in greater antitension strength than the conventional end-to-end method (Bunnell's method) or weaving method. Statistically, difference was significant. Dynamic studies on tendon healing showed that a prominent reaction of surrounding tissues occurred in 3 to 5 days after operation. In this period the antitension strength is likely to decrease and be broken with a rate of 28.1% in Bunnell's method, 5.25% in weaving method and 0% in embedding method. Clinically, the embedding method has been used in 125 cases of tendon-broken repair in which a 87.8% of good and excellent effect was resulted.
Animals↗
[Effects of Coxsackie B-2 virus infection on electrophysiologic properties of beating cultured rat heart cells].
Beating rat heart cell cultures were prepared in vitro and infected with Coxsackie B-2 virus. The cells were evaluated in the post infected period for changes in beating frequency, percentage of active cells and cytopathic effect (CPE), and for alterations of the electrical activity by standard intracellular microelectrode techniques. The beating frequency and percentage of active cells began to decrease in infected group at 24 h, and the beating percentage was less than 30% at 96 h after virus challenge. Meanwhile the CPE appeared rapidly from 1+ to 3+. In contrast, the beating percentage was 95% and no CPE was shown in the control group. Decrease of maximum diastolic potential (MDP), maximum upstroke rate (Vmax) and overshoot (os) and amplitude (APA) of action potential, and shortened action potential duration (APD50 and APD100) were found 24 h after infection. Multiform arrhythmias occurred commonly during the experiment. Complete loss of cardiac electrical activities and maximal CPE occurred at 96 h post-infection. Our findings may be useful for the study of pathogenesis and treatment of viral myocarditis in human being.
Action Potentials↗
Competitive inhibition of phospholipase A2 in vesicles.
Kinetic studies with phospholipase A2 are complicated by the fact that binding of the enzyme to the interface precedes catalytic turnover. This difficulty can be overcome by monitoring interfacial catalysis in the scooting mode where the enzyme does not leave the interface. The kinetics of inhibition by transition-state analogues shows that specific competitive inhibition is the result of competition between inhibitor and substrate for the binding to the active site of the enzyme in the interface. Several lipophilic compounds, including alkanols, substituted butyrophenones, aristolochic acid, and mepacrine apparently reduce the rate of lipolysis by promoting the desorption of phospholipase A2 from the interface.
Binding Sites↗