The downregulation of asparagine synthetase expression can increase the sensitivity of cells resistant to l-asparaginase.
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Animals↗
Biomedical subjects
W S Li
Publications and source records attributed to W S Li.
Stereochemical specificity of organophosphorus acid anhydrolase toward p-nitrophenyl analogs of soman and sarin.
Organophosphorus acid anhydrolase (OPAA) catalyzes the hydrolysis of p-nitrophenyl analogs of the organophosphonate nerve agents, sarin and soman. The enzyme is stereoselective toward the chiral phosphorus center by displaying a preference for the R(P)-configuration of these analogs. OPAA also exhibits an additional preference for the stereochemical configuration at the chiral carbon center of the soman analog. The preferred configuration of the chiral carbon center is dependent upon the configuration at the phosphorus center. The enzyme displays a two- to four-fold preference for the R(P)-enantiomer of the sarin analog. The k(cat)/K(m) of the R(P)-enantiomer is 250 M(-1) s(-1), while that of the S(P)-enantiomer is 110 M(-1) s(-1). The order of preference for the stereoisomers of the soman analog is R(P)S(C) > R(P)R(C) > S(P)R(C) > S(P)S(C). The k(cat)/K(m) values are 36,300 M(-1)s(-1), 1250 M(-1) s(-1), 80 M(-1) s(-1) and 5 M(-1) s(-1), respectively. The R(P)S(C)-isomer of the soman analog is therefore preferred by a factor of 7000 over the S(P)S(C)-isomer.
Alteromonas↗
Stereoselective detoxification of chiral sarin and soman analogues by phosphotriesterase.
The catalytic activity of the bacterial phosphotriesterase (PTE) toward a series of chiral analogues of the chemical warfare agents sarin and soman was measured. Chemical procedures were developed for the chiral syntheses of the S(P)- and R(P)-enantiomers of O-isopropyl p-nitrophenyl methylphosphonate (sarin analogue) in high enantiomeric excess. The R(P)-enantiomer of the sarin analogue (k(cat)=2600 s(-1)) was the preferred substrate for the wild-type PTE relative to the corresponding S(P)-enantiomer (k(cat)=290 s(-1)). The observed stereoselectivity was reversed using the PTE mutant, I106A/F132A/H254Y where the k(cat) values for the R(P)- and S(P)-enantiomers were 410 and 4200 s(-1), respectively. A chemo-enzymatic procedure was developed for the chiral synthesis of the four stereoisomers of O-pinacolyl p-nitrophenyl methylphosphonate (soman analogue) with high diastereomeric excess. The R(P)R(C)-stereoisomer of the soman analogue was the preferred substrate for PTE. The k(cat) values for the soman analogues were measured as follows: R(P)R(C,) 48 s(-1); R(P)S(C), 4.8 s(-1); S(P)R(C), 0.3 s(-1), and S(P)S(C), 0.04 s(-1). With the I106A/F132A/H254Y mutant of PTE the stereoselectivity toward the chiral phosphorus center was reversed. With the triple mutant the k(cat) values for the soman analogues were found to be as follows: R(P)R(C,) 0.3 s(-1); R(P)S(C), 0.3 s(-1); S(P)R(C), 11s(-1), and S(P)S(C), 2.1 s(-1). Prior investigations have demonstrated that the S(P)-enantiomers of sarin and soman are significantly more toxic than the R(P)-enantiomers. This investigation has demonstrated that mutants of the wild-type PTE can be readily constructed with enhanced catalytic activities toward the most toxic stereoisomers of sarin and soman.
Aryldialkylphosphatase↗
[Autogenous bone marrow graft for the management of nonunion of tibia].
OBJECTIVE: To investigate the effect of percutaneous bone marrow graft for the management of nonunion of tibia. METHODS: From March 1996 to June 2000, 56 cases with nonunion of tibia were treated by autogenous bone marrow graft. Among them, there were 38 males and 18 females, aged from 19 to 72 years. A marrow needle was inserted into the site of the nonunion under the X-ray, the autogenous bone marrow was injected into the site of nonunion. Compression bandage and appropriate immobilization material were applied after operation. This procedure was repeated every month, 2 or 3 times was needed. RESULTS: 56 patients were followed-up for 4 months to 4 years and 2 months, averaged 2.8 years. Fracture healed in 53 cases and X-ray displayed fracture line disappeared and a great deal of continuous callus formed, and nonunion in 3 cases. CONCLUSION: Percutaneous autogenous bone marrow graft can play a role in osteogenesis at the site of nonunion. It is easy to aspirate bone marrow and the operation is simple. It has clinical application value for the satisfactory effect.
Adult↗
Experimental verification of a predicted, previously unseen separation selectivity pattern in the capillary electrophoretic separation of noncharged enantiomers by octakis(2,3-diacetyl-6-sulfato)-gamma-cyclodextrin.
The capillary electrophoretic separation of noncharged enantiomers with single-isomer anionic resolving agents is reexamined here with the help of the charged resolving agent migration model. Two general model parameters have been identified that influence the effective mobility, separation selectivity and mobility difference curves of the enantiomers: parameter b, called binding selectivity (K(RCD)/K(SCD)), and parameter s, called size selectivity (mu(o)RCD/mu(o)SCD). Analysis of the model in terms of these parameters indicates that in addition to the known, previously observed separation selectivity vs. resolving agent concentration patterns, a new pattern, increasing separation selectivity with increasing resolving agent concentration, is also possible provided that (i) K(RCD)/K(SCD)<1 and mu(o)RCD/mu(o)SCD>1 and (K(RCD)mu(o)RCD)/(K(SCD)mu(o)SCD)>1, or (ii) K(RCD)/ K(SCD)>1 and mu(o)SCD/mu(o)SCD<1 and (K(RCD)mu(o)RCD)/(K(SCD)mu(o)SCD)<1. This hitherto unseen separation selectivity pattern was experimentally verified during the capillary electrophoretic separation of the enantiomers of O-isopropyl p-nitrophenyl methylphosphonate with the single-isomer octakis(2,3-diacetyl-6-sulfato)-gamma-cyclodextrin as resolving agent.
Cyclodextrins↗
Pituitary adenylate cyclase activating polypeptide as a novel hypophysiotropic factor in fish.
Pituitary adenylate cyclase activating polypeptide (PACAP) is a novel member of the secretin-glucagon peptide family. In mammals, this peptide has been located in a wide range of tissues and is involved in a variety of biological functions. In lower vertebrates, especially fish, increasing evidence suggests that PACAP may function as a hypophysiotropic factor regulating pituitary hormone secretion. PACAP has been identified in the brain-pituitary axis of representative fish species. The molecular structure of fish PACAP is highly homologous to mammalian PACAP. The prepro-PACAP in fish, however, is distinct from that of mammals as it also contains the sequence of fish GHRH. In teleosts, the anterior pituitary is under direct innervation of the hypothalamus and PACAP nerve fibers have been identified in the pars distalis. Using the goldfish as a fish model, mRNA transcripts of PACAP receptors, namely the PAC1 and VPACI receptors, have been identified in the pituitary as well as in various brain areas. Consistent with the pituitary expression of PACAP receptors, PACAP analogs are effective in stimulating growth hormone (GH) and gonadotropin (GTH)-II secretion in the goldfish both in vivo and in vitro. The GH-releasing action of PACAP is mediated via pituitary PAC1 receptors coupled to the adenylate cyclase-cAMP-protein kinase A and phospholipase C-IP3-protein kinase C pathways. Subsequent stimulation of Ca2+ entry through voltage-sensitive Ca2+ channels followed by activation of Ca2+-calmodulin protein kinase II is likely the downstream mechanism mediating PACAP-stimulated GH release in goldfish. Although the PACAP receptor subtype(s) and the associated post-receptor signaling events responsible for PACAP-stimulated GTH-II release have not been characterized in goldfish, these findings support the hypothesis that PACAP is produced in the hypothalamus and delivered to the anterior pituitary to regulate GH and GTH-II release in fish.
Amino Acid Sequence↗
[The use of two-route Cisplatin chemotherapy in the treatment of oral squamous cell carcinoma].
OBJECTIVE: To study the feasibility and efficacy of two-route cisplatin chemotherapy for locally advanced squamous cell carcinoma of oral cavity. METHODS: 23 cases with clinical advanced biopsy-proven oral squamous cell carcinoma received intraarterial chemotherapy with cisplatin (DDP), Pingyangmycin (PYM) and 5-fluorouracilum (5-Fu), at the same time intravenous infusion with natrii thiosulfas (STS) for rescue. DDP at 40-60 mg/d, PYM at 16 mg/d and 5-Fu at 500 mg/d were applied for 5-7 consecutive days. RESULTS: 7 cases (33.3%) obtained a complete response (CR), 11(52.4%) had partial response (PR) with an objective response rate (RR) of 85.7%. No severe toxicity was observed, whereas the most frequent grade I and II drug related toxicities were nausea and vomiting. No nephrotoxicity,hepatotoxicity and severe bone marrow suppression were noted. CONCLUSION: Two-route cisplatin chemotherapy is, in our experience,a new,effective and safe therapeutic method for oral squamous cell carcinoma.
English Abstract↗
Deep vein thrombosis and pulmonary embolism in the Chinese population.
Deep vein thrombosis and pulmonary embolism is a well-recognised major health problem in the West. There is a deep-rooted belief among clinicians that deep vein thrombosis is rare in Asians, particularly in the Chinese population. However, it appears that the incidence of venous thrombosis and pulmonary embolism is increasing in Chinese patients. Prophylaxis reduces the incidence of venous thrombosis by 66% and of pulmonary embolism by 50%--- prophylaxis should therefore be considered for Chinese patients who have a high risk of developing postoperative deep vein thrombosis. This report reviews the current literature on this subject.
Journal Article↗
Double filtration plasmapheresis for the treatment of rheumatoid arthritis: a study of 21 cases.
The treatment of rheumatoid arthritis remains difficult and often controversial. Plasma exchange has been advocated in some cases. In the present study 71 sessions of double filtration plasmapheresis (DFPP) were performed in 21 patients with rheumatoid arthritis in an average of 3.7 +/- 1.1 sessions per patient within 1-2 weeks. Seven patients had received prednisone, and all the patients had received nonsteroid anti-inflammatory drugs with poor results. Although after the DFPP therapy, only 2 patients were still receiving nonsteroid anti-inflammatory drugs, the function capacities improved in all patients. Five out of 8 positive rheumatoid factors became negative for the group. These results suggest that DFPP could be a regular therapy for rheumatoid arthritis.
Adolescent↗
Retarding photoreceptor degeneration in Pdegtm1/Pdegtml mice by an apoptosis suppressor gene.
PURPOSE: Mice (Pdegtm1/Pdegtm1) homozygous for a mutant allele of the gamma subunit of retinal cyclic guanosine monophosphate phosphodiesterase (PDE gamma) suffer a severe photoreceptor degeneration. To determine whether the antiapoptotic BCL2 gene is effective in delaying the cell death pathway in this new strain of mutant mice, a transgene encoding the BCL2 gene product was introduced by mating into the mutant background, and the resulting mice were examined for possible rescue of the retinal degeneration. METHODS: Electroretinograms (ERGs) of the Pdegtm1/Pdegtm1 mice carrying BCL2 were taken to monitor the responses to light. Light and electron microscopy of sections were used to examine degeneration at different times after birth. RESULTS: The ERGs of the mutants with the transgene were larger than those without the transgene at 2 and 3 weeks after birth. The maximum differences occurred at 2 weeks postpartum. At 4 weeks after birth, no ERG could be detected in either strain. Histologic analysis showed a greater preservation of photoreceptor nuclei in the Pdegtm1/Pdegtm1 mice containing the BCL2 transgene, which paralleled the electroretinography. CONCLUSIONS: The introduction of an antiapoptotic transgene BCL2 can delay temporarily and partially the degeneration of photoreceptors in a new autosomal-recessive murine model of retinal degeneration.
3',5'-Cyclic-GMP Phosphodiesterases↗
trans-2-phenylcyclopropylamine is a substrate for and inactivator of horseradish peroxidase.
Horseradish peroxidase (HRP) is well known for mediating the electron-transfer oxidation of electron-rich aromatic 'donors' such as phenols and anilines, but has not been described to oxidize aliphatic amines. We here confirm the inability of HRP to oxidize typical aliphatic amines, even those which would exist significantly as free bases at the operative pH. In contrast, trans-2-phenylcyclopropylamine (2-PCPA) is both a substrate (turnover product is cinnamaldehyde) and a time-dependent inactivator of HRP. These activities of 2-PCPA are consistent with either a concerted or rapid sequential one-electron-oxidation/ring-opening to give an intermediate capable of covalent binding to the enzyme. 2-PCPA is the first known example of a simple aliphatic amine which serves as a substrate for HRP under turnover conditions.
Amines↗
Phase I trial of 2B1, a bispecific monoclonal antibody targeting c-erbB-2 and Fc gamma RIII.
2B1 is a bispecific murine monoclonal antibody (BsMAb) with specificity for the c-erbB-2 and Fc gamma RIII extracellular domains. This BsMAb promotes the targeted lysis of malignant cells overexpressing the c-erbB-2 gene product of the HER2/neu proto-oncogene by human natural killer cells and mononuclear phagocytes expressing the Fc gamma RIII A isoform. In a Phase I clinical trial of 2B1, 15 patients with c-erbB-2-overexpressing tumors were treated with 1 h i.v. infusions of 2B1 on days 1, 4, 5, 6, 7, and 8 of a single course of treatment. Three patients were treated with daily doses of 1.0 mg/m2, while six patients each were treated with 2.5 mg/m2 and 5.0 mg/m2, respectively. The principal non-dose-limiting transient toxicities were fevers, rigors, nausea, vomiting, and leukopenia. Thrombocytopenia was dose limiting at the 5.0 mg/m2 dose level in two patients who had received extensive prior myelosuppressive chemotherapy. Murine antibody was detectable in serum following 2B1 administration, and its bispecific binding properties were retained. The pharmacokinetics of this murine antibody were variable and best described by nonlinear kinetics with an average t 1/2 of 20 h. Murine antibody bound extensively to all neutrophils and to a proportion of monocytes and lymphocytes. The initial 2B1 treatment induced more than 100-fold increases in circulating levels of tumor necrosis factor-alpha, interleukin 6, and interleukin 8 and lesser rises in granulocyte-monocyte colony-stimulating factor and IFN-gamma. Brisk human anti-mouse antibody responses were induced in 14 of 15 patients. Several minor clinical responses were observed, with reductions in the thickness of chest wall disease in one patient with disseminated breast cancer. Resolution of pleural effusions and ascites, respectively, were noted in two patients with metastatic colon cancer, and one of two liver metastases resolved in a patient with metastatic colon cancer. Treatment with 2B1 BsMAb has potent immunological consequences. The maximum tolerated dose and Phase II daily dose for patients with extensive prior myelosuppressive chemotherapy was 2.5 mg/m2. Continued dose escalation is required to identify the maximally tolerated dose for patients who have been less heavily pretreated.
Adult↗
[Clinical and experimental study of yangxueshengru oral liquor in promoting puerperal breast milk secretion].
Applying Yangxueshengru Oral Liquor (YXSR) to treat 103 cases of puerperal insufficient lactation. Six hours after delivery, the parturient took YXSR, its effective rate was 98.06%. The results revealed that it could improve breast milk secretion significantly and increase daily lactation amount of parturient, insufficient lactation rate was reduced. The content of protein and trace elements (Fe, Zn and Mn, etc) in colostrum increased, the difference between medicated group and control group was significant (P < 0.05-0.001). Animal experiment showed that YXSR could increase the response of prolactin (PRL) level of model rats (P < 0.01), the serum, PRL and cortisol level of the rats were also raised significantly (P < 0.01).
Adult↗
Enzymic preparation of (3R-cis)-3-(acetyloxy)-4-phenyl-2-azetidinone: a taxol side-chain synthon.
A key chiral intermediate [(3R-cis)-3-(acetyloxy)-4-phenyl-2-azetidinone (2)] for the semi-synthesis of paclitaxel (taxol; 5), an anti-cancer compound, was prepared by an enzymic process. The stereoselective enzymic hydrolysis of cis-3-(acetyloxy)-4-phenyl-2-azetidinone (1) to the corresponding (S)-(-)-alcohol (3) was carried out using various lipases. Lipase PS-30 (Pseudomonas cepacia) and BMS (Bristol-Myers Squibb) lipase (Pseudomonas sp. SC13856) catalysed hydrolysis of the undesired enantiomer of racemic compound 1, producing the (S)-(-)-alcohol (3) and the desired (R)-(+)-acetate (2). Reaction yields of > 96% and optical purities of > 99.5% were obtained. For a very efficient enzyme source (BMS lipase), a lipase fermentation using Pseudomonas sp. SC13856 was developed. In a fed-batch process using soybean oil, the fermentation resulted in 1500 units of extracellular lipase activity/ml. Crude BMS lipase (1.7 kg, containing 140,000 units/g) was recovered from the filtrate by ethanol precipitation. BMS lipase and commercially available lipase PS-30 were independently immobilized on Accurel polypropylene. These immobilized lipases were re-used (ten cycles) without loss of enzyme activity, productivity or optical purity of the product. The enzymic reaction process was scaled up to 75 and 150 litres using immobilized BMS lipase and lipase PS-30 respectively. From the reaction mixture, compound 2 was isolated in 88-90 mol% yield and 99.5% optical purity. A purity of 99.9 (area %) was demonstrated by g.c. for isolated compound 2.
Antineoplastic Agents↗
Preparation of potential anti-inflammatory agents from dehydroabietic acid.
Methyl 16-nor-16-carboxydehydroabietate (22), 16-nor-16-carboxydehydroabietinol acetate (23), methyl 7-keto-16-nor-16-carboxydehydroabietate (29), 16-nor-16-carboxydehydroabietic acid (30), 16-nor-16-carboxydehydroabietinol (31), 7-keto-16-nor-16-carboxydehydroabietic acid (32), methyl 7-hydroxy-16-nor-16-carboxydehydroabietate (33), and 7-hydroxy-16-nor-16-carboxydehydroabietic acid (34) were prepared from dehydroabietic acid. Only 22 and 32 had weak anti-inflammatory activity.
Abietanes↗
Metabolism of carcinogenic nitrosamines by rat nasal mucosa and the effect of diallyl sulfide.
Rat nasal cavity is one of the target organs for carcinogenesis induced by N-nitrosodimethylamine (NDMA), N-nitrosodiethylamine (NDEA), and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). The present work investigated the metabolism of these nitrosamines by rat nasal microsomes, as well as the possible modulating factors. Microsomes prepared from rat nasal mucosa were efficient in metabolizing these nitrosamines. In general, the metabolism of the nitrosamines was slightly higher in 9-week-old rats than in 4-week-old animals, and there was no sex-related difference. Fasting of rats for 48 h, which is known to induce hepatic cytochrome P450IIE1 and NDMA metabolism, did not increase the nasal metabolism of NDMA, NDEA, or NNK. Pretreatment of rats with acetone, another inducer of hepatic P450IIE1, did not increase the metabolism of NDMA. Furthermore, it decreased the nasal metabolism of NDEA and NNK. Immunoinhibition studies suggest that, in the nasal mucosa, P450IIE1 is only partially responsible for the oxidation of NDMA and other P450 isozymes are responsible for the metabolism of NDEA. A single p.o. pretreatment of male rats with diallyl sulfide (DAS), a component of garlic oil, caused a significant decrease in the oxidative metabolism of NDEA and NNK in rat nasal mucosa. Whereas the nasal metabolism of NDMA was reduced by DAS pretreatment, there was no change in the amount of the nasal microsomal proteins immunoreactive with the antibodies against P450IIE1. The inhibitory effect of DAS on the nasal oxidative metabolism of NDMA, NDEA, and NNK was also observed in experiments in vitro. The results demonstrate the ability of nasal mucosa to metabolically activate these nitrosamines and the inhibition of this process by DAS, suggesting that DAS may be effective in inhibiting the related nasal tumorigenesis.
Acetone↗
Dynamic study on iliac trabeculae of normal Chinese.
We studied 41 iliac bone blocks taken by biopsies from normal Chinese who were divided into several groups by age. On the schedule of 3-11-3-5 days, double tetracycline labellings were administered before bone biopsies. Ten microns undecalcified sections were made with Reichert-Jung microtome and analyzed with Zeizz MOP-Videoplan by light and fluorescent microscopy. The results showed that bone formation had a peak value at adolescence and the mean wall thickness decreased gradually with age. Bone dynamics fluctuated with age because of endocrinological changes in the intrinsic environment. The data we obtained may be used as a reference for clinical investigation of various metabolic bone disorders.
Adult↗
Clinical and experimental studies of chronic gastritis in patients with qi-deficiency of spleen.
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Adult↗